A Study of the Hedgehog Pathway Inhibitor GDC-0449 in Healthy Female Subjects of Non-Childbearing Potential
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: A On Day 1, subjects received a single oral dose of non-labeled GDC-0449 and a single IV tracer dose of 14C-GDC-0449. |
Drug: GDC-0449 oral capsules (non-labeled)
150 mg oral capsule
Drug: GDC-0449 IV injection (labeled)
10 mcg (in 2 mL) IV dose of 14C-GDC-0449
|
| Experimental: B On Day 1, subjects received a single oral dose of 14C-GDC-0449. |
Drug: CDC-0449 oral suspension (labeled)
30-mL oral suspension containing 6.5 mcg 14CGDC-0449 and 150 mg GDC-0449
|
| Experimental: C On Days 1-7, subjects received a single oral dose of non-labeled GDC-0449. On Day 7, subjects also received a single IV tracer dose of 14C-GDC-0449. |
Drug: GDC-0449 oral capsules (non-labeled)
150 mg oral capsule
Drug: GDC-0449 IV injection (labeled)
10 mcg (in 2 mL) IV dose of 14C-GDC-0449
|
| Experimental: D On Days 1-6, subjects received a single oral dose of non-labeled GDC-0449. On Day 7, subjects received a single oral dose of 14C-GDC-0449. |
Drug: GDC-0449 oral capsules (non-labeled)
150 mg oral capsule
Drug: CDC-0449 oral suspension (labeled)
30-mL oral suspension containing 6.5 mcg 14CGDC-0449 and 150 mg GDC-0449
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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]
Eligibility Criteria
Criteria
Inclusion Criteria
-
Female
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Non-childbearing potential
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Body mass index (BMI) between 18 and 32 kg/m^2, inclusive
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In good health, determined by no clinically significant findings on physical examination, medical history, 12-lead ECG, and vital signs
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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
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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
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History of symptomatic hypotension, idiopathic orthostatic hypotension, or other autonomous-failure syndromes
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History of severe physical injury, direct impact trauma, or neurological trauma within 6 months prior to Day -1
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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)
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History of alcoholism, drug abuse, or drug addiction (including soft drugs like cannabis products)
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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
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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 14C-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
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Receipt of any vaccination or immunization within 1 month prior to Day -1
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Use of any nicotine-containing or nicotine-replacement products within 6 months prior to Day -1
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Consumption of alcohol or methylxanthine-containing beverages or food
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Receipt of blood products within 2 months prior to Day -1
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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
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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)
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Poor peripheral venous access
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Genentech, Inc.
Investigators
- Study Director: Jennifer Low, M.D., Genentech, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SHH4683g