Bioavailability of GDC-0134 and the Effect of Food and Proton Pump Inhibitor on Pharmacokinetics of GDC-0134 in Healthy Female Participants

NCT ID: NCT03237741

Last Updated: 2024-03-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-07
• Study Completion Date: 2017-12-14

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).

Conditions

Amyotrophic Lateral Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment Sequence 1: ABC1D1

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.

Group Type: EXPERIMENTAL

Reference capsule GDC-0134

Intervention Type: DRUG

Oral administration of a single dose of 200 milligrams (mg) GDC-0134 reference capsule administered as two 100 mg capsules.

Prototype capsule GDC-0134

Intervention Type: DRUG

Oral administration of a single dose of 200 mg GDC-0134 prototype capsule administered as one 200 mg capsule.

rabeprazole

Intervention Type: DRUG

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.

Treatment Sequence 2: ABC2D2

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.

Group Type: EXPERIMENTAL

Reference capsule GDC-0134

Intervention Type: DRUG

Oral administration of a single dose of 200 milligrams (mg) GDC-0134 reference capsule administered as two 100 mg capsules.

Prototype capsule GDC-0134

Intervention Type: DRUG

Oral administration of a single dose of 200 mg GDC-0134 prototype capsule administered as one 200 mg capsule.

rabeprazole

Intervention Type: DRUG

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.

Treatment Sequence 3: BAC1D1

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.

Group Type: EXPERIMENTAL

Reference capsule GDC-0134

Intervention Type: DRUG

Oral administration of a single dose of 200 milligrams (mg) GDC-0134 reference capsule administered as two 100 mg capsules.

Prototype capsule GDC-0134

Intervention Type: DRUG

Oral administration of a single dose of 200 mg GDC-0134 prototype capsule administered as one 200 mg capsule.

rabeprazole

Intervention Type: DRUG

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.

Treatment Sequence 4: BAC2D2

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.

Group Type: EXPERIMENTAL

Reference capsule GDC-0134

Intervention Type: DRUG

Oral administration of a single dose of 200 milligrams (mg) GDC-0134 reference capsule administered as two 100 mg capsules.

Prototype capsule GDC-0134

Intervention Type: DRUG

Oral administration of a single dose of 200 mg GDC-0134 prototype capsule administered as one 200 mg capsule.

rabeprazole

Intervention Type: DRUG

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.

Interventions

Reference capsule GDC-0134

Oral administration of a single dose of 200 milligrams (mg) GDC-0134 reference capsule administered as two 100 mg capsules.

Intervention Type: DRUG

Prototype capsule GDC-0134

Oral administration of a single dose of 200 mg GDC-0134 prototype capsule administered as one 200 mg capsule.

Intervention Type: DRUG

rabeprazole

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.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Quotient Clinical

OTHER

Sponsor Role: collaborator

Genentech, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Quotient Clinical Ltd, Clinical Research Unit

Nottingham, , United Kingdom

Countries

United Kingdom

Other Identifiers

2017-000299-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GP39778

Identifier Type: -

Identifier Source: org_study_id