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

August 4, 2020 updated by: Genentech, Inc.

A Phase I, Double-Blind, Randomized, Placebo-Controlled, Multicenter, Single- and Multiple-Ascending-Dose Study to Determine Initial Safety, Tolerability, and Pharmacokinetics of GDC-0134 in Patients With Amyotrophic Lateral Sclerosis

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
54

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H3A 2B4
        • MUCH - Montreal Neurological Institute & Hospital
  • Netherlands
      • Utrecht, Netherlands, 3508 GA
        • UMC Utrecht
  • United States
    • California
      • San Francisco, California, United States, 94115
        • Forbes Norris Mda/als Ctr; Research Center
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic Hospital - Florida
      • Miami, Florida, United States, 33136
        • University of Miami Miller School of Medicine
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • The Emory ALS Clinic
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Johns Hopkins University School of Medicine
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • North Carolina
      • Raleigh, North Carolina, United States, 27612
        • Wake Research Associates
    • Tennessee
      • Knoxville, Tennessee, United States, 37920
        • New Orleans Center for Clinical Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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: Rabeprazole
Rabeprazole 20 mg twice daily orally
Drug: Placebo
Placebo matching to GDC-0134
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Percentage of Participants With Adverse Events (AEs)
Time Frame: From randomization up to approximately 48 months
From randomization up to approximately 48 months
Percentage of Participants With Clinically Significant Laboratory Abnormalities
Time Frame: From randomization up to approximately 48 months
From randomization up to approximately 48 months
Percentage of Participants With Clinically Significant Vital Signs Abnormalities
Time Frame: From randomization up to approximately 48 months
From randomization up to approximately 48 months
Percentage of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
Time Frame: From randomization up to approximately 48 months
From randomization up to approximately 48 months
Percentage of Participants With Clinically Significant Abnormalities in Physical Examination Findings
Time Frame: From randomization up to approximately 48 months
From randomization up to approximately 48 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Maximum Plasma Concentration (Cmax) of GDC-0134
Time Frame: From Day 1 up to 28 days after last dose
From Day 1 up to 28 days after last dose
Time to Maximum Plasma Concentration (tmax) of GDC-0134
Time Frame: From Day 1 up to 28 days after last dose
From Day 1 up to 28 days after last dose
Area Under the Plasma Concentration Versus Time Curve (AUC) of GDC-0134
Time Frame: From Day 1 up to 28 days after last dose
From Day 1 up to 28 days after last dose
Apparent Clearance (CL/F) of GDC-0134
Time Frame: From Day 1 up to 28 days after last dose
From Day 1 up to 28 days after last dose
Apparent Terminal Volume of Distribution (Vz/F) of GDC-0134
Time Frame: From Day 1 up to 28 days after last dose
From Day 1 up to 28 days after last dose
Apparent Terminal Half-Life (t1/2) of GDC-0134
Time Frame: From Day 1 up to 28 days after last dose
From Day 1 up to 28 days after last dose
PK-Dose Proportionality of GDC-0134 as Assessed With Cmax and AUC
Time Frame: From Day 1 up to 28 days after last dose
From Day 1 up to 28 days after last dose
Accumulation Ratio of GDC-0134
Time Frame: From Day 1 up to 28 days after last dose
From Day 1 up to 28 days after last dose
Dose Normalized Cmax (Cmax/Dose) of GDC-0134
Time Frame: From Day 1 up to 28 days after last dose
From Day 1 up to 28 days after last dose
Dose Normalized AUC (AUC/Dose) of GDC-0134
Time Frame: From Day 1 up to 28 days after last dose
From Day 1 up to 28 days after last dose
t1/2 of Midazolam
Time Frame: From Day -1 up to 28 days after last dose
From Day -1 up to 28 days after last dose
t1/2 of 1-Hydroxymidazolam (Metabolite of Midazolam)
Time Frame: From Day -1 up to 28 days after last dose
From Day -1 up to 28 days after last dose
t1/2 of Caffeine
Time Frame: From Day -1 up to 28 days after last dose
From Day -1 up to 28 days after last dose
t1/2 of Paraxanthine (Metabolite of Caffeine)
Time Frame: From Day -1 up to 28 days after last dose
From Day -1 up to 28 days after last dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Genentech, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 31, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 16, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 16, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 7, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 13, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 14, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 6, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 4, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GN29823
  • 2017-002931-41 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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