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

• ClinicalTrials.gov Identifier: NCT02013388
• Recruitment Status: Completed
• First Posted: December 17, 2013
• Results First Posted: March 18, 2015
• Last Update Posted: December 21, 2016
• 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

• 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

• 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

United States, Colorado

DaVita Clinical Research

Lakewood, Colorado, United States, 80228

Sponsors and Collaborators

Nivalis Therapeutics, Inc.

Investigators

• 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.

• Responsible Party: Nivalis Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT02013388
• 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