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

Phase 1
Completed
Conditions
Breast Cancer
Interventions
Registration Number
NCT02621957
Lead Sponsor
Genentech, Inc.
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
15
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Female Healthy VolunteersPravastatinHealthy 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.
Female Healthy VolunteersGDC-0810Healthy 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.
Primary Outcome Measures
NameTimeMethod
Area Under the Concentration-Time Curve from Hour 0 to the Last Measurable Concentration (AUC0-t) of PravastatinDays 1-3 (Period 1) and Days 7-10 (Period 2)
Area Under the Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of PravastatinDays 1-3 (Period 1) and Days 7-10 (Period 2)
Maximum Observed Concentration (Cmax) of PravastatinDays 1-3 (Period 1) and Days 7-10 (Period 2)
Time to Maximum Concentration (Tmax) of PravastatinDays 1-3 (Period 1) and Days 7-10 (Period 2)
Apparent Terminal Elimination Rate Constant (lambda z) of PravastatinDays 1-3 (Period 1) and Days 7-10 (Period 2)
Apparent Volume of Distribution (Vz/F) of PravastatinDays 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)
Apparent Clearance (CL/F) of PravastatinDays 1-3 (Period 1) and Days 7-10 (Period 2)
Apparent Terminal Elimination Half-Life (t1/2) of PravastatinDays 1-3 (Period 1) and Days 7-10 (Period 2)
Renal Clearance (CLR) of PravastatinDay 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 PravastatinDays 1-3 (Period 1) and Days 7-10 (Period 2)
Secondary Outcome Measures
NameTimeMethod
Time to Maximum Concentration (Tmax) of GDC-0810Days 7-10 (Period 2)
Maximum Observed Concentration (Cmax) of GDC-0810Days 7-10 (Period 2)
Area Under the Concentration-Time Curve from Hour 0 to the Last Measurable Concentration (AUC0-t) of GDC-0810Days 7-10 (Period 2)
Area Under the Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of GDC-0810Days 7-10 (Period 2)
Apparent Volume of Distribution (Vz/F) of GDC-0810Days 7-10 (Period 2)
Apparent Clearance (CL/F) of GDC-0810Days 7-10 (Period 2)
Apparent Terminal Elimination Rate Constant (lambda z) of GDC-0810Days 7-10 (Period 2)
Apparent Terminal Elimination Half-Life (t1/2) of GDC-0810Days 7-10 (Period 2)
Amount of GDC-0810 Excreted in Urine (Ae)Day 7 (Period 2)
Renal Clearance (CLr) of GDC-0810Day 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-0810Days 7-10 (Period 2)
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