Clinical trial NCT01980953: A Study to Evaluate the Effect of Particle Size, Formulation and Food on the Pharmacokinetics of GDC-0032 in Healthy Volunteers
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2013-11-11
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.


Eligibility criteria: 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

Primary outcomes:
measure: Area Under the Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t)
timeFrame: Pre-dose (Hour 0), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 168, 192 hour post-dose
measure: Area Under the Concentration-Time Curve Extrapolated to Infinity (AUC0-infinity)
timeFrame: Pre-dose (Hour 0), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 168, 192 hour post-dose
measure: Maximum Plasma Concentration (Cmax)
timeFrame: Pre-dose (Hour 0), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 168, 192 hour postdose
Secondary outcomes:
measure: Time to Maximum Plasma Concentration (tmax)
timeFrame: Pre-dose (Hour 0), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 168, 192 hour post-dose
measure: Apparent Terminal Elimination Rate Constant
timeFrame: Pre-dose (Hour 0), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 168, 192 hour post-dose
measure: Apparent Terminal Elimination Constant (t1/2)
timeFrame: Pre-dose (Hour 0), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 168, 192 hour post-dose
measure: Apparent Total Clearance (CL/F)
timeFrame: Pre-dose (Hour 0), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 168, 192 hour post-dose
measure: Apparent Volume of Distribution (Vz/F)
timeFrame: Pre-dose (Hour 0), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 168, 192 hour post-dose
measure: Percentage of Participants With Adverse Events
timeFrame: From Baseline up to approximately 15 weeks
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Covance Research Unit - Dallas
state: Texas
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References: