A Study to Determine the Safety, Tolerability, and Pharmacokinetics of GDC-0310 in Healthy Volunteers
- Registration Number
- NCT02742779
- Lead Sponsor
- Genentech, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 95
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Low-Fat Meal SD Cohort: Solution Formulation (Part 3) GDC-0310 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. MD Cohort: PIC (Part 2) GDC-0310 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. MD Cohort: Solution Formulation (Part 4) GDC-0310 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. SD Cohort: Solution Formulation (Part 3) GDC-0310 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. SD Cohort: PIC (Part 1) GDC-0310 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. High-Fat Meal SD Cohort: PIC (Part 1) GDC-0310 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. Placebo PIC Placebo 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. High-Fat Meal SD Cohort: Solution Formulation (Part 3) GDC-0310 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. Low-Fat Meal SD Cohort: PIC (Part 1) GDC-0310 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. Placebo Solution Placebo 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs) Baseline up to Month 9
- Secondary Outcome Measures
Name Time Method Apparent Terminal Elimination Rate Constant (ke) of GDC-0310 Pre dose up to Day 15 (detailed timeframe has been reported in the description) 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
Apparent Terminal Volume of Distribution (Vz/F) of GDC-0310 Pre dose up to Day 15 (detailed timeframe has been reported in the description) 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
Apparent Terminal Half-Life (t1/2) of GDC-0310 Pre dose up to Day 15 (detailed timeframe has been reported in the description) 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
PK Dose Proportionality as Assessed With AUC of GDC-0310 Pre dose up to Day 15 (detailed timeframe has been reported in the description) 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
Accumulation Ratio for MD Cohort Pre dose up to Day 15 (detailed timeframe has been reported in the description) 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
Maximum Plasma Concentration (Cmax) of GDC-0310 Pre dose up to Day 15 (detailed timeframe has been reported in the description) 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
Minimum Plasma Concentration (Cmin) of GDC-0310 Pre dose up to Day 15 (detailed timeframe has been reported in the description) 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
Time to Maximum Plasma Concentration (tmax) of GDC-0310 Pre dose up to Day 15 (detailed timeframe has been reported in the description) 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
Area Under the Concentration-Time Curve (AUC) of GDC-0310 Pre dose up to Day 15 (detailed timeframe has been reported in the description) 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
Apparent Clearance (CL/F) of GDC-0310 Pre dose up to Day 15 (detailed timeframe has been reported in the description) 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
Pharmacokinetics (PK) Dose Proportionality as Assessed With Cmax of GDC-0310 Pre dose up to Day 15 (detailed timeframe has been reported in the description) 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
Trial Locations
- Locations (1)
PRA Health Sciences
🇺🇸Salt Lake City, Utah, United States