Clinical trial NCT02655614: A Study of GDC-0134 to Determine Initial Safety, Tolerability, and Pharmacokinetic Parameters in Participants With Amyotrophic Lateral Sclerosis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Amyotrophic Lateral Sclerosis
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2016-01-14
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: From randomization up to approximately 48 months
measure: Percentage of Participants With Clinically Significant Laboratory Abnormalities
timeFrame: From randomization up to approximately 48 months
measure: Percentage of Participants With Clinically Significant Vital Signs Abnormalities
timeFrame: From randomization up to approximately 48 months
measure: Percentage of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
timeFrame: From randomization up to approximately 48 months
measure: Percentage of Participants With Clinically Significant Abnormalities in Physical Examination Findings
timeFrame: From randomization up to approximately 48 months
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) of GDC-0134
timeFrame: From Day 1 up to 28 days after last dose
measure: Time to Maximum Plasma Concentration (tmax) of GDC-0134
timeFrame: From Day 1 up to 28 days after last dose
measure: Area Under the Plasma Concentration Versus Time Curve (AUC) of GDC-0134
timeFrame: From Day 1 up to 28 days after last dose
measure: Apparent Clearance (CL/F) of GDC-0134
timeFrame: From Day 1 up to 28 days after last dose
measure: Apparent Terminal Volume of Distribution (Vz/F) of GDC-0134
timeFrame: From Day 1 up to 28 days after last dose
measure: Apparent Terminal Half-Life (t1/2) of GDC-0134
timeFrame: From Day 1 up to 28 days after last dose
measure: PK-Dose Proportionality of GDC-0134 as Assessed With Cmax and AUC
timeFrame: From Day 1 up to 28 days after last dose
measure: Accumulation Ratio of GDC-0134
timeFrame: From Day 1 up to 28 days after last dose
measure: Dose Normalized Cmax (Cmax/Dose) of GDC-0134
timeFrame: From Day 1 up to 28 days after last dose
measure: Dose Normalized AUC (AUC/Dose) of GDC-0134
timeFrame: From Day 1 up to 28 days after last dose
measure: t1/2 of Midazolam
timeFrame: From Day -1 up to 28 days after last dose
measure: t1/2 of 1-Hydroxymidazolam (Metabolite of Midazolam)
timeFrame: From Day -1 up to 28 days after last dose
measure: t1/2 of Caffeine
timeFrame: From Day -1 up to 28 days after last dose
measure: t1/2 of Paraxanthine (Metabolite of Caffeine)
timeFrame: From Day -1 up to 28 days after last dose
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Forbes Norris Mda/als Ctr; Research Center
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic Hospital - Florida
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Atlanta
country: United States
facility: The Emory ALS Clinic
state: Georgia
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Raleigh
country: United States
facility: Wake Research Associates
state: North Carolina
city: Knoxville
country: United States
facility: New Orleans Center for Clinical Research
state: Tennessee
city: Montreal
country: Canada
facility: MUCH - Montreal Neurological Institute & Hospital
state: Quebec
city: Utrecht
country: Netherlands
facility: UMC Utrecht
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: