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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 5 mg/N6022 | Active Comparator | Injectable formulation, given at doses per cohort of 5 mg given QD each day over 7 days. |
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| Placebo | Placebo Comparator | Injectable formulation normal saline |
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| 10mg/N6022 | Active Comparator | Injectable formulation, given at doses of 10 mg given QD each day over 7 days. |
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| 20mg/N6022 | Active Comparator | Injectable formulation, given at doses per cohort of 20 mg given QD each day over 7 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 5 mg/N6022 | Drug | Intravenous formulation, given at doses of 5 mg once each day over 7 days. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety of Escalating Multiple Doses of N6022 in Healthy Subjects | Safety variables (adverse events, vital signs, physical examination, telemetry, 12-lead ECG, infusion site reactions, O2 saturation, and clinical laboratory assessments) | Over 7 days |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics of N6022 | N6022 AUC0-tau measurements from Day 1 | Day 1, 24 hours |
| Pharmacokinetics of N6022 Over 7 Days | Analysis of N6022 AUC0-tau values from Study Day 7 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ronald Goldwater, MDCM, MSc(A) | Parexel | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Parexel International | Baltimore | Maryland | 21225 | United States |
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Recruitment occurred between 06April2011 and 09August2011. This study was done at a single Phase 1 site.
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| ID | Title | Description |
|---|---|---|
| FG000 | 5 mg/N6022 | Active Group- 5 mg by IV administration (5 mg/minute) |
| FG001 | Placebo | Non-Active |
| FG002 | 10 mg/N6022 | Active Group- 10 mg by IV administration (5 mg/minute) |
| FG003 | 20 mg/N6022 | Active Group- 20 mg by IV administration (5 mg/minute) |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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|
All randomized subjects who received any amount of IMP
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 | N6022 - Active 5 mg |
| BG001 | Cohort 2 | N6022 - Active 10 mg |
| BG002 |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Safety of Escalating Multiple Doses of N6022 in Healthy Subjects | Safety variables (adverse events, vital signs, physical examination, telemetry, 12-lead ECG, infusion site reactions, O2 saturation, and clinical laboratory assessments) | Any subject that received any dose of N6022 or placebo. | Posted | Number | participants | Over 7 days |
|
7 Days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1 | N6022 - Active 5 mg |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ventricular Arrythmia | Cardiac disorders | MedDRA (Unspecified) | Systematic Assessment | Isolated episode, non-sustained |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Janice M Troha | N30 Pharmaceuticals Inc. | 720-945-7714 | janice.troha@n30pharma.com |
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| ID | Term |
|---|---|
| C571360 | N6022 |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
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| Placebo | Drug | Same administration procedures as active |
|
|
| 10mg/N6022 | Drug | Intravenous formulation given at doses of 10 mg once each day over 7 days. |
|
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| 20mg/N6022 | Drug | Intravenous formulation given at doses of 20 mg once each day over 7 days. |
|
|
| Day 7, 24 hours |
| Pharmacokinetics of N6022 on Study Day 1 | Analysis of N6022 Cmax values on Study Day 1 | Day 1, 24 hours |
| Pharmacokinetics of N6022 Cmax Values on Study Day 7 | Pharmacokinetic Analysis of N6022 Cmax values on Study Day 7 | Day 7, 24 hours |
| Cohort 3 |
N6022 - Active 20 mg |
| BG003 | Placebo | Non-Active |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
N6022 - Active 20 mg |
| OG003 | Placebo | Non-Active |
|
|
| Secondary | Pharmacokinetics of N6022 | N6022 AUC0-tau measurements from Day 1 | Any subject that completed N6022 or placebo PK sampling | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Day 1, 24 hours |
|
|
|
| Secondary | Pharmacokinetics of N6022 Over 7 Days | Analysis of N6022 AUC0-tau values from Study Day 7 | N6022 AUC0-tau values from Study Day 7 | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Day 7, 24 hours |
|
|
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| Secondary | Pharmacokinetics of N6022 on Study Day 1 | Analysis of N6022 Cmax values on Study Day 1 | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Day 1, 24 hours |
|
|
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| Secondary | Pharmacokinetics of N6022 Cmax Values on Study Day 7 | Pharmacokinetic Analysis of N6022 Cmax values on Study Day 7 | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Day 7, 24 hours |
|
|
|
| 0 |
| 7 |
| 7 |
| 7 |
| EG001 | Cohort 2 | N6022 Active - 10 mg | 0 | 6 | 2 | 6 |
| EG002 | Cohort 3 | N6022 - Active 20 mg | 0 | 6 | 4 | 6 |
| EG003 | Placebo | Non-Active | 0 | 6 | 5 | 6 |
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| Abdominal Pain | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Fatigue | General disorders | MedDRA (Unspecified) | Systematic Assessment | administration and site conditions |
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| Injection Site Extravasation | General disorders | MedDRA (Unspecified) | Systematic Assessment | administration and site conditions |
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| Pain | General disorders | MedDRA (Unspecified) | Systematic Assessment | administration and site conditions |
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| Otitis Externa | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
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| Musculosketetal Pain | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Vessel Puncture Site Hematoma | General disorders | MedDRA (Unspecified) | Systematic Assessment | administration and site conditions |
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| Upper Respiratory tract Infection | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
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| Traumatic Hematoma | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Systematic Assessment |
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| Abdominal Discomfort | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Blood Magnesium Abnormal | Investigations | MedDRA (Unspecified) | Systematic Assessment |
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| Pre-syncope | Nervous system disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Vertigo Positional | Ear and labyrinth disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Aphthous Stomatitis | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Injection Site Induration | General disorders | MedDRA (Unspecified) | Systematic Assessment | administration and site conditions |
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| Injection Site Pain | General disorders | MedDRA (Unspecified) | Systematic Assessment | administration and site conditions |
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| Pain in Extremity | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Contact Dermatitis | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Phlebitis Superficial | Vascular disorders | MedDRA (Unspecified) | Systematic Assessment |
|
The investigator agrees with the use of results of the clinical study for the purposes of national and international registration, publication, and information for medical and pharmaceutical professionals. If necessary, the competent authorities will be notified of the investigator's name, address, qualifications, and extent of involvement. An investigator shall not publish any data (poster, abstract, paper, etc.) without having consulted with the Sponsor in advance.