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

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03222310
• Other study ID #: GP30057
• Status: Completed
• Phase: Phase 1
• First received: July 17, 2017
• Last updated: November 7, 2017
• Start date: July 18, 2017
• Est. completion date: September 6, 2017

Study information

• Verified date: November 2017
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: September 6, 2017
• Est. primary completion date: September 6, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Ipatasertib
Ipatasertib 100 mg tablet orally once daily.
• Itraconazole
Itraconazole 100 mg capsules orally once daily.

Locations

Country	Name	City	State
United States	Covance Research Unit - Dallas	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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)