Bioavailability and food effect of GDC-6036 in healthy subjects Not Applicable
Conditions
Interventions
GDC-6036 will be administered to healthy participants to determine the relative bioavailability of the film-coated immediate release (FCIR) tablet formulation compared to the Phase I powder in capsule
Sponsors
Genentech, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males or females of non-childbearing potential, between 18 and 60 years of age, inclusive 2. Within body mass index (BMI) range 18.0 to 32.0 kg/m², inclusive 3. In good health, determined by no clinically significant findings from medical history, physical examination, triplicate 12-lead ECGs, and vital signs 4. Negative test for selected drugs of abuse at Screening (does not include alcohol) and at Check-in (Day -1 of Period 1) (does include alcohol) 5. Negative hepatitis panel (hepatitis B surface antigen, hepatitis B virus core antibody, and hepatitis C virus antibody) and negative HIV antibody screens 6. Able and willing to consume 100% of a high-fat breakfast meal (two eggs fried in butter, two strips of bacon, two slices of toast with butter, 4 ounces of hash brown potatoes, and 8 ounces of whole milk) 7. Receive an explanation of the mandatory whole genome sequencing component of the study
Exclusion criteria
Exclusion criteria: 1. Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disorder (as determined by the Investigator) 2. History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator 3. History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs except that appendectomy and hernia repair will be allowed 4. History or presence of an abnormal ECG, which, in the Investigator’s opinion, is clinically significant 5. Have a QTc interval corrected for heart rate using Fridericia’s formula >450 msec for males, >470 msec for females, PR interval >210 msec, or QRS complex >120 msec. Triplicate ECGs will be performed at Screening and at Check-in and the mean value of the 3 measurements will be used. If intervals are out of range, ECGs may be repeated once at Screening and once at Check-in, and the average of the intervals will be used to determine eligibility 6. History of alcoholism or drug addiction within 1 year prior to Check-in (Day -1 of Period 1) 7. 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 8. Receipt of a coronavirus disease 2019 (COVID-19) vaccine in the past 28 days prior to dosing 9. Use of any prescription medications/products within 14 days prior to Check-in (Day -1 of Period 1), unless deemed acceptable by the Investigator 10. 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 11. Use of tobacco- or nicotine-containing products (including, but not limited to, cigarettes, e-cigarettes, pipes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum) within 3 months prior to Check-in (Day -1 of Period 1) and during the entire study 12. Use of poppy seed-, grapefruit-, star fruit-, pomegranate-, pawpaw-, or Seville orange-containing foods or beverages within 7 days prior to Check-in (Day -1 of Period 1) and until completion of Period 3, unless deemed acceptable by the Investigator 13. Use of alcohol-containing foods or beverages within 48 hours prior to Check-in (Day -1 of Period 1) and until completion of Period 3 14. Use of caffeine-containing foods or beverages within 48 hours prior to Check-in (Day -1 of Period 1) and until completion of Period 3, unless deemed acceptable by the Investigator 15. Participation in strenuous exercise from 48 hours prior to Check-in (Day -1 of Period 1) and during the period of confinement at the study site (e.g., will not begin a new exercise program or participate in any unusually strenuous physical exertion) 16. Poor peripheral venous access 17. History of malignancy, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetic (PK) parameters of GDC-6036 measured using blood samples at predose, 0.25, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 12 h on day 1 of periods 1, 2 and 3; at 24 and 30 h on day 2 of periods 1, 2 and 3; at 48 and 56 h on day 3 of periods 1, 2 and 3; at 72 h on day 4 of periods 1, 2 and 3. The following PK parameters will be calculated if data allows: 1. Maximum concentration (Cmax) of GDC-6036 measured using plasma concentrations of GDC-6036 2. Time to maximum observed concentration (tmax) of GDC-6036 measured using plasma concentrations of GDC-6036 3. Time to first quantifiable concentration (tlag) measured using plasma concentrations of GDC-6036 4. Time of last quantifiable concentration (tlast) measured using plasma concentrations of GDC-6036 5. Area under the concentration-time curve from Hour 0 to the time of last quantifiable concentration (AUC0-t) measured using plasma concentrations of GDC-6036 6. Area under the concentration-time curve extrapolated to infinity (AUC0-inf) measured using plasma concentrations of GDC-6036 7. Percentage of AUC that is due to extrapolation from the last quantifiable concentration to infinity (%AUCextrap) 8. Apparent terminal elimination rate constant (?z) 9. Apparent terminal elimination half-life (t1/2) 10. Apparent total clearance (CL/F) 11. Apparent volume of distribution during the terminal elimination phase (Vz/F) All measured at: Day 1 of periods 1, 2 and 3 at predose, 0.25, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 12 h Day 2 of periods 1, 2 and 3 at 24 and 30 h Day 3 of periods 1, 2 and 3 at 48 and 56 h Day 4 of periods 1, 2 and 3 at 72 h | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Frequency and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0), recorded throughout the study 2. Incidence of abnormalities in clinical laboratory test results, measured by the evaluation of blood and urine tests at screening, check-in, days 1 and 2 of periods 1, 2 and 3 and at study completion 3. Incidence of electrocardiogram (ECG) abnormalities as measured by triplicate 12-lead ECG at screening, check-in, day 1 of periods 1, 2 and 3 at predose, 1, 2, 3, 4, 6, 8, 12 h; day 2, periods 1, 2 and 3 at 24 h and at study completion 4. Incidence of abnormalities in vital signs (blood pressure, pulse and oral temperature measured by an automated device and respiration rate measured manually by counting the rise and fall of the subject’s chest for 30 seconds and multiplying by 2) measured at screening, check-in, day 1 of periods 1, 2 and 3 at predose, 1, 2, 3, 4, 6, 8, 12 h; day 2, periods 1, 2 and 3 at 24 h and at study completion 5. Physical examination conducted at check-in and at study completion | — |
Countries
United States of America
Contacts
Public ContactClinical Trials
Outcome results
None listed