A Study of the Hedgehog Pathway Inhibitor GDC-0449 in Healthy Female Subjects of Non-Childbearing Potential

A Phase I, Open-Label Absorption, Distribution, Metabolism, and Excretion (ADME) Study of the Hedgehog Pathway Inhibitor GDC-0449 in Healthy Female Subjects of Non-Childbearing Potential

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.

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