MAD Study Evaluating the Safety, Tolerability, and Pharmacokinetic Effects of N91115 in Healthy Subjects (SNO2)

• Sponsor: Nivalis Therapeutics, Inc.
• Information provided by (Responsible Party): Nivalis Therapeutics, Inc.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: N91115; Drug: Placebo; Drug: Placebo-Day 1 only	Phase 1

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.

Study Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	49 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
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 Start Date :	February 2014
Actual Primary Completion Date :	December 2014
Actual Study Completion Date :	February 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: 10 mg; single oral daily dose of 10 mg N91115 for 14 days	Drug: N91115; Given PO daily for 14 days; Other Name: Cavosonstat
Placebo Comparator: Placebo; single oral daily dose of placebo for 14 days	Drug: Placebo; Given PO daily for 14 days
Experimental: 50 mg; single oral daily dose of 50 mg N91115 for 14 days	Drug: N91115; Given PO daily for 14 days; Other Name: Cavosonstat
Experimental: 50 mg (single dose); single oral dose of 50 mg N91115	Drug: N91115; Given PO only on Day 1; Other Name: Cavosonstat
Experimental: 250 mg; single oral daily dose of 250 mg N91115 for 14 days (fasted)	Drug: N91115; Given PO daily for 14 days; Other Name: Cavosonstat
Experimental: 250 mg (Fed); single oral daily dose of 250 mg N91115 for 1 day (fed fat meal)	Drug: N91115; Given PO only on Day 1; Other Name: Cavosonstat
Experimental: 500 mg; single oral daily dose of 500 mg N91115 for 14 days	Drug: N91115; Given PO daily for 14 days; Other Name: Cavosonstat
Placebo Comparator: Placebo-Day 1 only; Single oral dose of placebo (Day 1 only)	Drug: Placebo-Day 1 only; Given PO- only on Day 1 (single dosed to match single dose treatments); Other Name: Placebo

Outcome Measures

Primary Outcome Measures :

1. Safety and Tolerability of N91115 [ Time Frame: 21 Days ]
   Assessments are based on numbers of subjects with abnormal clinical evaluations, abnormal laboratory assessments, and adverse events.
2. Pharmacokinetics: Day 1 AUClast [ Time Frame: Day 1 ]
   Day 1 AUClast plasma values from treatment groups completing 14 days of N91115 administration
3. Pharmacokinetics: AUCtau Day 14 [ Time Frame: Day 14 ]
   Plasma analysis of AUCtau values from the end of the dosing period (Day 14) with N91115
4. Pharmacokinetics: Day 1 Plasma Cmax Values [ Time Frame: Day 1 ]
   All subjects who completed sample collections for Day 1 plasma N91115
5. Pharmacokinetics: Plasma Cmax Values on Day 14 [ Time Frame: Day 14 ]
   Plasma Cmax values from Day 14 subjects with repeat administration of N91115

Eligibility Criteria

Layout table for eligibility information

Ages Eligible for Study:	18 Years to 55 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

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.

Contacts and Locations

Locations

Layout table for location information

United States, Colorado
DaVita Clinical Research
Lakewood, Colorado, United States, 80228

Sponsors and Collaborators

Nivalis Therapeutics, Inc.

Investigators

Layout table for investigator information

Principal Investigator:	Christopher Galloway, MD	Davita Clinical Research
Study Director:	Steven A Shoemaker, MD	Nivalis Therapeutics, Inc.

More Information

Additional Information:

Home Page  Phase 1 Unit 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Layout table for additonal information

Responsible Party:	Nivalis Therapeutics, Inc.
ClinicalTrials.gov Identifier:	NCT02013388 History of Changes
Other Study ID Numbers:	N91115-1H-01
First Posted:	December 17, 2013
Results First Posted:	March 18, 2015
Last Update Posted:	December 21, 2016
Last Verified:	November 2016

Keywords provided by Nivalis Therapeutics, Inc.:

N91115; GSNORi; SNO; Cavosonstat