A Phase I Bioavailability and Pharmacokinetic Study of [14C]-Ipatasertib Single Oral and Intravenous Doses in Healthy Male Subjects

Phase 1

Completed

• Conditions: Healthy Volunteer
• Interventions: Drug: Period 1 treatment; Drug: Period 2 treatment

• Registration Number: NCT02390492
• Lead Sponsor: Genentech, Inc.

Brief Summary

This 2-period, open-label, nonrandomized study will be conducted to determine the absolute bioavailability as well as the absorption, metabolism, and excretion of ipatasertib and its metabolite(s). Healthy male participants will receive a single 200-mg oral dose of ipatasertib followed 1 hour later by an 80-mcg/800-nCi intravenous dose of \[14C\]-ipatasertib. After a 4-day observation period and 10-day washout, participants will receive a single 200-mg/100-mcCi oral dose of \[14C\]-ipatasertib with subsequent data collection for an additional 7 to 14 days until discharge criteria are met.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-03
• Study First Submitted: 2015-03-11
• Study First Submitted QC: 2015-03-16
• Study First Posted: 2015-03-17
• Primary Completion: 2015-04
• Study Completion: 2015-04
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-01
• Last Update Posted: 2016-11-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 8

Inclusion Criteria

• Healthy male volunteers 18 to 55 years of age, inclusive
• Body mass index (BMI) 18 to 32 kg/m2, inclusive

Exclusion Criteria

• Females
• Clinically significant findings from medical history or screening evaluations
• Recent participation in any other investigational drug study or biologic agent study, or receipt of a previous radiolabeled investigational drug within 6 months prior to check-in
• Significant radiation exposure within 12 months prior to check-in

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ipatasertib/[14C]-ipatasertib	Period 1 treatment	-
Ipatasertib/[14C]-ipatasertib	Period 2 treatment	-

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics of [14C]-ipatasertib/ipatasertib (oral): maximum observed concentration (Cmax)	Period 2: Approximately 2 weeks
Pharmacokinetics of [14C]-ipatasertib/ipatasertib (oral): area under the concentration-time curve from Hour 0 to the last measurable concentration (AUC0-t)	Period 2: Approximately 2 weeks
Pharmacokinetics of [14C]-ipatasertib/ipatasertib (oral): apparent terminal elimination rate constant	Period 2: Approximately 2 weeks
Pharmacokinetics of [14C]-ipatasertib/ipatasertib (oral): area under the concentration-time curve extrapolated to infinity (AUC0-inf)	Period 2: Approximately 2 weeks
Pharmacokinetics of [14C]-ipatasertib/ipatasertib (oral): apparent terminal elimination half-life	Period 2: Approximately 2 weeks
Pharmacokinetics of ipatasertib (oral): apparent total clearance (CL/F)	Period 2: Approximately 2 weeks
Pharmacokinetics of ipatasertib (oral): apparent volume of distribution (Vz/F)	Period 2: Approximately 2 weeks
Elimination and pharmacokinetics: Total radioactivity concentration in whole blood, plasma, urine, and feces	Period 2: Approximately 2 weeks
Bioavailability: Absolute bioavailability of ipatasertib (area under the concentration-time curve)	Period 1: Approximately 4 days
Mass balance	Period 2: Approximately 2 weeks
Pharmacokinetics of [14C]-ipatasertib/ipatasertib (oral): time to maximum observed concentration (Tmax)	Period 2: Approximately 2 weeks

Secondary Outcome Measures

Name	Time	Method
Safety: Incidence of adverse events	Approximately 4 weeks
Pharmacokinetics of ipatasertib (oral and IV): terminal elimination half-life adjusted for oral bioavailability as applicable	Period 1: Approximately 4 days
Pharmacokinetics of ipatasertib (oral and IV): total clearance adjusted for oral bioavailability as applicable	Period 1: Approximately 4 days
Pharmacokinetics of ipatasertib (oral and IV): volume of distribution adjusted for oral bioavailability as applicable	Period 1: Approximately 4 days
Elimination and pharmacokinetics: Metabolite concentration(s) in plasma, urine, and feces	Period 2: Approximately 2 weeks
Pharmacokinetics of ipatasertib (oral and IV): Cmax	Period 1: Approximately 4 days
Pharmacokinetics of ipatasertib (oral and IV): AUC0-inf	Period 1: Approximately 4 days
Pharmacokinetics of ipatasertib (oral and IV): AUC0-t	Period 1: Approximately 4 days
Pharmacokinetics of ipatasertib (oral and IV): terminal elimination rate constant adjusted for oral bioavailability as applicable	Period 1: Approximately 4 days
Pharmacokinetics of ipatasertib (oral and IV): Tmax	Period 1: Approximately 4 days