An Absolute Bioavailability Study in Healthy Participants Comparing Oral to Intravenous Administration of GDC-0973 (Cobimetinib)

Genentech

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteers

Treatments: Drug: GDC-0973 IV Infusion; Drug: GDC-0973 Oral Capsules

Study type: Interventional

Funder types: Industry

Identifiers

NCT01249118

MEK4952g

Details and patient eligibility

About

The primary objective of Part 1 of this study is to evaluate the safety and tolerability of the intravenous (IV) dose of GDC-0973. The primary objectives of Part 2 of this study are to evaluate the absolute bioavailability of GDC-0973 and to evaluate the pharmacokinetic (PK) of GDC-0973 following IV and oral administration. The secondary objective of Part 2 of this study is to evaluate the safety of GDC-0973 administered orally and intravenously.

Enrollment: 13 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• Within body mass index range 18.5 to 29.9 kilograms per square meter (kg/m^2)
• In good health, determined by no clinically significant findings from medical history, 12-lead electrocardiogram (ECG), and vital signs
• Clinical laboratory evaluations within the reference range for the test laboratory
• Negative test for selected drugs of abuse at Screening and at each Check-in
• Negative hepatitis panel and anti-hepatitis C virus and negative human immunodeficiency virus (HIV) antibody screens
• Healthy males and females of non-child-bearing potential or who agree to use effective contraception

Exclusion Criteria

• Significant history or clinical manifestation of any significant metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disorder
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance
• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs except that appendectomy, hernia repair, and cholecystectomy will be allowed
• History or presence of an abnormal ECG
• History of alcoholism or drug addiction prior to period 1 check-in
• Use of any tobacco-containing or nicotine-containing products prior to period 1 check-in
• Participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 28 days or 5 half-lives, whichever is longer, prior to period 1 check-in
• Use of any prescription medications/products, including proton pump inhibitors, within 14 days prior to period 1 check-in
• Poor peripheral venous access
• Any acute or chronic condition that would limit the participants ability to complete and/or participate in this clinical study
• Female participant is pregnant, lactating, or breastfeeding
• Predisposing factors to retinal vein occlusion (RVO)

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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13 participants in 3 patient groups

Part 1: GDC-0973 IV Infusion First, Then GDC-0973 Capsules

Experimental group

Description:

Participants will receive single dose of GDC-0973 2 milligrams (mg) IV infusion in first intervention period followed by single dose of GDC-0973 20 mg oral capsules (four 5-mg capsules) in second intervention period. The washout period between each period will be a minimum of 10 days.

Treatment:

Drug: GDC-0973 Oral Capsules

Drug: GDC-0973 IV Infusion

Part 2: GDC-0973 IV Infusion First, Then GDC-0973 Capsules

Experimental group

Description:

Participants will receive single dose of GDC-0973 2 mg IV infusion in first intervention period followed by single dose of GDC-0973 20 mg oral capsules (four 5-mg capsules) in second intervention period. The washout period between each period will be a minimum of 10 days.

Treatment:

Drug: GDC-0973 Oral Capsules

Drug: GDC-0973 IV Infusion

Part 2: GDC-0973 Capsules First, Then GDC-0973 IV Infusion

Experimental group

Description:

Participants will receive single dose of GDC-0973 20 mg oral capsules (four 5-mg capsules) in first intervention period followed by single dose of GDC-0973 2 mg IV infusion in second intervention period. The washout period between each period will be a minimum of 10 days.

Treatment:

Drug: GDC-0973 Oral Capsules

Drug: GDC-0973 IV Infusion