FindTrial
Sign In

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

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

Status
Completed
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02013388
Acronym
SNO2
Enrollment
49
Registered
2013-12-17
Start date
2014-02-28
Completion date
2015-02-28
Last updated
2016-12-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Keywords

N91115, GSNORi, SNO, Cavosonstat

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.

Interventions

DRUGN91115

Given PO daily for 14 days

DRUGPlacebo

Given PO daily for 14 days

DRUGPlacebo-Day 1 only

Given PO- only on Day 1 (single dosed to match single dose treatments)

Sponsors

Nivalis Therapeutics, Inc.
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes

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.

Design outcomes

Primary

MeasureTime frameDescription
Safety and Tolerability of N9111521 DaysAssessments are based on numbers of subjects with abnormal clinical evaluations, abnormal laboratory assessments, and adverse events.
Pharmacokinetics: Day 1 AUClastDay 1Day 1 AUClast plasma values from treatment groups completing 14 days of N91115 administration
Pharmacokinetics: AUCtau Day 14Day 14Plasma analysis of AUCtau values from the end of the dosing period (Day 14) with N91115
Pharmacokinetics: Day 1 Plasma Cmax ValuesDay 1All subjects who completed sample collections for Day 1 plasma N91115
Pharmacokinetics: Plasma Cmax Values on Day 14Day 14Plasma Cmax values from Day 14 subjects with repeat administration of N91115

Countries

United States

Participant flow

Participants by arm

ArmCount
Placebo
single oral daily dose of placebo for 14 days Placebo: Given PO daily for 14 days
9
10 mg
single oral daily dose of 10 mg N91115 for 14 days N91115: Given PO daily for 14 days
6
50 mg
single oral daily dose of 50 mg N91115 for 14 days N91115: Given PO daily for 14 days
6
250 mg
single oral daily dose of 250 mg N91115 for 14 days (fasted) N91115: Given PO daily for 14 days
6
500 mg
single oral daily dose of 500 mg N91115 for 14 days N91115: Given PO daily for 14 days
6
50 mg (Single Dose)
single oral dose of 50 mg N91115 N91115: Given PO only on Day 1
6
250 mg (Fed)
single oral daily dose of 250 mg N91115 for 1 day (fed fat meal) N91115: Given PO only on Day 1
6
Placebo- Single Dose
single oral dose Placebo: Given PO daily for 1day
4
Total49

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003FG004FG005FG006FG007
Overall Studywork emergency10001000

Baseline characteristics

Characteristic10 mg50 mg250 mg500 mgPlacebo50 mg (Single Dose)250 mg (Fed)Placebo- Single DoseTotal
Age, Continuous41.3 years
STANDARD_DEVIATION 14.9
40.2 years
STANDARD_DEVIATION 14.25
39.7 years
STANDARD_DEVIATION 10.03
37.3 years
STANDARD_DEVIATION 10.91
35.6 years
STANDARD_DEVIATION 12.32
42.3 years
STANDARD_DEVIATION 9.4
37.8 years
STANDARD_DEVIATION 11.84
41.3 years
STANDARD_DEVIATION 11.59
39.1 years
STANDARD_DEVIATION 11.4
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants1 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
6 Participants6 Participants6 Participants6 Participants8 Participants6 Participants6 Participants4 Participants48 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Gender
Female
2 Participants2 Participants2 Participants5 Participants1 Participants0 Participants2 Participants2 Participants16 Participants
Gender
Male
4 Participants4 Participants4 Participants1 Participants8 Participants6 Participants4 Participants2 Participants33 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Black or African American
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants1 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
6 Participants6 Participants6 Participants6 Participants8 Participants6 Participants6 Participants4 Participants48 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
EG004
affected / at risk
EG005
affected / at risk
EG006
affected / at risk
EG007
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —— / —— / —— / —— / —— / —
other
Total, other adverse events
9 / 96 / 66 / 66 / 66 / 61 / 64 / 62 / 4
serious
Total, serious adverse events
0 / 90 / 60 / 60 / 60 / 60 / 60 / 60 / 4

Outcome results

Primary

Pharmacokinetics: AUCtau Day 14

Plasma analysis of AUCtau values from the end of the dosing period (Day 14) with N91115

Time frame: Day 14

Population: All patients that completed the required days of dosing to study end

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
PlaceboPharmacokinetics: AUCtau Day 14423 h*ng/mLGeometric Coefficient of Variation 17.1
10 mgPharmacokinetics: AUCtau Day 142240 h*ng/mLGeometric Coefficient of Variation 23.4
50 mgPharmacokinetics: AUCtau Day 1414500 h*ng/mLGeometric Coefficient of Variation 17.9
250 mgPharmacokinetics: AUCtau Day 1436000 h*ng/mLGeometric Coefficient of Variation 41.7
Primary

Pharmacokinetics: Day 1 AUClast

Day 1 AUClast plasma values from treatment groups completing 14 days of N91115 administration

Time frame: Day 1

Population: All patients that had plasma samples collected were included in the analysis

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
PlaceboPharmacokinetics: Day 1 AUClast327 h*ng/mLGeometric Coefficient of Variation 24
10 mgPharmacokinetics: Day 1 AUClast1530 h*ng/mLGeometric Coefficient of Variation 23.5
50 mgPharmacokinetics: Day 1 AUClast12000 h*ng/mLGeometric Coefficient of Variation 20.6
250 mgPharmacokinetics: Day 1 AUClast32400 h*ng/mLGeometric Coefficient of Variation 44.4
Primary

Pharmacokinetics: Day 1 Plasma Cmax Values

All subjects who completed sample collections for Day 1 plasma N91115

Time frame: Day 1

Population: All subjects that completed the plasma collection sampling were included in the analysis

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
PlaceboPharmacokinetics: Day 1 Plasma Cmax Values33.0 ng/mLGeometric Coefficient of Variation 32.2
10 mgPharmacokinetics: Day 1 Plasma Cmax Values245 ng/mLGeometric Coefficient of Variation 55.4
50 mgPharmacokinetics: Day 1 Plasma Cmax Values1810 ng/mLGeometric Coefficient of Variation 50.2
250 mgPharmacokinetics: Day 1 Plasma Cmax Values3840 ng/mLGeometric Coefficient of Variation 39.6
Primary

Pharmacokinetics: Plasma Cmax Values on Day 14

Plasma Cmax values from Day 14 subjects with repeat administration of N91115

Time frame: Day 14

Population: All subjects completing plasma collection sampling for N91115

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
PlaceboPharmacokinetics: Plasma Cmax Values on Day 1484.3 ng/mLGeometric Coefficient of Variation 44.4
10 mgPharmacokinetics: Plasma Cmax Values on Day 14445 ng/mLGeometric Coefficient of Variation 48.6
50 mgPharmacokinetics: Plasma Cmax Values on Day 142410 ng/mLGeometric Coefficient of Variation 30.3
250 mgPharmacokinetics: Plasma Cmax Values on Day 145800 ng/mLGeometric Coefficient of Variation 67.2
Primary

Safety and Tolerability of N91115

Assessments are based on numbers of subjects with abnormal clinical evaluations, abnormal laboratory assessments, and adverse events.

Time frame: 21 Days

Population: All patients enrolled in the study were evaluated for safety endpoints

ArmMeasureGroupValue (NUMBER)
PlaceboSafety and Tolerability of N91115Subjects with at least one TEAE9 participants
PlaceboSafety and Tolerability of N91115Subjects with at least one study treatment TEAE5 participants
10 mgSafety and Tolerability of N91115Subjects with at least one TEAE6 participants
10 mgSafety and Tolerability of N91115Subjects with at least one study treatment TEAE4 participants
50 mgSafety and Tolerability of N91115Subjects with at least one TEAE6 participants
50 mgSafety and Tolerability of N91115Subjects with at least one study treatment TEAE4 participants
250 mgSafety and Tolerability of N91115Subjects with at least one TEAE6 participants
250 mgSafety and Tolerability of N91115Subjects with at least one study treatment TEAE2 participants
500 mgSafety and Tolerability of N91115Subjects with at least one TEAE6 participants
500 mgSafety and Tolerability of N91115Subjects with at least one study treatment TEAE2 participants
50 mg (Single Dose)Safety and Tolerability of N91115Subjects with at least one TEAE1 participants
50 mg (Single Dose)Safety and Tolerability of N91115Subjects with at least one study treatment TEAE1 participants
250 mg (Fed)Safety and Tolerability of N91115Subjects with at least one study treatment TEAE0 participants
250 mg (Fed)Safety and Tolerability of N91115Subjects with at least one TEAE4 participants
Placebo- Single DoseSafety and Tolerability of N91115Subjects with at least one TEAE2 participants
Placebo- Single DoseSafety and Tolerability of N91115Subjects with at least one study treatment TEAE1 participants

Source: ClinicalTrials.gov · Data processed: Mar 10, 2026