Fine margins, that's been the story in the top division all through this League.
And so it proved again in this final-round game in frozen (albeit sunny) Nowlan Park yesterday.
Two points, that's all that separated the teams at the end of an exhilarating game, two points that Cork could easily have prevented at one end had the defence been just that little bit smarter after Luke O'Farrell had blasted home their first goal on 47 minutes — two points that could easily have been scored at the other end but for some outstanding shot-stopping by new Kilkenny keeper Eoin Murphy.
Two points is also all that separates the teams on the final league table and yet, exemplifying just how daft is the current structure, Kilkenny now happily head into a league semi-final in three weeks, against Galway, while Cork face the dreaded relegation final, against equally unlucky Clare.
He has every reason to feel satisfied, does Brian. Defender Paul Murphy and ace attackers Henry Shefflin and TJ Reid have yet to come back, Michael Rice will have the next few weeks to get rid of whatever rustiness remains from his long injury break, yet — as Cody noted — Kilkenny were still strong enough to forge those three wins on the trot, against Waterford, Clare and now, Cork.
Yesterday's win was the most impressive of the lot. Cork came to Nowlan Park with real fire and purpose, were 0-7 to 0-3 ahead after 24 minutes and it should have been more. Corner-forward Patrick Horgan was in on Eoin Murphy within 20 seconds of the start, took the right option, but his bullet was superbly saved by Murphy who then denied Luke O'Farrell on the rebound.
Again in the 30th minute Murphy denied O'Farrell and really, Cork should have been ahead at the break, well ahead even, though in fairness Cork keeper Anthony Nash was also in action, denied Richie Hogan from a well-struck penalty. Instead, and with Kilkenny scoring the last four points of the half, the sides went in level at 0-7 apiece.
Where the first-half had been a chess-match, both defences doing superbly in end-to-end action, the second saw the game begin to open up. Cork finally got the goal they had threatened (47m) and fittingly, it was O'Farrell with the finish, capitalising on superb setup work by Paudie O'Sullivan and Stephen Moylan.
That score put the visitors 1-10 to 0-11 in front and when O'Farrell again split the defence open a few minutes later for a fine point, the signs were good for Cork.
Worthy winners, Kilkenny, but Cork selector Seanie McGrath was looking on the bright side, unconcerned with the possibility of relegation. "We're not looking at 2014, we're looking at 2013 and will look for another encouraging performance again against Clare. Obviously we'd prefer not to be relegated, that goes without saying, but there have been enough encouraging signs from week to week this year so that even if we do end up going down, it's still been positive.


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redpajama_set_name: RedPajamaCommonCrawl


text:
Entering Goa
with a pet
Entering Goa with a pet
Rabies controlled area
Report any suspect animal to the Goa Rabies Hotline 7744029586
Goa is on the brink of eliminating rabies
There have been no human deaths from rabies for over two years due to a campaign by the Government of Goa to control the disease in collaboration with the NGO, Mission Rabies. The project focuses on three areas of work:
Mass dog vaccination
Community education about rabies
Enhanced rabies surveillance
As is the case across most of India, Goa suffered the consequences of rabies circulating in the roaming dog population, with human deaths occurring where people did not get vaccinated following a bite from a rabid dog. Over 4,00,000 doses of rabies vaccine have been delivered to dogs in Goa since 2013 in the largest continuous rabies control effort to have ever taken place in India. The campaign aims to get most dogs in the state vaccinated against rabies every year, to educate all children about the risk of rabies through lessons in schools and to increase testing for the disease through widespread public reporting of any possible rabies case across the state.
Campaign Supporters
We thank those who have supported the campaign:
The government of Goa
The government of Goa provide funding through a grant for implementing vaccination and surveillance work, which was renewed for a further three years in 2018.
Mission Rabies
Mission Rabies is an international NGO working to develop effective methods for rabies control where it is needed most. The charity has been responsible for implementing mass dog vaccination, community education and rabies surveillance activities in Goa under the leadership of the Government of Goa since 2013.
Dogs Trust Worldwide has supported the campaign through providing grant funding to Mission Rabies for dog vaccination, surveillance, research and education since 2013.
MSD Animal Health have donated over 300,000 doses of Nobivac Rabies to Mission Rabies for use in Goa state since 2013, a high quality and thermostable vaccine to control the disease.
The University of Edinburgh provides support for campaign data analysis, reporting and operational research to explore ways of optimising campaign structure and improving the efficiency of the vaccination methods.
NIMHANS
NIMHANS has supported the Goa Campaign since 2014 through providing Rabies diagnostic testing capacity in Bangalore, and supporting the training of staff to establish rabies testing capacity through the Goa Disease Investigation Unit in 2016 in collaboration with Mission Rabies and the Department for Animal Husbandry and Veterinary Services.
Rotary International supported the Goa campaign through the donation of three Vaccination vehicles in 2017, which have been used to transport vaccination teams across the entire state, vaccinating over 200,000 dogs. They also donated three scooters to support the evaluation of efforts through post-vaccination surveys.
4 Castle Street
Cranborne
BH21 5PZ
Mission Rabies is registered with the Charity Commission for England and Wales (1162293)
Mission Rabies USA, Inc is a 501(c)3 non-profit organization – EIN 81-5065473
© Mission Rabies 2021 - All rights reserved.


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Math is one of the oldest sciences and is a cornerstone in many disciplines. Due to the advancement of technology, mathematicians today do not have to limit themselves to the academe to practice their craft. They can pursue lucrative and high-paying careers in the corporate world. They can use their talent with numbers to help companies run their operations more efficiently, as with finance, or they can help businesses come up with innovative products and solutions, as with information technology and software development.
The typical coursework of an online mathematics degree would generally include topics such as computational mathematics, mathematical modelling, statistical design, bio statistical methods, calculus, matrix algebra, mathematics, management science, statistical data analysis and databases.
People who have math degrees have a lot of career opportunities in their hands. They can work in different sectors and industries, even those not directly related to mathematical science in the technical sense of the word. Examples of businesses that need the services of mathematicians are banks, pharmaceutical companies, software companies, insurance companies, and accounting firms. The pay is another huge draw, with salaries of math professionals averaging $81,240 per year.


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AMPAS invitees represent 77 countries
This year, the the Academy of Motion Picture Arts and Sciences invited 928 new members, 49 percent are female filmmakers from all over the world (up from last year's 683 invitees).
Diverse female directors invited to AMPAS
The Academy of Motion Picture Arts and Sciences (AMPAS) has invited 928 new members; 49 percent are women. According to Variety, this class will bring the total AMPAS membership to 31 percent female, up from 25 percent in 2015. This year there is a very diverse and international female representation of filmmakers from around the world.
Diverse female screenwriters invited to AMPAS
The Academy of Motion Picture Arts and Sciences (AMPAS) has invited 928 new members; 49 percent are women. According to Variety, this class will bring the total AMPAS membership to 31 percent female, up from 25 percent in 2015.
Sonja O'Hara talks filmmaking, breaking stereotypes and not waiting for permission
Writer, director and actress Sonja O'Hara is a filmmaker to watch – at least according to Independent Magazine. Born in Nova Scotia, Canada and pursuing an acting career by age 17, she has created work that is bold, original, provocative and meant to change the way Hollywood and audiences see films.
Abbie Reese documents life and sacrifice of cloistered nuns in 'Chosen'
Director Abbie Reese, an Illinois native and dual citizen of Luxembourg, documents Rockford's Corpus Christi Monastery in her debut film Chosen: Custody of the Eye. The film unveils the hidden lives of the monastery nuns and their sacrifice, purity, divine life and commitment to God.


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July 2017: Alliance Announces New Headquarters in Clifton Park
Home / News and Updates / July 2017: Alliance Announces New Headquarters in Clifton Park
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July 2017: Alliance Announces New Headquarters in Clifton Park2017-09-112020-11-09https://allianceriskgroup.com/wp-content/uploads/2017/03/ai2x.pngAlliance Risk Group Inc.https://allianceriskgroup.com/wp-content/uploads/2017/09/ribboncutting.jpg200px200px
As summer draws to a close, we'd like to share some of the recent highlights for our company…
Alliance Risk Group celebrated the opening of our new headquarters with a Ribbon Cutting Ceremony and Open House on July 12, 2017. Here is our official announcement:
Mario Pecoraro, President/CEO of Alliance Risk Group, is pleased to announce the opening of the company's new expanded headquarters located at 23 Executive Park Drive. The company will celebrate with a Ribbon Cutting ceremony immediately followed by an Open House until 7 pm.
According to Mario Pecoraro, "We would like to extend a heartfelt thanks to our clients, friends and partners in the Capital Region and beyond for our continued growth and success as we embrace our 13th year in operation. We hope you will come and take a tour of our new location." Refreshments will be served following the ribbon cutting ceremony including hors d'oeuvres and cigars along with live music.
Alliance Risk Group. (AWIG) provides effective due-diligence based background investigations customizable to a variety of industries including pharmaceutical, service, financial, IT, staffing, retail and more. The company also performs complete claims investigations for insurance and corporate professionals. In addition, Avvocato Litigation Support International and Preferred Adjustment Company are powered by Alliance Risk Group and operate out of the Clifton Park office. Avvocato offers complete legal support including service of process on a local, state, national and international level. This division serves law firms of all sizes, in-house legal departments of major corporations and government agencies that need service of process anywhere. Preferred Adjustment Company provides full service claims handling and property/casualty adjusting services for insurance carriers, self-insured companies and attorneys. Preferred lead adjusters hold CPCU designation, are strategically located throughout all of New York and can service claims on a regional and multi-state level.
Alliance Risk Group Fact Sheet: Interview with CEO Mario Pecoraro
Please describe what inspired you to open your own business.
I have had a strong passion for the investigative industry since I was a young child watching my parents operate their private investigative agency. Seeing the entrepreneurial spirit of my own parents and working as a young child in their firm inspired me to open my own business. In 2005, I founded Alliance Risk Group, which specializes in helping organizations of all sizes manage risk from an investigative perspective at all levels, from pre-employment to post hire challenges. My work ranges from background screening to insurance and other fraud investigations.
Why you chose this type of business
I chose this business because it's literally been in my blood since as long as I can remember. While most kids were playing ball, and hanging out on street corners after school, I already had a part-time job: riding along with my Mom and Dad while they did investigations on behalf of their small, family-owned private investigation firm. It was the only business I ever knew. It was what my parents talked about at breakfast, lunch and dinner, and I got hooked from a very young age. How young? I can remember being twelve or thirteen years old and riding along with my folks as they did surveillance, tracked down missing persons and pursued various leads.
Please give us some background information on yourself, include your training and education, hobbies and work history prior to opening this business
Prior to founding the company, I worked for more than 15 years as a private investigator in my parents' firm and conducted more than 2,500 hours of field investigative work, skip-tracing, and asset investigations, and located missing person, heirs and witnesses. I met with clients and eventually handled my own investigations. After high school, I worked nonstop while pursuing my Bachelor of Science degree in Criminal Justice with a double major in Italian from the State University of New York at Albany, where I graduated Cum Laude.
Tell us why/what made you pick your location
I live in Clifton Park with my wife, Jo Jo, and established the Alliance Risk Group headquarters here in 2008. At that time, it was our third expansion in 3 years! In 2016, when a building became available for purchase directly across the street, I jumped at the chance to renovate and own our own headquarter building. Our new location at 23 Executive Park Drive, accommodates our staff beautifully and eliminates wasted space without sacrificing roominess. We have spacious reception area, eat-in kitchen with all the amenities, a large and small conference room, several private offices and a large open floor space with workstations for investigators. In addition, one of the most exciting opportunities with this purchase is that my wife has relocated her business from Latham and now operates SKINCARE by Jo Jo out of the east end of the building.
Please give us the key aspects of your business that you would like people to know
Alliance Risk Group has grown into a national/international investigative firm offering a variety of services. We focus on helping organizations increase their bottom line, and manage challenges that are associated with their most critical assets: its people or "human capital." With more than 25 years of proven experience in due-diligence based investigative services, Alliance Risk Group has become a leader in the insurance and background investigation fields, property and casualty adjusting, and process service industries.
What can customers expect to experience from your business? What sets you apart?
Customers can expect an excellent service experience from Alliance Risk Group. When anyone contacts Alliance Risk Group, they will be greeted by one of our employees telling them that "we inspire confidence." We do this by providing complete risk mitigation services globally. Our goal, which we measure through tracking key performance indicators and reporting in our Monday morning huddles, is to constantly provide actionable intelligence, detailed, timely communication and on-time performance. Inspired by John D. Rockefeller's disciplined approach to business growth, the huddle keeps the company aligned and provides our clients with excellent service.
Another key area that sets us apart is our corporate culture which is based on a set of core values that the team strives to achieve daily. The most important core values being, "Integrity First – Always Tell the Truth; Successfully Engaged – Be Successfully Engaged in All You Do; Positive Attitude – Always Exhibit a Positive Attitude and Professional Demeanor; and Passion for Excellence – Strive for Excellence in All Your Endeavors! Alex Chargen, CEO of a business consulting company wrote, "Throughout my career consulting to the Fortune 500 and thousands of entrepreneurs, I've found that a strong, unified company culture, built around performance, is a key identifier of future success."
Adjustment Services, Alliance Worldwide Investigative Group, Avvocato Litigation Support International, Background Checks, background investigation services, Background Investigations, expanded headquarters, headquarters, insurance fraud investigations, Mario Pecoraro, Preferred Adjustment Company, Process Service, service of process, Workers Compensation Fraud
Join Us at our Happy Hour- Boston PLRB Claims Conference & Insurance Services Expo – Monday 3/27 6-8 pm!News and Updates
8/31/17: Alliance Team Enjoys Tri-City Valley Cats Baseball GameNews and Updates


Physics is the scientific study of nature and how its laws and theories relate to energy and matter. Explore job options in the field of theoretical and mathematical physics, and read about the education requirements, employment outlook and salary potential for several positions.
Are Theoretical and Mathematical Physics For Me?
Physicists often work at high-tech international research facilities. Many mathematical and theoretical physicists work as college professors. High school physics teachers, and many careers in academia or industry also heavily draw upon deep theoretical physical concepts, leaving you with many physics-related career options.
As a physicist, you can work in classrooms, laboratories and other controlled environments, both in conjunction with large groups and independently, during regular hours or during odd hours when rare natural phenomena or test results are expected. As a professional, you could mainly give public lectures and write popular science books or do extensive lab work and technical writing for academic journals.
According to the U.S. Bureau of Labor Statistics (BLS), physicists are expected to see average job growth at a rate of 10% during the 2012-2022 decade (www.bls.gov). Furthermore, in May of 2012, the median wage for physicists was $106,840, and the top-earning 10% of theoretical and mathematical physicists made $176,630 or more. The BLS also reported that in the same year, astronomers received a median wage of $96,460.
How Can I Work in Theoretical and Mathematical Physics?
While some research posts are available to master's degree holders, nearly all professional positions in theoretical and mathematical physics require a Doctor of Philosophy (Ph.D.). Students who enroll in a mathematics or physics bachelor's degree program take advanced mathematics classes in algebra, calculus, trigonometry and analysis. They also take classes in technical physics, electricity, magnetism, quantum mechanics, aerodynamics and scientific computing. Opportunities for online physics bachelor's degrees are available as well.
Next, you will need to pursue a master's degree in physics or a Ph.D. program in physics. In a mathematical physics or theoretical physics graduate degree program, you can specialize and assist in researching areas of study like string theory, quantum field theory, quantum computing, particle physics, astronomy, cosmology and energy.
A Ph.D. program in physics requires passing a candidacy exam and completing advanced physics courses, like experimental physics, condensed matter physics, particle physics and large-scale physics. Students must conduct independent research in a specific area of theoretical or mathematical physics of their choice and write and defend a dissertation to a faculty committee.
You can study theoretical physics while completing a physics degree program. Read about physics programs, online offerings and employment options in this field.
A degree in mathematical physics explores the intersection of math and physics as they relate to explaining the natural phenomena and characteristics of the Earth. Read further to learn about available degrees and the careers in the field.


Are you looking for the map of San Miguel? Find any address on the map of San Miguel or calculate your itinerary to and from San Miguel, find all the tourist attractions and Michelin Guide restaurants in San Miguel. The ViaMichelin map of San Miguel: get the famous Michelin maps, the result of more than a century of mapping experience.


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Religious and spiritual sites
Basilique-cathédrale de la paroisse de Notre-Dame-de-Québec
Cathedral of the Holy Trinity
Shrine of Notre-Dame-de-Rocamadour
Father Frédéric Janssoone Museum
Val Notre-Dame Abbey
Sanctuary of Sainte-Marguerite-d'Youville
Ste-Thérèse-de-L'Enfant-Jésus
Shrine of the Sacred Heart of Beauvoir
Albert Gilles Copper Art - Art Studio & Museum
Shrine of Sainte-Anne-de-Beaupré
Our Lady of the Cape Shrine
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Saint Joseph's Oratory of Mount-Royal
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Notre-Dame-de-Bon-Secours Chapel
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Mauricie is a region of wide-open spaces, a vast area of possibilities for discovery. Explore small chapels, the majestic Notre-Dame-du-Cap Shrine and the Frederic Janssoone Museum that pays tribute…
Québec is the continent's oldest catholic parish in North America as well as the city where the first Anglican cathedral was built outside the British Isles. The Roman Catholic cathedral basilica of…
If you're interested in history, you'll find the religious heritage of the Eastern Townships fascinating! Built during the English colonization of the 18th and 19th centuries, the Baptist, Methodist…
Montréal is a place where people have come together for millennia, from the Kanien'kéha (Mohawk) people who call the island Tiohtiá:ke, to the arrival of European settlers, to the myriad of cultures…
Peace, tranquility, relaxation and discovery. Saguenay-Lac-Saint-Jean, nestled in the heart of Québec, is a popular destination for travellers in search of a spiritual and religious journey. With its…
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Dr. Michael M. Connors is an Independent Director of the Company. He has served as a director of DZS since November 2003 following the consummation of Legacy Zhone's merger with Tellium, Inc. Dr. Connors had been a member of Tellium's board of directors since June 2000. From 1992 to 1998, Dr. Connors held the office of President of AOL Technologies, an Internet service provider, where he led the creation and growth of AOLnet and the development of AOL software and services. Dr. Connors is currently a director of The Connors Foundation. Dr. Connors earned a B.S. in Engineering, an M.S. in Statistics and a Ph.D. in Operations Research from Stanford University.


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Maia (also spelled Maya) is a Papuan language spoken in the Madang Province of Papua New Guinea, and is a member of the Trans-New Guinea language family. It has a language endangerment status of 6a, which means that it is a vigorous and sustainable language spoken by all generations. According to a 2000 census, there are approximately 4,500 living speakers of the language, who are split between twenty-two villages in the Almani district of the Bogia sub-district.

There are variations in the Maia spoken between villages, but they can be generally categorized into two primary dialects. Of these two dialects, the Main Dialect accounts for approximately three-fourths of speakers and the Southern Dialect accounts for the remaining one-fourth. Variations of the Main Dialect tend to be predictable with only minor variations in pronunciation. The information presented in this article is based on the Wagedav dialect, a sub-dialect of the Main Dialect spoken in the Wagedav village.

Other names for the language are Banar, Pila, Saki, Suaro, Turutap, and Yakiba.

Phonology
The phonemic inventory of Maia is fairly small, as is typical of languages from Papua New Guinea.

In some cases, vowels and consonants are modified or deleted across morphemes in a word. These morphophonemic rules are detailed in this section.

Consonants
The following table details these consonant phonemes and allophones for each, if any.

The voiced labiovelar approximant /w/ is the sole multi-place consonant in Maia.

Vowels
Maia contains the five basic vowel phonemes in the chart below:

Syllable Structure
Possible syllable structures in Maia are illustrated in the chart below. Onsets in Maia can end with a vowel, while codas can end in either a vowel or consonant.

Morphophonemic Rules

Vowel Deletion
There are two instantiations of this rule. The first instance applies to adjacent vowels in a verb: when two vowels are adjacent to each other at the junction of two morphemes within a verb, the first vowel is deleted. For example, 'he is eating' is not nimɛ - a, as the 'ɛ' is deleted to give nima (p. 11).

The second instance is more general: when there are two identical vowels adjacent to each other at the junction of two morphemes within any word, one is deleted. For example, 'he worked' is not 'malip-a-a' , as one 'a' is deleted to give malipa (p. 11).

Vowel Harmony
In words with two verb suffixes, the vowel in the final suffix is repeated in the penultimate suffix. For example, 'I heard' is not 'damɛ - mi' but is instead 'damimi (p. 12).

 Consonant Deletion
The consonant deletion rule applies to a few select clitics: -gat, -di, -no, -waka. When these clitics are appended to the end of another word that ends in a consonant, the initial consonant of the clitic is deleted. For example, 'always' is not inaβ - gat' but is 'inaβat' (p. 12).

Morphology
Maia is a synthetic fusional language, in which word-building is accomplished primarily through clitics and derivational affixes.

Maia does not have case markings, but does have agreement between nouns and their adjectives and between verbs and their objects.

Clitics
Clitics are an especially common means of word-building in Maia. Some clitics can be combined sequentially to produce a cumulative meaning, as in the case of combining the contrast marker clitic =(d)i and the topic marker =(n)o to indicate a topic that is in contrast with something else. The upper limit on the number of clitics that can be combined appears to be three.

The following table summarizes the clitics in the Maia language. Consonants in parentheses are typically included only if the word to which the clitic is appended ends in a vowel.
{| class="wikitable"
|+
!Clitic
!Function
!Examples
|-
|=(w)aka
|
 Limitation marker
 Adverbializer
|
 Depending on the context it is placed in, can indicate limitations such s 'just', 'only', alone', 'exactly', 'completely', 'absolutely'.
 The adverb 'lovaka' ('well') is derived from the noun 'lov' ('good').
|-
|=(g)at
|
 Comitative marker to indicate an association or possession
 Adverbializer
 Nominalizer
|
 Appending =(g)at to the end of a name indicates that something is with that named individual.
 'toromo' ('new'); 'toromogato' (firstly)
 'ukum' ('head'); 'ukumat' ('leader')
|-
|=yag
|Collective marker
|'bisibis' ('descendants'); 'bisibisyag' ('descendants' (collectively))
|-
|=mate
|Manner marker to indicate similarity
|'wageva onomate means 'like the cockatoo': 'wageva' means 'cockatoo', 'ono' indicates a reference to a third person singular object. So, 'onomate' means 'like the [insert object]'
|-
|=ga
|Specific locative marker to indicate a location, position, time frame, origin, or recipient. This can be both in the literal or abstract sense. In all of these cases, it refers to a defined object.
|Literal example:
ya u-parar=ga

water 3s-on.top.of=LOC1

'on top of the water'

Abstract example:

no-nor viol lovavan ono u-podav=ga

2s-INTP curse very.good D1 3s-under=LOC1

'under your blessing'
|-
|=ra
|
 Non-specific locative marker to indicate an approximate or unspecific location, time, motion. In all of these cases, it refers to a more vague object.
 Indicator of the addition of numbers, as Maia only has unique words for numbers one through five.
|
 'muanigo' means 'today', and 'muanigora' means 'sometime today'.
 anuv igur=ga kuvik=ra duwa=ga

time five=LOC1 other.side=LOC2 one=LOC1

'on the sixth day' (lit 'on the five plus one day')
|-
|=(n)o
|Topic marker to indicate referential information. This clitic frequently marks the subject of the clause.
|Yo-nor awn winim=o Dasti
1s=INTP dog name=TP Dasti

'My dog's name is Dasti.'
|-
|=(d)i
|Contrast marker to indicate a shift or contrast in the clause.
|No=no ta kenai=di av-inek+an-ini di=no yo=no wabona=di avio...
2s=TP DIR left=CT go-DES.s+say-IR.2s DS=TP 1s=TP right=CT go-IR.1s

'If you want to go to the left, I'll go the right.'
|-
|=git
|Contrafactual marker to indicate what did not or could not happen.
|Ma-ne=mate=waka, wi-nor nada maia bu badaka u-dogo=waka lovavan onor=aka katu ilika-mo=git.
E-do=MN=LIM 3p-INTP child PL AD1 all 3s-straight-LIM very.good INTS=LIM enough/able come.up-RL.1s/3p=CFT.

'In view of that, all of their children too could have come up really good and straight (but they didn't).'
|-
|=ma
|Emphatic marker used to emphasize a prominent person or situation in a clause.
|=ma can be appended to the end of a person's name to signal importance, as in the name Abram: 'Abramma'
|-
|=na
|Attention marker used to signal to the audience that the next statement will be important. It can be used to indicate the turning point of a story, for example. It is placed at the end of the statement preceding the important one.
|Avia-sa wae=ra ilika-mi bada imara-sa=na sae nam buas+u-simi
go-SEQ garden=LOC2 come.up-RL.1p SS meet-SEQ=ATN garden tree cut+3s-give.RL.1p

'We went and arrived in the garden, then we met (and) we cut garden trees for him.' (The cutting of the garden trees is a critical point in the story.)
|}

 Derivational affixes
Affixes in Maia are predominantly derivational suffixes.

The nominalizing suffix -arav can be used to create nouns from verb roots. For example, 'wadib' means 'to argue', but 'wadib-arav' means 'the arguing' (p. 40).

The verbalizing suffix -(n)a can be used to create verbs from nouns and adjectives, as in the case of the word for white, 'waia' (p. 45):

There are four classes of derived causative verb suffixes, which may be affixed to the end of a preexisting verb root to emphasize a causal relationship. These suffixes are -tate, -te, -rate, and -de. For example, 'ebe' ('wake up') is the progenitor of 'ebetate' ('to wake up (somebody)') (p. 46).

 Non-derivational affixes
The only class of non-derivational affixes in Maia are possessor prefixes. These prefixes are appended in front of an adjective to indicate the possessor of the noun, as summarized in the table below. The distinction between singularity and plurality is established with a difference in stress patterns.

These prefixes indicate that an adjective "belongs" to the object being described. In the following example, the prefix u-indicates that the quality of being short belongs to the tree (p. 59).These prefixes are also frequently, but not always, appended to verbs to indicate the recipient of an action. Transitive verbs with objects require the presence of such a prefix, while intransitive verbs are more variable. The following example illustrates this (p. 43):

 Compounds
There are a few words in Maia in which two existing nouns are combined to give rise to a new word. This includes compounds such as 'muado nanum': separately, 'muado' means 'man' and 'nanum' means 'woman', but compounding together gives rise to the new meaning of 'people' (p. 41). Similarly, 'kakape' ('bee') and 'yag' ('water') together are the compound word kakapeyag' ('honey') (p. 42).

Reduplication
Full or partial reduplication of nouns in Maia can indicate plurality, a diminutive form of the original word or alternatively, the derived adverb form of the word. The Maia word 'kuvik' ('side') can be repeated as 'kuvik kuvik' to mean 'each side' (p. 41). The word for 'house' is 'dawa' and the word for small house is 'dawadawa' (p. 41). Lastly, an example of the third case is 'riwaro' ('nothing') partially reduplicated into 'ririwaro' to mean 'aimlessly' (p. 41).

Full or partial reduplication of verb roots indicates an augmentation of the action or indicates a repeated action. Typically reduplication occurs in two different forms: either repetition of only the first syllable or repetition of the entire root. For example, 'gubue' means 'to fold' while 'gugubue' means 'to fold repeatedly', and 'ipua' means 'to peel' while ipuaipua' means 'to peel repeatedly' (p. 49).

Reduplication or partial reduplication of adjectives can serve three different purposes: to indicate augmentation, plurality, or diminishment. An example of reduplication used to express augmentation, repeating the Maia word for 'good' ('lov') changes the meaning to 'very good' ('lovlov'). Reduplication can also indicate plurality, as in the example of 'nanam kani' ('big tree') and 'nanam kanikani' ('big trees'), or 'maia' ('thing') and 'maiamaia' ('things'). Lastly, reduplication can signal the diminutive form of a word, as in the case of 'isav' ('hot') and '''isisav' ('warm').

Numeral quantifiers utilize a special case of reduplication. Complete reduplication of a number indicates something in succession ('iner' alone means 'two', but 'ineriner' means 'two by two'), while partial reduplication of a number acts as a multiplier (ininer' means 'double').

 Stress
Stress patterns are used to differentiate between 1st and 2nd person singular and plural inalienably possessed nouns. (Maia has some nouns that are inalienably possessed, which include body parts, kinship terms, and position nouns.) For example, 'my skin' is /i' dia/, but 'our skin' is /'idia/ (p. 13).

 Agreement
In transitive clauses, the verb must agree in both person and number with the object. In the following example, the verb for 'divide' must include the third-person-singular marker 'a' to indicate that it applies to a singular object in the third person (the pig):In intransitive clauses, the verb must agree in both person and number with the subject. The example below demonstrates that the verb for 'go' must be modified to indicate that it applies to a first-person plural subject:The non-derivational possessor affixes described above in this section also agree in person and number with the noun they describe.

 Syntax

 Basic Word Order

 Transitive Clauses
The basic word order of Maia is SOV for transitive clauses, as illustrated by the transitive sentence example below:

 Intransitive Clauses
The basic word order is SV for intransitive clauses:

 Ditransitive Clauses
For clauses that have both an indirect object and a direct object, the indirect object typically comes before the direct object. The following example, in which 'Kunia' is the indirect object and 'plate' is the direct object, illustrates this:

 Core Phrase Types

 Verb + Object Phrase
The verb phrase in the example above illustrates that the verb + object phrase in Maia is head final, as the verb 'chase' comes after the object 'pig'.

 Determiner + Noun Phrase
The example above also demonstrates that the determiner+noun phrase is also head final, as the determiner ono ('that') comes after its complement kani'' ('pig').

Possessee + Possessor Phrase
The possessee+possessor phrase is also head final, as the possessee 'garden' comes after the possessor 'Mamudia':

Complementizer/Subordinator + Clause Phrase
An exception is the complementizer/subordinator+clause phrase, which is head-initial. In the example below, 'me maianane' translates to 'because'. This complementizer precedes the rest of the clause.

Modifiers

Adverbials
Adverbs are placed before the verb in adverbial phrases:

Adjectives
Adjectives are placed immediately after the noun that they describe:

References

External links
 Maia - English - Tok Pisin Dictionary

Kaukombaran languages
Languages of Madang Province

redpajama_set_name: RedPajamaWikipedia


NEW YORK — The spotlight shines brightly on British Prime Minister Winston Churchill in "Darkest Hour" (Focus), a historical drama about political leadership and backroom intrigue during a pivotal moment of World War II.
Churchill (1874-1965) was 65 years old and, it was thought, in the twilight of his political career when he was tapped to lead a wartime coalition government in May 1940. The war was going badly for the Allies, and Nazi Germany was marching into Belgium and France, threatening an invasion of Britain.
It was truly the country's darkest hour, and director Joe Wright ("Atonement"), working from a screenplay by Anthony McCarten, offers a thrilling take on Churchill's first three weeks in power.
The film is in some respects a companion piece to the 2017 film "Dunkirk," taking place at the same time. While "Dunkirk" neglected politics in favor of personal stories, "Darkest Hour" goes behind the scenes, revealing how Churchill rallied a skeptical cabinet to fight the enemy rather than sue for peace, and arranged the miraculous evacuation of nearly 350,000 soldiers stranded on the French beach.
Beneath some remarkable facial prosthetics and layers of padding, Gary Oldman disappears into the role of Churchill, capturing the gait, cadence and charisma of the man. This is a warts-and-all portrayal of a decidedly quirky individual who loved his cigars and booze, was often rude and sarcastic, but who in private had moments of self-doubt.
At his side was his stalwart wife, Clementine (Kristin Scott Thomas), proud that her husband was finally getting his chance to lead, however late in life.
Churchill succeeds the feckless Neville Chamberlain (Ronald Pickup), whose policy of appeasement with Nazi Germany has left Britain woefully unprepared for war. But Chamberlain enjoys the king's favor, as does the politically ambitious Viscount Halifax (Stephen Dillane). The trio schemes to disgrace Churchill and put Halifax in power.
As Europe is overrun, Churchill is pressured to sue for peace. The idea of bowing to Adolf Hitler and the Nazis is anathema to his lifelong belief in justice and liberty.
"You cannot reason with a tiger when your head is in its mouth!" he roars at Halifax.
"Darkest Hour" proceeds at a breakneck pace as Churchill gradually convinces his colleagues to fight and rallies the nation. Although some liberties are taken with the facts (including a marvelous moment when Churchill interacts with ordinary people on the subway, which never happened), the film offers an important history lesson for young and old about a time when statesmanship mattered most.
Churchill's greatest asset was his voice, which he used to great effect on the radio and in Parliament to inspire the nation. As he composed his stirring speeches, Churchill was aided by his secretary, Elizabeth Layton (Lily James), and his most faithful ally, the secretary of state for war — and future prime minister — Anthony Eden (Samuel West).
The film contains brief scenes of wartime violence and some mature themes. The Catholic News Service classification is A-II — adults and adolescents. The Motion Picture Association of America rating is PG-13 — parents strongly cautioned. Some material may be inappropriate for children under 13.


ANZAC Day is a remembrance day in Australia, New Zealand and a few other Pacific Island countries. The day honours the soldiers of the Australian and New Zealand Army Corp at Gallipoli in Turkey in World War I. It is held on 25 April each year with dawn services being held and is a public holiday.
↑ Recap: Anzac Day commemorations. Stuff.co.nz. Retrieved on April 30, 2018.
This page was last modified on 29 April 2018, at 21:47.


This course includes Lessons 26-30 from the Danish Level 1 program featuring 2.5 hours of language instruction. Each lesson provides 30 minutes of spoken language practice, with an introductory conversation, and new vocabulary and structures. Detailed instructions enable you to understand and participate in the conversation. Practice for vocabulary introduced in previous lessons is included in each lesson. The emphasis is on pronunciation and comprehension, and on learning to speak Danish.
These lessons contain Reading Lessons designed to provide you with an introduction to reading Danish. The combined Reading Lessons are also included at the end of Lesson 30. These lessons, which total about one hour, are designed to teach you to sound out words with correct pronunciation and accent. The Reading Booklet to be used with the audio Reading Lessons is included.


text:
A Medical Research Study Designed to Determine if Venglustat Can be a Future Treatment for ADPKD Patients (STAGED-PKD)
Recruitment Status : Terminated (Interim analysis for futility of the Stage 1 of the EFC15392 study met the protocol specified stopping rule based on the primary endpoint. EFC15392 study was stopped for futility based on prespecified criteria and recommendation from DMC)
First Posted : May 14, 2018
Results First Posted : November 9, 2022
Genzyme, a Sanofi Company
Sanofi ( Genzyme, a Sanofi Company )
Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Polycystic Kidney, Autosomal Dominant
Drug: Venglustat
Drug: Placebo
Participant Flow
Top of Page Participant Flow Baseline Characteristics Outcome Measures Adverse Events Limitations and Caveats Information More Information
Recruitment Details This study was conducted at 93 sites that enrolled participants in 23 countries. A total of 478 participants were enrolled from 04 October 2018 to 01 June 2021. Study was conducted in 2 stages: Stage 1 and Stage 2.
Pre-assignment Details Participants who completed 24 months of treatment in either Stage 1 or Stage 2 of EFC15392 had option to enroll in an open-label long-term extension study LTS15823 (NCT ID: NCT04705051).
Arm/Group Title
Stage 1- Placebo
Stage 1- Venglustat 8 mg
Stage 1- Venglustat 15 mg
Arm/Group Description Participants from Stage 1 were rand... Participants from Stage 1 were rand... Participants from Stage 1 were rand... Participants from Stage 2 were rand... Participants from Stage 2 were rand...
Arm/Group Description Participants from Stage 1 were randomized to receive 2 capsules of placebo matched to venglustat once daily for treatment period of 24 months. Participants from Stage 1 were randomized to receive venglustat 8 milligrams (mg) (i.e., 2 capsules of 4 mg) once daily for treatment period of 24 months. Participants from Stage 1 were randomized to receive 1 capsule of venglustat 15 mg and 1 capsule of placebo matched to venglustat once daily for treatment period of 24 months. Participants from Stage 2 were randomized to receive 1 capsule of placebo matched to venglustat once daily for treatment period of 24 months. Participants from Stage 2 were randomized to receive 1 capsule of venglustat 15 mg once daily for treatment period of 24 months.
Period Title: Stage 1 (24 Months)
Started 78 78 80 0 0
Completed 12 10 12 0 0
Not Completed 66 68 68 0 0
Reason Not Completed
Adverse Event 2 2 4 0 0
Progressive disease 0 0 1 0 0
Lack of Efficacy 2 0 0 0 0
Poor compliance to protocol 1 0 0 0 0
Withdrawal by Subject 6 5 7 0 0
Study terminated by sponsor 54 59 56 0 0
Other-Unspecified 1 2 0 0 0
Started 0 0 0 123 [1] 119 [1]
Treated 0 0 0 122 119
Estimated Glomerular Filtration Rate (eGFR) Between 45 and 89.9 mL/Min/1.73 m^2 at Screening 0 0 0 97 90
eGFR Between 30 and 44.9 mL/Min/1.73 m^2 at Screening 0 0 0 25 29
Completed 0 0 0 0 0
Not Completed 0 0 0 123 119
Study terminated by sponsor 0 0 0 119 110
Randomized and not treated 0 0 0 1 0
Stage 1 and Stage 2 were separate population.
Total Title
Arm/Group Description Participants from Stage 1 were rand... Participants from Stage 1 were rand... Participants from Stage 1 were rand... Participants from Stage 2 were rand... Participants from Stage 2 were rand... [Not Specified]
Arm/Group Description Participants from Stage 1 were randomized to receive 2 capsules of placebo matched to venglustat once daily for treatment period of 24 months. Participants from Stage 1 were randomized to receive venglustat 8 mg (i.e., 2 capsules of 4 mg) once daily for treatment period of 24 months. Participants from Stage 1 were randomized to receive 1 capsule of venglustat 15 mg and 1 capsule of placebo matched to venglustat once daily for treatment period of 24 months. Participants from Stage 2 were randomized to receive 1 capsule of placebo matched to venglustat once daily for treatment period of 24 months. Participants from Stage 2 were randomized to receive 1 capsule of venglustat 15 mg once daily for treatment period of 24 months. [Not Specified]
Overall Number of Baseline Participants
Baseline Analysis Population Description ...
Baseline Analysis Population Description
Analysis was performed on all participants randomized in the study.
Age, Continuous
Mean (Standard Deviation)
Unit of measure: Years
Number Analyzed 78 participants 78 participants 80 participants 123 participants 119 participants 478 participants
42.6 (6.0) 41.7 (6.9) 43.6 (5.7) 41.7 (6.9) 42.1 (6.7) 42.2 (6.5)
Sex: Female, Male
Measure Type: Count of Participants
Unit of measure: Participants
Race (NIH/OMB)
Unknown or Not Reported
1.Primary Outcome
Annualized Slope of Change in Total Kidney Volume (TKV) From Baseline to Month 18: Stage 1
Total kidney volume is a measure for assessing disease progression in ...
Total kidney volume is a measure for assessing disease progression in participants with ADPKD, a prognostic biomarker of renal function decline and progression to end-stage renal disease. Kidney volume was assessed using magnetic resonance imaging (MRI). The annualized slope of change in TKV (in percentage [%] per year) in each treatment group was obtained from the back-transformation of the mean slope of log10-transformed TKV obtained from the linear mixed effect model. The model included fix effects of treatment (venglustat 15 mg, venglustat 8 mg or placebo), mayo imaging classification (as per randomization stratification factor: class 1C versus 1D versus 1E), time (as continuous variable in years), treatment * time interaction and mayo imaging classification * time interaction and included random intercept and slope.
From Baseline to Month 18
Outcome Measure Data Outcome Measure Data
Analysis Population Description
Analysis was performed on Stage 1 intent-to-treat (ITT) population that includes all participants randomized in Stage 1 and were analyzed according to the intervention allocated by randomization (venglustat 15 mg, venglustat 8 mg or placebo). Here, 'Overall number of participants analyzed' signifies participants who were evaluable for the outcome measure.
Arm/Group Description: Participants from Stage 1 were rand... Participants from Stage 1 were rand... Participants from Stage 1 were rand...
Arm/Group Description:
Participants from Stage 1 were randomized to receive 2 capsules of placebo matched to venglustat once daily for treatment period of 24 months.
Participants from Stage 1 were randomized to receive venglustat 8 mg (i.e., 2 capsules of 4 mg) once daily for treatment period of 24 months.
Participants from Stage 1 were randomized to receive 1 capsule of venglustat 15 mg and 1 capsule of placebo matched to venglustat once daily for treatment period of 24 months.
Overall Number of Participants Analyzed
Geometric Least Squares Mean (95% Confidence Interval)
Unit of Measure: percent change in TKV/year
(5.10 to 7.62)
Statistical Analysis 1
Statistical Analysis Overview
Comparison Group Selection
Stage 1- Placebo, Stage 1- Venglustat 8 mg
[Not Specified]
Type of Statistical Test
Statistical Test of Hypothesis
=0.1367
linear mixed effect model
Method of Estimation
Estimation Parameter
Relative difference
(2-Sided) 95%
-5.77 to 58.22
Estimation Comments
Stage 1- Placebo, Stage 1- Venglustat 15 mg
-24.57 to 33.36
Annualized Rate of Change in Estimated Glomerular Filtration Rate (eGFR) (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) From Baseline to Month 24: Combined Stage 1 and Stage 2
An eGFR was used to measure level of kidney function and determine the...
An eGFR was used to measure level of kidney function and determine the stage of kidney disease in ADPKD participants. Baseline eGFR was defined for each participant as the average of eGFR values assessed prior or equal to first dose of study drug or randomization for participants randomized and not exposed. Annualized rate of change in eGFR in each treatment group was obtained from the linear mixed effect model including the fixed categorical effects of treatment group (venglustat 15 mg, venglustat 8 mg or placebo), mayo imaging classification (as per interactive response technology [IRT]: 1C, 1D, 1E), time (as continuous variable in years), treatment-by-time, mayo imaging classification-by-time, and included random intercept and slope.
Analysis was performed on Combined Stage 1 and Stage 2 ITT population that included all participants with an eGFR between 45 and 89.9 mL/min/1.73 m^2 at screening who are randomized in Stage 1 or Stage 2 and were analyzed according to the intervention allocated by randomization (venglustat 15 mg, venglustat 8 mg or placebo). Data for this outcome measure (OM) was planned to be collected and analyzed for combined Stage 1 and Stage 2 population as pre-specified in protocol.
Venglustat 8 mg
Venglustat 15 mg
Arm/Group Description: All participants from Stage 1 or St... Participants from Stage 1 were rand... All participants from Stage 1 or St...
All participants from Stage 1 or Stage 2 were randomized to receive placebo matched to venglustat once daily for treatment period of 24 months.
All participants from Stage 1 or Stage 2 were randomized to receive 1 capsule of venglustat 15 mg once daily for treatment period of 24 months.
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mL/min/1.73 m^2/year
(-3.30 to -1.49)
Placebo, Venglustat 8 mg
Placebo, Venglustat 15 mg
3.Secondary Outcome
Annualized Rate of Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Month 24: Stage 1
An eGFR was used to measure level of kidney function and determine the stage of kidney disease in ADPKD participants. Baseline eGFR was defined for each participant as the average of eGFR values assessed prior or equal to first dose of study drug or randomization for participants randomized and not exposed. Annualized rate of change in eGFR was obtained from the linear mixed effect model including the fixed categorical effects of treatment group, mayo imaging classification (as per IRT), time (as continuous variable in years), treatment-by-time, mayo imaging classification-by-time, and included random intercept and slope. Due to early termination of study for futility, the two-steps analysis initially planned was not applicable, then the annualized rate of change from baseline in eGFR in Stage 1 population were assessed using all data available up to database lock (i.e., including Month 24 assessment). As this is a slope, it allowed to have more data and to reduce variability.
Analysis was performed on Stage 1 ITT population.
7.01 to 125.45
Annualized Slope of Change in Total Kidney Volume (TKV) From Baseline to Month 18: Combined Stage 1 and Stage 2
Total kidney volume is a measure for assessing disease progression in participants with ADPKD, a prognostic biomarker of renal function decline and progression to end-stage renal disease. Kidney volume was assessed using MRI. The annualized slope of change in TKV (in % per year) in each treatment group was obtained from the back-transformation of the mean slope of log10-transformed TKV obtained from the linear mixed effect model. The model included fix effects of treatment (venglustat 15 mg, venglustat 8 mg or placebo), mayo imaging classification (as per randomization stratification factor: class 1C versus 1D versus 1E), time (as continuous variable in years), treatment * time interaction and mayo imaging classification * time interaction and included random intercept and slope.
As no post-baseline MRI data were collected in Stage 2 due to early study discontinuation, the analysis of TKV in Combined Stage 1 and Stage 2 was not done.
No data displayed because Outcome Measure has zero total analyzed.
Change in Pain Severity as Measured by Brief Pain Inventory-Short Form (BPI-SF)-Item 3 Scale Score From Baseline to Month 18: Stage 1
The BPI-SF is a validated, self-administered questionnaire designed to...
The BPI-SF is a validated, self-administered questionnaire designed to measure a participant's perceived level of pain. The BPI-SF consisted of 15 items that use a numeric rating scale (NRS) to assess pain severity and pain interference in the past 24 hours and the past week. BPI-SF Item 3 asks participants to "Please rate your pain by marking the box beside the number that best describes your pain at its worst in the past 24 hours." The NRS ranged from 0 (no pain) to 10 (worst imaginable pain), where higher scores indicates greater intensity of pain. Least-squares (LS) means, and standard errors (SE) were estimated from mixed-effect model with repeated measures (MMRM) analysis.
Analysis was performed on Stage 1 ITT population. Here, 'Overall number of participants analyzed' signifies participants who were evaluable for the outcome measure.
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-0.09 (0.15) 0.01 (0.17) -0.35 (0.16)
Mixed effect model with repeated measure
Least square mean difference
-0.342 to 0.556
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.23
Change in Pain Severity as Measured by Brief Pain Inventory-Short Form (BPI-SF)-Item 3 Scale Score From Baseline to Month 24: Combined Stage 1 and Stage 2
The BPI-SF is a validated, self-administered questionnaire designed to measure a participant's perceived level of pain. The BPI-SF consisted of 15 items that use a NRS to assess pain severity and pain interference in the past 24 hours and the past week. BPI-SF Item 3 asks participants to "Please rate your pain by marking the box beside the number that best describes your pain at its worst in the past 24 hours." The NRS ranged from 0 (no pain) to 10 (worst imaginable pain), where higher scores indicate greater intensity of pain. LS means and SE were estimated from MMRM analysis.
Analysis was performed on Combined Stage 1 and Stage 2 ITT population. Here, 'Overall number of participants analyzed' signifies participants who were evaluable for the outcome measure. Data for this OM was planned to be collected and analyzed for combined Stage 1 and Stage 2 population as pre-specified in protocol.
-0.20 (0.23) -0.31 (0.36) -0.36 (0.23)
Change in Fatigue Severity as Measured by Brief Fatigue Inventory (BFI-SF)-Item 3 Scale Score From Baseline to Month 18: Stage 1
The BFI-SF is a 10-item, validated, self-administered questionnaire th...
The BFI-SF is a 10-item, validated, self-administered questionnaire that was originally developed to assess fatigue severity. The 10-items were measured on a 0-10 scale, with 0 being 'does not interfere' and 10 being 'completely interferes.' BFI - Item 3 asks participants to 'Please rate your fatigue (weariness, tiredness) by circling the one number that best describes your worst level of fatigue during the past 24 hours. The NRS ranged from 0 (no fatigue) to 10 (worst imaginable fatigue). Higher global scores were associated with more severe fatigue. LS means and SE were estimated from MMRM analysis.
Stage I- Venglustat 15 mg
Stage 1- Placebo, Stage I- Venglustat 15 mg
Change in Fatigue Severity as Measured by Brief Fatigue Inventory (BFI-SF)-Item 3 Scale Score From Baseline to Month 24: Combined Stage 1 and Stage 2
The BFI-SF is a 10-item, validated, self-administered questionnaire that was originally developed to assess fatigue severity. The 10-items were measured on a 0-10 scale, with 0 being 'does not interfere' and 10 being 'completely interferes.' BFI - Item 3 asks participants to "Please rate your fatigue (weariness, tiredness) by circling the one number that best describes your worst level of fatigue during the past 24 hours. The NRS ranged from 0 (no fatigue) to 10 (worst imaginable fatigue). Higher global scores were associated with more severe fatigue. LS means and SE were estimated from MMRM analysis.
0.02 (0.38) -0.85 (0.55) -0.51 (0.38)
Pharmacokinetics: Plasma Concentration of Venglustat: Stage 1
Venglustat plasma concentrations was determined using a validated liqu...
Venglustat plasma concentrations was determined using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Data for this outcome measure was not planned to be collected and analyzed for placebo arm.
Day 1: 3 hours Post-Dose, Month 1: Pre-Dose and 3 hours Post-Dose, Month 6: Pre-Dose, Month 18: Pre-Dose
Analysed on Stage 1 pharmacokinetic (PK) population that included all participants randomized in Stage 1 who took at least one dose of study drug and had at least one post-baseline PK assessment; analyzed according to the intervention they actually received. Here, "number analyzed" signifies participants with available data for each specified category.
Arm/Group Description: Participants from Stage 1 were rand... Participants from Stage 1 were rand...
Unit of Measure: nanograms per milliliter
Day 1: 3 hours Post-Dose
Number Analyzed
65 participants 73 participants
27.8 (11.9) 50.9 (22.5)
Month 1: Pre-Dose
54.7 (19.2) 103.9 (50.2)
Month 1: 3 hours Post-Dose
Months 6: Pre-Dose
Months 18: Pre-Dose
10.Secondary Outcome
Venglustat plasma concentrations was determined using a validated LC-M...
Venglustat plasma concentrations was determined using a validated LC-MS/MS method. Data for this outcome measure was not planned to be collected and analyzed for placebo arm.
Month 1: Pre-dose and 3 hours Post-dose
Analysis was performed on Stage 2 PK population that included all participants with an eGFR between 45 and 89.9 mL/min/1.73 m^2 at screening who were randomized in Stage 2, who took at least one dose of study drug and who had at least one post-baseline PK assessment. Participants were analyzed according to study drug they actually received. Here, "number analyzed" signifies participants with available data for each specified category.
Arm/Group Description: Participants from Stage 2 were rand...
Participants from Stage 2 were randomized to receive 1 capsule of venglustat 15 mg once daily for treatment period of 24 months.
109.3 (60.7)
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs): Stage 1
An adverse event (AE) was any untoward medical occurrence in a partici...
An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. A serious adverse event (SAE) was any untoward medical occurrence that at any dose: results in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was a medically important event. TEAEs were AEs that developed, worsened or became serious during the treatment-emergent (TE) period (defined as the time from the first investigational medicinal product [IMP] administration up to the last IMP administration in EFC15392 study + 30 days or up to the first visit in LTS15823 study, whichever comes earlier).
From the first IMP administration up to the last IMP administration in EFC15392 study + 30 days (i.e., up to 25 months) or up to the first visit in LTS15823 study, whichever comes earlier
Analysis was performed on Stage 1 safety population that included all participants randomized in Stage 1 who took at least one dose or part of a dose of the double-blind IMP, analyzed according to the treatment actually received (venglustat 15 mg, venglustat 8 mg, or placebo)
TEAEs
TESAEs
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs): Combined Stage 1 and Stage 2
An AE was any untoward medical occurrence in a participant or clinical...
An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. SAE was any untoward medical occurrence that at any dose: results in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was a medically important event. TEAEs were AEs that developed, worsened or became serious during the TE period (defined as the time from the first IMP administration up to the last IMP administration in EFC15392 study + 30 days or up to the first visit in LTS15823 study, whichever comes earlier).
Analysis was performed on extended Combined Stage 1 and Stage 2 safety population that included all participants with an eGFR between 45 and 89.9 mL/min/1.73 m^2 at screening who were randomized in Stage 1 or Stage 2 and who took at least one dose or part of a dose of IMP, analyzed according to treatment actually received. Data for this OM was planned to be collected and analyzed for combined Stage 1 and Stage 2 population as pre-specified in protocol.
Number of Participants With Potentially Clinically Significant Abnormalities: Hematology: Combined Stage 1 and Stage 2
Criteria for potentially clinically significant abnormalities: Hemoglo...
Criteria for potentially clinically significant abnormalities: Hemoglobin: less than or equal to (<=) 115 grams per liter (g/L) [Male]; <=95 g/L [Female]; greater than or equal to (>=) 185 g/L [Male]; >=165 g/L [Female]; Decrease from baseline >=20 g/L; Hematocrit: <=0.37 volume/volume (v/v) [Male]; <=0.32 v/v [Female]; >=0.55 v/v [Male]; >=0.5 v/v [Female]; Erythrocyte (red blood cells [RBC]): >=6*10^12 per liter (/L); Platelet: less than (<) 100*10^9/L; >=700*10^9/L; Leukocyte (white blood cells [WBC]): <3*10^9/L [Non-Black]; <2*10^9/L [Black], >=16*10^9/L; Neutrophils: <1.5*10^9/L [Non-Black]; <1*10^9/L [Black]; Lymphocytes: greater than (>) 4*10^9/L, Monocytes: >0.7*10^9/L; Basophils: >0.1*10^9/L; and Eosinophils: >0.5*10^9/L or >upper limit of normal (ULN) (if ULN >=0.5*10^9/L).
Analysis was performed on extended Combined Stage 1 and Stage 2 safety population. Here, "number analyzed" signifies participants with available data for specified category. Data for this OM was planned to be collected and analyzed for combined Stage 1 and Stage 2 population as pre-specified in protocol.
Hemoglobin: <=115 g/L (Male); <=95 g/L (Female)
187 participants 78 participants 190 participants
Hemoglobin: >=185 g/L (Male); >=165 g/L (Female)
Hemoglobin: Decrease from baseline >=20 g/L
Hematocrit: <=0.37 v/v (Male); <=0.32 v/v (Female)
Hematocrit: >=0.55 v/v (Male); >=0.5 v/v (Female)
Erythrocyte (RBC): >=6 * 10^12/L
Platelet: <100*10^9/L
Platelet: >=700*10^9/L
Leukocyte (WBC): <3*10^9/L (Non-Black); <2*10^9/L (Black)
Leukocyte (WBC): >=16*10^9/L
Neutrophils: <1.5*10^9/L (Non-Black); <1*10^9/L (Black)
Lymphocytes: >4*10^9/L
Monocytes >0.7*10^9/L
Basophils: >0.1*10^9/L
Eosinophils: >0.5*10^9/L or >ULN
Number of Participants With Potentially Clinically Significant Abnormalities: Clinical Chemistry: Combined Stage 1 and Stage 2
Criteria for potentially clinically significant abnormalities: Glucose...
Criteria for potentially clinically significant abnormalities: Glucose: <=3.9 millimoles per liter (mmol/L) and <lower limit of normal (LLN): >=11.1 mmol/L (unfasted); >=7 mmol/L (fasted); Albumin:<=25 g/L; Sodium: <=129 mmol/L; >=160 mmol/L; Potassium: <3 mmol/L; >=5.5 mmol/L; Chloride: <80 mmol/L, >115 mmol/L; Creatinine: >=150 micro millimoles per liter (mcmol/L) (Adults); >=30% change from Baseline; >=100% change from Baseline, Urea Nitrogen: >=17 mmol/L; Alanine Aminotransferase (ALT): >3 ULN; Aspartate Aminotransferase (AST): >3 ULN; Alkaline Phosphatase: >1.5 ULN; Total Bilirubin: >1.5 ULN, >2 ULN; ALT >3 ULN and Bilirubin >2 ULN; and Direct Bilirubin >35% Bilirubin and Bilirubin >1.5 ULN.
Analysis was performed on extended Combined Stage 1 and Stage 2 safety population. Here, "number analyzed" signifies participants with available data for each specified category. Data for this OM was planned to be collected and analyzed for combined Stage 1 and Stage 2 population as pre-specified in protocol.
Glucose: <=3.9 mmol/L and <LLN
Glucose: >=11.1 mmol/L (unfasted); >=7 mmol/L (fasted)
Albumin: <=25 g/L
Sodium: <=129 mmol/L
Sodium: >=160 mmol/L
Potassium: <3 mmol/L
Potassium: >=5.5 mmol/L
Chloride: <80 mmol/L
Chloride: >115 mmol/L
Creatinine: >=150 mcmol/L (Adults)
Creatinine: >=30% change from Baseline
Creatinine: >=100% change from Baseline
Urea Nitrogen: >=17 mmol/L
ALT: > 3 ULN
AST: >3 ULN
Alkaline Phosphatase: >1.5 ULN
Total Bilirubin: >1.5 ULN
Total Bilirubin: >2 ULN
ALT >3 ULN and Bilirubin >2 ULN
Direct Bilirubin >35% Bilirubin and Bilirubin >1.5 ULN
Number of Participants With Potentially and Clinically Significant Abnormalities: Urinalysis: Combined Stage 1 and Stage 2
Criteria for potentially clinically significant abnormalities: Urine p...
Criteria for potentially clinically significant abnormalities: Urine pH: <=4.6 and >=8.
Urine pH: <=4.6
Urine pH: >=8
Number of Participants With Potentially and Clinically Significant Abnormalities: Vital Signs: Combined Stage 1 and Stage 2
Criteria for potentially clinically significant abnormalities: Sitting...
Criteria for potentially clinically significant abnormalities: Sitting Systolic Blood Pressure: <=95 millimeters of Mercury (mmHg) and decrease from Baseline >=20 mmHg; >=160 mmHg and increase from Baseline >=20 mmHg; Sitting Diastolic Blood Pressure: <=45 mmHg and decrease from Baseline >=10 mmHg, >=110 mmHg and increase from Baseline >=10 mmHg; Sitting Heart Rate: <=50 beats/minute and decrease from Baseline >=20 beats/minute; >=120 beats/minute and increase from Baseline >=20 beats/minute; and Weight: >=5% decrease from Baseline; >=5% increase from Baseline.
Sitting Systolic Blood Pressure: <=95 mmHg and decrease from Baseline >=20 mmHg
Sitting Systolic Blood Pressure: >=160 mmHg and increase from Baseline >=20 mmHg
Sitting Diastolic Blood Pressure: <= 45 mmHg and decrease from Baseline >=10 mmHg
Sitting Diastolic Blood Pressure: >=110 mmHg and increase from Baseline >=10 mmHg
Sitting Heart Rate: <=50 beats/min and decrease from Baseline >=20 beats/min
Sitting Heart Rate: >=120 beats/min and increase from Baseline >=20 beats/min
Weight: >=5% decrease from Baseline
Weight: >=5% increase from Baseline
Number of Participants With Potentially Clinically Significant Abnormalities: Electrocardiogram: Combined Stage 1 and Stage 2
Criteria for potentially clinically significant abnormalities: Heart R...
Criteria for potentially clinically significant abnormalities: Heart Rate: <50 beats/minute; <50 beats/minute and decrease from Baseline >=20 beats/minute; <40 beats/minute; <40 beats/minute and decrease from Baseline >=20 beats/min; <30 beats/minute; >90 beats/minute; >90 beats/minute and increase from Baseline >=20 beats/minute; >100 beats/minute; >100 beats/minute and increase from Baseline >=20 beats/minute; >120 beats/minute; >120 beats/minute, increase from Baseline >=20 beats/minute; PR Interval: >200 milliseconds (msec); >200 msec and increase from Baseline >=25%; >220 msec, >240 msec; QRS Interval: >110 msec; >110 msec and increase from Baseline >=25%; >120 msec; >120 msec and increase from Baseline >=25%; QT Interval: >500 msec; QT corrected for heart rate (QTc) Bazett: >450 msec; >480 msec; increase from Baseline (30-60) msec; increase from Baseline >60 msec; QTc Fridericia: >450 msec; >480 msec; increase from Baseline (30-60) msec and increase from Baseline > 60 msec.
Heart Rate: <50 beats/min
Heart Rate: <50 beats/min and decrease from Baseline >=20 beats/min
Heart Rate: >90 beats/min
Heart Rate: >90 beats/min and increase from Baseline >=20 beats/min
Heart Rate: >100 beats/min
Heart Rate: >100 beats/min and increase from Baseline >=20 beats/min
PR Interval: >200 msec
PR Interval: >200 msec and increase from Baseline >=25%
QRS Interval: >110 msec
QRS Interval: > 110 msec and increase from Baseline >=25%
QRS Interval: >120 msec and increase from Baseline >=25%
QT Interval: >500 msec
QTc Bazett: >450 msec
QTc Bazett: Increase from Baseline [30-60] msec
QTc Bazett: Increase from Baseline >60 msec
QTc Fridericia: >450 msec
QTc Fridericia: Increase from Baseline [30-60] msec
QTc Fridericia: Increase from Baseline >60 msec
Number of Participants With Physical Examination Abnormalities: Combined Stage 1 and Stage 2
Physical examination included: Head, Heart, Lung, Abdomen, Musculo/Ske...
Physical examination included: Head, Heart, Lung, Abdomen, Musculo/Skeletal, Skin, and Mental Status. Abnormality in physical examination was based on investigator's discretion. Results are based on the treatment emergent period which was defined as time from the first IMP administration up to the last IMP administration in EFC15392 study + 30 days or up to the first visit in LTS15823 study, whichever comes earlier.
Baseline, Month 18, Month 24
Baseline: Head
Baseline: Heart
Baseline: Lung
Baseline: Abdomen
Baseline: Musculo/Skeletal
Baseline: Skin
Baseline: Mental Status
Month 18: Head
49 participants 49 participants 47 participants
Month 18: Heart
Month 18: Lung
Month 18: Abdomen
Month 18: Musculo/Skeletal
Month 18: Skin
Month 18: Mental Status
7 participants 4 participants 7 participants
Change From Baseline in Beck Depression Inventory-II (BDI-II) Score: Combined Stage 1 and Stage 2
The Beck Depression Inventory-II (BDI-II) is a 21-item questionnaire u...
The Beck Depression Inventory-II (BDI-II) is a 21-item questionnaire used to assess depression. Most items are rated on a 4-point scale from 0 to 3, and a few items are rated on a 7-point scale. Individual item scores are added to get a total BDI-II score from 0 to 63. The higher the total score, the more severe the depression, and the lower the total score, the less severe the depression.
Baseline, Months 3, 6, 9, 12, 15, 18, 21, and 24, Last on-treatment value up to last IMP + 1 day (anytime during the maximum duration of 25 months)
4.0 (4.7) 3.0 (4.1) 3.4 (4.1)
Change at Month 3
-0.1 (4.0) 0.7 (4.0) 0.7 (4.3)
92 participants 67 participants 100 participants
Change at Month 12
-1.5 (4.4) -0.1 (4.4) -0.3 (4.0)
1.0 (9.5) -0.1 (1.3) 1.1 (2.8)
Change at Last on-treatment value
Number of Participants With Worsening Lens Opacity From Baseline During the Treatment-emergent Period: Combined Stage 1 and Stage 2
Worsening of lens opacity classification system (LOCS) III score or Wo...
Worsening of lens opacity classification system (LOCS) III score or World Health Organization (WHO) grade in nuclear opacification, cortical opacification and posterior subcapsular opacification were assessed for 'Any eye', 'Unilateral' and 'Bilateral' separately. A participant could be counted in all the 3 categories. In each category, the worst case was taken into account. To be evaluable for 'Any', a participant had to have at least one eye evaluable, whereas, for 'Unilateral' and 'Bilateral', a participant had to have both eyes evaluable. Therefore, the sum of 'Unilateral' + 'Bilateral' is not necessarily equal to 'Any' in the below table. The difference observed in 'Nuclear Opacification' in 15 mg group, comes from that 1 participant who had Unilateral worsening at a given visit and a Bilateral worsening at another visit. Therefore, this participant was counted as 'Unilateral', 'Bilateral' and counted only once in 'Any'. Results are based on the TE period.
Analysis was performed on extended Combined Stage 1 and Stage 2 safety population. Here, "number analyzed" signifies participants with available data for each specified category. Data for this OM was planned to be collected and analyzed for combined Stage 1 and Stage 2 population as pre-specified in protocol. TE period: time from first IMP administration up to the last IMP administration in EFC15392 study + 30 days or up to the first visit in LTS15823 study, whichever comes earlier.
Worsening of LOCS III score >= 0.5 or WHO grade >= 1.0 in nuclear opacification: Any eye
Worsening of LOCS III score >= 0.5 or WHO grade >= 1.0 in nuclear opacification: Unilateral
Worsening of LOCS III score >= 0.5 or WHO grade >= 1.0 in nuclear opacification: Bilateral
Worsening of LOCS III score >= 0.8 or WHO grade >= 1.0 in cortical opacification: Any eye
Worsening of LOCS III score >= 0.8 or WHO grade >= 1.0 in cortical opacification: Unilateral
Worsening of LOCS III score >= 0.8 or WHO grade >= 1.0 in cortical opacification: Bilateral
Worsening of LOCS III score>=0.5 or WHO grade >= 1.0 in posterior subcapsular opacification:Any eye
Worsening of LOCS III score>=0.5 or WHO grade >=1.0 in posterior subcapsularopacification:Unilateral
Worsening of LOCS III score>=0.5 or WHO grade >=1.0 in posterior subcapsular opacification:Bilateral
Time Frame From the first IMP administration up to the last IMP administration in EFC15392 study + 30 days (i.e., up to 25 months) or up to the first visit in LTS15823 study, whichever comes earlier
Adverse Event Reporting Description Reported AEs were TEAEs that developed/worsened in grade or became serious during TE period (time from the first IMP administration up to the last IMP administration in EFC15392 study + 30 days or up to the first visit in LTS15823 study, whichever comes earlier). Analysis was performed on the Stage 1 and Stage 2 safety population.
Arm/Group Title Stage 1- Placebo Stage 1- Venglustat 8 mg Stage 1- Venglustat 15 mg Stage 2- Placebo Stage 2- Venglustat 15 mg
Arm/Group Description Participants from Stage 1 were randomized to receive 2 capsules of placebo matched to venglustat once daily for treatment period of 24 months. Participants from Stage 1 were randomized to receive venglustat 8 mg (i.e., 2 capsules of 4 mg) once daily for treatment period of 24 months. Participants from Stage 1 were randomized to receive 1 capsule of venglustat 15 mg and 1 capsule of placebo matched to venglustat once daily for treatment period of 24 months. Participants from Stage 2 were randomized to receive 1 capsule of placebo matched to venglustat once daily for treatment period of 24 months. Participants from Stage 2 were randomized to receive 1 capsule of venglustat 15 mg once daily for treatment period of 24 months.
All-Cause Mortality
Stage 1- Placebo Stage 1- Venglustat 8 mg Stage 1- Venglustat 15 mg Stage 2- Placebo Stage 2- Venglustat 15 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total 0/78 (0.00%) 0/78 (0.00%) 0/80 (0.00%) 0/122 (0.00%) 0/119 (0.00%)
Serious Adverse Events Serious Adverse Events
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 8/78 (10.26%) 15/78 (19.23%) 19/80 (23.75%) 6/122 (4.92%) 7/119 (5.88%)
Cardiac disorders
Arteriosclerosis Coronary Artery † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 0/80 (0.00%) 0 1/122 (0.82%) 1 0/119 (0.00%) 0
Coronary Artery Stenosis † 1 0/78 (0.00%) 0 1/78 (1.28%) 2 0/80 (0.00%) 0 0/122 (0.00%) 0 0/119 (0.00%) 0
Mitral Valve Incompetence † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 0/80 (0.00%) 0 1/122 (0.82%) 2 0/119 (0.00%) 0
Supraventricular Tachycardia † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 0/80 (0.00%) 0 1/122 (0.82%) 1 0/119 (0.00%) 0
Dental Cyst † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 1/80 (1.25%) 1 0/122 (0.00%) 0 0/119 (0.00%) 0
Inguinal Hernia † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 0/80 (0.00%) 0 1/122 (0.82%) 1 0/119 (0.00%) 0
Large Intestinal Stenosis † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 1/80 (1.25%) 1 0/122 (0.00%) 0 0/119 (0.00%) 0
Pancreatitis Acute † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 0/80 (0.00%) 0 0/122 (0.00%) 0 1/119 (0.84%) 1
Rectal Haemorrhage † 1 0/78 (0.00%) 0 1/78 (1.28%) 1 0/80 (0.00%) 0 0/122 (0.00%) 0 0/119 (0.00%) 0
General disorders
Haemorrhagic Cyst † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 1/80 (1.25%) 1 0/122 (0.00%) 0 0/119 (0.00%) 0
Non-Cardiac Chest Pain † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 1/80 (1.25%) 1 0/122 (0.00%) 0 0/119 (0.00%) 0
Hepatobiliary disorders
Hepatic Pain † 1 1/78 (1.28%) 1 0/78 (0.00%) 0 0/80 (0.00%) 0 0/122 (0.00%) 0 0/119 (0.00%) 0
Infections and infestations
Appendicitis † 1 1/78 (1.28%) 1 1/78 (1.28%) 1 2/80 (2.50%) 2 0/122 (0.00%) 0 0/119 (0.00%) 0
Covid-19 † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 0/80 (0.00%) 0 2/122 (1.64%) 2 0/119 (0.00%) 0
Diverticulitis † 1 0/78 (0.00%) 0 1/78 (1.28%) 1 1/80 (1.25%) 1 0/122 (0.00%) 0 0/119 (0.00%) 0
Gastroenteritis Viral † 1 0/78 (0.00%) 0 1/78 (1.28%) 1 0/80 (0.00%) 0 0/122 (0.00%) 0 0/119 (0.00%) 0
Infected Cyst † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 1/80 (1.25%) 1 0/122 (0.00%) 0 0/119 (0.00%) 0
Influenza † 1 0/78 (0.00%) 0 1/78 (1.28%) 1 0/80 (0.00%) 0 0/122 (0.00%) 0 0/119 (0.00%) 0
Kidney Infection † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 1/80 (1.25%) 2 0/122 (0.00%) 0 0/119 (0.00%) 0
Pneumonia † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 1/80 (1.25%) 1 0/122 (0.00%) 0 0/119 (0.00%) 0
Renal Cyst Infection † 1 0/78 (0.00%) 0 3/78 (3.85%) 3 1/80 (1.25%) 1 0/122 (0.00%) 0 1/119 (0.84%) 1
Urinary Tract Infection † 1 1/78 (1.28%) 1 0/78 (0.00%) 0 2/80 (2.50%) 2 0/122 (0.00%) 0 0/119 (0.00%) 0
Injury, poisoning and procedural complications
Back Injury † 1 0/78 (0.00%) 0 1/78 (1.28%) 1 0/80 (0.00%) 0 0/122 (0.00%) 0 0/119 (0.00%) 0
Hand Fracture † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 1/80 (1.25%) 1 0/122 (0.00%) 0 0/119 (0.00%) 0
Jaw Fracture † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 1/80 (1.25%) 1 0/122 (0.00%) 0 0/119 (0.00%) 0
Subdural Haematoma † 1 1/78 (1.28%) 1 0/78 (0.00%) 0 0/80 (0.00%) 0 0/122 (0.00%) 0 0/119 (0.00%) 0
Tibia Fracture † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 0/80 (0.00%) 0 1/122 (0.82%) 1 0/119 (0.00%) 0
Metabolism and nutrition disorders
Fluid Overload † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 1/80 (1.25%) 1 0/122 (0.00%) 0 0/119 (0.00%) 0
Hyperkalaemia † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 1/80 (1.25%) 1 0/122 (0.00%) 0 0/119 (0.00%) 0
Musculoskeletal and connective tissue disorders
Flank Pain † 1 1/78 (1.28%) 1 0/78 (0.00%) 0 0/80 (0.00%) 0 0/122 (0.00%) 0 0/119 (0.00%) 0
Osteoarthritis † 1 0/78 (0.00%) 0 1/78 (1.28%) 1 0/80 (0.00%) 0 0/122 (0.00%) 0 0/119 (0.00%) 0
Rotator Cuff Syndrome † 1 1/78 (1.28%) 1 0/78 (0.00%) 0 0/80 (0.00%) 0 0/122 (0.00%) 0 0/119 (0.00%) 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma † 1 1/78 (1.28%) 1 0/78 (0.00%) 0 0/80 (0.00%) 0 0/122 (0.00%) 0 0/119 (0.00%) 0
Breast Cancer † 1 0/78 (0.00%) 0 1/78 (1.28%) 1 0/80 (0.00%) 0 0/122 (0.00%) 0 0/119 (0.00%) 0
Intraductal Proliferative Breast Lesion † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 0/80 (0.00%) 0 0/122 (0.00%) 0 1/119 (0.84%) 1
Invasive Ductal Breast Carcinoma † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 0/80 (0.00%) 0 0/122 (0.00%) 0 1/119 (0.84%) 1
Mediastinum Neoplasm † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 0/80 (0.00%) 0 0/122 (0.00%) 0 1/119 (0.84%) 1
Carpal Tunnel Syndrome † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 1/80 (1.25%) 1 0/122 (0.00%) 0 0/119 (0.00%) 0
Intracranial Aneurysm † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 1/80 (1.25%) 1 0/122 (0.00%) 0 0/119 (0.00%) 0
Loss Of Consciousness † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 0/80 (0.00%) 0 0/122 (0.00%) 0 1/119 (0.84%) 1
Polyneuropathy † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 1/80 (1.25%) 1 0/122 (0.00%) 0 0/119 (0.00%) 0
Syncope † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 1/80 (1.25%) 1 0/122 (0.00%) 0 0/119 (0.00%) 0
Depression † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 1/80 (1.25%) 1 0/122 (0.00%) 0 0/119 (0.00%) 0
Suicidal Ideation † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 1/80 (1.25%) 1 0/122 (0.00%) 0 0/119 (0.00%) 0
Renal and urinary disorders
Acute Kidney Injury † 1 0/78 (0.00%) 0 1/78 (1.28%) 1 0/80 (0.00%) 0 0/122 (0.00%) 0 0/119 (0.00%) 0
Calculus Urinary † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 0/80 (0.00%) 0 0/122 (0.00%) 0 1/119 (0.84%) 1
Chronic Kidney Disease † 1 1/78 (1.28%) 1 0/78 (0.00%) 0 0/80 (0.00%) 0 0/122 (0.00%) 0 0/119 (0.00%) 0
Haematuria † 1 0/78 (0.00%) 0 3/78 (3.85%) 3 0/80 (0.00%) 0 0/122 (0.00%) 0 0/119 (0.00%) 0
Renal Cyst Haemorrhage † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 0/80 (0.00%) 0 0/122 (0.00%) 0 2/119 (1.68%) 2
Renal Cyst Ruptured † 1 0/78 (0.00%) 0 2/78 (2.56%) 2 0/80 (0.00%) 0 0/122 (0.00%) 0 0/119 (0.00%) 0
Renal Haemorrhage † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 1/80 (1.25%) 2 0/122 (0.00%) 0 0/119 (0.00%) 0
Ureterolithiasis † 1 0/78 (0.00%) 0 1/78 (1.28%) 1 0/80 (0.00%) 0 0/122 (0.00%) 0 0/119 (0.00%) 0
Reproductive system and breast disorders
Adenomyosis † 1 0/78 (0.00%) 0 0/78 (0.00%) 0 1/80 (1.25%) 1 0/122 (0.00%) 0 0/119 (0.00%) 0
Skin and subcutaneous tissue disorders
Rash † 1 1/78 (1.28%) 1 0/78 (0.00%) 0 0/80 (0.00%) 0 0/122 (0.00%) 0 0/119 (0.00%) 0
Term from vocabulary, MedDRA 24.0
Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Total 42/78 (53.85%) 46/78 (58.97%) 48/80 (60.00%) 32/122 (26.23%) 48/119 (40.34%)
Cataract Cortical † 1 5/78 (6.41%) 5 2/78 (2.56%) 4 3/80 (3.75%) 3 1/122 (0.82%) 1 2/119 (1.68%) 2
Cataract Nuclear † 1 5/78 (6.41%) 5 2/78 (2.56%) 2 3/80 (3.75%) 4 1/122 (0.82%) 1 2/119 (1.68%) 2
Dry Eye † 1 5/78 (6.41%) 5 0/78 (0.00%) 0 2/80 (2.50%) 2 1/122 (0.82%) 1 0/119 (0.00%) 0
Constipation † 1 0/78 (0.00%) 0 4/78 (5.13%) 4 3/80 (3.75%) 3 0/122 (0.00%) 0 8/119 (6.72%) 8
Diarrhoea † 1 2/78 (2.56%) 4 0/78 (0.00%) 0 6/80 (7.50%) 6 3/122 (2.46%) 3 2/119 (1.68%) 2
Dyspepsia † 1 4/78 (5.13%) 5 1/78 (1.28%) 1 0/80 (0.00%) 0 1/122 (0.82%) 1 2/119 (1.68%) 2
Nausea † 1 1/78 (1.28%) 1 6/78 (7.69%) 6 7/80 (8.75%) 9 0/122 (0.00%) 0 6/119 (5.04%) 6
Fatigue † 1 1/78 (1.28%) 1 4/78 (5.13%) 5 9/80 (11.25%) 9 3/122 (2.46%) 3 2/119 (1.68%) 2
Influenza Like Illness † 1 1/78 (1.28%) 1 5/78 (6.41%) 5 1/80 (1.25%) 1 1/122 (0.82%) 2 0/119 (0.00%) 0
Conjunctivitis † 1 4/78 (5.13%) 5 0/78 (0.00%) 0 1/80 (1.25%) 1 1/122 (0.82%) 1 1/119 (0.84%) 1
Nasopharyngitis † 1 10/78 (12.82%) 13 5/78 (6.41%) 5 6/80 (7.50%) 9 2/122 (1.64%) 2 0/119 (0.00%) 0
Upper Respiratory Tract Infection † 1 0/78 (0.00%) 0 4/78 (5.13%) 4 6/80 (7.50%) 8 4/122 (3.28%) 4 6/119 (5.04%) 7
Urinary Tract Infection † 1 6/78 (7.69%) 6 5/78 (6.41%) 6 7/80 (8.75%) 15 3/122 (2.46%) 4 1/119 (0.84%) 1
Arthralgia † 1 4/78 (5.13%) 4 3/78 (3.85%) 3 2/80 (2.50%) 2 2/122 (1.64%) 2 2/119 (1.68%) 2
Back Pain † 1 8/78 (10.26%) 9 6/78 (7.69%) 7 8/80 (10.00%) 8 5/122 (4.10%) 5 2/119 (1.68%) 2
Pain In Extremity † 1 0/78 (0.00%) 0 4/78 (5.13%) 4 0/80 (0.00%) 0 1/122 (0.82%) 1 0/119 (0.00%) 0
Dizziness † 1 2/78 (2.56%) 2 4/78 (5.13%) 4 4/80 (5.00%) 4 2/122 (1.64%) 2 3/119 (2.52%) 3
Headache † 1 6/78 (7.69%) 6 8/78 (10.26%) 9 11/80 (13.75%) 14 7/122 (5.74%) 8 8/119 (6.72%) 8
Respiratory, thoracic and mediastinal disorders
Cough † 1 1/78 (1.28%) 1 5/78 (6.41%) 8 8/80 (10.00%) 8 1/122 (0.82%) 1 7/119 (5.88%) 8
Vascular disorders
Hypertension † 1 2/78 (2.56%) 2 5/78 (6.41%) 5 7/80 (8.75%) 7 4/122 (3.28%) 4 4/119 (3.36%) 4
Limitations and Caveats
Following decision to discontinue EFC15392 based on the futility analysis, the two-steps analysis initially planned were not applicable, therefore only the final analysis of all safety endpoints (laboratory, vital sign, ECG, physical examination, BDI-II, and lens opacity) were performed on extended combined Stage 1 and Stage 2 safety population only.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Trial Transparency Team
Organization: Sanofi aventis recherche & développement
Phone: 800-633-1610 ext 6#
EMail: Contact-US@sanofi.com
Perrone RD, Hariri A, Minini P, Ahn C, Chapman AB, Horie S, Knebelmann B, Mrug M, Ong ACM, Pei YPC, Torres VE, Modur V, Gansevoort RT. The STAGED-PKD 2-Stage Adaptive Study With a Patient Enrichment Strategy and Treatment Effect Modeling for Improved Study Design Efficiency in Patients With ADPKD. Kidney Med. 2022 Aug 27;4(10):100538. doi: 10.1016/j.xkme.2022.100538. eCollection 2022 Oct.
Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
Other Study ID Numbers: EFC15392
2017-004084-12 ( EudraCT Number )
U1111-1202-0775 ( Other Identifier: UTN )
First Submitted: May 1, 2018
First Posted: May 14, 2018
Results First Submitted: July 29, 2022
Results First Posted: November 9, 2022
Last Update Posted: November 9, 2022


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Maxine Waters Attacks Ben Carson at Town Hall, Wants to 'Take Him Apart'
Democrats just can't seem to stop with the violent rhetoric. They need some form of psychological counseling.
Via Free Beacon:
Rep. Maxine Waters (D., Calif.) went after Secretary of Housing and Urban Development Dr. Ben Carson at a town hall on Saturday.
At the town hall in Gardena, Calif., Waters said that Carson should go back to his former profession of being a surgeon, the Los Angeles Times reports.
Waters also told the crowd that the next time Carson went before the House Financial Services Committee, she would "take him apart." Waters is the top Democrat on that committee.
Nickarama | June 28, 2017 9:13 pm