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

ArmDescriptionAssigned 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).
  • Drug: GDC-0134
    GDC-0134 capsule will be administered orally at various doses, depending on the cohort and treatment period.
  • Drug: Rabeprazole
    Rabeprazole 20 mg twice daily orally
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.
  • Drug: Placebo
    Placebo matching to GDC-0134
  • Drug: Rabeprazole
    Rabeprazole 20 mg twice daily orally
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.
  • Drug: GDC-0134
    GDC-0134 capsule will be administered orally at various doses, depending on the cohort and treatment period.
  • Drug: Midazolam
    2mg of liquid formulation of midazolam orally
  • Drug: Caffeine
    100 mg tablet or solution of caffeine orally
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.
  • Drug: Placebo
    Placebo matching to GDC-0134
  • Drug: Midazolam
    2mg of liquid formulation of midazolam orally
  • Drug: Caffeine
    100 mg tablet or solution of caffeine orally
Other
Open-Label Safety Expansion (OSE)
Participants will receive GDC-0134 at a dose determined by the corresponding MAD cohort.
  • Drug: GDC-0134
    GDC-0134 capsule will be administered orally at various doses, depending on the cohort and treatment period.

More Details

NCT ID
NCT02655614
Status
Active, not recruiting
Sponsor
Genentech, Inc.

Study Contact