A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of N91115 in Healthy Subjects
Overview
- Phase
- Phase 1
- Intervention
- Cavosonstat
- Conditions
- Cystic Fibrosis
- Sponsor
- Nivalis Therapeutics, Inc.
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
The present study is designed to assess the safety and tolerability of escalating, multiple ascending doses of Cavosonstat (N91115) in healthy subjects.
Detailed Description
This study will assess the safety and tolerability of escalating, multiple ascending doses of Cavosonstat (N91115) in healthy subjects. Approximately 5 ascending cohorts are planned with approximately 8 subjects per cohort (6 active, 2 placebo). Each subject will undergo screening (Day -28 to Day -2) and, if eligible, return to the unit on Day -1 when eligibility will be reconfirmed. Eligible subjects will be randomized in a 3:1 ratio to receive investigational medicinal product (IMP) N91115 (daily \[QD\] or every 12 hours \[Q12H\]) or matching placebo (QD or Q12H) for 7 days and will be followed for safety while housed in the clinical research unit (CRU) until discharge on Day 8. Pharmacokinetics will be followed from Study Day 1 through the morning of Study Day 8. The subjects will be discharged from the CRU and complete the post treatment withdrawal phase, including a follow-up phone call on Day 15.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Written informed consent
- •Healthy, determined at the screening medical evaluation (including but not limited to medical history, physical examination, and clinical laboratory evaluations)
- •Male or female, between 18 and 55 years of age, inclusive at screening
- •Caucasian (as reported by patient)
- •The following applies to female subjects:
- •Negative serum pregnancy test (for women of child-bearing potential) at screening and negative urine pregnancy at Day -1
- •Willing to use at least 1 highly effective method of birth control (excluding hormonal contraceptives) after signing consent, including abstinence which must be in use from the time of consent through the 30 days after completing the double-blind study drug
- •The following applies to male subjects:
- •Agrees to use a condom or abstinence, and agrees to refrain from sperm donation from date of informed consent signing through the 30 days after completing the double-blind study drug or
- •Has documentation of azoospermia or vasectomy
Exclusion Criteria
- •History of any illness or condition that in the opinion of the investigator could confound the results of the study or pose additional risk when administered IMP, such as clinically significant history or evidence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurological, immunological, or psychiatric disorder(s) as determined by the investigator or designee
- •Concurrent disease or condition, that, in the opinion of the investigator, would make the subject unsuitable for participation in the clinical study
- •Any of the following findings on a 12-lead ECG done at screening:
- •HR \< 45 bpm or \> 95 bpm
- •QTcF \> 450 msec for males and \>470 msec for females
- •PR \> 220 msec
- •QRS duration \> 110 msec
- •ST segment abnormal
- •T-wave changes
- •QRS, ST, or T-wave findings making it technically difficult to determine the QT intervals
Arms & Interventions
Cavosonstat (N91115) 400 mg
Every 12 hour oral dosing of N91115 for 7 days
Intervention: Cavosonstat
Cavosonstat (N91115) 600 mg
Every 12 hour oral dosing of N91115 for 7 days
Intervention: Cavosonstat
Cavosonstat (N91115) 1200 mg
Once daily oral dosing of N91115 for 7 days
Intervention: Cavosonstat
Cavosonstat (N91115) 800 mg
Every 12 hour oral dosing of N91115 for 7 days
Intervention: Cavosonstat
Placebo
Matched placebo. Oral dosing every 12 hour or once daily for 7 days
Intervention: Placebo
Outcomes
Primary Outcomes
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame: 14 days
Safety assessments based on clinical evaluations, laboratory assessments, and adverse events
Secondary Outcomes
- Pharmacokinetic parameters of N91115 and metabolites (Amount of analyte excreted in the urine [Ae])(7 days)
- Pharmacokinetic parameters of N91115 and metabolites (% analyte excreted in the urine [Fe])(7 days)
- Pharmacokinetic parameters of N91115 and metabolites (area under the curve [AUC])(7 days)
- Pharmacokinetic parameters of N91115 and metabolites (maximum concentration [Cmax])(7 days)
- Pharmacokinetic parameters of N91115 and metabolites (clearance [CL])(7 days)
- Pharmacokinetic parameters of N91115 and metabolites (accumulation index [Racc])(7 days)
- Pharmacokinetic parameters of N91115 and metabolites (Terminal elimination half-life [t1/2])(7 days)
- Pharmacokinetic parameters of N91115 and metabolites (time of maximum concentration [Tmax])(7 days)
- Pharmacokinetic parameters of N91115 and metabolites (metabolite to parent exposure ratio [M/P ratio])(7 days)
- Pharmacokinetic parameters of N91115 and metabolites (terminal elimination rate constant [lambda z])(7 days)