<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/NCT03237741</url>
  </required_header>
  <id_info>
    <org_study_id>GP39778</org_study_id>
    <secondary_id>2017-000299-27</secondary_id>
    <nct_id>NCT03237741</nct_id>
  </id_info>
  <brief_title>Bioavailability of GDC-0134 and the Effect of Food and Proton Pump Inhibitor on Pharmacokinetics of GDC-0134 in Healthy Female Participants</brief_title>
  <official_title>A Phase I Open-Label Study to Determine the Relative Bioavailability of GDC-0134 and to Investigate the Effect of Food and Proton Pump Inhibitor on Pharmacokinetics of GDC-0134 in Healthy Female Subjects of Non-childbearing Potential</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Genentech, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Quotient Clinical</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Genentech, Inc.</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will evaluate the pharmacokinetics and safety of GDC-0134 in healthy female&#xD;
      volunteers of non-childbearing potential. The first part of the study will compare the&#xD;
      bioavailability of a prototype capsule of GDC-0134 relative to an existing GDC-0134 reference&#xD;
      capsule (Periods 1 and 2). The second part of the study will assess the effect of&#xD;
      GDC-0134-in-applesauce preparation under fasting conditions, the effect of low and high fat&#xD;
      foods as well as the effect of elevated stomach pH via pre-treatment with rabeprazole, a&#xD;
      proton pump inhibitor (PPI), under fasted and high-fat meal conditions (Periods 3 and 4).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 7, 2017</start_date>
  <completion_date type="Actual">December 14, 2017</completion_date>
  <primary_completion_date type="Actual">December 14, 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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of GDC-0134</measure>
    <time_frame>Periods 1-4: Day 1: pre-dose, post-dose at 0.5 hours (h), 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h and 16 h, Day 2: post-dose 24 h and 36 h, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
    <description>The AUC0-inf is calculated in a plot of concentration of drug in blood plasma against time and extrapolated to infinity.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve up to Time Tau (AUC0-t) of GDC-0134</measure>
    <time_frame>Periods 1-4: Day 1: pre-dose, post-dose at 0.5 hours (h), 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h and 16 h, Day 2: post-dose 24 h and 36 h, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
    <description>The AUC0-t is calculated in a plot of concentration of drug in blood plasma against time and calculated up to the time of the last measurable GDC-0134 concentration.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Observed Concentration (Cmax) of GDC-0134</measure>
    <time_frame>Periods 1-4: Day 1: pre-dose, post-dose at 0.5 hours (h), 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h and 16 h, Day 2: post-dose 24 h and 36 h, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
    <description>Cmax is the maximum observed concentration of drug in blood plasma.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to Maximum Concentration (Tmax) of GDC-0134</measure>
    <time_frame>Periods 1-4: Day 1: pre-dose, post-dose at 0.5 hours (h), 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h and 16 h, Day 2: post-dose 24 h and 36 h, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
    <description>Tmax is the time elapsed from the time of drug administration to maximum plasma concentration.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent Half-Life (t1/2) of GDC-0134</measure>
    <time_frame>Periods 1-4: Day 1: pre-dose, post-dose at 0.5 hours (h), 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h and 16 h, Day 2: post-dose 24 h and 36 h, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22</time_frame>
    <description>Half-life is defined as the time required for the drug plasma concentration to be reduced to half.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Adverse Events</measure>
    <time_frame>From baseline until 21 days after the last dose of study drug up to approximately 16 weeks</time_frame>
    <description>An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">24</enrollment>
  <condition>Amyotrophic Lateral Sclerosis</condition>
  <arm_group>
    <arm_group_label>Treatment Sequence 1: ABC1D1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of reference capsule GDC-0134 (Treatment A) during Period 1. Single dose of prototype capsule GDC-0134 (Treatment B) during Period 2. Single dose of GDC-0134 prototype capsule administered as GDC-0134-in-applesauce preparation under fasting conditions (Treatment C1) during Period 3. Single dose of GDC-0134 prototype capsule administered under fasting conditions in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D1) during Period 4. The washout period between doses will be a minimum of 21 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment Sequence 2: ABC2D2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of reference capsule GDC-0134 (Treatment A) during Period 1. Single dose of prototype capsule GDC-0134 (Treatment B) during Period 2. Single dose of GDC-0134 prototype capsule administered after a high-fat meal (Treatment C2) during Period 3. Single dose of GDC-0134 prototype capsule administered after a high-fat meal in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D2) during Period 4. The washout period between doses will be a minimum of 21 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment Sequence 3: BAC1D1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of prototype capsule GDC-0134 (Treatment B) during Period 1. Single dose of reference capsule GDC-0134 (Treatment A) during Period 2. Single dose of GDC-0134 prototype capsule administered as GDC-0134-in-applesauce preparation under fasting conditions (Treatment C1) during Period 3. Single dose of GDC-0134 prototype capsule administered under fasting conditions in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D1) during Period 4. The washout period between doses will be a minimum of 21 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment Sequence 4: BAC2D2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of prototype capsule GDC-0134 (Treatment B) during Period 1. Single dose of reference capsule GDC-0134 (Treatment A) during Period 2. Single dose of GDC-0134 prototype capsule administered after a high-fat meal (Treatment C2) during Period 3. Single dose of GDC-0134 prototype capsule administered after a high-fat meal in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D2) during Period 4. The washout period between doses will be a minimum of 21 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Reference capsule GDC-0134</intervention_name>
    <description>Oral administration of a single dose of 200 milligrams (mg) GDC-0134 reference capsule administered as two 100 mg capsules.</description>
    <arm_group_label>Treatment Sequence 1: ABC1D1</arm_group_label>
    <arm_group_label>Treatment Sequence 2: ABC2D2</arm_group_label>
    <arm_group_label>Treatment Sequence 3: BAC1D1</arm_group_label>
    <arm_group_label>Treatment Sequence 4: BAC2D2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prototype capsule GDC-0134</intervention_name>
    <description>Oral administration of a single dose of 200 mg GDC-0134 prototype capsule administered as one 200 mg capsule.</description>
    <arm_group_label>Treatment Sequence 1: ABC1D1</arm_group_label>
    <arm_group_label>Treatment Sequence 2: ABC2D2</arm_group_label>
    <arm_group_label>Treatment Sequence 3: BAC1D1</arm_group_label>
    <arm_group_label>Treatment Sequence 4: BAC2D2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>rabeprazole</intervention_name>
    <description>Oral administration of 20 mg rabeprazole once daily on Days -3, -2 and -1 as well as on Day 1 two hours prior to each administration of GDC-0134 during Period 4.</description>
    <arm_group_label>Treatment Sequence 1: ABC1D1</arm_group_label>
    <arm_group_label>Treatment Sequence 2: ABC2D2</arm_group_label>
    <arm_group_label>Treatment Sequence 3: BAC1D1</arm_group_label>
    <arm_group_label>Treatment Sequence 4: BAC2D2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy female participants between 30 and 65 years of age, inclusive;&#xD;
&#xD;
          -  Within body mass index range 18.0 to 35.0 kilograms per square meter (kg/m^2),&#xD;
             inclusive;&#xD;
&#xD;
          -  Female participants will be of non-childbearing potential;&#xD;
&#xD;
          -  In good health, determined by no clinically significant findings from medical history,&#xD;
             12-lead echocardiogram (ECG), and vital signs;&#xD;
&#xD;
          -  Clinical laboratory evaluations within the reference range for the test laboratory,&#xD;
             unless deemed not clinically significant by the investigator;&#xD;
&#xD;
          -  Normal ophthalmology assessment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Males and females of childbearing potential;&#xD;
&#xD;
          -  Significant history or clinical manifestation of any significant metabolic, allergic,&#xD;
             dermatological, hepatic, renal, hematological, pulmonary, cardiovascular,&#xD;
             gastrointestinal (GI), neurological, or psychiatric disorder (as determined by the&#xD;
             investigator;&#xD;
&#xD;
          -  History of significant hypersensitivity, intolerance, or allergy to any drug compound,&#xD;
             food, or other substance, unless approved by the investigator;&#xD;
&#xD;
          -  History of stomach or intestinal surgery or resection that would potentially alter&#xD;
             absorption and/or excretion of orally administered drugs;&#xD;
&#xD;
          -  History of GI bleeding or GI ulcers;&#xD;
&#xD;
          -  Any personal or family history of bleeding disorders, and any personal use of drugs&#xD;
             known to affect blood clotting within 30 days of dosing;&#xD;
&#xD;
          -  Any acute or chronic medical condition or abnormality in clinical laboratory tests&#xD;
             that, in the investigator's judgment, precludes the subject's safe participation in&#xD;
             and completion of the study.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>65 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>Quotient Clinical Ltd, Clinical Research Unit</name>
      <address>
        <city>Nottingham</city>
        <zip>NG11 6JS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>April 2018</verification_date>
  <study_first_submitted>July 31, 2017</study_first_submitted>
  <study_first_submitted_qc>July 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 2, 2017</study_first_posted>
  <last_update_submitted>April 16, 2018</last_update_submitted>
  <last_update_submitted_qc>April 16, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">April 18, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Motor Neuron Disease</mesh_term>
    <mesh_term>Amyotrophic Lateral Sclerosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rabeprazole</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03237741
org study id: GP39778
secondary id: 2017-000299-27
nct id: NCT03237741
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
This study will evaluate the pharmacokinetics and safety of GDC-0134 in healthy female
      volunteers of non-childbearing potential. The first part of the study will compare the
      bioavailability of a prototype capsule of GDC-0134 relative to an existing GDC-0134 reference
      capsule (Periods 1 and 2). The second part of the study will assess the effect of
      GDC-0134-in-applesauce preparation under fasting conditions, the effect of low and high fat
      foods as well as the effect of elevated stomach pH via pre-treatment with rabeprazole, a
      proton pump inhibitor (PPI), under fasted and high-fat meal conditions (Periods 3 and 4).
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of GDC-0134
time frame: Periods 1-4: Day 1: pre-dose, post-dose at 0.5 hours (h), 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h and 16 h, Day 2: post-dose 24 h and 36 h, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
description: The AUC0-inf is calculated in a plot of concentration of drug in blood plasma against time and extrapolated to infinity.
measure: Area Under the Plasma Concentration-Time Curve up to Time Tau (AUC0-t) of GDC-0134
time frame: Periods 1-4: Day 1: pre-dose, post-dose at 0.5 hours (h), 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h and 16 h, Day 2: post-dose 24 h and 36 h, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
description: The AUC0-t is calculated in a plot of concentration of drug in blood plasma against time and calculated up to the time of the last measurable GDC-0134 concentration.
measure: Maximum Observed Concentration (Cmax) of GDC-0134
time frame: Periods 1-4: Day 1: pre-dose, post-dose at 0.5 hours (h), 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h and 16 h, Day 2: post-dose 24 h and 36 h, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
description: Cmax is the maximum observed concentration of drug in blood plasma.
measure: Time to Maximum Concentration (Tmax) of GDC-0134
time frame: Periods 1-4: Day 1: pre-dose, post-dose at 0.5 hours (h), 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h and 16 h, Day 2: post-dose 24 h and 36 h, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
description: Tmax is the time elapsed from the time of drug administration to maximum plasma concentration.
measure: Apparent Half-Life (t1/2) of GDC-0134
time frame: Periods 1-4: Day 1: pre-dose, post-dose at 0.5 hours (h), 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h and 16 h, Day 2: post-dose 24 h and 36 h, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
description: Half-life is defined as the time required for the drug plasma concentration to be reduced to half.
measure: Percentage of Participants with Adverse Events
time frame: From baseline until 21 days after the last dose of study drug up to approximately 16 weeks
description: An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
arm group label: Treatment Sequence 1: ABC1D1
arm group type: Experimental
description: Single dose of reference capsule GDC-0134 (Treatment A) during Period 1. Single dose of prototype capsule GDC-0134 (Treatment B) during Period 2. Single dose of GDC-0134 prototype capsule administered as GDC-0134-in-applesauce preparation under fasting conditions (Treatment C1) during Period 3. Single dose of GDC-0134 prototype capsule administered under fasting conditions in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D1) during Period 4. The washout period between doses will be a minimum of 21 days.
arm group label: Treatment Sequence 2: ABC2D2
arm group type: Experimental
description: Single dose of reference capsule GDC-0134 (Treatment A) during Period 1. Single dose of prototype capsule GDC-0134 (Treatment B) during Period 2. Single dose of GDC-0134 prototype capsule administered after a high-fat meal (Treatment C2) during Period 3. Single dose of GDC-0134 prototype capsule administered after a high-fat meal in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D2) during Period 4. The washout period between doses will be a minimum of 21 days.
arm group label: Treatment Sequence 3: BAC1D1
arm group type: Experimental
description: Single dose of prototype capsule GDC-0134 (Treatment B) during Period 1. Single dose of reference capsule GDC-0134 (Treatment A) during Period 2. Single dose of GDC-0134 prototype capsule administered as GDC-0134-in-applesauce preparation under fasting conditions (Treatment C1) during Period 3. Single dose of GDC-0134 prototype capsule administered under fasting conditions in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D1) during Period 4. The washout period between doses will be a minimum of 21 days.
arm group label: Treatment Sequence 4: BAC2D2
arm group type: Experimental
description: Single dose of prototype capsule GDC-0134 (Treatment B) during Period 1. Single dose of reference capsule GDC-0134 (Treatment A) during Period 2. Single dose of GDC-0134 prototype capsule administered after a high-fat meal (Treatment C2) during Period 3. Single dose of GDC-0134 prototype capsule administered after a high-fat meal in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D2) during Period 4. The washout period between doses will be a minimum of 21 days.
intervention type: Drug
intervention name: Reference capsule GDC-0134
description: Oral administration of a single dose of 200 milligrams (mg) GDC-0134 reference capsule administered as two 100 mg capsules.
arm group label: Treatment Sequence 1: ABC1D1
arm group label: Treatment Sequence 2: ABC2D2
arm group label: Treatment Sequence 3: BAC1D1
arm group label: Treatment Sequence 4: BAC2D2
intervention type: Drug
intervention name: Prototype capsule GDC-0134
description: Oral administration of a single dose of 200 mg GDC-0134 prototype capsule administered as one 200 mg capsule.
arm group label: Treatment Sequence 1: ABC1D1
arm group label: Treatment Sequence 2: ABC2D2
arm group label: Treatment Sequence 3: BAC1D1
arm group label: Treatment Sequence 4: BAC2D2
intervention type: Drug
intervention name: rabeprazole
description: Oral administration of 20 mg rabeprazole once daily on Days -3, -2 and -1 as well as on Day 1 two hours prior to each administration of GDC-0134 during Period 4.
arm group label: Treatment Sequence 1: ABC1D1
arm group label: Treatment Sequence 2: ABC2D2
arm group label: Treatment Sequence 3: BAC1D1
arm group label: Treatment Sequence 4: BAC2D2
criteria: 
gender: Female
minimum age: 30 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Motor Neuron Disease
mesh term: Amyotrophic Lateral Sclerosis
mesh term: Rabeprazole