Clinical trial NCT02742779: A Study to Determine the Safety, Tolerability, and Pharmacokinetics of GDC-0310 in Healthy Volunteers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2016-04-19
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs)
timeFrame: Baseline up to Month 9
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) of GDC-0310
timeFrame: Pre dose up to Day 15 (detailed timeframe has been reported in the description)
measure: Minimum Plasma Concentration (Cmin) of GDC-0310
timeFrame: Pre dose up to Day 15 (detailed timeframe has been reported in the description)
measure: Time to Maximum Plasma Concentration (tmax) of GDC-0310
timeFrame: Pre dose up to Day 15 (detailed timeframe has been reported in the description)
measure: Area Under the Concentration-Time Curve (AUC) of GDC-0310
timeFrame: Pre dose up to Day 15 (detailed timeframe has been reported in the description)
measure: Apparent Clearance (CL/F) of GDC-0310
timeFrame: Pre dose up to Day 15 (detailed timeframe has been reported in the description)
measure: Apparent Terminal Volume of Distribution (Vz/F) of GDC-0310
timeFrame: Pre dose up to Day 15 (detailed timeframe has been reported in the description)
measure: Apparent Terminal Elimination Rate Constant (ke) of GDC-0310
timeFrame: Pre dose up to Day 15 (detailed timeframe has been reported in the description)
measure: Apparent Terminal Half-Life (t1/2) of GDC-0310
timeFrame: Pre dose up to Day 15 (detailed timeframe has been reported in the description)
measure: Pharmacokinetics (PK) Dose Proportionality as Assessed With Cmax of GDC-0310
timeFrame: Pre dose up to Day 15 (detailed timeframe has been reported in the description)
measure: PK Dose Proportionality as Assessed With AUC of GDC-0310
timeFrame: Pre dose up to Day 15 (detailed timeframe has been reported in the description)
measure: Accumulation Ratio for MD Cohort
timeFrame: Pre dose up to Day 15 (detailed timeframe has been reported in the description)
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: PRA Health Sciences
state: Utah
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: