Clinical trial NCT03222310: A Study to Evaluate the Effect of a Potent Cytochrome P450 (CYP) 3A Inhibitor on Ipatasertib
Official title: Effect of a Potent CYP3A and P-gp Inhibitor (Itraconazole) on Ipatasertib Pharmacokinetics in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2017-07-19
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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).


Eligibility criteria: 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

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of ipatasertib and its Metabolite (G-037720)
timeFrame: 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
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf]) of Ipatasertib and its Metabolite (G-037720)
timeFrame: 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
measure: Area Under the Plasma Concentration-Time Curve From Hour 0 to the Last Measureable Concentration (AUC0-t) of Ipatasertib and its Metabolite (G-037720)
timeFrame: 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 outcomes:
measure: Number of Participants Who Experienced at Least 1 Adverse Event
timeFrame: Up to 28 days after the last dose of the study drug (approximately up to 51 days)
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Covance Research Unit - Dallas
state: Texas
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: