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

Genentech

Status and phase: Completed; Phase 1

Conditions: Amyotrophic Lateral Sclerosis

Treatments: Drug: Prototype capsule GDC-0134; Drug: rabeprazole; Drug: Reference capsule GDC-0134

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03237741

2017-000299-27 (EudraCT Number)

GP39778

Details and patient eligibility

About

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).

Enrollment: 18 patients

Sex: Female

Ages: 30 to 65 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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18 participants in 4 patient groups

Treatment Sequence 1: ABC1D1

Experimental group

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.

Treatment:

Drug: rabeprazole

Drug: Reference capsule GDC-0134

Drug: Prototype capsule GDC-0134

Treatment Sequence 2: ABC2D2

Experimental group

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.

Treatment:

Drug: rabeprazole

Drug: Reference capsule GDC-0134

Drug: Prototype capsule GDC-0134

Treatment Sequence 3: BAC1D1

Experimental group

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.

Treatment:

Drug: rabeprazole

Drug: Reference capsule GDC-0134

Drug: Prototype capsule GDC-0134

Treatment Sequence 4: BAC2D2

Experimental group

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.

Treatment:

Drug: rabeprazole

Drug: Reference capsule GDC-0134

Drug: Prototype capsule GDC-0134