Amyotrophic lateral sclerosis
Conditions
Interventions
VRG50635 or placebo oral administration of capsules
Part 1: single dose of VRG50635 or placebo (Food effect cohort 3 : 2 single
doses of VRG50635 or placebo)
Part 2: multiple dose of VRG50635 or pla
Sponsors
Verge Genomics
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Inclusion criteria - Parts 1 and 2 1. Healthy male or female between 18 to 65 years of age at screening (inclusive). 4. For male and female subjects of childbearing potential: Subjects and their spouse/partners who are of childbearing potential must use highly effective contraception when engaging in sexual activity consisting of 2 forms of birth control (1 of which must be a barrier method such as latex or polyurethane condoms) starting at screening and continue throughout the clinical study period, and for 90 days after the final study drug administration. 5. For males: Subject must not donate sperm starting at screening and throughout the clinical study period, and for 90 days after the final study drug administration.
Exclusion criteria
Exclusion criteria: Exclusion criteria - Parts 1 and 2 1. History of clinically significant hematological, renal, neurologic, pancreatic, gastrointestinal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, immunological, allergic disease, or other major disorders. 2. Current significant medical or psychiatric condition. 4. Evidence of clinically significant hepatic or renal impairment in the opinion of the investigator, including alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >1.5 the upper limit of normal (ULN) or bilirubin > 1.5 ULN. Patients with Gilbert syndrome without evidence of hepatic impairment may be enrolled. 14. Poor peripheral venous access. 21. A lifetime history of suicidal behavior or suicidal ideation as determined by a positive response (**Yes**) to either question 4 or question 5 of the C-SSRS at screening. 26. For part 2 only: Subjects not eligible for lumbar puncture (anti-coagulation, anti-aggregation or blood coagulation pathologies, recent spine surgery, acquired or congenital spine malformation, clinical signs of intracranial hypertension, cutaneous infection at the punction site)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1; Single ascending dose: • Assessment of adverse events (AEs), vital signs, electrocardiograms (ECGs), physical examinations, Columbia Suicide Severity Rating Scale (C-SSRS) and laboratory safety tests Part 2; Multiple ascending dose • Assessment of AEs, vital signs, ECGs, physical examinations, C-SSRS and laboratory safety tests | — |
Secondary
| Measure | Time frame |
|---|---|
| Part 1 Single ascending dose Food effect •VRG50635 and VRG50468 measured by LC-MS/MS in plasma samples following single oral doses of VRG50635. The pharmacokinetic parameters include: Tmax, tlag, Cmax, AUC(0-last), AUC(0-inf) and T1/2 •Urine PK parameters: cumulative total amount excreted in urine and cumulative percentage of dose in urine Food Effect part 1 •PK of VRG50635 and VRG50468 following single oral dose to healthy adult subjects in the fed and fasted states, based on the following parameters where possible and appropriate: Tmax, tlag, Cmax, AUC(0-last), AUC(0-inf) and T1/2 Part 2; Multiple ascending dose • VRG50635 and VRG50468 measured by LC-MS/MS in plasma samples and CSF following multiple oral doses of VRG50635. The pharmacokinetic parameters include: Tmax, tlag, Cmax, AUC(0-tau), Ctrough, Cavg, T1/2 and ARAUC • VRG50635 and VRG50468 concentrations measured by LC-MS/MS in CSF and plasma/CSF ratio | — |
Countries
Netherlands
Outcome results
None listed