Healthy Volunteer
Conditions
Brief summary
This is a phase 1, randomized, open-label, single center, crossover study to investigate the effect of formulation and food on the pharmacokinetics of GDC-0810 in female healthy participants of non-childbearing potential. This study is divided into three parts. Participants in each part will be randomized to one of three treatment sequences. Part 1 study in 4 periods will investigate the effect of formulation on the pharmacokinetics (PK) of GDC-0810 administered with low-fat food. Each participant in this part will receive a single dose of GDC-0810 dose level A following consumption of a low fat meal (30 minutes after the start of the meal) in each treatment period. Part 2 is an optional Phase I study in 3 periods to investigate the effect of formulation on the PK of GDC-0810 administered with low-fat food in healthy female participants of non-childbearing potential. Part 3 study in three periods will compare the PK of a Phase III prototype tablet formulation selected from Parts 1 and 2 of the study with the Phase II tablet formulation (both administered 30 minutes after the start of a low fat meal) at dose level B and to investigate the PK of the Phase III prototype formulation administered in the fasted state.
Interventions
DRUGGDC-0810 Phase II Tablet
Participants will receive dose level A (in Parts 1 and 2) or dose level B (in Part 3) tablets.
DRUGGDC-0810 Phase III Prototype Tablet
Participants will receive dose level A (in Parts 1 and 2) or dose level B (in Part 3) tablets.
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Female participants of non-childbearing potential including non-pregnant, non-lactating, and either postmenopausal or surgically sterile for at least 45 days post procedure * Body mass index (BMI) range 18.0 to 32.0 kilograms per square meter (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 pharmacogenomics (PgX) component of the study
Exclusion criteria
* Any history of endometrial polyps, endometrial cancer, atypical endometrial hyperplasia, or other endometrial disorders unless subjects have undergone total hysterectomy and there is no evidence of active disease * Significant history or clinical manifestation of any significant metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disorder * History of any thrombophilic condition, inflammatory bowel disease, active bowel inflammation, chronic diarrhea, short bowel syndrome, and upper gastro-intestinal (GI) surgery including gastric resection * Any history of venous thrombosis (including pulmonary embolism \[PE\]) * Participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 90 days 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 inhibitors, or any other endocrine agent for the treatment of breast cancer
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Relative Bioavailability Based on AUC0-t (Frel AUC0-t) of GDC-0810 (Fed vs Fasted) | Pre-dose (1 hour before dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 16 hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3) of each treatment period |
| Maximum Observed Plasma Concentration (Cmax) of GDC-0810 | Pre-dose (1 hour before dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 16 hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3) of each treatment period |
| Time to Reach Cmax (Tmax) of GDC-0810 | Pre-dose (1 hour before dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 16 hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3) of each treatment period |
| Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) of GDC-0810 | Pre-dose (1 hour before dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 16 hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3) of each treatment period |
| Area Under the Plasma Concentration Versus Time Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) of GDC-0810 | Pre-dose (1 hour before dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 16 hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3) of each treatment period |
| Apparent Terminal Elimination Rate Constant (lambda Z) of GDC-0810 | Pre-dose (1 hour before dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 16 hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3) of each treatment period |
| Apparent Terminal Elimination Half-Life (t1/2) of GDC-0810 | Pre-dose (1 hour before dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 16 hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3) of each treatment period |
| Apparent Oral Clearance (CL/F) of GDC-0810 | Pre-dose (1 hour before dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 16 hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3) of each treatment period |
| Apparent Volume of Distribution (Vz/F) of GDC-0810 | Pre-dose (1 hour before dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 16 hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3) of each treatment period |
| Relative Bioavailability Based on Cmax (Frel Cmax) of GDC-0810 (Test vs Reference) | Pre-dose (1 hour before dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 16 hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3) of each treatment period |
| Relative Bioavailability Based on AUC0-t (Frel AUC0-t) of GDC-0810 (Test vs Reference) | Pre-dose (1 hour before dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 16 hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3) of each treatment period |
| Relative Bioavailability Based on Cmax (Frel Cmax) of GDC-0810 (Fed vs Fasted) | Pre-dose (1 hour before dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 16 hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3) of each treatment period |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With Adverse Events (AEs) | Baseline up to 28 days after last GDC-0810 dose (Up to 57 days) |
Countries
United Kingdom
Outcome results
None listed