A Study of GDC-0134 to Determine Initial Safety, Tolerability, and Pharmacokinetic Parameters in Participants With Amyotrophic Lateral Sclerosis

Genentech

Status and phase: Completed; Phase 1

Conditions: Amyotrophic Lateral Sclerosis

Treatments: Drug: Placebo; Drug: Rabeprazole; Drug: GDC-0134; Drug: Midazolam; Drug: Caffeine

Study type: Interventional

Funder types: Industry

Identifiers

NCT02655614

GN29823

2017-002931-41 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 54 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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54 participants in 5 patient groups, including a placebo group

SAD Stage: GDC-0134

Experimental group

Description:

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).

Treatment:

Drug: Rabeprazole

Drug: GDC-0134

SAD Stage: Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Rabeprazole

Drug: Placebo

MAD Stage: GDC-0134

Experimental group

Description:

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.

Treatment:

Drug: GDC-0134

Drug: Caffeine

Drug: Midazolam

MAD Stage: Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Drug: Caffeine

Drug: Midazolam

Open-Label Safety Expansion (OSE)

Other group

Description:

Participants will receive GDC-0134 at a dose determined by the corresponding MAD cohort.

Treatment:

Drug: GDC-0134