Conditions: Healthy
Keywords: N6022, GSNORi
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 25
Healthy volunteers: yes

Brief summary:
This Phase 1 study will evaluate multiple doses across a range that has been found to be effective in mouse models of asthma and safe in one Phase 1 clinical trial. It is intended to provide evidence of the tolerability of multiple doses as well as provide information on the Pharmacokinetic (PK) and metabolism of N6022 in humans.

Detailed description:
This is a double-blind, randomized, placebo-controlled, multiple ascending dose study, in at least three ascending cohorts. Twenty-four subjects will be enrolled initially in the first three cohorts, with up to 40 subjects to be enrolled overall if additional cohorts are required to reach the maximum tolerated dose (MTD). The cohorts will be enrolled in two groups of 4 each with approximately 7 days between groups to conduct safety monitoring committee review for approval to proceed to the second group in the cohort. Eight subjects will be enrolled per cohort, randomized 3:1 to N6022: placebo. Each subject will undergo screening (Day -28 to Day -2) and, if eligible, they will be instructed to begin a low-nitrate diet on Day -4. Subjects will return to the clinical site on Day -1, and eligibility will be reconfirmed. Eligible subjects will receive a dose of investigational medicinal product (\[IMP\], N6022 or placebo) by intravenous (IV) infusion on study Days 1 through 7 and will be followed for safety, PK, and PD until discharge on the morning of Day 8. Subjects will return to the clinic for a follow-up visit on Day 15 (± 1 day) and will be contacted via telephone on Day 28 (± 1 day) for the end-of-study safety follow-up visit. Participation of an individual subject may last approximately 56 days from the time of screening until the end-of-study follow-up visit.

A Safety Monitoring Committee (SMC) will review the safety data in each cohort after the Day 15 Follow-up visit, before proceeding to the next ascending dose cohort, modifying the dose, repeating a dose, or stopping the study according to the stopping rules outlined in the protocol.

Arms:
arm 1: Injectable formulation, given at doses per cohort of 5 mg given QD each day over 7 days. arm 2: Injectable formulation normal saline arm 3: Injectable formulation, given at doses of 10 mg given QD each day over 7 days. arm 4: Injectable formulation, given at doses per cohort of 20 mg given QD each day over 7 days.

Interventions: intervention 1: 5 mg/N6022 intervention 2: Placebo intervention 3: 10mg/N6022 intervention 4: 20mg/N6022
Intervention descriptions: intervention 1: Intravenous formulation, given at doses of 5 mg once each day over 7 days. intervention 2: Same administration procedures as active intervention 3: Intravenous formulation given at doses of 10 mg once each day over 7 days. intervention 4: Intravenous formulation given at doses of 20 mg once each day over 7 days.

Protocol document: