A Study of GDC-0134 to Determine Initial Safety, Tolerability, and Pharmacokinetic Parameters in Participants With Amyotrophic Lateral Sclerosis
Purpose
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.
Condition
- Amyotrophic Lateral Sclerosis
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts 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
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Arm Groups
Arm | Description | Assigned Intervention |
---|---|---|
Experimental SAD Stage: 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). |
|
Placebo Comparator SAD Stage: 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. |
|
Experimental MAD Stage: 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. |
|
Placebo Comparator MAD Stage: 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. |
|
Other Open-Label Safety Expansion (OSE) |
Participants will receive GDC-0134 at a dose determined by the corresponding MAD cohort. |
|
More Details
- Status
- Completed
- Sponsor
- Genentech, Inc.