A Study to Evaluate Effect of Itraconazole on the Pharmacokinetics of Cobimetinib in Healthy Participants

NCT01929876 | Completed Phase 1 Results

• 1 other identifier: GP28620
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Participants

Outcome Measures

Primary Outcomes (2)

• Maximum Observed Plasma Concentration (Cmax) of Cobimetinib With and Without Itraconazole

  Maximum observed plasma concentration of cobimetinib with and without itraconazole was assessed using a model independent approach.

  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

• Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of Cobimetinib With and Without Itraconazole

  AUC (0 - inf) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf). It is obtained from AUC (0 - t) plus AUC (t - inf) of cobimetinib with and without itraconazole, assessed using a model independent approach.

  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 (8)

• Time to Reach Maximum Observed Plasma Concentration (Tmax) of Cobimetinib With and Without Itraconazole

  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

• Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of Cobimetinib With and Without Itraconazole

  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

• Plasma Half-Life (t1/2) of Cobimetinib With and Without Itraconazole

  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

• Apparent Clearance (CL/F) of Cobimetinib With and Without Itraconazole

  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

• Apparent Volume of Distribution (Vz/F) of Cobimetinib With and Without Itraconazole

  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

Study Arms (1)

Cobimetinib + Itraconazole

EXPERIMENTAL

Drug: Cobimetinib; Drug: Itraconazole

Interventions

Cobimetinib DRUG

10 milligram (mg) (2\* 5 mg capsules) will be administered orally on Day 1 of Period 1 and Day 4 of Period 2

Also known as: GDC-0973

Cobimetinib + Itraconazole

Itraconazole DRUG

200 mg oral solution will be administered once daily from Day 1 to Day 14 of Period 2

Cobimetinib + Itraconazole

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (1)

Unknown Facility

Dallas, Texas, 75247, United States

Location

MeSH Terms

Interventions

cobimetinib; Itraconazole

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Genentech, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2013
• First Posted: August 28, 2013
• Study Start: July 1, 2013
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: August 4, 2016
• Results First Posted: August 4, 2016

Record last verified: 2016-06

Locations

US (1)