<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/NCT03770234</url>
  </required_header>
  <id_info>
    <org_study_id>HP5303/04</org_study_id>
    <nct_id>NCT03770234</nct_id>
  </id_info>
  <brief_title>Clinical Study in Healthy Men to Investigate the Uptake of Buprenorphine and Its Elimination From the Body After Dermal Application as Patches for 96 Hours and for 72 Hours</brief_title>
  <official_title>Investigation of the Pharmacokinetics of a Transtec® 35 µg/h Transdermal Patch Application for 96 Hours and a Patch Application for 72 Hours in an Open, Randomised, Single Application, Two-period Crossover, Phase I Study in 30 Healthy Male Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Grünenthal GmbH</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Grünenthal GmbH</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study was to investigate the pharmacokinetics (i.e. the uptake,&#xD;
      distribution and elimination from the body) of dermally applied buprenorphine during and&#xD;
      after different application periods, i.e., a 96-hour and a 72-hour application of the&#xD;
      Transtec (Registered Trademark) patch (release rate 35 micrograms per hour [µg/hour]). In the&#xD;
      Transtec summary of product characteristics (prescribing information for the physician), the&#xD;
      wearing time per patch is restricted to three days (72 hours) after which the patch has to be&#xD;
      replaced. However, market experience has shown that the Transtec patches are sometimes worn&#xD;
      for a period longer than three days, i.e. they sometimes happen to be only replaced every&#xD;
      four days. There was currently no data available as how to evaluate this longer wearing&#xD;
      period.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 5, 2004</start_date>
  <completion_date type="Actual">May 26, 2004</completion_date>
  <primary_completion_date type="Actual">May 26, 2004</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>Crossover Assignment</intervention_model>
    <intervention_model_description>Each participant will apply Transtec 35 µg/hour transdermal patch, once for 96 hours (Treatment A) and once for 72 hours (Treatment B) in randomized order. Between removal of the first patch and application of the second patch, there will be a washout period of at least 10 days.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetic parameter: AUC48-72 for buprenorphine</measure>
    <time_frame>From 48 hours to 72 hours</time_frame>
    <description>Partial area under the plasma concentration-time curve (from 48 hours after application until 72 hours after application).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic parameter: AUC72-96 for buprenorphine</measure>
    <time_frame>From 72 hours to 96 hours</time_frame>
    <description>Partial area under the plasma concentration-time curve (from 72 hours after application until 96 hours after application).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameter: Cmax for buprenorphine</measure>
    <time_frame>Before application and after 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, 104,112,120,132,144,156, and 168 hours</time_frame>
    <description>Maximum observed plasma concentration of the measured concentration-time profile. Blood samples will be taken for the determination of buprenorphine plasma concentrations at distinct time points: Before application to 144 hours after patch application. If the patch was applied for 96 hours, additional samples were taken at 156 and 168 hours after application. For the analysis of buprenorphine in human plasma, a validated liquid chromatography mass spectrometry (LC/MS/MS)-method will be used.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameter: tmax for buprenorphine</measure>
    <time_frame>Before application and after 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, 104,112,120,132,144,156, and 168 hours</time_frame>
    <description>Time of maximum concentration, time after transdermal patch application at which Cmax occurs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameter: AUC0-t for buprenorphine</measure>
    <time_frame>Before application and after 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, 104,112,120,132,144,156, and 168 hours</time_frame>
    <description>Area under plasma concentration-time curve from application until the last sampling point (t) with a quantifiable concentration, calculated by the linear/log trapezoidal method, i.e., the linear trapezoidal rule is applied up to Cmax and then the log trapezoidal rule is applied for the remainder of the curve.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameter: t1/2z for buprenorphine</measure>
    <time_frame>Before application and after 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, 104,112,120,132,144,156, and 168 hours</time_frame>
    <description>Apparent terminal elimination half-life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameter: AUC0-inf for buprenorphine</measure>
    <time_frame>Before application and after 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, 104,112,120,132,144,156, and 168 hours</time_frame>
    <description>Area under the plasma concentration-time curve extrapolated to infinity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of treatment emergent adverse events</measure>
    <time_frame>From patch application (Day 1) until Final check (Day 12)</time_frame>
    <description>Number of adverse events and number of participants with adverse events.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Characteristics of treatment emergent adverse events</measure>
    <time_frame>From patch application (Day 1) until Final check (Day 12)</time_frame>
    <description>Adverse events with information on intensity, seriousness, relationship to the investigational product, outcome and action taken will be determined.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Onset and duration of treatment emergent adverse events</measure>
    <time_frame>From patch application (Day 1) until Final check (Day 12)</time_frame>
    <description>Adverse events with information on onset and duration to the investigational product will be determined.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Pain</condition>
  <condition>Pharmacokinetics</condition>
  <arm_group>
    <arm_group_label>Treatment A: Transtec patch application for 96 hours</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Transtec 35 µg/hour transdermal patch wearing period of 96 hours, with application of patch on Study Day 1 and removal on Study Day 5.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment B: Transtec patch application for 72 hours</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Transtec 35 µg/hour transdermal patch wearing period of 72 hours, with application of patch on Study Day 1 and removal on Study Day 4.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Transtec 35 µg/hour transdermal patch</intervention_name>
    <description>Transdermal patch containing 20 mg buprenorphine in an active surface area of 25 squared centimeters. Buprenorphine release rate 35 µg/hour.</description>
    <arm_group_label>Treatment A: Transtec patch application for 96 hours</arm_group_label>
    <arm_group_label>Treatment B: Transtec patch application for 72 hours</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male Caucasian volunteers, aged 25-45 years.&#xD;
&#xD;
          -  Body mass index (BMI) between 18 and 30 kilogram/squared meter (extremes included).&#xD;
&#xD;
          -  Good physical and mental health status (no current acute illness) determined on the&#xD;
             basis of the medical history and a general clinical examination.&#xD;
&#xD;
          -  Systolic blood pressure between 90 millimeter mercury (mmHg) and 150 mmHg (extremes&#xD;
             included).&#xD;
&#xD;
          -  Diastolic blood pressure between 45 mmHg and 90 mmHg (extremes included).&#xD;
&#xD;
          -  Pulse rate between 45 beats per minute (bpm) and 100 bpm (extremes included).&#xD;
&#xD;
          -  Electrocardiogram (12 lead) considered as normal by the investigator.&#xD;
&#xD;
          -  Results of laboratory tests within the normal ranges for the testing laboratory. The&#xD;
             investigator may include a participant having values outside the accepted range if, in&#xD;
             his/her opinion, these values are of no clinical relevance. The decision will be&#xD;
             justified.&#xD;
&#xD;
          -  The participant has been informed using the informed consent approved by the local&#xD;
             ethics committee.&#xD;
&#xD;
          -  The consent was obtained by participant's signature.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diseases and functional disorders of the central nervous system (CNS),&#xD;
             endocrinological system, gastrointestinal tract, hepatobiliary system, renal system,&#xD;
             respiratory system or cardiovascular system including marked repolarization&#xD;
             abnormality (e.g. suspicious or definite congenital long QT syndrome) or co-medication&#xD;
             that is known to influence cardiac repolarization substantially.&#xD;
&#xD;
          -  History of seizures or at risk (i.e. head trauma, epilepsy in family anamnesis,&#xD;
             unclear loss of consciousness).&#xD;
&#xD;
          -  Malignancy.&#xD;
&#xD;
          -  History of orthostatic hypotension.&#xD;
&#xD;
          -  Positive human immunodeficiency virus (HIV) 1/2-antibodies, hepatitis B surface (HBs)&#xD;
             -antigen, hepatitis B core (HBc) -antibodies, hepatitis C virus (HCV) -antibody tests&#xD;
             at the screening examination.&#xD;
&#xD;
          -  Drug allergy.&#xD;
&#xD;
          -  Bronchial asthma.&#xD;
&#xD;
          -  Participation in another clinical study within three month prior to the start of this&#xD;
             study (exception: characterization of metabolizer status).&#xD;
&#xD;
          -  Blood donation (more than 100 milliliters) within three month prior to the start of&#xD;
             this study.&#xD;
&#xD;
          -  Use of any medication within four weeks prior to the start of the study&#xD;
             (self-medication or prescription).&#xD;
&#xD;
          -  Evidence of alcohol, medication or drug abuse.&#xD;
&#xD;
          -  Positive Naloxone challenge test.&#xD;
&#xD;
          -  Positive drug abuse screening test.&#xD;
&#xD;
          -  Extremely unbalanced diet (in the opinion of the investigator).&#xD;
&#xD;
          -  Excessive consumption of food or beverages containing caffeine or other xanthines&#xD;
             (more than five cups of coffee or equivalent per day).&#xD;
&#xD;
          -  Smoking of more than 20 cigarettes per day.&#xD;
&#xD;
          -  Neurotic personality, psychiatric illness or suicide risk.&#xD;
&#xD;
          -  Known or suspected of not being able to comply with the study protocol.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>25 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Grünenthal Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Grünenthal GmbH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Institut für Klinische Pharmakologie Bobenheim</name>
      <address>
        <city>Grünstadt</city>
        <zip>67269</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 7, 2018</study_first_submitted>
  <study_first_submitted_qc>December 7, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 10, 2018</study_first_posted>
  <last_update_submitted>December 7, 2018</last_update_submitted>
  <last_update_submitted_qc>December 7, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 10, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <patient_data>
    <sharing_ipd>No</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/NCT03770234
org study id: HP5303/04
nct id: NCT03770234
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of the study was to investigate the pharmacokinetics (i.e. the uptake,
      distribution and elimination from the body) of dermally applied buprenorphine during and
      after different application periods, i.e., a 96-hour and a 72-hour application of the
      Transtec (Registered Trademark) patch (release rate 35 micrograms per hour [µg/hour]). In the
      Transtec summary of product characteristics (prescribing information for the physician), the
      wearing time per patch is restricted to three days (72 hours) after which the patch has to be
      replaced. However, market experience has shown that the Transtec patches are sometimes worn
      for a period longer than three days, i.e. they sometimes happen to be only replaced every
      four days. There was currently no data available as how to evaluate this longer wearing
      period.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Each participant will apply Transtec 35 µg/hour transdermal patch, once for 96 hours (Treatment A) and once for 72 hours (Treatment B) in randomized order. Between removal of the first patch and application of the second patch, there will be a washout period of at least 10 days.
primary purpose: Treatment
masking: None (Open Label)
measure: Pharmacokinetic parameter: AUC48-72 for buprenorphine
time frame: From 48 hours to 72 hours
description: Partial area under the plasma concentration-time curve (from 48 hours after application until 72 hours after application).
measure: Pharmacokinetic parameter: AUC72-96 for buprenorphine
time frame: From 72 hours to 96 hours
description: Partial area under the plasma concentration-time curve (from 72 hours after application until 96 hours after application).
measure: Pharmacokinetic parameter: Cmax for buprenorphine
time frame: Before application and after 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, 104,112,120,132,144,156, and 168 hours
description: Maximum observed plasma concentration of the measured concentration-time profile. Blood samples will be taken for the determination of buprenorphine plasma concentrations at distinct time points: Before application to 144 hours after patch application. If the patch was applied for 96 hours, additional samples were taken at 156 and 168 hours after application. For the analysis of buprenorphine in human plasma, a validated liquid chromatography mass spectrometry (LC/MS/MS)-method will be used.
measure: Pharmacokinetic parameter: tmax for buprenorphine
time frame: Before application and after 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, 104,112,120,132,144,156, and 168 hours
description: Time of maximum concentration, time after transdermal patch application at which Cmax occurs.
measure: Pharmacokinetic parameter: AUC0-t for buprenorphine
time frame: Before application and after 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, 104,112,120,132,144,156, and 168 hours
description: Area under plasma concentration-time curve from application until the last sampling point (t) with a quantifiable concentration, calculated by the linear/log trapezoidal method, i.e., the linear trapezoidal rule is applied up to Cmax and then the log trapezoidal rule is applied for the remainder of the curve.
measure: Pharmacokinetic parameter: t1/2z for buprenorphine
time frame: Before application and after 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, 104,112,120,132,144,156, and 168 hours
description: Apparent terminal elimination half-life.
measure: Pharmacokinetic parameter: AUC0-inf for buprenorphine
time frame: Before application and after 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, 104,112,120,132,144,156, and 168 hours
description: Area under the plasma concentration-time curve extrapolated to infinity.
measure: Incidence of treatment emergent adverse events
time frame: From patch application (Day 1) until Final check (Day 12)
description: Number of adverse events and number of participants with adverse events.
measure: Characteristics of treatment emergent adverse events
time frame: From patch application (Day 1) until Final check (Day 12)
description: Adverse events with information on intensity, seriousness, relationship to the investigational product, outcome and action taken will be determined.
measure: Onset and duration of treatment emergent adverse events
time frame: From patch application (Day 1) until Final check (Day 12)
description: Adverse events with information on onset and duration to the investigational product will be determined.
arm group label: Treatment A: Transtec patch application for 96 hours
arm group type: Experimental
description: Transtec 35 µg/hour transdermal patch wearing period of 96 hours, with application of patch on Study Day 1 and removal on Study Day 5.
arm group label: Treatment B: Transtec patch application for 72 hours
arm group type: Experimental
description: Transtec 35 µg/hour transdermal patch wearing period of 72 hours, with application of patch on Study Day 1 and removal on Study Day 4.
intervention type: Drug
intervention name: Transtec 35 µg/hour transdermal patch
description: Transdermal patch containing 20 mg buprenorphine in an active surface area of 25 squared centimeters. Buprenorphine release rate 35 µg/hour.
arm group label: Treatment A: Transtec patch application for 96 hours
arm group label: Treatment B: Transtec patch application for 72 hours
criteria: 
gender: Male
minimum age: 25 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Grünenthal Study Director
role: Study Director
affiliation: Grünenthal GmbH
facility: 
country: Germany
responsible party type: Sponsor
sharing ipd: No