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

Genentech, Inc.50 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Healthy Volunteer

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Part 1: Relative Bioavailability of GDC-0853 tablet Compared to GDC-0853 Capsule

Time frame: Part 1 (Periods 1 to 2 [Period length=5 days]): Predose (</=1 hour before dosing), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose on Day 1; 24, 36 hours postdose on Day 2; 48 hours postdose on Day 3; 72 hours postdose on Day 4

Part 1: Area Under the Concentration Time-Curve From Time 0 to Infinity (AUC0-inf) of GDC-0853 Capsule

Part 1: Area Under the Concentration Time-Curve From Time 0 to Last Reported Plasma Concentration (AUC0-t) of GDC-0853 Capsule

Part 1: Maximum Plasma Concentration (Cmax) of GDC-0853 Capsule

Part 1: Time to Maximum Plasma Concentration (Tmax) of GDC-0853 Capsule

Part 1: Apparent half-life (t1/2) of GDC-0853 Capsule

Parts 1 and 2: AUC0-inf of GDC-0853 Tablet

Time frame: Parts 1 and 2 (Periods 1 to 2 [Period length=5 days]): Predose (</=1 hour before dosing), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose on Day 1; 24, 36 hours postdose on Day 2; 48 hours postdose on Day 3; 72 hours postdose on Day 4

Parts 1 and 2: AUC0-t of GDC-0853 Tablet

Parts 1 and 2: Cmax of GDC-0853 Tablet

Parts 1 and 2: Tmax of GDC-0853 Tablet

Parts 1 and 2: Apparent t1/2 of GDC-0853 Tablet

Parts 1 and 2: AUC0-inf of GDC-0853 Tablet When Administered With Rabeprazole

Time frame: Parts 1 and 2 (Period 3 [Period length=8 days]): Predose (</=1 hour before dosing), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose on Day 1; 24, 36 hours postdose on Day 2; 48 hours postdose on Day 3; 72 hours postdose on Day 4

Parts 1 and 2: AUC0-t of GDC-0853 Tablet When Administered With Rabeprazole

Parts 1 and 2: Cmax of GDC-0853 Tablet When Administered With Rabeprazole

Parts 1 and 2: Tmax of GDC-0853 Tablet When Administered With Rabeprazole

Parts 1 and 2: Apparent t1/2 of GDC-0853 Tablet When Administered With Rabeprazole

Part 3: Area Under the Concentration Time-Curve From Time 0 to 24 Hours, Steady State (AUC0-24, ss) of GDC0853 Tablet