Healthy
Conditions
Keywords
GDC0449
Brief summary
This is an open-label, Phase I, single-center, single-dose administration study to determine the absolute bioavailability, clearance, and volume of distribution of GDC-0449 (Part A) and to determine the routes of excretion and extent of metabolism of GDC-0449 (Part B). Parts A and B will be conducted sequentially, with ≥ 7 days between dosing the sixth subject in Part A and dosing the first subject in Part B. In each part, 6 healthy female subjects of non-childbearing potential, between 18 and 65 years of age (inclusive), will be dosed.
Interventions
DRUGGDC-0449 oral capsules (non-labeled)
150 mg oral capsule
DRUGGDC-0449 IV injection (labeled)
10 mcg (in 2 mL) IV dose of 14C-GDC-0449
DRUGCDC-0449 oral suspension (labeled)
30-mL oral suspension containing 6.5 mcg 14CGDC-0449 and 150 mg GDC-0449
Sponsors
Genentech, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Female * Non-childbearing potential * Body mass index (BMI) between 18 and 32 kg/m\^2, inclusive * In good health, determined by no clinically significant findings on physical examination, medical history, 12-lead ECG, and vital signs * Negative test for drugs of abuse at screening (does not include alcohol) and at admission to the clinical research facility (does include alcohol)
Exclusion criteria
* History or clinical manifestations of clinically significant metabolic, hepatic, renal, hematologic, pulmonary, cardiovascular, endocrine, gastrointestinal (including gastric or duodenal ulcers), urologic, neurologic, inflammatory, or psychiatric disorders, or cancer * History of symptomatic hypotension, idiopathic orthostatic hypotension, or other autonomous-failure syndromes * History of severe physical injury, direct impact trauma, or neurological trauma within 6 months prior to Day -1 * History of stomach or intestinal surgery, stomach disease, or resection that would potentially alter absorption and/or excretion of orally administered drugs (appendectomy, hernia repair, and/or cholecystectomy are allowed) * History of alcoholism, drug abuse, or drug addiction (including soft drugs like cannabis products) * Use of any prescription medications/products, including known enzyme-inducing/inhibiting agents, over-the-counter medication, or other non-prescription preparations (including supplements, vitamins, minerals, phytotherapeutic/herbal/ plant-derived preparations, the tryptophans, and St. John's wort or other hypericum perforatum-containing substance) within 2 weeks prior to Day -1, with the exception of hormone-replacement therapy * Participation in any other investigational drug study in which receipt of an investigational study drug occurred within 60 days prior to Day -1 or within 5 times the elimination half-life of the respective drug; participation in a trial involving administration of \^1\^4C-radiolabeled compound(s) within 6 months prior to Day -1; participation in more than two other drug trials within 1 year prior to Day -1 * Receipt of any vaccination or immunization within 1 month prior to Day -1 * Use of any nicotine-containing or nicotine-replacement products within 6 months prior to Day -1 * Consumption of alcohol or methylxanthine-containing beverages or food * Receipt of blood products within 2 months prior to Day -1 * Donation of \> 100 mL of blood within 60 days prior to Day -1; donation of \> 1.0 litres of blood within 10 months prior to Day -1 * Irregular defecation pattern, i.e., less than once per 2 days within 6 months prior to Day -1; acute constipation problems within 3 weeks prior to Day -1 (Part B subjects only) * Poor peripheral venous access
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PK (Max observed and time to max plasma concentrations, area under the plasma concentration-time curve, absolute bioavailability, total plasma clearance, vol of dist, plasma terminal phase half-life, cumulative % excretion in urine and feces [Part B]) | Until study discontinuation |
Secondary
| Measure | Time frame |
|---|---|
| Safety outcome measures (incidence, nature, and severity of adverse events; change in clinical laboratory results; change in vital signs; change in electrocardiogram [ECG]; and change in physical examination findings) | Until study discontinuation |
Outcome results
None listed