Clinical trial NCT01929876: A Study to Evaluate Effect of Itraconazole on the Pharmacokinetics of Cobimetinib in Healthy Participants
Official title: A Phase 1, Open-Label Study to Evaluate the Effect of Itraconazole on the Pharmacokinetics of Cobimetinib in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2013-08-28
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP

Brief 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.


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

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Cobimetinib With and Without Itraconazole
timeFrame: Period 1: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192 hours postdose on Day 1; Period 2: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192, 240 hours post cobimetinib dose on Day 4
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of Cobimetinib With and Without Itraconazole
timeFrame: Period 1: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192 hours postdose on Day 1; Period 2: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192, 240 hours post cobimetinib dose on Day 4
Secondary outcomes:
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Cobimetinib With and Without Itraconazole
timeFrame: Period 1: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192 hours postdose on Day 1; Period 2: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192, 240 hours post cobimetinib dose on Day 4
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of Cobimetinib With and Without Itraconazole
timeFrame: Period 1: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192 hours postdose on Day 1; Period 2: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192, 240 hours post cobimetinib dose on Day 4
measure: Plasma Half-Life (t1/2) of Cobimetinib With and Without Itraconazole
timeFrame: Period 1: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192 hours postdose on Day 1; Period 2: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192, 240 hours post cobimetinib dose on Day 4
measure: Apparent Clearance (CL/F) of Cobimetinib With and Without Itraconazole
timeFrame: Period 1: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192 hours postdose on Day 1; Period 2: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192, 240 hours post cobimetinib dose on Day 4
measure: Apparent Volume of Distribution (Vz/F) of Cobimetinib With and Without Itraconazole
timeFrame: Period 1: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192 hours postdose on Day 1; Period 2: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192, 240 hours post cobimetinib dose on Day 4
measure: Cmax of Itraconazole and Hydroxy-Itraconazole
timeFrame: Period 2: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192, 240 hours post cobimetinib dose on Day 4
measure: Tmax of Itraconazole and Hydroxy-Itraconazole
timeFrame: Period 2: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192, 240 hours post cobimetinib dose on Day 4
measure: Area Under the Curve From Time Zero to 24 Hours [AUC (0-24)] of Itraconazole and Hydroxy-Itraconazole
timeFrame: Period 2: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24 hours post cobimetinib dose on Day 4
Other outcomes:
Locations:
city: Dallas
country: United States
state: Texas
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References: