Phase 1
Completed N=16
A Study to Evaluate Effect of Itraconazole on the Pharmacokinetics of Cobimetinib in Healthy Participants
Healthy Participants
Source: ClinicalTrials.gov NCT01929876 ↗
Enrolled (actual)
16
Serious AEs
0.0%
Results posted
Aug 2016
Primary outcomePrimary: Maximum Observed Plasma Concentration (Cmax) of Cobimetinib With and Without Itraconazole — 5.21; 16.5 nanogram per milliliter (ng/mL)
Summary
This open-label, 2-period, fixed sequence, drug interaction study will investigate the effect of co-administration of itraconazole on the pharmacokinetics of cobimetinib in healthy participants. Participants will receive multiple repeating doses of cobimetinib and itraconazole.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Observed Plasma Concentration (Cmax) of Cobimetinib With and Without Itraconazole |
5.21; 16.5 | — |
| PRIMARY Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of Cobimetinib With and Without Itraconazole |
241; 1596 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) of Cobimetinib With and Without Itraconazole |
2.00; 4.00 | — |
| SECONDARY Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of Cobimetinib With and Without Itraconazole |
209; 1220 | — |
| SECONDARY Plasma Half-Life (t1/2) of Cobimetinib With and Without Itraconazole |
58.6; 118 | — |
| SECONDARY Apparent Clearance (CL/F) of Cobimetinib With and Without Itraconazole |
41.4; 6.27 | — |
| SECONDARY Apparent Volume of Distribution (Vz/F) of Cobimetinib With and Without Itraconazole |
3233; 1065 | — |
| SECONDARY Cmax of Itraconazole and Hydroxy-Itraconazole |
1480; 1243 | — |
| SECONDARY Tmax of Itraconazole and Hydroxy-Itraconazole |
2.00; 4.00 | — |
| SECONDARY Area Under the Curve From Time Zero to 24 Hours [AUC (0-24)] of Itraconazole and Hydroxy-Itraconazole |
15607; 23176 | — |
Eligibility Criteria
Inclusion Criteria
- Healthy adult participants
- Within body mass index (BMI) range 18.5 to 32 kilogram per meter square (kg/m^2), inclusive
- Creatine phosphokinase levels below 2.5 times the upper limit of normal (ULN) and if elevated, not clinically significant
- Liver function tests for aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase below 2 times the ULN; bilirubin below 1.5 times the ULN; and all liver function test elevations not clinically significant
- 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, unless deemed not clinically significant by the Investigator
- Negative test for selected drugs of abuse at screening and at each check-in
- Negative hepatitis panel (including hepatitis B surface antigen [HBsAg] and anti-hepatitis C virus [HCV]) and negative human immunodeficiency virus (HIV) antibody screens
- Females non-pregnant or non-lactating
- Males and females (of child-bearing potential) to use two forms of adequate contraception
Exclusion Criteria
- Significant history or clinical manifestation of any 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, unless approved by the Investigator
- 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/or cholecystectomy will be allowed
- History of diabetes mellitus and/or elevated fasting glucose at baseline
- History or presence of an abnormal ECG, which in the Investigator's opinion, is clinically significant
- History of alcoholism or drug addiction within 1 year prior to study start
- Use of any tobacco- or nicotine-containing products (within 6 months prior to study start and during the entire study
- Participation in any other investigational study or biologic agent trial in which receipt of an investigational study drug occurred within 5 half-lives or 30 days, whichever is longer, or exposure to any biological therapy or investigational biological agent within 90 days prior to study entry and during the entire study from study start to study completion, inclusive
Data sourced from ClinicalTrials.gov (NCT01929876). 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.