A Study to Assess the Relative Bioavailability And Food Effect of a Tablet Formulation of GDC-0276 in Healthy Participants

NCT02856152 | Withdrawn Phase 1

• 2 other identifiers: GX298412016-001572-30
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This open-label, randomized, 4-way crossover study in healthy participants will determine the relative bioavailability of the tablet formulation relative to the capsule formulation and the effect of a high-fat and low-fat meal on the relative bioavailability of the tablet formulation.

Conditions

Healthy Volunteer

Keywords

Healthy Volunteer

Outcome Measures

Primary Outcomes (9)

• Relative Bioavailability: Geometric Mean Ratio (Tablet/Capsule) of Log Transformed Cmax of M12 Metabolite of GDC-0276

  Pre-dose (within 0.5 hours of dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, 144 hours post-Day 1, or Day 7, or Day 13, or Day 19 dose

• Relative Bioavailability: Geometric Mean Ratio (Tablet/Capsule) of Log Transformed Maximum Plasma Concentration (Cmax) of GDC-0276

  Pre-dose (within 0.5 hours of dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, 144 hours post-Day 1, or Day 7, or Day 13, or Day 19 dose

• Relative Bioavailability: Geometric Mean Ratio (Tablet/Capsule) of Log Transformed Cmax of M16 Metabolite of GDC-0276

  Pre-dose (within 0.5 hours of dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, 144 hours post-Day 1, or Day 7, or Day 13, or Day 19 dose

• Relative Bioavailability: Geometric Mean Ratio (Tablet/Capsule) of Log Transformed Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of GDC-0276

  Pre-dose (within 0.5 hours of dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, 144 hours post-Day 1, or Day 7, or Day 13, or Day 19 dose

• Relative Bioavailability: Geometric Mean Ratio (Tablet/Capsule) of Log Transformed Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClastu) of M12 Metabolite of GDC-0276

  Pre-dose (within 0.5 hours of dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, 144 hours post-Day 1, or Day 7, or Day 13, or Day 19 dose

• Relative Bioavailability: Geometric Mean Ratio (Tablet/Capsule) of Log Transformed Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClastu) of M16 Metabolite of GDC-0276

  Pre-dose (within 0.5 hours of dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, 144 hours post-Day 1, or Day 7, or Day 13, or Day 19 dose

• Relative Bioavailability: Geometric Mean Ratio (Tablet/Capsule) of Log Transformed Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - inf)] of GDC-0276

  Pre-dose (within 0.5 hours of dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, 144 hours post-Day 1, or Day 7, or Day 13, or Day 19 dose

• Relative Bioavailability: Geometric Mean Ratio (Tablet/Capsule) of Log Transformed Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - inf)] of M12 Metabolite of GDC-0276

  Pre-dose (within 0.5 hours of dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, 144 hours post-Day 1, or Day 7, or Day 13, or Day 19 dose

• Relative Bioavailability: Geometric Mean Ratio (Tablet/Capsule) of Log Transformed Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - inf)] of M16 Metabolite of GDC-0276

  Pre-dose (within 0.5 hours of dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, 144 hours post-Day 1, or Day 7, or Day 13, or Day 19 dose

Secondary Outcomes (13)

• Time to Reach Maximum Observed Plasma Concentration (Tmax) of GDC-0276 Following High-fat Meals, low-fat Meals and in Fasted State on a Tablet Dosing

  Pre-dose (within 0.5 hours of dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, 144 hours post-Day 1, or Day 7, or Day 13, or Day 19 dose

• Time to Reach Maximum Observed Plasma Concentration (Tmax) of M12 Metabolite of GDC-0276 Following High-fat Meals, low-fat Meals and in Fasted State on a Tablet Dosing

  Pre-dose (within 0.5 hours of dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, 144 hours post-Day 1, or Day 7, or Day 13, or Day 19 dose

• Time to Reach Maximum Observed Plasma Concentration (Tmax) of M16 Metabolite of GDC-0276 Following High-fat Meals, low-fat Meals and in Fasted State on a Tablet Dosing

  Pre-dose (within 0.5 hours of dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, 144 hours post-Day 1, or Day 7, or Day 13, or Day 19 dose

• Apparent Oral Clearance (CL/F) of GDC-0276 Following Tablet and Capsule Dosing

  Pre-dose (within 0.5 hours of dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, 144 hours post-Day 1, or Day 7, or Day 13, or Day 19 dose

• Apparent Oral Clearance (CL/F) of M12 Metabolite of GDC-0276 Following Tablet and Capsule Dosing

  Pre-dose (within 0.5 hours of dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, 144 hours post-Day 1, or Day 7, or Day 13, or Day 19 dose

Study Arms (4)

Treatment A Then B Then D Then C

EXPERIMENTAL

Treatment A: a single dose of three 90-mg capsules of GDC-0276 administered orally after at least an 8-hour fast. Treatment B: a single dose of three 90-mg tablets GDC-0276 administered orally after at least an 8-hour fast. Treatment C: a single dose of three 90-mg tablets of GDC-0276 administered orally within 30 minutes of eating a standardized FDA high-fat meal. Treatment D: a single dose of three 90-mg tablets of GDC-0276 administered orally within 30 minutes of eating a standardized low-fat meal. Participants will receive Treatment A on Day 1 of first intervention period, followed by Treatment B on Day 1 of second intervention period, followed by Treatment D on Day 1 of third intervention period, and then Treatment C on Day 1 of fourth intervention period. A washout period of 6 days will be maintained between each intervention period.

Drug: GDC-0276 capsule; Drug: GDC-0276 tablets

Treatment B, Then C, Then A, Then D

EXPERIMENTAL

Treatment A: a single dose of three 90-mg capsules of GDC-0276 administered orally after at least an 8-hour fast. Treatment B: a single dose of three 90-mg tablets GDC-0276 administered orally after at least an 8-hour fast. Treatment C: a single dose of three 90-mg tablets of GDC-0276 administered orally within 30 minutes of eating a standardized FDA high-fat meal. Treatment D: a single dose of three 90-mg tablets of GDC-0276 administered orally within 30 minutes of eating a standardized low-fat meal. Participants will receive Treatment B on Day 1 of first intervention period, followed by Treatment C on Day 1 of second intervention period, followed by Treatment A on Day 1 of third intervention period, and then Treatment D on Day 1 of fourth intervention period. A washout period of 6 days will be maintained between each intervention period.

Drug: GDC-0276 capsule; Drug: GDC-0276 tablets

Treatment C, Then D, Then B, Then A

EXPERIMENTAL

Treatment A: a single dose of three 90-mg capsules of GDC-0276 administered orally after at least an 8-hour fast. Treatment B: a single dose of three 90-mg tablets GDC-0276 administered orally after at least an 8-hour fast. Treatment C: a single dose of three 90-mg tablets of GDC-0276 administered orally within 30 minutes of eating a standardized FDA high-fat meal. Treatment D: a single dose of three 90-mg tablets of GDC-0276 administered orally within 30 minutes of eating a standardized low-fat meal. Participants will receive Treatment C on Day 1 of first intervention period, followed by Treatment D on Day 1 of second intervention period, followed by Treatment B on Day 1 of third intervention period, and then Treatment A on Day 1 of fourth intervention period. A washout period of 6 days will be maintained between each intervention period.

Drug: GDC-0276 capsule; Drug: GDC-0276 tablets

Treatment D, Then A, Then C, Then B

EXPERIMENTAL

Treatment A: a single dose of three 90-mg capsules of GDC-0276 administered orally after at least an 8-hour fast. Treatment B: a single dose of three 90-mg tablets GDC-0276 administered orally after at least an 8-hour fast. Treatment C: a single dose of three 90-mg tablets of GDC-0276 administered orally within 30 minutes of eating a standardized FDA high-fat meal. Treatment D: a single dose of three 90-mg tablets of GDC-0276 administered orally within 30 minutes of eating a standardized low-fat meal. Participants will receive Treatment D on Day 1 of first intervention period, followed by Treatment A on Day 1 of second intervention period, followed by Treatment C on Day 1 of third intervention period, and then Treatment B on Day 1 of fourth intervention period. A washout period of 6 days will be maintained between each intervention period.

Drug: GDC-0276 capsule; Drug: GDC-0276 tablets

Interventions

GDC-0276 capsule DRUG

Three 90 milligram \[mg\] capsules of GDC-0276 administered orally.

Treatment A Then B Then D Then C; Treatment B, Then C, Then A, Then D; Treatment C, Then D, Then B, Then A; Treatment D, Then A, Then C, Then B

GDC-0276 tablets DRUG

Three 90 mg GDC-0276 tablets administered orally.

Treatment A Then B Then D Then C; Treatment B, Then C, Then A, Then D; Treatment C, Then D, Then B, Then A; Treatment D, Then A, Then C, Then B

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Body mass index within the range 18.0 to 32.0 kilograms per meter squared (kg/m\^2), inclusive, and a minimum weight of 50.0 kg
• Male participants of reproductive potential must be and willing to continue using medically acceptable contraception and must avoid sperm donation from screening and for at least 90 days after the last study drug administration

You may not qualify if:

• Self-reported substance or alcohol dependence (excluding nicotine and caffeine) within the past 2 years, and/or participants who have ever been in a substance or alcohol rehabilitation program to treat their substance or alcohol dependence
• Have used any prescription or over-the-counter (OTC) medication or supplement within 14 days or 5 times the elimination half-life (whichever is longer) before Day -1 until the end of their participation in the study
• Have used any vaccine within 7 days before GDC-0276 administration
• Female participants with a positive serum or urine pregnancy test or are breast feeding
• Donation or loss of more than 500 milliliter (mL) whole blood within 3 months preceding entry into the treatment period
• Blood transfusion within 30 days preceding entry into the treatment period

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (1)

Quotient Clinical Ltd, Clinical Research Unit

Nottingham, NG11 6JS, United Kingdom

Location

MeSH Terms

Interventions

GDC-0276

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: July 29, 2016
• First Posted: August 4, 2016
• Study Start: June 1, 2016
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: February 19, 2018

Record last verified: 2018-02

Locations

GB (1)