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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: GDC-0449 oral capsules (non-labeled); Drug: GDC-0449 IV injection (labeled); Drug: CDC-0449 oral suspension (labeled)

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Jennifer Low, M.D., Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2009
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: October 6, 2009
• First Submitted That Met QC Criteria: October 7, 2009
• First Posted (Estimate): October 8, 2009

Study Record Updates

• Last Update Posted (Actual): June 26, 2017
• Last Update Submitted That Met QC Criteria: June 23, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: GDC0449
• Other Study ID Numbers: SHH4683g