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

Genentech

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteer

Treatments: Drug: Placebo; Drug: GDC-0310

Study type: Interventional

Funder types: Industry

Identifiers

NCT02742779

GN29829

Details and patient eligibility

About

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.

Enrollment: 95 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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95 participants in 10 patient groups, including a placebo group

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

Experimental group

Description:

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.

Treatment:

Drug: GDC-0310

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

Experimental group

Description:

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.

Treatment:

Drug: GDC-0310

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

Experimental group

Description:

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.

Treatment:

Drug: GDC-0310

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

Experimental group

Description:

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.

Treatment:

Drug: GDC-0310

MD Cohort: PIC (Part 2)

Experimental group

Description:

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.

Treatment:

Drug: GDC-0310

MD Cohort: Solution Formulation (Part 4)

Experimental group

Description:

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.

Treatment:

Drug: GDC-0310

Placebo PIC

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Placebo Solution

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

SD Cohort: PIC (Part 1)

Experimental group

Description:

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.

Treatment:

Drug: GDC-0310

SD Cohort: Solution Formulation (Part 3)

Experimental group

Description:

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.

Treatment:

Drug: GDC-0310