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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: GDC-0310
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High-Fat Meal SD Cohort: PIC (Part 1)<br>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<br>* Participants will receive single or multiple ascending doses of GDC-0310 orally in fasted or fed state.<br>|
| Experimental: High-Fat Meal SD Cohort: Solution Formulation (Part 3)<br>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<br>* Participants will receive single or multiple ascending doses of GDC-0310 orally in fasted or fed state.<br>|
| Experimental: Low-Fat Meal SD Cohort: PIC (Part 1)<br>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<br>* Participants will receive single or multiple ascending doses of GDC-0310 orally in fasted or fed state.<br>|
| Experimental: Low-Fat Meal SD Cohort: Solution Formulation (Part 3)<br>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<br>* Participants will receive single or multiple ascending doses of GDC-0310 orally in fasted or fed state.<br>|
| Experimental: MD Cohort: PIC (Part 2)<br>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<br>* Participants will receive single or multiple ascending doses of GDC-0310 orally in fasted or fed state.<br>|
| Experimental: MD Cohort: Solution Formulation (Part 4)<br>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<br>* Participants will receive single or multiple ascending doses of GDC-0310 orally in fasted or fed state.<br>|
| Placebo Comparator: Placebo PIC<br>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<br>* Participants will receive placebo matched to GDC-0310 as single or multiple oral dose in fasted or fed state.<br>|
| Placebo Comparator: Placebo Solution<br>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<br>* Participants will receive placebo matched to GDC-0310 as single or multiple oral dose in fasted or fed state.<br>|
| Experimental: SD Cohort: PIC (Part 1)<br>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<br>* Participants will receive single or multiple ascending doses of GDC-0310 orally in fasted or fed state.<br>|
| Experimental: SD Cohort: Solution Formulation (Part 3)<br>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<br>* Participants will receive single or multiple ascending doses of GDC-0310 orally in fasted or fed state.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs) |  | Baseline up to Month 9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) |