Ipatasertib (GDC-0068) Study to Evaluate Formulation Change and Food Effect on Bioavailability in Healthy Subjects

Study Overview
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Brief Summary
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This Phase I, open-label, randomized, 3-period crossover study was designed to determine the relative bioavailability of ipatasertib administered as capsule and tablet formulations to healthy volunteers. In addition, the influence of food on ipatasertib exposure will also be determined. Participants will be randomized to one of six treatment sequences to receive three treatments of a single oral administration of ipatasertib in, 1) tablet formulation in the fasted state, 2) capsule formulation in the fasted state or 3) tablet formulation in the fed state. Pharmacokinetics will be assessed, and standard physical and clinical evaluations will be performed throughout the study. Time on study is expected to be 3 weeks.

Official Title
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A Phase 1, Single-Dose, Randomized, Cross-Over, Relative Bioavailability, and Food Effect Study of Ipatasertib (GDC-0068) in Healthy Subjects

Conditions
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Cancer

Intervention / Treatment
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* Drug: Ipatasertib (capsule)
* Drug: Ipatasertib (tablet)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males or females, between 18 and 55 years of age, inclusive Body mass index between 18.5 and 29.9 kg/m^2, inclusive Exclusion Criteria: - Clinically significant findings from medical history or screening evaluations.

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

Sexes Eligible for Study
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All

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

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1: Tablet/Capsule/Tablet with food<br>Day 1: ipatasertib tablet administered after fast, Day 8: ipatasertib capsule administered after fast, Day 15: ipatasertib tablet administered after high-fat meal. | Drug: Ipatasertib (capsule)<br>* Orally administered single dose of Ipatasertib formulated as a capsule.<br>* Other names: GDC-0068 (capsule);Drug: Ipatasertib (tablet)<br>* Orally administered single dose of Ipatasertib formulated as a tablet.<br>* Other names: GDC-0068 (tablet);|
| Experimental: Sequence 2: Tablet/Tablet with food/Capsule<br>Day 1: ipatasertib tablet administered after fast, Day 8: ipatasertib tablet administered after high-fat meal, Day 15: ipatasertib capsule administered after fast. | Drug: Ipatasertib (capsule)<br>* Orally administered single dose of Ipatasertib formulated as a capsule.<br>* Other names: GDC-0068 (capsule);Drug: Ipatasertib (tablet)<br>* Orally administered single dose of Ipatasertib formulated as a tablet.<br>* Other names: GDC-0068 (tablet);|
| Experimental: Sequence 3: Capsule/Tablet/Tablet with food<br>Day 1: ipatasertib capsule administered after fast, Day 8: ipatasertib tablet administered after fast, Day 15: ipatasertib tablet administered after high-fat meal. | Drug: Ipatasertib (capsule)<br>* Orally administered single dose of Ipatasertib formulated as a capsule.<br>* Other names: GDC-0068 (capsule);Drug: Ipatasertib (tablet)<br>* Orally administered single dose of Ipatasertib formulated as a tablet.<br>* Other names: GDC-0068 (tablet);|
| Experimental: Sequence 4: Capsule/Tablet with food/Tablet<br>Day 1: ipatasertib capsule administered after fast, Day 8: ipatasertib tablet administered after high-fat meal, Day 15: ipatasertib tablet administered after fast. | Drug: Ipatasertib (capsule)<br>* Orally administered single dose of Ipatasertib formulated as a capsule.<br>* Other names: GDC-0068 (capsule);Drug: Ipatasertib (tablet)<br>* Orally administered single dose of Ipatasertib formulated as a tablet.<br>* Other names: GDC-0068 (tablet);|
| Experimental: Sequence 5: Tablet with food/Tablet/Capsule<br>Day 1: ipatasertib tablet administered after high-fat meal, Day 8: ipatasertib tablet administered after fast, Day 15: ipatasertib capsule administered after fast. | Drug: Ipatasertib (capsule)<br>* Orally administered single dose of Ipatasertib formulated as a capsule.<br>* Other names: GDC-0068 (capsule);Drug: Ipatasertib (tablet)<br>* Orally administered single dose of Ipatasertib formulated as a tablet.<br>* Other names: GDC-0068 (tablet);|
| Experimental: Sequence 6: Tablet with food/Capsule/Tablet<br>Day 1: ipatasertib tablet administered after high-fat meal, Day 8: ipatasertib capsule administered after fast, Day 15: ipatasertib tablet administered after fast. | Drug: Ipatasertib (capsule)<br>* Orally administered single dose of Ipatasertib formulated as a capsule.<br>* Other names: GDC-0068 (capsule);Drug: Ipatasertib (tablet)<br>* Orally administered single dose of Ipatasertib formulated as a tablet.<br>* Other names: GDC-0068 (tablet);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Concentration (Cmax) of Ipatasertib |  | Days 1, 8 and 15 | 
| Time to Maximum Concentration (tmax) of Ipatasertib |  | Days 1, 8 and 15 | 
| Area Under the Concentration-time Curve (AUC) from Hour 0 to the Last Quantifiable Concentration (AUC0-t) of Ipatasertib |  | Days 1, 8 and 15 | 
| Area Under the Concentration-time Curve (AUC) from Hour 0 Extrapolated to Infinity |  | Days 1, 8 and 15 | 
| Apparent Terminal Elimination Half-Life (t1/2) of Ipatasertib |  | Days 1, 8 and 15 | 
| Apparent Total Clearance (CL/F) of Ipatasertib |  | Days 1, 8 and 15 | 
| Apparent Volume of Distribution (Vz/F) of Ipatasertib |  | Days 1, 8 and 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Adverse Events |  | From check in (Day -1) to 30 days after the last dose of study drug |