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

This study is currently recruiting participants.
Verified October 2017 by Genentech, Inc.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02655614
First Posted: January 14, 2016
Last Update Posted: October 4, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Genentech, Inc.
  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 two components: a Single-Ascending-Dose (SAD) stage and a Multiple-Ascending-Dose (MAD) stage.

Condition Intervention Phase
Amyotrophic Lateral Sclerosis Drug: GDC-0134 Drug: Placebo Drug: Rabeprazole Drug: Midazolam Drug: Caffeine Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Percentage of Participants With Adverse Events (AEs) [ Time Frame: From randomization up to approximately 36 months ]
  • Percentage of Participants With Clinically Significant Laboratory Abnormalities [ Time Frame: From randomization up to approximately 36 months ]
  • Percentage of Participants With Clinically Significant Vital Signs Abnormalities [ Time Frame: From randomization up to approximately 36 months ]
  • Percentage of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities [ Time Frame: From randomization up to approximately 36 months ]
  • Percentage of Participants With Clinically Significant Abnormalities in Physical Examination Findings [ Time Frame: From randomization up to approximately 36 months ]

Secondary Outcome Measures:
  • Maximum Plasma Concentration (Cmax) of GDC-0134 [ Time Frame: From Day 1 up to 14 days after last dose ]
  • Time to Maximum Plasma Concentration (tmax) of GDC-0134 [ Time Frame: From Day 1 up to 14 days after last dose ]
  • Area Under the Plasma Concentration Versus Time Curve (AUC) of GDC-0134 [ Time Frame: From Day 1 up to 14 days after last dose ]
  • Apparent Clearance (CL/F) of GDC-0134 [ Time Frame: From Day 1 up to 14 days after last dose ]
  • Apparent Terminal Volume of Distribution (Vz/F) of GDC-0134 [ Time Frame: From Day 1 up to 14 days after last dose ]
  • Apparent Terminal Half-Life (t1/2) of GDC-0134 [ Time Frame: From Day 1 up to 14 days after last dose ]
  • PK-Dose Proportionality of GDC-0134 as Assessed With Cmax and AUC [ Time Frame: From Day 1 up to 14 days after last dose ]
  • Accumulation Ratio of GDC-0134 [ Time Frame: From Day 1 up to 14 days after last dose ]
  • Dose Normalized Cmax (Cmax/Dose) of GDC-0134 [ Time Frame: From Day 1 up to 14 days after last dose ]
  • Dose Normalized AUC (AUC/Dose) of GDC-0134 [ Time Frame: From Day 1 up to 14 days after last dose ]
  • t1/2 of Midazolam [ Time Frame: From Day -1 up to 14 days after last dose ]
  • t1/2 of 1-Hydroxymidazolam (Metabolite of Midazolam) [ Time Frame: From Day -1 up to 14 days after last dose ]
  • t1/2 of Caffeine [ Time Frame: From Day -1 up to 14 days after last dose ]
  • t1/2 of Paraxanthine (Metabolite of Caffeine) [ Time Frame: From Day -1 up to 14 days after last dose ]

Estimated Enrollment: 72
Actual Study Start Date: May 31, 2016
Estimated Study Completion Date: September 30, 2018
Estimated Primary Completion Date: August 31, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02655614


Contacts
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

Locations
United States, California
Forbes Norris Mda/als Ctr; Research Center Recruiting
San Francisco, California, United States, 94115
United States, Florida
Mayo Clinic Hospital - Florida Recruiting
Jacksonville, Florida, United States, 32224
University of Miami Miller School of Medicine Recruiting
Miami, Florida, United States, 33136
Compass Research Recruiting
Orlando, Florida, United States, 32806
United States, Georgia
The Emory ALS Clinic Recruiting
Atlanta, Georgia, United States
United States, Maryland
Johns Hopkins University School of Medicine Recruiting
Baltimore, Maryland, United States, 21205
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
United States, North Carolina
Wake Research Associates Recruiting
Raleigh, North Carolina, United States, 27612
United States, Tennessee
New Orleans Center for Clinical Research Recruiting
Knoxville, Tennessee, United States, 37920
United States, Texas
Methodist Neurological Institute Not yet recruiting
Houston, Texas, United States, 77030
Canada, Quebec
MUCH - Montreal Neurological Institute & Hospital Not yet recruiting
Montreal, Quebec, Canada, H3A 2B4
Netherlands
UMC Utrecht Not yet recruiting
Utrecht, Netherlands, 3508 GA
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT02655614     History of Changes
Other Study ID Numbers: GN29823
2017-002931-41 ( EudraCT Number )
First Submitted: January 7, 2016
First Posted: January 14, 2016
Last Update Posted: October 4, 2017
Last Verified: October 2017

Studies a U.S. FDA-regulated Drug Product: Yes

Additional relevant MeSH terms:
Sclerosis
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Midazolam
Caffeine
Rabeprazole
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Central Nervous System Stimulants