Phase 1
Completed N=18
Evaluation of the Relative Bioavailability and Food Effect of GDC-9545 in Healthy Females of Non-Childbearing Potential
Healthy Volunteers
Source: ClinicalTrials.gov NCT04274075 ↗
Enrolled (actual)
18
Serious AEs
0.0%
Results posted
Apr 2021
Primary outcomePrimary: Maximum Observed Plasma Concentration (Cmax) of GDC-9545 — 126; 129; 102 nanograms per millilitre (ng/mL)
Summary
This study will be an open-label, randomized, three-period, six-sequence crossover study of GDC-9545 administered to healthy females of non-childbearing potential to determine the relative bioavailability of the Phase 3 capsule formulation to the Phase 1 tablet formulation in the fasted state and the effect of food on the Phase 3 capsule formulation.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Observed Plasma Concentration (Cmax) of GDC-9545 |
126; 129; 102 | — |
| PRIMARY Time to Maximum Observed Plasma Concentration (Tmax) of GDC-9545 |
2.25; 2.28; 5.00 | — |
| PRIMARY Time of Last Quantifiable Plasma Concentration (Tlast) of GDC-9545 |
168; 168; 168 | — |
| PRIMARY Time to First Quantifiable Plasma Concentration (Tlag) of GDC-9545 |
0; 0; 0 | — |
| PRIMARY Area Under the Plasma Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of GDC-9545 |
3710; 3600; 3310 | — |
| PRIMARY Area Under the Plasma Concentration-Time Curve From Hour 0 Extrapolated to Infinity (AUC0-∞) of GDC-9545 |
3860; 3770; 3460 | — |
| PRIMARY Percentage of Area Under the Plasma Concentration-Time Curve (AUC) That is Due to Extrapolation From Last Measurable Concentration to Infinity (%AUCextrap) of GDC-9545 |
3.40; 3.87; 3.78 | — |
| PRIMARY Apparent Terminal Elimination Rate Constant (λz) of GDC-9545 |
0.0196; 0.0185; 0.0188 | — |
| PRIMARY Apparent Terminal Elimination Half-Life (t1/2) of GDC-9545 |
35.4; 37.4; 36.9 | — |
| PRIMARY Apparent Total Clearance (CL/F) of GDC-9545 |
7.76; 7.97; 8.68 | — |
| PRIMARY Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of GDC-9545 |
397; 430; 462 | — |
| SECONDARY Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) |
2; 2; 3; 5; 2; 2 | — |
| SECONDARY Number of Participants With Clinically Significant Abnormalities in Clinical Chemistry, Hematology, and Urinalysis Laboratory Tests |
0; 0; 1 | — |
| SECONDARY Change From Baseline in Systolic Blood Pressure Over Time |
104.5; 103.1; 102.6; -1.7; 0.7; -3.8 | — |
| SECONDARY Change From Baseline in Diastolic Blood Pressure Over Time |
64.2; 62.5; 62.8; -2.8; -3.1; -3.3 | — |
| SECONDARY Change From Baseline in Pulse Rate Over Time |
62.2; 62.4; 65.3; -2.1; -4.1; -1.3 | — |
| SECONDARY Change From Baseline in Respiratory Rate Over Time |
15.6; 15.6; 15.6; 1.6; 1.2; 2.0 | — |
| SECONDARY Change From Baseline in Oral Body Temperature Over Time |
36.65; 36.64; 36.72; 0.06; 0.00; 0.04 | — |
| SECONDARY Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram |
170.2; 171.5; 165.8; -3.6; -6.1; -2.7 | — |
| SECONDARY Change From Baseline in Heart Rate Over Time, as Measured by Electrocardiogram |
62.3; 61.2; 62.4; -2.9; -4.1; 0.5 | — |
Eligibility Criteria
Inclusion Criteria
- Females of non-childbearing potential including non-pregnant, non-lactating, and either postmenopausal or surgically sterile for at least 90 days prior to screening, as defined in the protocol
- Body mass index (BMI) from 18.5 to 30.0 kilograms per square metre of body surface area (kg/m^2) at screening
- In good health, determined by no clinically significant findings from medical history, 12-lead ECG, or vital signs
- Clinical laboratory evaluations within the reference range for the test laboratory, unless deemed not clinically significant by the investigator
- Negative test for selected drugs of abuse at Screening (does not include alcohol) and at Check-in (Day -1) for Period 1 (does include alcohol)
- Negative hepatitis panel (hepatitis B surface antigen and hepatitis C virus antibody) and negative human immunodeficiency virus (HIV) antibody screens
- Subject must receive an explanation of the mandatory Research Biosample Repository (RBR) component of the study and be able to comprehend and willing to sign an Informed Consent Form (ICF)
Exclusion Criteria
- Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal (GI), neurological, or psychiatric disorder (as determined by the investigator)
- History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator
- History of allergy to GDC-9545 or any of its excipients
- History of stomach or intestinal surgery (including cholecystectomy) or resection that would potentially alter absorption and/or excretion of orally administered drugs (except that appendectomy and hernia repair will be allowed)
- History or presence of an abnormal ECG that, in the investigator's opinion, is clinically significant including complete left bundle branch block; right bundle branch block; first-, second-, or third-degree heart block; sick sinus syndrome; or evidence of prior myocardial infarction
- Having a QTc interval greater than (>)470 milliseconds (msec), PR interval >210 msec, or QRS complex >120 msec
- Confirmed (e.g., 2 consecutive measurements) baseline heart rate ≤50 beats per minute (bpm) prior to enrollment
- History of alcoholism or drug addiction within 1 year prior to Check-in (Day -1) of Period 1
- The use of tobacco- or nicotine-containing products within 6 months prior to Check-in (Day -1) of Period 1
- History of active or latent tuberculosis (TB), regardless of treatment history
- History of previous use of tamoxifen, aromatase inhibitors, or any other endocrine agent for the treatment of breast cancer
- The use of hormone replacement therapy or selective ER modulators (SERMs; e.g., raloxifene) within 1 year prior to Check-in (Day -1) of Period 1
- The use of oral antibiotics within 4 weeks or intravenous antibiotics within 8 weeks prior to Check-in (Day -1) of Period 1
- The use or intent to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to Check-in (Day -1) of Period 1
- The participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 5 half-lives or 30 days, whichever is longer, prior to Check-in (Day -1) of Period 1
- The use of drugs of abuse (including opioids) within 4 weeks of Screening
- The use of any prescription medications/products within 14 days prior to Check-in (Day -1) of Period 1, unless deemed acceptable by the investigator
- The use of any over-the-counter, non-prescription preparations (including vitamins; minerals; and phytotherapeutic-, herbal-, and plant-derived preparations) within 7 days prior to Check-in (Day -1) of Period 1, unless deemed acceptable by the investigator
- The use of poppy seed-containing foods or beverages within 7 days prior to Check-in (Day -1) of Period 1,
Data sourced from ClinicalTrials.gov (NCT04274075). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.