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

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.

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114

More Details

NCT ID
NCT02655614
Status
Recruiting
Sponsor
Genentech, Inc.

Study Contact

Reference Study ID Number: GN29823 www.roche.com/about_roche/roche_worldwide.htm
888-662-6728 (U.S. and Canada)
global-roche-genentech-trials@gene.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.