Clinical trial NCT01339897: A Safety Study Evaluating N6022 in Multiple-Ascending Doses in Healthy Subjects
Official title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Multiple-Ascending Dose Study Evaluating the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Effects of N6022 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: N6022, GSNORi
Lead sponsor: Nivalis Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2011-04-21
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Subject is healthy, determined by pre-study medical evaluation (medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory evaluations
2. Subject is a non-smoker (or other nicotine user) as determined by history (no nicotine use over the past year) and a negative urine cotinine test at screening and Day 1.
3. Subject has a body weight \> 50 kg and BMI between 19.5 and 29.5 kg/m2, inclusive, at screening.
4. Subject has systolic BP \> 90 mmHg and diastolic BP \> 50 mmHg at screening or Day-1.

Exclusion Criteria:

1. 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.
2. Subject is a current alcohol abuser and/or has a history of illicit drug abuse within six months of entry.
3. Subject has donated blood (\> 500 mL) or blood products within 56 days prior to Day -1.
4. Subject has a history of bleeding disorders (i.e., severe hemorrhage, melena, rectal bleeding, nosebleeds, bruising, etc.).

Primary outcomes:
measure: Safety of Escalating Multiple Doses of N6022 in Healthy Subjects
timeFrame: Over 7 days
Secondary outcomes:
measure: Pharmacokinetics of N6022
timeFrame: Day 1, 24 hours
measure: Pharmacokinetics of N6022 Over 7 Days
timeFrame: Day 7, 24 hours
measure: Pharmacokinetics of N6022 on Study Day 1
timeFrame: Day 1, 24 hours
measure: Pharmacokinetics of N6022 Cmax Values on Study Day 7
timeFrame: Day 7, 24 hours
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Parexel International
state: Maryland
Study officials:
affiliation: Parexel
name: Ronald Goldwater, MDCM, MSc(A)
role: PRINCIPAL_INVESTIGATOR
References: