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

NCT01980953 | Completed Phase 1

• 1 other identifier: GP28619
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Volunteer

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (6)

• 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

Study Arms (4)

Part 1: Food Effect

EXPERIMENTAL

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; Drug: GDC-0032 Capsule

Part 2: Tablet Formulation Comparison

EXPERIMENTAL

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

Part 3: Capsule API Lot Comparison

EXPERIMENTAL

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

Part 4: Tablet Relative Bioavailibity

EXPERIMENTAL

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; Drug: GDC-0032 Capsule

Interventions

GDC-0032 Phase III Tablet DRUG

Participants will receive 2 mg or 3 mg Phase III tablet after 10 hour fasting from food.

Part 1: Food Effect; Part 4: Tablet Relative Bioavailibity

GDC-0032 Tablet DRUG

Participants will receive 3 mg Tablet A or Tablet B formulation after 10 hour fasting from food.

Part 2: Tablet Formulation Comparison

GDC-0032 Capsule DRUG

Participants will receive 3 mg GDC-0032 capsule formulation after 10 hour fasting from food.

Part 1: Food Effect; Part 3: Capsule API Lot Comparison; Part 4: Tablet Relative Bioavailibity

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (1)

Covance Research Unit - Dallas

Dallas, Texas, 75247, United States

Location

MeSH Terms

Interventions

2-(3-(2-(1-isopropyl-3-methyl-1H-1,2-4-triazol-5-yl)-5,6-dihydrobenzo(f)imidazo(1,2-d)(1,4)oxazepin-9-yl)-1H-pyrazol-1-yl)-2-methylpropanamide

Study Officials

• Clinical Trials

  Genentech, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2013
• First Posted: November 11, 2013
• Study Start: November 1, 2013
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: February 1, 2017

Record last verified: 2017-01

Locations

US (1)