Study to Evaluate the Bronchoprotective Effects of a Single Dose of N6022 in Patients With Mild Asthma

A Double-Blind, Randomized, Placebo-Controlled, Two-Period, Cross-Over Study to Evaluate the Bronchoprotective Effects of a Single Dose of N6022 in Patients With Mild Asthma

The purpose of this study is to determine whether a single IV dose of N6022 will have a significant bronchoprotective effect, compared with placebo, during methacholine challenge.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Active; Drug: Placebo

Detailed Description

The number of patients with adverse events measured in both the treated and placebo groups from start of dosing until Day 28 post dose.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • North Carolina
    • Durham, North Carolina, United States, 27704
      • Duke Asthma, Allergy and Airway Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Body mass index (BMI) between 18.5 and 35 kg/m2, inclusive, at screening.
• Patient has a ≤ 5 pack years smoking history and nonsmoking for ≥ one year.
• Documented history of mild bronchial asthma, first diagnosed at least 6 months and currently being treated only with intermittent short-acting beta-agonist therapy by inhalation.
• Pre-bronchodilator FEV1 ≥ 75% of predicted at screening.
• Sensitivity to methacholine with a provocation concentration of methacholine resulting in a 20% fall in FEV1 (PC20 methacholine) of ≤ 8 mg/ml at screening.
• Demonstrated stable lung function during screening with ≤10% variability between two assessments of FEV1 taken at least 7 days apart at approximately the same time of day.

Exclusion Criteria:

• Hypertension at screening is defined as systolic blood pressure (BP) >150 mmHg or diastolic BP > 90mmHg.
• Respiratory tract infection and/or exacerbation of asthma within prior 4 weeks
• History of life-threatening asthma
• Administration of steroids within 4 weeks of the screening visit.
• History of being unable to tolerate or complete MCh testing.
• Blood donation (500 mL) within 3 months of starting the clinical study.
• Tested positive for hepatitis C antibody or hepatitis B surface antigen.
• Tested positive for human immunodeficiency virus (HIV) antibodies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Same as active
Experimental: Active; N6022 - 5 mg	Drug: Active; A 5 mg single dose given intravenously via syringe pump over 1 minute.; Other Names: N6022

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of Change in Methacholine PC20 From Baseline Compared With Placebo 24 Hours After Dosing	These assessments will be recorded at various times over the study - Methacholine PC20 at screening, and at 8, 24, 48 hours postdose and Day 7; spirometry assessments will be recorded at screening, at 2, 4, 6, 8, 24, 48 hours postdose and Day 7.	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of Change in Methacholine PC20 From Baseline Compared With Placebo 8 Hours After Dosing	These assessments will be recorded at various times over the study - Methacholine PC20 at screening, and at 8, 24, 48 hours postdose and Day 7; spirometry assessments will be recorded at screening, at 2, 4, 6, 8, 24, 48 hours postdose and Day 7.	8 hours
To Assess the Safety and Tolerability of Single Dose Administration of N6022 in Patients With Mild Asthma.	Adverse event (AE) reporting will begin upon signing of the consent and will continue until end-of-study (follow up phone call Day 28 +/- 2 days after dosing in the second treatment period). Number of patients with an adverse event will be documented and analyzed.	10 Weeks

Other Outcome Measures

Outcome Measure	Time Frame
Measurement of Change in Methacholine PC20 From Baseline Compared With Placebo After 7 Days of Dosing	7 Days

Collaborators and Investigators

• Sponsor: Nivalis Therapeutics, Inc.
• Investigators: Principal Investigator: Rhohit K Katial, MD, National Jewish Health; Principal Investigator: Monica Kraft, MD, Duke Asthma, Allergy and Airway Center

Publications and helpful links

General Publications

• Que LG, Yang Z, Lugogo NL, Katial RK, Shoemaker SA, Troha JM, Rodman DM, Tighe RM, Kraft M. Effect of the S-nitrosoglutathione reductase inhibitor N6022 on bronchial hyperreactivity in asthma. Immun Inflamm Dis. 2018 Jun;6(2):322-331. doi: 10.1002/iid3.220. Epub 2018 Apr 11.

Helpful Links

• Sponsor

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: March 7, 2011
• First Submitted That Met QC Criteria: March 15, 2011
• First Posted (Estimate): March 16, 2011

Study Record Updates

• Last Update Posted (Estimate): May 5, 2014
• Last Update Submitted That Met QC Criteria: April 17, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: N6022-2A1-02