A Phase 1, Double-Blind, Placebo-Controlled, Single-Ascending-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BIIB100 Administered Orally to Adult Participants With Amyotrophic Lateral Sclerosis
Overview
- Phase
- Phase 1
- Intervention
- BIIB100
- Conditions
- Amyotrophic Lateral Sclerosis
- Sponsor
- Biogen
- Enrollment
- 49
- Locations
- 7
- Primary Endpoint
- Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The primary objective of this study is to evaluate the safety, tolerability of single-ascending doses of BIIB100 in adults with amyotrophic lateral sclerosis (ALS). The secondary objective of the study is to characterize the pharmacokinetic profile of BIIB100.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Must meet the laboratory-supported probable, probable, or definite criteria for diagnosing ALS according to the World Federation of Neurology El Escorial criteria.
- •Participants taking concomitant riluzole at study entry must be on a stable dose for greater than or equals to (\>=) 30 days prior to the first dose of study treatment (Day 1). Participants taking concomitant riluzole must be willing to continue with the same dose regimen throughout the study, unless the Investigator determines that riluzole should be discontinued for medical reasons, in which case it may not be restarted during the study.
- •Participants taking concomitant edaravone at study entry must be on a stable dose for \>= 60 days prior to the first dose of study treatment (Day 1).
- •Adequate respiratory function as indicated by slow vital capacity (SVC) \>= 65% of predicted value as adjusted for sex, age, and height (from the sitting position).
Exclusion Criteria
- •Ongoing medical condition (e.g., wasting or cachexia, severe anemia) that would, in the opinion of the Investigator, interfere with the conduct or assessments of the study.
- •Significant cognitive impairment or unstable psychiatric illness, including psychosis, suicidal ideation, suicide attempt, or untreated major depression less than or equals to (\<=) 90 days of Screening, which in the opinion of the Investigator would interfere with the study procedures.
- •Treatment with drugs that are transported by Breast Cancer Resistance Protein (BCRP) and P-glycoprotein (P-gp) including, but not limited to, rosuvastatin, sulfasalazine, dabigatran, digoxin and fexofenadine.
- •Current enrollment or plan to enroll in any interventional clinical study in which an investigational treatment or approved therapy for investigational use is administered within 30 days or 5 half-lives of the agent, whichever is longer, prior to the Baseline Visit (pre-dose on Day 1). Participation in a noninterventional study focused on ALS natural history may be allowed at the discretion of the Investigator and after consultation with the Sponsor.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Arms & Interventions
Cohort 1: BIIB100 Dose 1
Participants will receive single oral dose of BIIB100 on Day 1.
Intervention: BIIB100
Cohort 2: BIIB100 Dose 2
Participants will receive single oral dose of BIIB100 on Day 1.
Intervention: BIIB100
Cohort 3: BIIB100 Dose 3
Participants will receive single oral dose of BIIB100 on Day 1.
Intervention: BIIB100
Cohort 4: BIIB100 Dose 4
Participants will receive single oral dose of BIIB100 on Day 1.
Intervention: BIIB100
Cohort 5: BIIB100 Dose 5
Participants will receive single oral dose of BIIB100 on Day 1.
Intervention: BIIB100
Cohort 6: BIIB100 Dose 6
Participants will receive single oral dose of BIIB100 on Day 1.
Intervention: BIIB100
Cohort 1-6: Matching Placebo
Participants will receive single oral dose of matching placebo on Day 1.
Intervention: Placebo
Outcomes
Primary Outcomes
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Screening (Day -28 ) up to Day 15
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose results in death, is a life-threatening event, requires inpatient hospitalization or prolongation of existing hospitalization, results in a significant disability/incapacity or congenital anomaly, or is a medically important event.
Secondary Outcomes
- Area Under the Concentration-Time Curve From Time 0 to Time of the Last Measurable Concentration (AUClast) of BIIB100(Day 1 (pre-dose) up to Day 3)
- Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf) of BIIB100(Day 1 (pre-dose) up to Day 3)
- Maximum Observed Concentration (Cmax) of BIIB100(Day 1 (pre-dose) up to Day 3)
- Time to Reach Cmax (Tmax) of BIIB100(Day 1 (pre-dose) up to Day 3)
- Terminal Elimination Half-life (t1/2) of BIIB100(Day 1 (pre-dose) up to Day 3)
- Apparent Clearance (CL/F) of BIIB100(Day 1 (pre-dose) up to Day 3)
- Apparent Volume of Distribution During the Terminal Elimination (Vz/F) of BIIB100(Day 1 (pre-dose) up to Day 3)