Effect of GDC-0810 on the Pharmacokinetics of Pravastatin in Healthy Female Subjects of Non-Childbearing Potential

A Phase 1, Open-Label Study to Evaluate the Effect of GDC-0810 on the Pharmacokinetics of Pravastatin in Healthy Female Subjects of Non-Childbearing Potential

This study is to assess the pharmacokinetics (PK) of a single dose of pravastatin with and without concomitant GDC-0810 administration in healthy female subjects of non-childbearing potential. During Period 1 (Day -1 to Day 4) PK parameters of pravastatin will be determined in the absence of GDC-0810. During Period 2 (Days 5-28) PK parameters of pravastatin will be determined in the presence of GDC-0810.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: GDC-0810; Drug: Pravastatin

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Daytona Beach, Florida, United States, 32117

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female subjects between 18 and 65 years of age, inclusive.
• Female subjects of non-childbearing potential including non-pregnant, non-lactating, and either postmenopausal or surgically sterile for at least 45 days post procedure.
• Within BMI range 18.5 to </= 29.9 kg/m^2, inclusive.
• In good health, as determined by no clinically significant findings from medical history, physical examination, 12-lead electrocardiogram (ECG), vital signs, and clinical laboratory evaluations.
• Receive an explanation of the mandatory pharmacogenomic (PgX) component of the study.

Exclusion Criteria:

• Significant history or clinical manifestation of any significant metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disorder.
• Previous history of adverse reaction to statins.
• Participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 30 days or 5 half-lives, whichever is longer, prior to Check-in (Day -1) in Period 1.
• Use of systemic hormone replacement therapy within 1 year prior to Check-in (Day -1).
• History of use of tamoxifen, aromatase inhibitor or any other endocrine agent for treatment of breast cancer.
• Female subject is pregnant lactating, or breast feeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Female Healthy Volunteers; Healthy volunteer female subjects of non-childbearing potential will be administered pravastatin once on Day 1 during Period 1 (Day -1 to Day 4). During Period 2 (Days 5-28) GDC-0810 will be administered daily on Days 5-8. Pravastatin will be co-administered on Day 7.	Drug: GDC-0810; During Period 2 subjects will be administered an oral 600 mg dose GDC-0810 daily beginning on Day 5 for 4 consecutive days (from Days 5 to 8, inclusive).; Other Names: ARN-810; Drug: Pravastatin; Subjects will receive a single oral dose of 10 mg pravastatin on Day 1 in Period 1 and Day 7 in Period 2.; Other Names: Pravachol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Concentration (Cmax) of Pravastatin	Days 1-3 (Period 1) and Days 7-10 (Period 2)
Time to Maximum Concentration (Tmax) of Pravastatin	Days 1-3 (Period 1) and Days 7-10 (Period 2)
Area Under the Concentration-Time Curve from Hour 0 to the Last Measurable Concentration (AUC0-t) of Pravastatin	Days 1-3 (Period 1) and Days 7-10 (Period 2)
Area Under the Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of Pravastatin	Days 1-3 (Period 1) and Days 7-10 (Period 2)
Apparent Volume of Distribution (Vz/F) of Pravastatin	Days 1-3 (Period 1) and Days 7-10 (Period 2)
Apparent Clearance (CL/F) of Pravastatin	Days 1-3 (Period 1) and Days 7-10 (Period 2)
Apparent Terminal Elimination Rate Constant (lambda z) of Pravastatin	Days 1-3 (Period 1) and Days 7-10 (Period 2)
Apparent Terminal Elimination Half-Life (t1/2) of Pravastatin	Days 1-3 (Period 1) and Days 7-10 (Period 2)
Amount of Pravastatin Excreted in Urine (Ae)	Day 1 (Period 1) and Day 7 (Period 2)
Renal Clearance (CLR) of Pravastatin	Day 1 (Period 1) and Day 7 (Period 2)
Percentage of Pravastatin Excreted in Urine (%Excreted)	Day 1 (Period 1) and Day 7 (Period 2)
Plasma Concentrations of Pravastatin	Days 1-3 (Period 1) and Days 7-10 (Period 2)

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Concentration (Cmax) of GDC-0810	Days 7-10 (Period 2)
Time to Maximum Concentration (Tmax) of GDC-0810	Days 7-10 (Period 2)
Area Under the Concentration-Time Curve from Hour 0 to the Last Measurable Concentration (AUC0-t) of GDC-0810	Days 7-10 (Period 2)
Area Under the Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of GDC-0810	Days 7-10 (Period 2)
Apparent Volume of Distribution (Vz/F) of GDC-0810	Days 7-10 (Period 2)
Apparent Clearance (CL/F) of GDC-0810	Days 7-10 (Period 2)
Apparent Terminal Elimination Rate Constant (lambda z) of GDC-0810	Days 7-10 (Period 2)
Apparent Terminal Elimination Half-Life (t1/2) of GDC-0810	Days 7-10 (Period 2)
Amount of GDC-0810 Excreted in Urine (Ae)	Day 7 (Period 2)
Renal Clearance (CLr) of GDC-0810	Day 7 (Period 2)
Percentage of GDC-0810 Excreted in Urine (%Excreted)	Day 7 (Period 2)
Percentage of Participants with Adverse Events (AEs)	From baseline to study completion up to Day 28
Percentage of Participants with Serious Adverse Events (SAEs)	From baseline to study completion up to Day 28
Percentage of Participants with Clinically Significant Changes in Safety Measurements, Including Vital Signs, Electrocardiograms (ECGs), Physical Examination Findings and Clinical Laboratory Results.	From baseline to study completion up to Day 28
Plasma Concentrations of GDC-0810	Days 7-10 (Period 2)

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: December 2, 2015
• First Submitted That Met QC Criteria: December 2, 2015
• First Posted (Estimate): December 4, 2015

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pravastatin
• Other Study ID Numbers: GP29825