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

NCT02655614 | Completed Phase 1 FDA Drug

• 2 other identifiers: GN298232017-002931-41
• Study Type: interventional
• Target: 54
• Locations: 3 countries
• Sites: 10

Brief Summary

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.

Conditions

Amyotrophic Lateral Sclerosis

Outcome Measures

Primary Outcomes (5)

• Percentage of Participants With Adverse Events (AEs)

  From randomization up to approximately 48 months

• Percentage of Participants With Clinically Significant Laboratory Abnormalities

  From randomization up to approximately 48 months

• Percentage of Participants With Clinically Significant Vital Signs Abnormalities

  From randomization up to approximately 48 months

• Percentage of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities

  From randomization up to approximately 48 months

• Percentage of Participants With Clinically Significant Abnormalities in Physical Examination Findings

  From randomization up to approximately 48 months

Secondary Outcomes (14)

• Maximum Plasma Concentration (Cmax) of GDC-0134

  From Day 1 up to 28 days after last dose

• Time to Maximum Plasma Concentration (tmax) of GDC-0134

  From Day 1 up to 28 days after last dose

• Area Under the Plasma Concentration Versus Time Curve (AUC) of GDC-0134

  From Day 1 up to 28 days after last dose

• Apparent Clearance (CL/F) of GDC-0134

  From Day 1 up to 28 days after last dose

• Apparent Terminal Volume of Distribution (Vz/F) of GDC-0134

  From Day 1 up to 28 days after last dose

Study Arms (5)

SAD Stage: GDC-0134

EXPERIMENTAL

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; Drug: Rabeprazole

SAD Stage: Placebo

PLACEBO COMPARATOR

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; Drug: Rabeprazole

MAD Stage: GDC-0134

EXPERIMENTAL

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; Drug: Midazolam; Drug: Caffeine

MAD Stage: Placebo

PLACEBO COMPARATOR

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; Drug: Midazolam; Drug: Caffeine

Open-Label Safety Expansion (OSE)

OTHER

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

Drug: GDC-0134

Interventions

GDC-0134 DRUG

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

MAD Stage: GDC-0134; Open-Label Safety Expansion (OSE); SAD Stage: GDC-0134

Placebo DRUG

Placebo matching to GDC-0134

MAD Stage: Placebo; SAD Stage: Placebo

Rabeprazole DRUG

Rabeprazole 20 mg twice daily orally

SAD Stage: GDC-0134; SAD Stage: Placebo

Midazolam DRUG

2mg of liquid formulation of midazolam orally

MAD Stage: GDC-0134; MAD Stage: Placebo

Caffeine DRUG

100 mg tablet or solution of caffeine orally

MAD Stage: GDC-0134; MAD Stage: Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (10)

Forbes Norris Mda/als Ctr; Research Center

San Francisco, California, 94115, United States

Location

Mayo Clinic Hospital - Florida

Jacksonville, Florida, 32224, United States

Location

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

The Emory ALS Clinic

Atlanta, Georgia, 30322, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21205, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Wake Research Associates

Raleigh, North Carolina, 27612, United States

Location

New Orleans Center for Clinical Research

Knoxville, Tennessee, 37920, United States

Location

MUCH - Montreal Neurological Institute & Hospital

Montreal, Quebec, H3A 2B4, Canada

Location

UMC Utrecht

Utrecht, 3508 GA, Netherlands

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Rabeprazole; Midazolam; Caffeine

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzodiazepines; Benzazepines; Xanthines; Alkaloids; Purinones; Purines

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2016
• First Posted: January 14, 2016
• Study Start: May 31, 2016
• Primary Completion: March 16, 2020
• Study Completion: March 16, 2020
• Last Updated: August 6, 2020

Record last verified: 2020-08

Locations

NL (1); US (8); CA (1)