MAD Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Cavosonstat (N91115) in Healthy Subjects (SNO-9)

NCT02934139 | Completed Phase 1

• 1 other identifier: N91115-1HS-08
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The present study is designed to assess the safety and tolerability of escalating, multiple ascending doses of Cavosonstat (N91115) in healthy subjects.

Conditions

Cystic Fibrosis

Keywords

N91115; Cavosonstat; Healthy Volunteer

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  Safety assessments based on clinical evaluations, laboratory assessments, and adverse events

  14 days

Secondary Outcomes (10)

• 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

Study Arms (5)

Cavosonstat (N91115) 400 mg

EXPERIMENTAL

Every 12 hour oral dosing of N91115 for 7 days

Drug: Cavosonstat

Cavosonstat (N91115) 600 mg

EXPERIMENTAL

Every 12 hour oral dosing of N91115 for 7 days

Drug: Cavosonstat

Cavosonstat (N91115) 1200 mg

EXPERIMENTAL

Once daily oral dosing of N91115 for 7 days

Drug: Cavosonstat

Cavosonstat (N91115) 800 mg

EXPERIMENTAL

Every 12 hour oral dosing of N91115 for 7 days

Drug: Cavosonstat

Placebo

PLACEBO COMPARATOR

Matched placebo. Oral dosing every 12 hour or once daily for 7 days

Other: Placebo

Interventions

Cavosonstat DRUG

CFTR modulator that stabilizes CFTR

Also known as: N91115

Cavosonstat (N91115) 1200 mg; Cavosonstat (N91115) 400 mg; Cavosonstat (N91115) 600 mg; Cavosonstat (N91115) 800 mg

Placebo OTHER

Matched placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• Non-smoker (or other nicotine user) as determined by history (no nicotine use over the past 6 months) and a negative cotinine test at screening and Day -1
• Body mass index between 18 and 32 kg/m2 inclusive at screening, and weighs at least 50 kg at screening
• No clinically significant vital sign findings including no clinically significant abnormal findings related to their systolic or diastolic BP at screening or prior to dosing on Day 1, per the investigator's judgment.
• No clinically significant abnormal findings in 12-lead ECG, per the investigator's judgment, at screening or prior to dosing on Day 1
• No clinically significant abnormalities in hematology, clinical chemistry, and urinalysis results that would interfere with the study assessments at screening

You may not qualify if:

• 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
• Any of the following on 24-hour ambulatory ECG (Holter) monitoring at screening:
• a. Supraventricular ectopy i. Singlets: \> 200 / 24 hours ii. Couplets: \> 20 / hour iii. Runs: \> 10 beats b. Ventricular ectopy i. Unifocal singlets: \> 100 / 24 hours ii. Unifocal couplets: \> 20 / hour iii. Complex of multifocal singlets: \> 50 / 24 hours iv. Complex of multifocal couplets: \> 10 / 24 hours v. Any Run (ventricular tachycardia) c. Heart rate i. \< 40 bpm for 1 minute while awake ii. \< 35 bpm for 3 minutes while asleep iii. \> 120 bpm for 3 minutes (when not exercising) iv. Pauses \> 2000 msec d. 2nd or 3rd degree AV block e. Intraventricular conduction delay (IVCD) with QRS duration \> 120 msec or right bundle branch block (RBBB) or left buddle branch block (LBBB) other than rare RBBB f. Atrial flutter or atrial fibrillation regardless of rate
• Disorder that would interfere with the absorption, distribution, metabolism, or excretion of drugs as determined by the investigator
• History of alcohol abuse or drug abuse (including cannabis, cocaine, and opioids) in the year prior to screening
• Positive alcohol test at screening or Day -1.

Sponsors & Collaborators

• Nivalis Therapeutics, Inc.: lead

Study Sites (1)

DaVita Clinical Research

Lakewood, Colorado, 80228, United States

Location

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

cavosonstat

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Officials

• Robert Williams, MD

  Davita Clinical Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2016
• First Posted: October 14, 2016
• Study Start: October 1, 2016
• Primary Completion: December 1, 2016
• Study Completion: January 1, 2017
• Last Updated: January 31, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)