Clinical trial NCT02390492: A Phase I Bioavailability and Pharmacokinetic Study of [14C]-Ipatasertib Single Oral and Intravenous Doses in Healthy Male Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2015-03-17
Enrollment: 8
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP

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.


Eligibility criteria: 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

Primary outcomes:
measure: Pharmacokinetics of [14C]-ipatasertib/ipatasertib (oral): apparent terminal elimination half-life
timeFrame: Period 2: Approximately 2 weeks
measure: Pharmacokinetics of ipatasertib (oral): apparent total clearance (CL/F)
timeFrame: Period 2: Approximately 2 weeks
measure: Pharmacokinetics of ipatasertib (oral): apparent volume of distribution (Vz/F)
timeFrame: Period 2: Approximately 2 weeks
measure: Elimination and pharmacokinetics: Total radioactivity concentration in whole blood, plasma, urine, and feces
timeFrame: Period 2: Approximately 2 weeks
measure: Bioavailability: Absolute bioavailability of ipatasertib (area under the concentration-time curve)
timeFrame: Period 1: Approximately 4 days
measure: Mass balance
timeFrame: Period 2: Approximately 2 weeks
measure: Pharmacokinetics of [14C]-ipatasertib/ipatasertib (oral): maximum observed concentration (Cmax)
timeFrame: Period 2: Approximately 2 weeks
measure: Pharmacokinetics of [14C]-ipatasertib/ipatasertib (oral): time to maximum observed concentration (Tmax)
timeFrame: Period 2: Approximately 2 weeks
measure: Pharmacokinetics of [14C]-ipatasertib/ipatasertib (oral): area under the concentration-time curve from Hour 0 to the last measurable concentration (AUC0-t)
timeFrame: Period 2: Approximately 2 weeks
measure: Pharmacokinetics of [14C]-ipatasertib/ipatasertib (oral): area under the concentration-time curve extrapolated to infinity (AUC0-inf)
timeFrame: Period 2: Approximately 2 weeks
measure: Pharmacokinetics of [14C]-ipatasertib/ipatasertib (oral): apparent terminal elimination rate constant
timeFrame: Period 2: Approximately 2 weeks
Secondary outcomes:
measure: Pharmacokinetics of ipatasertib (oral and IV): terminal elimination rate constant adjusted for oral bioavailability as applicable
timeFrame: Period 1: Approximately 4 days
measure: Pharmacokinetics of ipatasertib (oral and IV): terminal elimination half-life adjusted for oral bioavailability as applicable
timeFrame: Period 1: Approximately 4 days
measure: Pharmacokinetics of ipatasertib (oral and IV): total clearance adjusted for oral bioavailability as applicable
timeFrame: Period 1: Approximately 4 days
measure: Pharmacokinetics of ipatasertib (oral and IV): volume of distribution adjusted for oral bioavailability as applicable
timeFrame: Period 1: Approximately 4 days
measure: Safety: Incidence of adverse events
timeFrame: Approximately 4 weeks
measure: Elimination and pharmacokinetics: Metabolite concentration(s) in plasma, urine, and feces
timeFrame: Period 2: Approximately 2 weeks
measure: Pharmacokinetics of ipatasertib (oral and IV): Cmax
timeFrame: Period 1: Approximately 4 days
measure: Pharmacokinetics of ipatasertib (oral and IV): Tmax
timeFrame: Period 1: Approximately 4 days
measure: Pharmacokinetics of ipatasertib (oral and IV): AUC0-t
timeFrame: Period 1: Approximately 4 days
measure: Pharmacokinetics of ipatasertib (oral and IV): AUC0-inf
timeFrame: Period 1: Approximately 4 days
Other outcomes:
Locations:
city: Madison
country: United States
state: Wisconsin
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: