Phase 1
Completed N=13
An Absolute Bioavailability Study in Healthy Participants Comparing Oral to Intravenous Administration of GDC-0973 (Cobimetinib)
Healthy Volunteers
Source: ClinicalTrials.gov NCT01249118 ↗
Enrolled (actual)
13
Serious AEs
0.0%
Results posted
Feb 2017
Primary outcomePrimary: Maximum Observed Plasma Concentration (Cmax) of IV and Oral GDC-0973 — 20.5; 15.2 nanograms per milliliter (ng/mL)
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Observed Plasma Concentration (Cmax) of IV and Oral GDC-0973 |
20.5; 15.2 | — |
| PRIMARY Dose Normalized Cmax [Cmax(dn)] of IV and Oral GDC-0973 |
10.2; 0.844 | — |
| PRIMARY Minimum Observed Plasma Trough Concentration (Cmin) of IV and Oral GDC-0973 |
0.261; 0.546 | — |
| PRIMARY Time to Reach Maximum Observed Plasma Concentration (Tmax) of IV and Oral GDC-0973 |
0.500; 4.00 | — |
| PRIMARY Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of IV and Oral GDC-0973 |
156; 688 | — |
| PRIMARY Dose Normalized AUC (0-t) [AUC (0-t)dn] of IV and Oral GDC-0973 |
77.8; 38.2 | — |
| PRIMARY Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of IV and Oral GDC-0973 |
188; 784 | — |
| PRIMARY Dose Normalized AUC (0 - ∞) [AUC (0 - ∞)dn] of IV and Oral GDC-0973 |
93.9; 43.5 | — |
| PRIMARY Plasma Decay Half-Life (t1/2) of IV and Oral GDC-0973 |
73.8; 66.2 | — |
| PRIMARY Systemic Clearance (CL) of IV GDC-0973 |
10.7 | — |
| PRIMARY Apparent Oral Clearance (CL/F) of Oral GDC-0973 |
23.0 | — |
| PRIMARY Volume of Distribution at Steady State (Vss) of IV GDC-0973 |
1052 | — |
| PRIMARY Apparent Volume of Distribution (Vz/F) of Oral GDC-0973 |
2197 | — |
| PRIMARY Absolute Oral Bioavailability (F) of GDC-0973 |
0.457 | — |
| PRIMARY Mean Absorption Time (MAT) |
2.67 | — |
| PRIMARY Amount of Drug Excreted in the Urine (Aeu) of IV and Oral GDC-0973 |
0.0761; 0.379 | — |
| PRIMARY Renal Clearance (CLR) of IV and Oral GDC-0973 |
0.405; 0.484 | — |
| PRIMARY Percent of GDC-0973 Excreted in the Urine (% Excreted) for IV and Oral GDC-0973 |
3.81; 1.90 | — |
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)
Data sourced from ClinicalTrials.gov (NCT01249118). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.