Clinical trial NCT01249118: An Absolute Bioavailability Study in Healthy Participants Comparing Oral to Intravenous Administration of GDC-0973 (Cobimetinib)
Official title: A Phase 1, Single Dose, Randomized, Cross-over Absolute Bioavailability Study in Healthy Subjects Comparing Oral to Intravenous Administration of GDC-0973
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2010-11-29
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility 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)

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of IV and Oral GDC-0973
timeFrame: Part 2: 0 hours (Hrs) (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
measure: Dose Normalized Cmax [Cmax(dn)] of IV and Oral GDC-0973
timeFrame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
measure: Minimum Observed Plasma Trough Concentration (Cmin) of IV and Oral GDC-0973
timeFrame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of IV and Oral GDC-0973
timeFrame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of IV and Oral GDC-0973
timeFrame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
measure: Dose Normalized AUC (0-t) [AUC (0-t)dn] of IV and Oral GDC-0973
timeFrame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of IV and Oral GDC-0973
timeFrame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
measure: Dose Normalized AUC (0 - ∞) [AUC (0 - ∞)dn] of IV and Oral GDC-0973
timeFrame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
measure: Plasma Decay Half-Life (t1/2) of IV and Oral GDC-0973
timeFrame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
measure: Systemic Clearance (CL) of IV GDC-0973
timeFrame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
measure: Apparent Oral Clearance (CL/F) of Oral GDC-0973
timeFrame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
measure: Volume of Distribution at Steady State (Vss) of IV GDC-0973
timeFrame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose of Day 1
measure: Apparent Volume of Distribution (Vz/F) of Oral GDC-0973
timeFrame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
measure: Absolute Oral Bioavailability (F) of GDC-0973
timeFrame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
measure: Mean Absorption Time (MAT)
timeFrame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
measure: Amount of Drug Excreted in the Urine (Aeu) of IV and Oral GDC-0973
timeFrame: Part 2: 0 to 12, 12 to 24, 24 to 48, 48 to 72, and 72 to 96 Hrs post-dose on Day 1
measure: Renal Clearance (CLR) of IV and Oral GDC-0973
timeFrame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1 for plasma; 0 to 12, 12 to 24, 24 to 48, 48 to 72, and 72 to 96 Hrs post-dose for urine
measure: Percent of GDC-0973 Excreted in the Urine (% Excreted) for IV and Oral GDC-0973
timeFrame: Part 2: 0 to 12, 12 to 24, 24 to 48, 48 to 72, and 72 to 96 Hrs post-dose
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Genentech, Inc.
name: Isabelle Rooney, M.D., PhD
role: STUDY_DIRECTOR
References: