A Study to Determine the Safety, Tolerability, and Pharmacokinetics of GDC-0310 in Healthy Volunteers

NCT02742779 | Completed Phase 1

• 1 other identifier: GN29829
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of single and multiple orally ascending doses of GDC-0310 administered in healthy participants as 4 parts including Part 1- a single dose (SD) part using a powder-in-capsule (PIC) formulation, Part 2- a multiple dose (MD) part using a PIC formulation, Part 3- a SD part using a solution formulation, and Part 4- a MD part using a solution formulation. Effects of food on pharmacokinetics (PK) will also be explored.

Conditions

Healthy Volunteer

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs)

  Baseline up to Month 9

Secondary Outcomes (11)

• Maximum Plasma Concentration (Cmax) of GDC-0310

  Pre dose up to Day 15 (detailed timeframe has been reported in the description)

• Minimum Plasma Concentration (Cmin) of GDC-0310

  Pre dose up to Day 15 (detailed timeframe has been reported in the description)

• Time to Maximum Plasma Concentration (tmax) of GDC-0310

  Pre dose up to Day 15 (detailed timeframe has been reported in the description)

• Area Under the Concentration-Time Curve (AUC) of GDC-0310

  Pre dose up to Day 15 (detailed timeframe has been reported in the description)

• Apparent Clearance (CL/F) of GDC-0310

  Pre dose up to Day 15 (detailed timeframe has been reported in the description)

Study Arms (10)

High-Fat Meal SD Cohort: PIC (Part 1)

EXPERIMENTAL

Participants will receive GDC-0310 single ascending dose based on PK results from earlier SD cohorts up to an established dose yielding at least a 2-fold exposure margin to the MTD administered orally following a high-fat meal after a 8-hour/overnight fast using PIC on Day 1 of the treatment period (5 days) in an additional cohort of Part 1.

Drug: GDC-0310

High-Fat Meal SD Cohort: Solution Formulation (Part 3)

EXPERIMENTAL

Participants will receive GDC-0310 single ascending dose based on PK results from earlier SD cohorts up to an established dose yielding at least a 2-fold exposure margin to the MTD administered orally following a high-fat meal after a 8-hour/overnight fast using solution on Day 1 of the treatment period (5 days) in an additional cohort of Part 3.

Drug: GDC-0310

Low-Fat Meal SD Cohort: PIC (Part 1)

EXPERIMENTAL

Participants will receive GDC-0310 single ascending dose given orally using PIC based on PK results from earlier SD cohorts up to an established dose yielding at least a 2-fold exposure margin to the MTD administered orally following a low-fat meal after an 8-hour/overnight fast using PIC on Day 1 of the treatment period (5 days) in an additional cohort of Part 1.

Drug: GDC-0310

Low-Fat Meal SD Cohort: Solution Formulation (Part 3)

EXPERIMENTAL

Participants will receive GDC-0310 single ascending dose given orally using PIC based on PK results from earlier SD cohorts up to an established dose yielding at least a 2-fold exposure margin to the MTD administered orally following a low-fat meal after an 8-hour/overnight fast using solution on Day 1 of the treatment period (5 days) in an additional cohort of Part 1.

Drug: GDC-0310

MD Cohort: PIC (Part 2)

EXPERIMENTAL

Participants will receive multiple ascending dose administered orally using PIC from Day 1 to Day 13 twice daily (BID) or may even be thrice daily (TID) or four times a day (QD) depending on clinical PK, followed by morning dose on Day 14 in 7 cohorts of Part 2.

Drug: GDC-0310

MD Cohort: Solution Formulation (Part 4)

EXPERIMENTAL

Participants will receive multiple ascending dose in fed or fast condition, administered orally using solution from Day 1 to Day 13 BID or may even be TID or QD depending on clinical PK, followed by morning dose on Day 14 in 7 cohorts of Part 2.

Drug: GDC-0310

Placebo PIC

PLACEBO COMPARATOR

Participants will receive placebo matched to GDC-0310 single or multiple ascending dose administered orally in the fasted (SD cohorts) or fed state using PIC on Day 1 of the treatment period (5 days) to the SD cohorts and from Day 1 to 14 BID or may even be TID or QD depending on clinical PK, to the MD cohorts.

Drug: Placebo

Placebo Solution

PLACEBO COMPARATOR

Participants will receive placebo matched to GDC-0310 single or multiple ascending dose administered orally in the fasted (SD cohorts) or fed state using PIC on Day 1 of the treatment period (5 days) to the SD cohorts and from Day 1 to 14 BID or may even be TID or QD depending on clinical PK, to the MD cohorts.

Drug: Placebo

SD Cohort: PIC (Part 1)

EXPERIMENTAL

Participants will receive GDC-0310 single ascending dose administered orally in the fasted state using PIC on Day 1 of the treatment period (5 days) in the 9 cohorts of Part 1.

Drug: GDC-0310

SD Cohort: Solution Formulation (Part 3)

EXPERIMENTAL

Participants will receive GDC-0310 single ascending dose administered orally in the fasted state using solution formulation on Day 1 of the treatment period (5 days) in the 9 cohorts of Part 3.

Drug: GDC-0310

Interventions

GDC-0310 DRUG

Participants will receive single or multiple ascending doses of GDC-0310 orally in fasted or fed state.

High-Fat Meal SD Cohort: PIC (Part 1); High-Fat Meal SD Cohort: Solution Formulation (Part 3); Low-Fat Meal SD Cohort: PIC (Part 1); Low-Fat Meal SD Cohort: Solution Formulation (Part 3); MD Cohort: PIC (Part 2); MD Cohort: Solution Formulation (Part 4); SD Cohort: PIC (Part 1); SD Cohort: Solution Formulation (Part 3)

Placebo DRUG

Participants will receive placebo matched to GDC-0310 as single or multiple oral dose in fasted or fed state.

Placebo PIC; Placebo Solution

Eligibility Criteria

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

You may qualify if:

• Female participants of non-childbearing potential must meet the criteria defined in the protocol
• Body mass index within the range of 18.0 to 30.0 kilograms per meter square (kg/m\^2), inclusive, and a minimum weight of 50.0 kg

You may not qualify if:

• Have a clinically significant medical condition (e.g., hypertension; diabetes; impaired cardiac, renal or hepatic function; hyperthyroidism or hypothyroidism; neurological disorder; pain condition; hematologic disorder; psychiatric disorders requiring chronic medication) including any medical condition requiring treatment with medication (other than study drugs and medications specifically allowed by this protocol) during participation in the study
• Evidence of any hepatic impairment including any abnormal levels (i.e., greater than \[\>\] 1 × the upper limit of normal) of alkaline phosphatase, gamma glutamyl transpeptidase, alanine transaminase, aspartate aminotransferase or bilirubin
• Evidence of clinically significant renal impairment defined as \>1.3 × upper limit of normal creatinine
• History or presence of alcoholism or alcohol or substance abuse (not including nicotine or caffeine) within the previous 2 years or routinely consume 2 or more alcohol-containing beverages per day or more than 10 units of alcohol per week (1 unit =150 milliliter (mL) of wine, 360 mL of beer, or 45 mL of 40 percent (%) alcohol)
• Have a positive urine drug test at screening or check-in or any other point during the study
• Are habituated to analgesic drugs (i.e., routine use of oral analgesics 5 or more times per week) or have a history of chronic pain requiring opiate use
• Have used tobacco or nicotine-containing products within 3 months before study drug administration
• Have clinically significant abnormal laboratory values as determined by the principal investigator
• Have used any prescription or over-the-counter medication or supplement within 14 days or 5 times the elimination half-life (whichever is longer) before administration of study drug and until the end of their participation in the study
• History of seizures, including in first degree relatives
• History of heritable myopathy, weakness, or paralysis, including in first degree relatives indicative of familial periodic paralysis
• Current treatment with medications that are well known to prolong the QT interval

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (1)

PRA Health Sciences

Salt Lake City, Utah, 84106, United States

Location

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2016
• First Posted: April 19, 2016
• Study Start: September 15, 2015
• Primary Completion: June 7, 2017
• Study Completion: June 7, 2017
• Last Updated: February 20, 2020

Record last verified: 2020-02

Locations

US (1)