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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase I Study to Investigate the Absorption, Metabolism, and Excretion of [14C]-Ipatasertib (GDC-0068) Following a Single Oral Dose and to Investigate the Absolute Bioavailability Following Single Oral and Intravenous Doses in a Single Cohort of Healthy Male Subjects

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: Period 1 treatment
* Drug: Period 2 treatment


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ipatasertib/[14C]-ipatasertib<br> | Drug: Period 1 treatment<br>* 200 mg oral ipatasertib followed 1 hour later by 80-mcg/800-nCi intravenous [14C]-ipatasertib on Day 1 of study<br>Drug: Period 2 treatment<br>* 200-mg/100-mcCi oral [14C]-ipatasertib on Day 15 of study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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): maximum observed concentration (Cmax) |  | Period 2: Approximately 2 weeks | 
| Pharmacokinetics of [14C]-ipatasertib/ipatasertib (oral): time to maximum observed concentration (Tmax) |  | 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): 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 rate constant |  | Period 2: Approximately 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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): 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 | 
| Safety: Incidence of adverse events |  | Approximately 4 weeks | 
| 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): Tmax |  | Period 1: Approximately 4 days | 
| Pharmacokinetics of ipatasertib (oral and IV): AUC0-t |  | Period 1: Approximately 4 days | 
| Pharmacokinetics of ipatasertib (oral and IV): AUC0-inf |  | Period 1: Approximately 4 days |