Amyotrophic Lateral Sclerosis
Conditions
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.
Interventions
DRUGGDC-0134
GDC-0134 capsule will be administered orally at various doses, depending on the cohort and treatment period.
DRUGPlacebo
Placebo matching to GDC-0134
DRUGRabeprazole
Rabeprazole 20 mg twice daily orally
DRUGMidazolam
2mg of liquid formulation of midazolam orally
DRUGCaffeine
100 mg tablet or solution of caffeine orally
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Adverse Events (AEs) | 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 Electrocardiogram (ECG) 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
| Measure | Time frame |
|---|---|
| Maximum Plasma Concentration (Cmax) of GDC-0134 | 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 |
| Area Under the Plasma Concentration Versus Time Curve (AUC) of GDC-0134 | 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 |
| Apparent Terminal Volume of Distribution (Vz/F) 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 |
| t1/2 of 1-Hydroxymidazolam (Metabolite of Midazolam) | From Day -1 up to 28 days after last dose |
| t1/2 of Caffeine | 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 |
| Dose Normalized AUC (AUC/Dose) of GDC-0134 | From Day 1 up to 28 days after last dose |
| Apparent Terminal Half-Life (t1/2) 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 |
| Accumulation Ratio 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 |
Countries
Canada, Netherlands, United States
Outcome results
None listed