Study to Investigate the Effect of Formulation and Food on the Pharmacokinetics of GDC-0810

NCT02722018 | Completed Phase 1

• 2 other identifiers: GP298262015-003730-27
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteer

Outcome Measures

Primary Outcomes (12)

• 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

• 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

Secondary Outcomes (1)

• Number of Participants With Adverse Events (AEs)

  Baseline up to 28 days after last GDC-0810 dose (Up to 57 days)

Study Arms (3)

Part 1: GDC-0810 dose level A - Low Fat Meal

EXPERIMENTAL

Participants will receive a single dose of GDC-0810 dose level A on Day 1 of each treatment period. GDC-0810 will be administered with low fat meal in the form of Phase II tablet or one of three Phase III prototype tablets (Prototype 1, 2 or 3) in a crossover fashion.

Drug: GDC-0810 Phase II Tablet; Drug: GDC-0810 Phase III Prototype Tablet

Part 2 (Optional): GDC-0810 dose level A - Low Fat Meal

EXPERIMENTAL

Participants will receive a single dose of GDC-0810 dose level A on Day 1 of each treatment period. GDC-0810 will be administered with low fat meal in the form of Phase II tablet or one of two Phase III prototype tablets (Prototype 4 or 5) in a crossover fashion.

Drug: GDC-0810 Phase II Tablet; Drug: GDC-0810 Phase III Prototype Tablet

Part 3: GDC-0810 dose level B - Low Fat Meal/Fasted

EXPERIMENTAL

Participants will receive a single dose of GDC-0810 dose level B on Day 1 of each treatment period. GDC-0810 will be administered with low fat meal or under fasted condition either as Phase II tablet (with low fat meal) or as the Phase III prototype tablet selected from Parts 1 or 2 (with low fat meal or under fasted conditions), in a crossover fashion.

Drug: GDC-0810 Phase II Tablet; Drug: GDC-0810 Phase III Prototype Tablet

Interventions

GDC-0810 Phase II Tablet DRUG

Participants will receive dose level A (in Parts 1 and 2) or dose level B (in Part 3) tablets.

Part 1: GDC-0810 dose level A - Low Fat Meal; Part 2 (Optional): GDC-0810 dose level A - Low Fat Meal; Part 3: GDC-0810 dose level B - Low Fat Meal/Fasted

GDC-0810 Phase III Prototype Tablet DRUG

Participants will receive dose level A (in Parts 1 and 2) or dose level B (in Part 3) tablets.

Part 1: GDC-0810 dose level A - Low Fat Meal; Part 2 (Optional): GDC-0810 dose level A - Low Fat Meal; Part 3: GDC-0810 dose level B - Low Fat Meal/Fasted

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (1)

Quotient Clinical Ltd, Clinical Research Unit

Nottingham, NG11 6JS, United Kingdom

Location

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2016
• First Posted: March 29, 2016
• Study Start: January 6, 2016
• Primary Completion: September 13, 2016
• Study Completion: September 13, 2016
• Last Updated: August 22, 2017

Record last verified: 2017-08

Locations

GB (1)