A Study of GDC-0134 to Determine Initial Safety, Tolerability, and Pharmacokinetic Parameters in Participants With Amyotrophic Lateral Sclerosis
Phase 1
Completed
- Conditions
- Amyotrophic Lateral Sclerosis
- Interventions
- Registration Number
- NCT02655614
- Lead Sponsor
- Genentech, Inc.
- Brief Summary
This first-in-human, double-blind, placebo-controlled Phase I study will be conducted in participants with amyotrophic lateral sclerosis (ALS) to explore safety, tolerability, and pharmacokinetic (PK) properties of GDC-0134. It will include three components: a Single-Ascending-Dose (SAD) stage, a Multiple-Ascending-Dose (MAD) stage, and an Open-Label Safety Expansion (OSE) stage.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 54
Inclusion Criteria
- Male or female participants with a diagnosis of possible, laboratory-supported probable, probable, or definite ALS according to modified El Escorial criteria
- Upright forced vital capacity of at least 50 percent (%)
- Ability to fast from food for 8 hours prior to dosing and 2 hours after dosing
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Exclusion Criteria
- Currently taking riluzole unless on a stable dose for the 3 months prior to Day -1 and without current liver enzyme or liver function abnormalities
- Currently taking edaravone unless after completion of at least the second 14-day drug-treatment period, as long as Day 1 occurs during a drug-free period at least 24 hours after the last edaravone dose and at least 5 days prior to the first dose of the next cycle
- Positive for hepatitis C antibody, hepatitis B surface antigen, or human immunodeficiency virus (HIV) antibody
- Clinically significant thrombocytopenia
- Currently taking nutritional/herbal supplements, except for over-the-counter vitamins that are within Recommended Dietary Allowance (RDA), unless discontinued at least 7 days prior to Day -1, except upon approval of both the investigator and Sponsor
- For participants participating in a designated drug-drug interaction (DDI) cohort in the MAD stage of the study, who require midazolam/caffeine administration: known allergy, religious prohibition, or other condition limiting midazolam or caffeine administration
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description SAD Stage: Placebo Placebo Participants in multiple cohorts and treatment periods will receive placebo matching to GDC-0134 under fed/fasting conditions. Few participants may receive rabeprazole 20 mg. MAD Stage: Placebo Placebo Participants will receive placebo matching to GDC-0134 for 28 days. To study the interactions between GDC-0134 and other drugs, some participants may receive single doses of midazolam and caffeine at various time points. SAD Stage: GDC-0134 Rabeprazole Participants in multiple cohorts and treatment periods will receive single doses of GDC-0134 oral capsules under fed/fasting conditions. To study the effect of proton pump inhibitor (PPI) medication rabeprazole on PK properties of GDC-0134, few participants may receive rabeprazole 20 milligrams (mg). SAD Stage: Placebo Rabeprazole Participants in multiple cohorts and treatment periods will receive placebo matching to GDC-0134 under fed/fasting conditions. Few participants may receive rabeprazole 20 mg. MAD Stage: GDC-0134 Midazolam Participants will receive multiple doses of GDC-0134 for 28 days. To study the interactions between GDC-0134 and other drugs, some participants may receive single doses of midazolam and caffeine at various time points. MAD Stage: GDC-0134 Caffeine Participants will receive multiple doses of GDC-0134 for 28 days. To study the interactions between GDC-0134 and other drugs, some participants may receive single doses of midazolam and caffeine at various time points. MAD Stage: Placebo Caffeine Participants will receive placebo matching to GDC-0134 for 28 days. To study the interactions between GDC-0134 and other drugs, some participants may receive single doses of midazolam and caffeine at various time points. MAD Stage: Placebo Midazolam Participants will receive placebo matching to GDC-0134 for 28 days. To study the interactions between GDC-0134 and other drugs, some participants may receive single doses of midazolam and caffeine at various time points. SAD Stage: GDC-0134 GDC-0134 Participants in multiple cohorts and treatment periods will receive single doses of GDC-0134 oral capsules under fed/fasting conditions. To study the effect of proton pump inhibitor (PPI) medication rabeprazole on PK properties of GDC-0134, few participants may receive rabeprazole 20 milligrams (mg). MAD Stage: GDC-0134 GDC-0134 Participants will receive multiple doses of GDC-0134 for 28 days. To study the interactions between GDC-0134 and other drugs, some participants may receive single doses of midazolam and caffeine at various time points. Open-Label Safety Expansion (OSE) GDC-0134 Participants will receive GDC-0134 at a dose determined by the corresponding MAD cohort.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Adverse Events (AEs) From randomization up to approximately 48 months Percentage of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities From randomization up to approximately 48 months Percentage of Participants With Clinically Significant Laboratory Abnormalities From randomization up to approximately 48 months Percentage of Participants With Clinically Significant Vital Signs Abnormalities From randomization up to approximately 48 months Percentage of Participants With Clinically Significant Abnormalities in Physical Examination Findings From randomization up to approximately 48 months
- Secondary Outcome Measures
Name Time Method Apparent Terminal Half-Life (t1/2) of GDC-0134 From Day 1 up to 28 days after last dose Dose Normalized AUC (AUC/Dose) of GDC-0134 From Day 1 up to 28 days after last dose Apparent Terminal Volume of Distribution (Vz/F) of GDC-0134 From Day 1 up to 28 days after last dose PK-Dose Proportionality of GDC-0134 as Assessed With Cmax and AUC From Day 1 up to 28 days after last dose t1/2 of 1-Hydroxymidazolam (Metabolite of Midazolam) From Day -1 up to 28 days after last dose Time to Maximum Plasma Concentration (tmax) of GDC-0134 From Day 1 up to 28 days after last dose t1/2 of Midazolam From Day -1 up to 28 days after last dose Maximum Plasma Concentration (Cmax) of GDC-0134 From Day 1 up to 28 days after last dose Area Under the Plasma Concentration Versus Time Curve (AUC) of GDC-0134 From Day 1 up to 28 days after last dose Accumulation Ratio of GDC-0134 From Day 1 up to 28 days after last dose t1/2 of Paraxanthine (Metabolite of Caffeine) From Day -1 up to 28 days after last dose Apparent Clearance (CL/F) of GDC-0134 From Day 1 up to 28 days after last dose Dose Normalized Cmax (Cmax/Dose) of GDC-0134 From Day 1 up to 28 days after last dose t1/2 of Caffeine From Day -1 up to 28 days after last dose
Trial Locations
- Locations (10)
Johns Hopkins University School of Medicine
๐บ๐ธBaltimore, Maryland, United States
Mayo Clinic Hospital - Florida
๐บ๐ธJacksonville, Florida, United States
Forbes Norris Mda/als Ctr; Research Center
๐บ๐ธSan Francisco, California, United States
The Emory ALS Clinic
๐บ๐ธAtlanta, Georgia, United States
Massachusetts General Hospital
๐บ๐ธBoston, Massachusetts, United States
New Orleans Center for Clinical Research
๐บ๐ธKnoxville, Tennessee, United States
Wake Research Associates
๐บ๐ธRaleigh, North Carolina, United States
MUCH - Montreal Neurological Institute & Hospital
๐จ๐ฆMontreal, Quebec, Canada
UMC Utrecht
๐ณ๐ฑUtrecht, Netherlands
University of Miami Miller School of Medicine
๐บ๐ธMiami, Florida, United States