A Study to Evaluate the Effect of a Potent Cytochrome P450 (CYP) 3A Inhibitor on Ipatasertib

Effect of a Potent CYP3A and P-gp Inhibitor (Itraconazole) on Ipatasertib Pharmacokinetics in Healthy Subjects

This study will be a single center, open-label, 2-period, fixed-sequence, Phase 1 drug-drug interaction study in healthy subjects. The primary purpose of this study is to evaluate the effect of itraconazole on the PK of ipatasertib and its primary metabolite (G-037720).

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Ipatasertib; Drug: Itraconazole

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75247
      • Covance Research Unit - Dallas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Within body mass index (BMI) range 18.5 to 32.0 kg/m2, inclusive
• In good health, determined by no clinically significant findings from medical history, 12-lead ECG, and vital signs
• Clinical laboratory evaluations (including chemistry panel [fasted at least 8 hours], hematology, and urinalysis [UA] with complete microscopic analysis 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 (does not include alcohol) and at Check-in (Day -2)
• Negative hepatitis panel (hepatitis B surface antigen and hepatitis C virus antibody) and negative human immunodeficiency virus (HIV) antibody screens

Exclusion Criteria:

• Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, GI, neurological, or psychiatric disorder (as determined by the Investigator)
• History of diabetes requiring insulin or fasting glucose ≥160 mg/dL
• 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, or other GI disorder that would potentially alter absorption and/or excretion of orally administered drugs, except that appendectomy, hernia repair, and/or cholecystectomy will be allowed
• history or presence of an abnormal ECG, which, in the Investigator's opinion, is clinically significant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ipatasertib; Participants will receive one 100 milligram (mg) ipatasertib tablet orally on Day 1 of treatment in treatment period 1 followed by two 100 mg itraconazole capsules orally on Days 15 to 23 along with one 100 mg of ipatasertib on Day 19 in treatment period 2. Both the treatment period will be separated by a washout period of 14 days.	Drug: Ipatasertib; Ipatasertib 100 mg tablet orally once daily.; Drug: Itraconazole; Itraconazole 100 mg capsules orally once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of ipatasertib and its Metabolite (G-037720)	Cmax is the maximum observed concentration.	Pre-dose, 0.167, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144 hours post dose on Day 1 and 19; 168, 192 hours post dose on Day 19
Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf]) of Ipatasertib and its Metabolite (G-037720)	AUC(0-inf) is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). AUC is a measure of the plasma concentration of a drug over time.	Pre-dose, 0.167, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144 hours post dose on Day 1 and 19; 168, 192 hours post dose on Day 19
Area Under the Plasma Concentration-Time Curve From Hour 0 to the Last Measureable Concentration (AUC0-t) of Ipatasertib and its Metabolite (G-037720)	Area Under the Plasma Concentration-Time Curve From Hour 0 to the Last Measureable Concentration (AUC0-t) will be reported.	Pre-dose, 0.167, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144 hours post dose on Day 1 and 19; 168, 192 hours post dose on Day 19

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experienced at Least 1 Adverse Event	An adverse event is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.	Up to 28 days after the last dose of the study drug (approximately up to 51 days)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 18, 2017
• Primary Completion (ACTUAL): September 6, 2017
• Study Completion (ACTUAL): September 6, 2017

Study Registration Dates

• First Submitted: July 17, 2017
• First Submitted That Met QC Criteria: July 17, 2017
• First Posted (ACTUAL): July 19, 2017

Study Record Updates

• Last Update Posted (ACTUAL): November 9, 2017
• Last Update Submitted That Met QC Criteria: November 7, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole
• Other Study ID Numbers: GP30057

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No