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

Phase 1CompletedNCT02621957

Genentech, Inc.15 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Breast Cancer

Interventions

GDC-0810DRUG

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).

PravastatinDRUG

Subjects will receive a single oral dose of 10 mg pravastatin on Day 1 in Period 1 and Day 7 in Period 2.

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

Unnamed facility

Daytona Beach, Florida, United States

Outcomes

Primary Outcomes

Maximum Observed Concentration (Cmax) of Pravastatin

Time frame: Days 1-3 (Period 1) and Days 7-10 (Period 2)

Time to Maximum Concentration (Tmax) of Pravastatin

Time frame: 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

Time frame: Days 1-3 (Period 1) and Days 7-10 (Period 2)

Area Under the Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of Pravastatin

Time frame: Days 1-3 (Period 1) and Days 7-10 (Period 2)

Apparent Volume of Distribution (Vz/F) of Pravastatin

Time frame: Days 1-3 (Period 1) and Days 7-10 (Period 2)

Apparent Clearance (CL/F) of Pravastatin

Time frame: Days 1-3 (Period 1) and Days 7-10 (Period 2)

Apparent Terminal Elimination Rate Constant (lambda z) of Pravastatin

Time frame: Days 1-3 (Period 1) and Days 7-10 (Period 2)

Apparent Terminal Elimination Half-Life (t1/2) of Pravastatin

Time frame: Days 1-3 (Period 1) and Days 7-10 (Period 2)

Amount of Pravastatin Excreted in Urine (Ae)

Time frame: Day 1 (Period 1) and Day 7 (Period 2)

Renal Clearance (CLR) of Pravastatin

Time frame: Day 1 (Period 1) and Day 7 (Period 2)

Percentage of Pravastatin Excreted in Urine (%Excreted)

Data from ClinicalTrials.gov

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Secondary Outcomes

Maximum Observed Concentration (Cmax) of GDC-0810

Time frame: Days 7-10 (Period 2)

Time to Maximum Concentration (Tmax) of GDC-0810

Time frame: Days 7-10 (Period 2)

Area Under the Concentration-Time Curve from Hour 0 to the Last Measurable Concentration (AUC0-t) of GDC-0810

Time frame: Days 7-10 (Period 2)

Area Under the Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of GDC-0810

Time frame: Days 7-10 (Period 2)

Apparent Volume of Distribution (Vz/F) of GDC-0810

Time frame: Days 7-10 (Period 2)

Apparent Clearance (CL/F) of GDC-0810

Time frame: Days 7-10 (Period 2)

Apparent Terminal Elimination Rate Constant (lambda z) of GDC-0810

Time frame: Days 7-10 (Period 2)

Apparent Terminal Elimination Half-Life (t1/2) of GDC-0810

Time frame: Days 7-10 (Period 2)

Amount of GDC-0810 Excreted in Urine (Ae)

Time frame: Day 7 (Period 2)

Renal Clearance (CLr) of GDC-0810

Time frame: Day 7 (Period 2)

Percentage of GDC-0810 Excreted in Urine (%Excreted)

Time frame: Day 7 (Period 2)

Percentage of Participants with Adverse Events (AEs)

Time frame: From baseline to study completion up to Day 28

Percentage of Participants with Serious Adverse Events (SAEs)

Time frame: 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.

Time frame: From baseline to study completion up to Day 28

Plasma Concentrations of GDC-0810

Time frame: Days 7-10 (Period 2)