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

Healthy Volunteer Clinical Trial

Official title:

A Phase I, Randomized, Single and Multiple Ascending Dose, Placebo-Controlled, Double-Blind Study to Determine the Safety, Tolerability, and Pharmacokinetics of GDC-0310 in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02742779
• Other study ID #: GN29829
• Status: Completed
• Phase: Phase 1
• Start date: September 15, 2015
• Est. completion date: June 7, 2017

Study information

• Verified date: February 2020
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 95
• Est. completion date: June 7, 2017
• Est. primary completion date: June 7, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Volunteer

Intervention

Drug:
• GDC-0310
Participants will receive single or multiple ascending doses of GDC-0310 orally in fasted or fed state.
• Placebo
Participants will receive placebo matched to GDC-0310 as single or multiple oral dose in fasted or fed state.

Locations

Country	Name	City	State
United States	PRA Health Sciences	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs)		Baseline up to Month 9
Secondary	Maximum Plasma Concentration (Cmax) of GDC-0310	SD Cohort: Pre-dose (PD) (Hour[H] 0),5 minutes,0.25,0.5,1,1.5,2,3,4,6,8,10,12,13,14,16,24,48,96H post-dose(PoD); MD Cohort:PD H0,5 minutes,0.25,0.5,1,1.5,2,3,4,6,8,10,12,13,14,16H PoD on Day 1,14;Pre a.m. dose (H0) on Day 2,3,4,5,7,9,11,13;24H PoD on Day 15	Pre dose up to Day 15 (detailed timeframe has been reported in the description)
Secondary	Minimum Plasma Concentration (Cmin) of GDC-0310	SD Cohort: PD H 0,5 minutes,0.25,0.5,1,1.5,2,3,4,6,8,10,12,13,14,16,24,48,96H PoD; MD Cohort: PD H0,5 minutes,0.25,0.5,1,1.5,2,3,4,6,8,10,12,13,14,16H PoD on Day 1,14; Pre a.m. dose (H0) on Day 2,3,4,5,7,9,11,13;24H PoD on Day 15	Pre dose up to Day 15 (detailed timeframe has been reported in the description)
Secondary	Time to Maximum Plasma Concentration (tmax) of GDC-0310	SD Cohort: PD H 0,5 minutes,0.25,0.5,1,1.5,2,3,4,6,8,10,12,13,14,16,24,48,96H PoD; MD Cohort: PD H0,5 minutes,0.25,0.5,1,1.5,2,3,4,6,8,10,12,13,14,16H PoD on Day 1,14; Pre a.m. dose (H0) on Day 2,3,4,5,7,9,11,13;24H PoD on Day 15	Pre dose up to Day 15 (detailed timeframe has been reported in the description)
Secondary	Area Under the Concentration-Time Curve (AUC) of GDC-0310	SD Cohort: PD H 0,5 minutes,0.25,0.5,1,1.5,2,3,4,6,8,10,12,13,14,16,24,48,96H PoD; MD Cohort: PD H0,5 minutes,0.25,0.5,1,1.5,2,3,4,6,8,10,12,13,14,16H PoD on Day 1,14; Pre a.m. dose (H0) on Day 2,3,4,5,7,9,11,13;24H PoD on Day 15	Pre dose up to Day 15 (detailed timeframe has been reported in the description)
Secondary	Apparent Clearance (CL/F) of GDC-0310	SD Cohort: PD H 0,5 minutes,0.25,0.5,1,1.5,2,3,4,6,8,10,12,13,14,16,24,48,96H PoD; MD Cohort: PD H0,5 minutes,0.25,0.5,1,1.5,2,3,4,6,8,10,12,13,14,16H PoD on Day 1,14; Pre a.m. dose (H0) on Day 2,3,4,5,7,9,11,13;24H PoD on Day 15	Pre dose up to Day 15 (detailed timeframe has been reported in the description)
Secondary	Apparent Terminal Volume of Distribution (Vz/F) of GDC-0310	SD Cohort: PD H 0,5 minutes,0.25,0.5,1,1.5,2,3,4,6,8,10,12,13,14,16,24,48,96H PoD; MD Cohort: PD H0,5 minutes,0.25,0.5,1,1.5,2,3,4,6,8,10,12,13,14,16H PoD on Day 1,14; Pre a.m. dose (H0) on Day 2,3,4,5,7,9,11,13;24H PoD on Day 15	Pre dose up to Day 15 (detailed timeframe has been reported in the description)
Secondary	Apparent Terminal Elimination Rate Constant (ke) of GDC-0310	SD Cohort: PD H 0,5 minutes,0.25,0.5,1,1.5,2,3,4,6,8,10,12,13,14,16,24,48,96H PoD; MD Cohort: PD H0,5 minutes,0.25,0.5,1,1.5,2,3,4,6,8,10,12,13,14,16H PoD on Day 1,14; Pre a.m. dose (H0) on Day 2,3,4,5,7,9,11,13;24H PoD on Day 15	Pre dose up to Day 15 (detailed timeframe has been reported in the description)
Secondary	Apparent Terminal Half-Life (t1/2) of GDC-0310	SD Cohort: PD H 0,5 minutes,0.25,0.5,1,1.5,2,3,4,6,8,10,12,13,14,16,24,48,96H PoD; MD Cohort: PD H0,5 minutes,0.25,0.5,1,1.5,2,3,4,6,8,10,12,13,14,16H PoD on Day 1,14; Pre a.m. dose (H0) on Day 2,3,4,5,7,9,11,13;24H PoD on Day 15	Pre dose up to Day 15 (detailed timeframe has been reported in the description)
Secondary	Pharmacokinetics (PK) Dose Proportionality as Assessed With Cmax of GDC-0310	SD Cohort: PD H 0,5 minutes,0.25,0.5,1,1.5,2,3,4,6,8,10,12,13,14,16,24,48,96H PoD; MD Cohort: PD H0,5 minutes,0.25,0.5,1,1.5,2,3,4,6,8,10,12,13,14,16H PoD on Day 1,14; Pre a.m. dose (H0) on Day 2,3,4,5,7,9,11,13;24H PoD on Day 15	Pre dose up to Day 15 (detailed timeframe has been reported in the description)
Secondary	PK Dose Proportionality as Assessed With AUC of GDC-0310	SD Cohort: PD H 0,5 minutes,0.25,0.5,1,1.5,2,3,4,6,8,10,12,13,14,16,24,48,96H PoD; MD Cohort: PD H0,5 minutes,0.25,0.5,1,1.5,2,3,4,6,8,10,12,13,14,16H PoD on Day 1,14; Pre a.m. dose (H0) on Day 2,3,4,5,7,9,11,13;24H PoD on Day 15	Pre dose up to Day 15 (detailed timeframe has been reported in the description)
Secondary	Accumulation Ratio for MD Cohort	PD H0,5 minutes,0.25,0.5,1,1.5,2,3,4,6,8,10,12,13,14,16H PoD on Day 1,14; Pre a.m. dose (H0) on Day 2,3,4,5,7,9,11,13;24H PoD on Day 15	Pre dose up to Day 15 (detailed timeframe has been reported in the description)