A Study to Evaluate the Effect of Particle Size, Formulation and Food on the Pharmacokinetics of GDC-0032 in Healthy Volunteers

Genentech

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteer

Treatments: Drug: GDC-0032 Capsule; Drug: GDC-0032 Phase III Tablet; Drug: GDC-0032 Tablet

Study type: Interventional

Funder types: Industry

Identifiers

NCT01980953

GP28619

Details and patient eligibility

About

This 4-part study will assess the effect of formulation, food, and active pharmaceutical ingredient (API) lot on the pharmacokinetics of GDC-0032 in healthy volunteers. Part 1 is an open-label, 3-period, 6-sequence study, and Parts 2, 3, and 4 are open-label 2-period crossover studies. Participants will receive single doses of GDC-0032 capsule or tablet formulation, in the fasted or fed state.

Enrollment: 76 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Males or females of non-childbearing potential, between 18 and 55 years of age, inclusive; females will meet the following criteria: they will be non-pregnant, non-lactating, and either postmenopausal for at least 1 year or surgically sterile for at least 90 days.
• Body mass index (BMI) 18.5 to 32 kg/m^2, inclusive
• In good health, determined by no clinically significant findings from medical history, 12-lead electrocardiogram (ECG), vital signs and clinical laboratory evaluations
• Negative test for selected drugs of abuse at Screening (does not include alcohol) and at each Check-in (Day -1; does include alcohol)
• Negative hepatitis panel (including hepatitis B surface antigen [HBsAg] and anti-hepatitis C virus [HCV]) and negative human immunodeficiency virus (HIV) antibody screens
• Males will either be sterile or agree to use approved methods of contraception as defined by protocol from Period 1 Check-in (Period 1, Day -1) until 90 days following the last dose of study drug

Exclusion criteria

• Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disorder (as determined by the Investigator)
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator
• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs, except for appendectomy, hernia repair, and/or cholecystectomy
• History of alcoholism or drug addiction within 1 year prior to Period 1 Check-in (Period 1, Day -1)
• Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
• History of Type 1 or 2 diabetes mellitus and/or elevated fasting glucose (greater than [>] 120 milligrams per deciliter [mg/dL]) at baseline (as confirmed by repeat)
• History of Gilbert's Syndrome
• Evidence of malabsorption syndrome or other condition that would interfere with enteral absorption
• Inability or unwillingness to swallow pills or consume high-fat breakfast
• Use of any tobacco- or nicotine-containing products within 6 months prior to Period 1 Check-in (Period 1, Day -1) and during the entire study
• Participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 5 half-lives or 30 days, whichever is longer, prior to Period 1 Check-in (Period 1, Day -1) and during the entire study duration

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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76 participants in 4 patient groups

Part 1: Food Effect

Experimental group

Description:

GDC-0032 will be administered orally over 3-Treatment Period (TP) in 6-sequence as one 3 milligrams (mg) capsule in TP-A after 10 hour fasting from food, one 3 mg Phase III tablet in TP-B after 10 hour fasting from food and one 3 mg Phase III tablet in TP-C following the start of standard Food and Drug Administration (FDA) high-fat breakfast. Washout period o 14 to 20 days will be given between each TP.

Treatment:

Drug: GDC-0032 Capsule

Drug: GDC-0032 Phase III Tablet

Part 2: Tablet Formulation Comparison

Experimental group

Description:

Different formulations of tablets (Tablet A and Tablet B) of GDC-0032 will be administered orally over 2-TP having 10 hour fasting from food. Participants will receive one 3 mg Tablet A in TP-A and one 3 mg Tablet B in TP-B after 14 to 20 days washout period.

Treatment:

Drug: GDC-0032 Tablet

Part 3: Capsule API Lot Comparison

Experimental group

Description:

Two different lots of GDC-0032 active pharmaceutical ingredient (API) capsule formulation will be administered orally in crossover fashion over 2-TP to 20 participants having 10 hour fasting from food. Participants will receive one 3 mg capsule in TP-A and one 3 mg capsule in TP-B after 14 to 20 days washout period.

Treatment:

Drug: GDC-0032 Capsule

Part 4: Tablet Relative Bioavailibity

Experimental group

Description:

GDC-0032 will be administered orally in crossover fashion over 2-TP to 20 participants having 10 hour fasting from food. Participants will receive one 3 mg capsule in TP-A and one 2 mg Phase III tablet in TP-B after 14 to 20 days washout period.

Treatment:

Drug: GDC-0032 Capsule

Drug: GDC-0032 Phase III Tablet