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

Amyotrophic Lateral Sclerosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02655614
• Other study ID #: GN29823
• Secondary ID: 2017-002931-41
• Status: Completed
• Phase: Phase 1
• Start date: May 31, 2016
• Est. completion date: March 16, 2020

Study information

• Verified date: August 2020
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: March 16, 2020
• Est. primary completion date: March 16, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• GDC-0134
GDC-0134 capsule will be administered orally at various doses, depending on the cohort and treatment period.
• Placebo
Placebo matching to GDC-0134
• Rabeprazole
Rabeprazole 20 mg twice daily orally
• Midazolam
2mg of liquid formulation of midazolam orally
• Caffeine
100 mg tablet or solution of caffeine orally

Locations

Country	Name	City	State
Canada	MUCH - Montreal Neurological Institute & Hospital	Montreal	Quebec
Netherlands	UMC Utrecht	Utrecht
United States	The Emory ALS Clinic	Atlanta	Georgia
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Mayo Clinic Hospital - Florida	Jacksonville	Florida
United States	New Orleans Center for Clinical Research	Knoxville	Tennessee
United States	University of Miami Miller School of Medicine	Miami	Florida
United States	Wake Research Associates	Raleigh	North Carolina
United States	Forbes Norris Mda/als Ctr; Research Center	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Canada,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Adverse Events (AEs)		From randomization up to approximately 48 months
Primary	Percentage of Participants With Clinically Significant Laboratory Abnormalities		From randomization up to approximately 48 months
Primary	Percentage of Participants With Clinically Significant Vital Signs Abnormalities		From randomization up to approximately 48 months
Primary	Percentage of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities		From randomization up to approximately 48 months
Primary	Percentage of Participants With Clinically Significant Abnormalities in Physical Examination Findings		From randomization up to approximately 48 months
Secondary	Maximum Plasma Concentration (Cmax) of GDC-0134		From Day 1 up to 28 days after last dose
Secondary	Time to Maximum Plasma Concentration (tmax) of GDC-0134		From Day 1 up to 28 days after last dose
Secondary	Area Under the Plasma Concentration Versus Time Curve (AUC) of GDC-0134		From Day 1 up to 28 days after last dose
Secondary	Apparent Clearance (CL/F) of GDC-0134		From Day 1 up to 28 days after last dose
Secondary	Apparent Terminal Volume of Distribution (Vz/F) of GDC-0134		From Day 1 up to 28 days after last dose
Secondary	Apparent Terminal Half-Life (t1/2) of GDC-0134		From Day 1 up to 28 days after last dose
Secondary	PK-Dose Proportionality of GDC-0134 as Assessed With Cmax and AUC		From Day 1 up to 28 days after last dose
Secondary	Accumulation Ratio of GDC-0134		From Day 1 up to 28 days after last dose
Secondary	Dose Normalized Cmax (Cmax/Dose) of GDC-0134		From Day 1 up to 28 days after last dose
Secondary	Dose Normalized AUC (AUC/Dose) of GDC-0134		From Day 1 up to 28 days after last dose
Secondary	t1/2 of Midazolam		From Day -1 up to 28 days after last dose
Secondary	t1/2 of 1-Hydroxymidazolam (Metabolite of Midazolam)		From Day -1 up to 28 days after last dose
Secondary	t1/2 of Caffeine		From Day -1 up to 28 days after last dose
Secondary	t1/2 of Paraxanthine (Metabolite of Caffeine)		From Day -1 up to 28 days after last dose