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

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

Detailed Description
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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.

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

Conditions
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Healthy

Intervention / Treatment
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* Drug: N91115
* Drug: Placebo
* Drug: N91115
* Drug: Placebo-Day 1 only


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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N91115, GSNORi, SNO, Cavosonstat