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

Genentech

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: GDC-0449 IV injection (labeled); Drug: CDC-0449 oral suspension (labeled); Drug: GDC-0449 oral capsules (non-labeled)

Study type: Interventional

Funder types: Industry

Identifiers

NCT00991718

SHH4683g

Details and patient eligibility

About

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.

Enrollment: 24 patients

Sex: Female

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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24 participants in 4 patient groups

A

Experimental group

Description:

On Day 1, subjects received a single oral dose of non-labeled GDC-0449 and a single IV tracer dose of 14C-GDC-0449.

Treatment:

Drug: GDC-0449 oral capsules (non-labeled)

Drug: GDC-0449 IV injection (labeled)

B

Experimental group

Description:

On Day 1, subjects received a single oral dose of 14C-GDC-0449.

Treatment:

Drug: CDC-0449 oral suspension (labeled)

C

Experimental group

Description:

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.

Treatment:

Drug: GDC-0449 oral capsules (non-labeled)

Drug: GDC-0449 IV injection (labeled)

D

Experimental group

Description:

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.

Treatment:

Drug: GDC-0449 oral capsules (non-labeled)

Drug: CDC-0449 oral suspension (labeled)