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

Healthy Volunteer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02722018
• Other study ID #: GP29826
• Secondary ID: 2015-003730-27
• Status: Completed
• Phase: Phase 1
• First received: March 23, 2016
• Last updated: August 17, 2017
• Start date: January 6, 2016
• Est. completion date: September 13, 2016

Study information

• Verified date: August 2017
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: September 13, 2016
• Est. primary completion date: September 13, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 40 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Volunteer

Intervention

Drug:
• GDC-0810 Phase II Tablet
Participants will receive dose level A (in Parts 1 and 2) or dose level B (in Part 3) tablets.
• GDC-0810 Phase III Prototype Tablet
Participants will receive dose level A (in Parts 1 and 2) or dose level B (in Part 3) tablets.

Locations

Country	Name	City	State
United Kingdom	Quotient Clinical Ltd, Clinical Research Unit	Nottingham

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Number of Participants With Adverse Events (AEs)		Baseline up to 28 days after last GDC-0810 dose (Up to 57 days)