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

A Single-dose, Open-label, Randomized, 4-way Crossover Study to Assess the Relative Bioavailability And Food Effect of a Tablet Formulation of GDC-0276 in Healthy Subjects

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.

Study Overview

• Status: Withdrawn
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: GDC-0276 capsule; Drug: GDC-0276 tablets

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham, United Kingdom, NG11 6JS
    • Quotient Clinical Ltd, Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A Then B Then D Then C; 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; Three 90 milligram [mg] capsules of GDC-0276 administered orally.; Drug: GDC-0276 tablets; Three 90 mg GDC-0276 tablets administered orally.
Experimental: Treatment B, Then C, Then A, Then D; 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; Three 90 milligram [mg] capsules of GDC-0276 administered orally.; Drug: GDC-0276 tablets; Three 90 mg GDC-0276 tablets administered orally.
Experimental: Treatment C, Then D, Then B, Then A; 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; Three 90 milligram [mg] capsules of GDC-0276 administered orally.; Drug: GDC-0276 tablets; Three 90 mg GDC-0276 tablets administered orally.
Experimental: Treatment D, Then A, Then C, Then B; 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; Three 90 milligram [mg] capsules of GDC-0276 administered orally.; Drug: GDC-0276 tablets; Three 90 mg GDC-0276 tablets administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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
Apparent Oral Clearance (CL/F) of M16 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
Apparent Volume of Distribution (Vz/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 Volume of Distribution (Vz/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
Plasma Terminal Half-Life (t1/2) 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
Plasma Terminal Half-Life (t1/2) 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
Plasma Terminal Half-Life (t1/2) 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
Number of Participants With Adverse Events and Serious Adverse Event	Baseline up to Follow up (Day 32)
Apparent Volume of Distribution (Vz/F) of M16 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

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Anticipated): November 1, 2016
• Study Completion (Anticipated): November 1, 2016

Study Registration Dates

• First Submitted: July 29, 2016
• First Submitted That Met QC Criteria: August 1, 2016
• First Posted (Estimate): August 4, 2016

Study Record Updates

• Last Update Posted (Actual): February 19, 2018
• Last Update Submitted That Met QC Criteria: February 16, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: Healthy Volunteer
• Other Study ID Numbers: GX29841; 2016-001572-30 (EudraCT Number)