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

NCT ID: NCT02655614

Last Updated: 2020-08-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

54 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-05-31

Study Completion Date

2020-03-16

Brief Summary

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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.

Detailed Description

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Conditions

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Amyotrophic Lateral Sclerosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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).

Group Type EXPERIMENTAL

GDC-0134

Intervention Type DRUG

GDC-0134 capsule will be administered orally at various doses, depending on the cohort and treatment period.

Rabeprazole

Intervention Type DRUG

Rabeprazole 20 mg twice daily orally

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo matching to GDC-0134

Rabeprazole

Intervention Type DRUG

Rabeprazole 20 mg twice daily orally

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.

Group Type EXPERIMENTAL

GDC-0134

Intervention Type DRUG

GDC-0134 capsule will be administered orally at various doses, depending on the cohort and treatment period.

Midazolam

Intervention Type DRUG

2mg of liquid formulation of midazolam orally

Caffeine

Intervention Type DRUG

100 mg tablet or solution of caffeine orally

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo matching to GDC-0134

Midazolam

Intervention Type DRUG

2mg of liquid formulation of midazolam orally

Caffeine

Intervention Type DRUG

100 mg tablet or solution of caffeine orally

Open-Label Safety Expansion (OSE)

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

Group Type OTHER

GDC-0134

Intervention Type DRUG

GDC-0134 capsule will be administered orally at various doses, depending on the cohort and treatment period.

Interventions

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GDC-0134

GDC-0134 capsule will be administered orally at various doses, depending on the cohort and treatment period.

Intervention Type DRUG

Placebo

Placebo matching to GDC-0134

Intervention Type DRUG

Rabeprazole

Rabeprazole 20 mg twice daily orally

Intervention Type DRUG

Midazolam

2mg of liquid formulation of midazolam orally

Intervention Type DRUG

Caffeine

100 mg tablet or solution of caffeine orally

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genentech, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Forbes Norris Mda/als Ctr; Research Center

San Francisco, California, United States

Site Status

Mayo Clinic Hospital - Florida

Jacksonville, Florida, United States

Site Status

University of Miami Miller School of Medicine

Miami, Florida, United States

Site Status

The Emory ALS Clinic

Atlanta, Georgia, United States

Site Status

Johns Hopkins University School of Medicine

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Wake Research Associates

Raleigh, North Carolina, United States

Site Status

New Orleans Center for Clinical Research

Knoxville, Tennessee, United States

Site Status

MUCH - Montreal Neurological Institute & Hospital

Montreal, Quebec, Canada

Site Status

UMC Utrecht

Utrecht, , Netherlands

Site Status

Countries

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United States Canada Netherlands

Other Identifiers

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2017-002931-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GN29823

Identifier Type: -

Identifier Source: org_study_id

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