A Study to Determine the Relative Bioavailability of Capsule and Tablet Formulations of GDC-0941 and the Effect of Food and Proton Pump Inhibition on GDC-0941 Tablet Pharmacokinetics in Healthy Volunteers

Study Overview
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Brief Summary
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This is a Phase I, randomized, two-part, single-center pharmacokinetics (PK) study to assess the relative bioavailability of capsule and tablet formulations of GDC-0941 in the fasted state (Part 1) and to determine the effect of food and proton pump inhibition on the PK of the tablet formulation of GDC-0941 (Part 2). Approximately 18 subjects will be enrolled in Part 1 and up to 32 subjects will be enrolled in Part 2. Subjects who participate in Part 1 are not eligible to participate in Part 2.

Official Title
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An Open-Label, Two-Part Study to Determine the Relative Bioavailability of Capsule and Tablet Formulations of GDC-0941 and the Effect of Food and Proton Pump Inhibition on GDC-0941 Tablet Pharmacokinetics in Healthy Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: GDC-0941
* Drug: rabeprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Male or female, between 18 and 65 years of age, inclusive (Part 1 only) Male or female, between 18 and 45 years of age, inclusive (Part 2 only) In good health, as determined by no clinically significant findings from medical history, 12-lead electrocardiogram (ECG), and vital signs assessment Body Mass Index (BMI) between 18-30 kg/m^2 inclusive, with a body weight >50 kg Clinical laboratory evaluations within the reference range for the test laboratory Negative test for selected drugs of abuse at screening (does not include alcohol) and at check-in (does include alcohol) Negative HIV, hepatitis B surface antigen (HBsAg), and hepatitis C virus antibody screens Agreement to use an effective form of contraception for the duration of the study Exclusion Criteria History or clinical manifestations of significant metabolic (including type 1 and 2 diabetes), hepatic, renal, hematological, pulmonary, cardiovascular, endocrine, gastrointestinal, urological, neurological, psychiatric disorders, or cancer History of inflammatory arthritis History of symptomatic hypotension History of severe physical injury, direct impact trauma, or neurological trauma within a specified timeframe prior to Day 1 History of seizure disorders History of bipolar or major depressive disorder History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (exceptions: appendectomy, hernia repair, and/or cholecystectomy) History or presence of an abnormal ECG Subjects with a history of ventricular dysrhythmias or with risk factors for ventricular dysrhythmias History of alcoholism, drug abuse, or drug addiction Use of any nicotine-containing or nicotine-replacement products within a specified timeframe prior to Day 1 Participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within a specified timeframe prior to Day 1 Use of any prescription medications/products within a specified timeframe prior to Day 1 (exceptions: hormone replacement therapy [HRT], oral, implantable, or transdermal contraception) Receipt of any vaccination or immunization within a specified timeframe prior to Day 1 Use of proton pump inhibitors or H2-receptor antagonists within a specified timeframe prior to Day 1 Known hypersensitivity to rabeprazole or any of its components, or to derived products of benzimidazoles Use of any over-the-counter (OTC), non-prescription preparations within a specified timeframe prior to Day 1 Use of alcohol-containing, grapefruit-containing, or caffeine-containing foods or beverages within a specified timeframe prior to Day 1 Poor peripheral venous access Donation of blood or plasma within a specified timeframe prior to Day 1 Receipt of blood products within a specified timeframe prior to Day 1 Vegetarians who are unable to consume a high-fat meal Women who are pregnant or nursing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Part 1<br> | Drug: GDC-0941<br>* Oral repeating dose<br>|
| Experimental: Part 2<br> | Drug: GDC-0941<br>* Oral repeating dose<br>Drug: rabeprazole<br>* Oral repeating dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence, nature, and severity of adverse events |  | Through study completion or early study discontinuation | 
| PK parameters of GDC-0941 (total exposure, maximum and minimum plasma concentration) |  | Following administration of study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PI3K inhibitor, PI3 kinase, PI3 kinase inhibitor