<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03040635</url>
  </required_header>
  <id_info>
    <org_study_id>NP39625</org_study_id>
    <nct_id>NCT03040635</nct_id>
  </id_info>
  <brief_title>A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Risdiplam (RO7034067) in Healthy Japanese Participants</brief_title>
  <official_title>An Investigator/Subject Blind, Randomized, Placebo-Controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Doses of RO7034067 in Healthy Japanese Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hoffmann-La Roche</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized, placebo-controlled study to investigate the safety, tolerability,&#xD;
      pharmacokinetics and pharmacodynamics of single oral doses of Risdiplam in healthy Japanese&#xD;
      participants.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 22, 2017</start_date>
  <completion_date type="Actual">October 2, 2017</completion_date>
  <primary_completion_date type="Actual">October 2, 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax) of Risdiplam</measure>
    <time_frame>Pre-dose (0 hour [hr]), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to Maximum Plasma Concentration (Tmax) of Risdiplam</measure>
    <time_frame>Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve up to the Last Measurable Concentration (AUClast) of Risdiplam</measure>
    <time_frame>Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of Risdiplam</measure>
    <time_frame>Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve up to Time t (AUC0-t) of Risdiplam</measure>
    <time_frame>Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent Terminal Half-Life (t1/2) of Risdiplam</measure>
    <time_frame>Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent Oral Clearance (CL/F) of Risdiplam</measure>
    <time_frame>Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent Oral Volume of Distribution (Vz/F) of Risdiplam</measure>
    <time_frame>Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cumulative Amount Excreted Unchanged into Urine (Ae) of Risdiplam</measure>
    <time_frame>Pre-dose (0 hr), and 5 urine samples at different time-ranges postdose (0-6 hr, 6-12 hr, 12-24 hr, 24-48 hr, and 48-72 hr)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Renal Clearance (CLR) of Risdiplam</measure>
    <time_frame>Pre-dose (0 hr), and 5 urine samples at different time-ranges postdose (0-6 hr, 6-12 hr, 12-24 hr, 24-48 hr, and 48-72 hr)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Fraction of Dose Excreted Unchanged Renally (Fe) of Risdiplam</measure>
    <time_frame>Pre-dose (0 hr), and 5 urine samples at different time-ranges postdose (0-6 hr, 6-12 hr, 12-24 hr, 24-48 hr, and 48-72 hr)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants with Adverse Events (AEs)</measure>
    <time_frame>Up to approximately 7 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Splicing Modifications of Survival of Motor Neuron (SMN) Messenger Ribonucleic Acids (mRNAs), Including SMN1, SMN2 Full Length (FL), and SMNdelta7 mRNA in Blood In Vivo</measure>
    <time_frame>Days -1, 1, 2, 3, 4, 6</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in mRNA Levels of Paired Box (PAX) Genes in Blood</measure>
    <time_frame>Days -1, 1, 2, 3, 4, 6</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in SMN Protein Levels in Blood</measure>
    <time_frame>Day -1, follow-up visit (Day 21)</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>Risdiplam '2' Milligrams (mg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single dose of 2 mg Risdiplam will be administered to all participants randomized to this arm under fasted conditions as an oral drinking solution on Day 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Risdiplam '6' mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single dose of 6 mg Risdiplam will be administered to all participants randomized to this arm under fasted conditions as an oral drinking solution on Day 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Risdiplam '12' mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single dose of 12 mg Risdiplam will be administered to all participants randomized to this arm under fasted conditions as an oral drinking solution on Day 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>A single dose of placebo will be administered to all participants randomized to this arm under fasted conditions as an oral drinking solution on Day 1.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Risdiplam</intervention_name>
    <description>Single oral doses of Risdiplam will be administered on Day 1.</description>
    <arm_group_label>Risdiplam '12' mg</arm_group_label>
    <arm_group_label>Risdiplam '2' Milligrams (mg)</arm_group_label>
    <arm_group_label>Risdiplam '6' mg</arm_group_label>
    <other_name>RO7034067</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Single oral doses of Risdiplam matching placebo will be administered on Day 1.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants of Japanese origin, with Japanese parents (for the provisional Caucasian&#xD;
             cohort, participants must be male or female Caucasians with 4 Caucasian grand-parents)&#xD;
&#xD;
          -  Healthy participants. Healthy status is defined by the absence of evidence of any&#xD;
             active or chronic disease following a detailed medical and surgical history, a&#xD;
             complete physical examination including ophthalmological examination, vital signs,&#xD;
             12-lead electrocardiogram (ECG), hematology, blood chemistry, serology and urinalysis&#xD;
&#xD;
          -  A body mass index (BMI) between 18 to 30 kilograms per square meter (kg/m^2) inclusive&#xD;
&#xD;
          -  Male participants must agree to use a barrier method of contraception from dosing&#xD;
             until completion of the study and for 4 months thereafter&#xD;
&#xD;
          -  Female participants must be either surgically sterile or post-menopausal&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Medical history of cardiovascular disease, renal disease, liver disease, digestive&#xD;
             system disease, blood dyscrasia, immunologic disease, diseases of the nervous system,&#xD;
             endocrine disease, metabolic disease, lung disease, or with anamnesis and obstacles in&#xD;
             kidney, liver, or cardiopulmonary function&#xD;
&#xD;
          -  Participants with any clinically significant eye pathology&#xD;
&#xD;
          -  Laboratory test (hematology, biochemistry, physical examination or vital signs) values&#xD;
             outside the institutional normal range and rated as clinically significant abnormal at&#xD;
             screening&#xD;
&#xD;
          -  Any clinically significant abnormalities in ECG at screening&#xD;
&#xD;
          -  Inherited long QT syndrome or known family history of arrhythmia&#xD;
&#xD;
          -  Systolic blood pressure (SBP) higher than 140 millimeters of mercury (mmHg) or below&#xD;
             90 mmHg, and/or diastolic blood pressure (DBP) higher than 90 mmHg or below 50 mmHg in&#xD;
             the supine position, as assessed at screening&#xD;
&#xD;
          -  Positive result for human immunodeficiency virus (HIV) antigen and antibody, hepatitis&#xD;
             B surface antigen (HBsAg) or hepatitis C virus (HCV) antibody at screening&#xD;
&#xD;
          -  Donation or loss of blood over 500 milliliters (mL) within three months prior to&#xD;
             screening&#xD;
&#xD;
          -  History of smoking more than 10 cigarettes a day. Participants who have quit smoking&#xD;
             or who have reduced their daily cigarette smoking to 10 or less for more than one&#xD;
             month prior to screening are allowed&#xD;
&#xD;
          -  Daily consumption of food or drink containing a large amount of methylxanthine&#xD;
             (caffeine, theophylline, theobromine)&#xD;
&#xD;
          -  Present or past history of substance addiction, dependence or abuse, such as abuse of&#xD;
             drugs or alcohol&#xD;
&#xD;
          -  Concomitant or previous participation in any clinical trial either within 90 days or 5&#xD;
             half-lives of the investigational drug, whichever is longer, before administration of&#xD;
             study drug in this study&#xD;
&#xD;
          -  Use of prescribed medications which have systemic exposure within one week before&#xD;
             enrolment&#xD;
&#xD;
          -  Use of any concomitant drug during the study (including over-the-counter medication&#xD;
             and medications used in dentistry)&#xD;
&#xD;
          -  Inability to meet the study requirements in the opinion of the Investigator&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Collaborative Neuroscience Network, Inc.</name>
      <address>
        <city>Garden Grove</city>
        <state>California</state>
        <zip>92845</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>February 1, 2017</study_first_submitted>
  <study_first_submitted_qc>February 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 2, 2017</study_first_posted>
  <last_update_submitted>October 2, 2018</last_update_submitted>
  <last_update_submitted_qc>October 2, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 4, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Risdiplam</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03040635
org study id: NP39625
nct id: NCT03040635
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a randomized, placebo-controlled study to investigate the safety, tolerability,
      pharmacokinetics and pharmacodynamics of single oral doses of Risdiplam in healthy Japanese
      participants.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Maximum Observed Plasma Concentration (Cmax) of Risdiplam
time frame: Pre-dose (0 hour [hr]), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1
measure: Time to Maximum Plasma Concentration (Tmax) of Risdiplam
time frame: Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1
measure: Area Under the Plasma Concentration-Time Curve up to the Last Measurable Concentration (AUClast) of Risdiplam
time frame: Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1
measure: Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of Risdiplam
time frame: Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1
measure: Area Under the Plasma Concentration-Time Curve up to Time t (AUC0-t) of Risdiplam
time frame: Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1
measure: Apparent Terminal Half-Life (t1/2) of Risdiplam
time frame: Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1
measure: Apparent Oral Clearance (CL/F) of Risdiplam
time frame: Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1
measure: Apparent Oral Volume of Distribution (Vz/F) of Risdiplam
time frame: Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1
measure: Cumulative Amount Excreted Unchanged into Urine (Ae) of Risdiplam
time frame: Pre-dose (0 hr), and 5 urine samples at different time-ranges postdose (0-6 hr, 6-12 hr, 12-24 hr, 24-48 hr, and 48-72 hr)
measure: Renal Clearance (CLR) of Risdiplam
time frame: Pre-dose (0 hr), and 5 urine samples at different time-ranges postdose (0-6 hr, 6-12 hr, 12-24 hr, 24-48 hr, and 48-72 hr)
measure: Fraction of Dose Excreted Unchanged Renally (Fe) of Risdiplam
time frame: Pre-dose (0 hr), and 5 urine samples at different time-ranges postdose (0-6 hr, 6-12 hr, 12-24 hr, 24-48 hr, and 48-72 hr)
measure: Percentage of Participants with Adverse Events (AEs)
time frame: Up to approximately 7 weeks
measure: Change from Baseline in Splicing Modifications of Survival of Motor Neuron (SMN) Messenger Ribonucleic Acids (mRNAs), Including SMN1, SMN2 Full Length (FL), and SMNdelta7 mRNA in Blood In Vivo
time frame: Days -1, 1, 2, 3, 4, 6
measure: Change from Baseline in mRNA Levels of Paired Box (PAX) Genes in Blood
time frame: Days -1, 1, 2, 3, 4, 6
measure: Change from Baseline in SMN Protein Levels in Blood
time frame: Day -1, follow-up visit (Day 21)
arm group label: Risdiplam '2' Milligrams (mg)
arm group type: Experimental
description: A single dose of 2 mg Risdiplam will be administered to all participants randomized to this arm under fasted conditions as an oral drinking solution on Day 1.
arm group label: Risdiplam '6' mg
arm group type: Experimental
description: A single dose of 6 mg Risdiplam will be administered to all participants randomized to this arm under fasted conditions as an oral drinking solution on Day 1.
arm group label: Risdiplam '12' mg
arm group type: Experimental
description: A single dose of 12 mg Risdiplam will be administered to all participants randomized to this arm under fasted conditions as an oral drinking solution on Day 1.
arm group label: Placebo
arm group type: Placebo Comparator
description: A single dose of placebo will be administered to all participants randomized to this arm under fasted conditions as an oral drinking solution on Day 1.
intervention type: Drug
intervention name: Risdiplam
description: Single oral doses of Risdiplam will be administered on Day 1.
arm group label: Risdiplam '12' mg
arm group label: Risdiplam '2' Milligrams (mg)
arm group label: Risdiplam '6' mg
other name: RO7034067
intervention type: Drug
intervention name: Placebo
description: Single oral doses of Risdiplam matching placebo will be administered on Day 1.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
facility: 
country: United States
responsible party type: Sponsor
mesh term: Risdiplam
sharing ipd: Undecided