Clinical trial NCT02013388: MAD Study Evaluating the Safety, Tolerability, and Pharmacokinetic Effects of N91115 in Healthy Subjects
Official title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Multiple-Ascending Dose Study Evaluating the Safety, Tolerability, and Pharmacokinetic Effects of N91115 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: N91115
GSNORi
SNO
Cavosonstat
Lead sponsor: Nivalis Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2013-12-17
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A study in healthy subjects to assess the safety, tolerability, and pharmacokinetics of N91115.

Detailed description: This Phase 1 study in healthy subjects is being conducted to assess the safety, tolerability, and pharmacokinetics of N91115. Also, a comparison of the fasted versus fed with a high fat meal were compared for PK.

Eligibility criteria: Inclusion Criteria:

* Subject voluntarily agrees to participate in this study and signs an Institutional Review Board (IRB)-approved informed consent prior to performing any of the screening procedures and in the opinion of the PI complies with all the requirements of the study.
* Subject is healthy, determined at the screening medical evaluation (including but not limited to medical history, physical examination and clinical laboratory evaluations).
* Subject is Caucasian.
* Female subject must be of non-childbearing potential (surgically sterile \[hysterectomy or bilateral tubal ligation\] or post-menopausal ≥ 1 year with follicle stimulating hormone \[FSH\] \> 40 U/L). Women receiving hormone replacement therapy (HRT) are eligible to enroll.
* Male subject must agree to use condoms and refrain from sperm donation from Day 1 until 30 days post last dose or have documentation of vasectomy.
* Subject has a body weight \> 50 kg and body mass index (BMI) between 19.5 and 32 kg/m2, inclusive, at screening.
* Subject has no clinically significant abnormal findings related to their systolic or diastolic blood pressure (BP), per the investigator's judgment, at screening or Day 1.
* Subject has no clinically significant abnormal findings in 12 lead ECG, per the investigator's judgment, at screening.

Exclusion Criteria:

* Subject has 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.
* Subject has clinically significant abnormalities on a 12 lead ECG done at screening
* Subject has clinically significant abnormalities on a 48-hour ambulatory ECG done at screening
* Subject has any disorder that would interfere with the absorption, distribution, metabolism, or excretion of drugs.
* Subject has any concurrent disease or condition that, in the opinion of the investigator, would make the subject unsuitable for participation in the clinical study.
* Subject is unlikely to comply with the protocol requirements, instructions, and study related restrictions; e.g., uncooperative attitude, unavailable for follow-up call, and/or improbability of completing the clinical study.

Primary outcomes:
measure: Safety and Tolerability of N91115
timeFrame: 21 Days
measure: Pharmacokinetics: Day 1 AUClast
timeFrame: Day 1
measure: Pharmacokinetics: AUCtau Day 14
timeFrame: Day 14
measure: Pharmacokinetics: Day 1 Plasma Cmax Values
timeFrame: Day 1
measure: Pharmacokinetics: Plasma Cmax Values on Day 14
timeFrame: Day 14
Secondary outcomes:
Other outcomes:
Locations:
city: Lakewood
country: United States
facility: DaVita Clinical Research
state: Colorado
Study officials:
affiliation: Davita Clinical Research
name: Christopher Galloway, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Nivalis Therapeutics, Inc.
name: Steven A Shoemaker, MD
role: STUDY_DIRECTOR
References:
citation: Donaldson SH, Solomon GM, Zeitlin PL, Flume PA, Casey A, McCoy K, Zemanick ET, Mandagere A, Troha JM, Shoemaker SA, Chmiel JF, Taylor-Cousar JL. Pharmacokinetics and safety of cavosonstat (N91115) in healthy and cystic fibrosis adults homozygous for F508DEL-CFTR. J Cyst Fibros. 2017 May;16(3):371-379. doi: 10.1016/j.jcf.2017.01.009. Epub 2017 Feb 13.