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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A | Experimental | On Day 1, subjects received a single oral dose of non-labeled GDC-0449 and a single IV tracer dose of 14C-GDC-0449. |
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| B | Experimental | On Day 1, subjects received a single oral dose of 14C-GDC-0449. |
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| C | Experimental | 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. |
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| D | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GDC-0449 oral capsules (non-labeled) | Drug | 150 mg oral capsule |
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| Measure | Description | 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 |
| Measure | Description | 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 |
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Inclusion Criteria
Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| Jennifer Low, M.D. | Genentech, Inc. | Study Director |
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| ID | Term |
|---|---|
| C538724 | HhAntag691 |
| D011356 | Product Labeling |
| ID | Term |
|---|---|
| D019064 | Product Packaging |
| D007221 | Industry |
| D013676 | Technology, Industry, and Agriculture |
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| GDC-0449 IV injection (labeled) |
| Drug |
10 mcg (in 2 mL) IV dose of 14C-GDC-0449 |
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| CDC-0449 oral suspension (labeled) | Drug | 30-mL oral suspension containing 6.5 mcg 14CGDC-0449 and 150 mg GDC-0449 |
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