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

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Multiple-Ascending Dose Study Evaluating the Safety, Tolerability, and Pharmacokinetic Effects of N91115 in Healthy Subjects

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: N91115; Drug: N91115; Drug: Placebo; Drug: Placebo-Day 1 only

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 Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Lakewood, Colorado, United States, 80228
      • Davita Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

8

Arms and Interventions

Participant Group / 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 Names: Cavosonstat; Drug: N91115; Given PO only on Day 1; Other Names: 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 Names: Cavosonstat; Drug: N91115; Given PO only on Day 1; Other Names: Cavosonstat
Experimental: 50 mg (single dose); single oral dose of 50 mg N91115	Drug: N91115; Given PO daily for 14 days; Other Names: Cavosonstat; Drug: N91115; Given PO only on Day 1; Other Names: 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 Names: Cavosonstat; Drug: N91115; Given PO only on Day 1; Other Names: Cavosonstat
Experimental: 250 mg (Fed); single oral daily dose of 250 mg N91115 for 1 day (fed fat meal)	Drug: N91115; Given PO daily for 14 days; Other Names: Cavosonstat; Drug: N91115; Given PO only on Day 1; Other Names: Cavosonstat
Experimental: 500 mg; single oral daily dose of 500 mg N91115 for 14 days	Drug: N91115; Given PO daily for 14 days; Other Names: Cavosonstat; Drug: N91115; Given PO only on Day 1; Other Names: 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 Names: Placebo

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.

Helpful Links

• Home Page
• Phase 1 Unit

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: December 9, 2013
• First Submitted That Met QC Criteria: December 16, 2013
• First Posted (Estimate): December 17, 2013

Study Record Updates

• Last Update Posted (Estimate): December 21, 2016
• Last Update Submitted That Met QC Criteria: November 3, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: N91115; Cavosonstat; GSNORi; SNO
• Other Study ID Numbers: N91115-1H-01