Effect of Food, Rabeprazole, Methotrexate and Formulation on the Pharmacokinetics (PK) of GDC-0853 and the Effect of GDC-0853 on the PK of Methotrexate in Healthy Subjects (QCL117578)

Genentech

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteer

Treatments: Drug: Folic Acid; Drug: Rabeprazole; Drug: Methotrexate; Drug: GDC-0853

Study type: Interventional

Funder types: Industry

Identifiers

NCT02699710

2015-002471-25 (EudraCT Number)

QCL117578 (Other Identifier)

GP29832

Details and patient eligibility

About

This study is a Phase I, single center, randomized (Parts 1 and 2 only), open-label, 3 part study. Parts 1 and 2 are 2-way crossover, with 1-fixed sequence, 3-period designs to investigate the effect of formulation, food and rabeprazole on the PK of GDC-0853 in healthy male and female (of non-childbearing potential) participants. Part 3 is a fixed-sequence study with 3 treatments to characterize the steady-state PK of the GDC-0853 tablet; the effect of simultaneous administration of a single dose of methotrexate on the steady-state kinetics of GDC-0853; and the effect of dosing GDC-0853 to steady-state on the single dose PK of methotrexate in healthy male participants.

Enrollment: 50 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Within body mass index range of 18.0 to 31.0 kilograms per square meter (kg/m^2), inclusive
• For women who are not postmenopausal (greater than or equal to [>/=] 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): these participants will be excluded
• For men: agreement to use a condom plus an additional contraceptive method with their partner during the treatment period and for at least 93 days after the last dose of study drug and agreement to refrain from donating sperm during this same period

Exclusion criteria

• Significant history or clinical manifestation of any significant metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, 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
• Participants previously enrolled in this study or participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 90 days prior to Period 1 Check-in (Day -1)
• History of malignancy, except for completely excised basal cell carcinoma or squamous cell carcinoma of the skin or cervical carcinoma in situ
• Female participant is pregnant, lactating or breastfeeding
• Current treatment with medications that are well known to prolong the QT interval
• Failure to satisfy the investigator of fitness to participate for any other reason

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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50 participants in 3 patient groups

Part 1: GDC-0853, Rabeprazole (Fasting State)

Experimental group

Description:

Participants will receive single dose of GDC-0853 (200 milligrams \[mg\]) in a crossover design as either the capsule or tablet formulation in the fasted state with the final fixed treatment consisting of the tablet formulation administered in the fasted state after prior administration of rabeprazole (20 mg twice daily \[BID\]) for 3 days.

Treatment:

Drug: GDC-0853

Drug: Rabeprazole

Part 2: GDC-0853, Rabeprazole (Fasting or Fed State)

Experimental group

Description:

Participants will receive single dose of GDC-0853 (200 mg) tablet formulation in the fasted or fed state in a crossover design with the final fixed treatment consisting of the tablet formulation administered in the fed state after prior administration of rabeprazole (20 mg BID) for 3 days.

Treatment:

Drug: GDC-0853

Drug: Rabeprazole

Part 3: GDC-0853, Methotrexate

Experimental group

Description:

Participants will receive single dose of methotrexate (7.5 mg) under fasting conditions on Day 1 (5 mg folic acid will be administered the following day \[Day 2\]) and then GDC-0853 (200 mg) tablet formulation twice daily (BID) under fasting conditions (an overnight fast for the morning dose and a 2 hour fast for the evening dose) from Days 15 to 20 after washout period from Days 2 to 14. On Day 21, participants will receive single dose of methotrexate (7.5 mg) with single dose of GDC-0853 (200 mg) tablet formulation under fasting conditions, and folic acid (5 mg) will be administered on Day 22.

Treatment:

Drug: GDC-0853

Drug: Folic Acid

Drug: Methotrexate