Clinical trial NCT02722018: Study to Investigate the Effect of Formulation and Food on the Pharmacokinetics of GDC-0810
Official title: A Phase I, Randomized, Open-Label, Single Center Study to Investigate the Effect of Formulation and Food on the Pharmacokinetics of GDC-0810 in Female Healthy Subjects on Non-Childbearing Potential
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2016-03-29
Enrollment: 45
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of GDC-0810
timeFrame: 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
measure: Time to Reach Cmax (Tmax) of GDC-0810
timeFrame: 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
measure: Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) of GDC-0810
timeFrame: 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
measure: Area Under the Plasma Concentration Versus Time Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) of GDC-0810
timeFrame: 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
measure: Apparent Terminal Elimination Rate Constant (lambda Z) of GDC-0810
timeFrame: 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
measure: Apparent Terminal Elimination Half-Life (t1/2) of GDC-0810
timeFrame: 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
measure: Apparent Oral Clearance (CL/F) of GDC-0810
timeFrame: 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
measure: Apparent Volume of Distribution (Vz/F) of GDC-0810
timeFrame: 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
measure: Relative Bioavailability Based on Cmax (Frel Cmax) of GDC-0810 (Test vs Reference)
timeFrame: 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
measure: Relative Bioavailability Based on AUC0-t (Frel AUC0-t) of GDC-0810 (Test vs Reference)
timeFrame: 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
measure: Relative Bioavailability Based on Cmax (Frel Cmax) of GDC-0810 (Fed vs Fasted)
timeFrame: 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
measure: Relative Bioavailability Based on AUC0-t (Frel AUC0-t) of GDC-0810 (Fed vs Fasted)
timeFrame: 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 outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Baseline up to 28 days after last GDC-0810 dose (Up to 57 days)
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Quotient Clinical Ltd, Clinical Research Unit
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: