Clinical trial NCT03237741: Bioavailability of GDC-0134 and the Effect of Food and Proton Pump Inhibitor on Pharmacokinetics of GDC-0134 in Healthy Female Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Amyotrophic Lateral Sclerosis
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Quotient Clinical
First posted: 2017-08-02
Enrollment: 18
Sex: FEMALE
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: Inclusion Criteria:

* Healthy female participants between 30 and 65 years of age, inclusive;
* Within body mass index range 18.0 to 35.0 kilograms per square meter (kg/m\^2), inclusive;
* Female participants will be of non-childbearing potential;
* In good health, determined by no clinically significant findings from medical history, 12-lead echocardiogram (ECG), and vital signs;
* Clinical laboratory evaluations within the reference range for the test laboratory, unless deemed not clinically significant by the investigator;
* Normal ophthalmology assessment.

Exclusion Criteria:

* Males and females of childbearing potential;
* Significant history or clinical manifestation of any significant metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal (GI), neurological, or psychiatric disorder (as determined by the investigator;
* History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator;
* History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs;
* History of GI bleeding or GI ulcers;
* Any personal or family history of bleeding disorders, and any personal use of drugs known to affect blood clotting within 30 days of dosing;
* Any acute or chronic medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the subject's safe participation in and completion of the study.

Primary outcomes:
measure: Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of GDC-0134
timeFrame: 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
measure: Area Under the Plasma Concentration-Time Curve up to Time Tau (AUC0-t) of GDC-0134
timeFrame: 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
measure: Maximum Observed Concentration (Cmax) of GDC-0134
timeFrame: 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
measure: Time to Maximum Concentration (Tmax) of GDC-0134
timeFrame: 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
measure: Apparent Half-Life (t1/2) of GDC-0134
timeFrame: 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
Secondary outcomes:
measure: Percentage of Participants with Adverse Events
timeFrame: From baseline until 21 days after the last dose of study drug up to approximately 16 weeks
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Quotient Clinical Ltd, Clinical Research Unit
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: