Asthma
Conditions
Brief summary
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.
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.
Interventions
DRUGActive
A 5 mg single dose given intravenously via syringe pump over 1 minute.
DRUGPlacebo
Same as active
Sponsors
Nivalis Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measurement of Change in Methacholine PC20 From Baseline Compared With Placebo 24 Hours After Dosing | 24 hours | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measurement of Change in Methacholine PC20 From Baseline Compared With Placebo 8 Hours After Dosing | 8 hours | 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. |
| To Assess the Safety and Tolerability of Single Dose Administration of N6022 in Patients With Mild Asthma. | 10 Weeks | 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. |
Other
| Measure | Time frame |
|---|---|
| Measurement of Change in Methacholine PC20 From Baseline Compared With Placebo After 7 Days of Dosing | 7 Days |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active N6022 - 5 mg | 7 |
| Placebo Non-Active | 7 |
| Total | 14 |
Baseline characteristics
| Characteristic | Placebo | Total | Active |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 14 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 13 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 7 Participants | 11 Participants | 4 Participants |
| Region of Enrollment United States | 7 participants | 14 participants | 7 participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 6 Participants | 12 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 14 | 9 / 13 |
| serious Total, serious adverse events | 0 / 14 | 0 / 13 |
Outcome results
Primary
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.
Time frame: 24 hours
Population: Any patient that received a dose of N6022 or placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| N6022 | Measurement of Change in Methacholine PC20 From Baseline Compared With Placebo 24 Hours After Dosing | 1.48 mg/mL | Standard Error 0.093 |
| Placebo | Measurement of Change in Methacholine PC20 From Baseline Compared With Placebo 24 Hours After Dosing | -0.2 mg/mL | Standard Error 0.3 |
Secondary
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.
Time frame: 8 hours
Population: Any patient that received a dose of N6022 or Placebo
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| N6022 | Measurement of Change in Methacholine PC20 From Baseline Compared With Placebo 8 Hours After Dosing | 0.3 mg/mL | Standard Error 0.63 |
| Placebo | Measurement of Change in Methacholine PC20 From Baseline Compared With Placebo 8 Hours After Dosing | -0.54 mg/mL | Standard Error 0.33 |
Secondary
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.
Time frame: 10 Weeks
Population: Any patient that received a dose of N6022 or placebo
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| N6022 | To Assess the Safety and Tolerability of Single Dose Administration of N6022 in Patients With Mild Asthma. | 11 Adverse Events |
| Placebo | To Assess the Safety and Tolerability of Single Dose Administration of N6022 in Patients With Mild Asthma. | 9 Adverse Events |
Other Pre-specified
Measurement of Change in Methacholine PC20 From Baseline Compared With Placebo After 7 Days of Dosing
Time frame: 7 Days
Population: Any patient that received a dose of N6022 or Placebo
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| N6022 | Measurement of Change in Methacholine PC20 From Baseline Compared With Placebo After 7 Days of Dosing | 0.74 mg/mL | Standard Error 1.01 |
| Placebo | Measurement of Change in Methacholine PC20 From Baseline Compared With Placebo After 7 Days of Dosing | -0.38 mg/mL | Standard Error 0.68 |