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

A Phase 1, Open-Label Study to Evaluate the Effect of Particle Size, Formulation, and Food on the Pharmacokinetics of GDC-0032 in Healthy Subjects

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: GDC-0032 Phase III Tablet; Drug: GDC-0032 Capsule; Drug: GDC-0032 Tablet

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75247
      • Covance Research Unit - Dallas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Food Effect; 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.	Drug: GDC-0032 Phase III Tablet; Participants will receive 2 mg or 3 mg Phase III tablet after 10 hour fasting from food.; Drug: GDC-0032 Capsule; Participants will receive 3 mg GDC-0032 capsule formulation after 10 hour fasting from food.
Experimental: Part 2: Tablet Formulation Comparison; 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.	Drug: GDC-0032 Tablet; Participants will receive 3 mg Tablet A or Tablet B formulation after 10 hour fasting from food.
Experimental: Part 3: Capsule API Lot Comparison; 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.	Drug: GDC-0032 Capsule; Participants will receive 3 mg GDC-0032 capsule formulation after 10 hour fasting from food.
Experimental: Part 4: Tablet Relative Bioavailibity; 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.	Drug: GDC-0032 Phase III Tablet; Participants will receive 2 mg or 3 mg Phase III tablet after 10 hour fasting from food.; Drug: GDC-0032 Capsule; Participants will receive 3 mg GDC-0032 capsule formulation after 10 hour fasting from food.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area Under the Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t)	Pre-dose (Hour 0), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 168, 192 hour post-dose
Area Under the Concentration-Time Curve Extrapolated to Infinity (AUC0-infinity)	Pre-dose (Hour 0), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 168, 192 hour post-dose
Maximum Plasma Concentration (Cmax)	Pre-dose (Hour 0), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 168, 192 hour postdose

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to Maximum Plasma Concentration (tmax)	Pre-dose (Hour 0), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 168, 192 hour post-dose
Apparent Terminal Elimination Rate Constant	Pre-dose (Hour 0), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 168, 192 hour post-dose
Apparent Terminal Elimination Constant (t1/2)	Pre-dose (Hour 0), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 168, 192 hour post-dose
Apparent Total Clearance (CL/F)	Pre-dose (Hour 0), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 168, 192 hour post-dose
Apparent Volume of Distribution (Vz/F)	Pre-dose (Hour 0), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 168, 192 hour post-dose
Percentage of Participants With Adverse Events	From Baseline up to approximately 15 weeks

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: November 5, 2013
• First Submitted That Met QC Criteria: November 8, 2013
• First Posted (Estimate): November 11, 2013

Study Record Updates

• Last Update Posted (Estimate): February 1, 2017
• Last Update Submitted That Met QC Criteria: January 31, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: GP28619