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Randomized, Placebo/Active Crossover Dose-ranging Study for Safety and Efficacy in Asthma Patients.

Primary Purpose

Asthma

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
E004 (epinephrine inhalation aerosol), 90 mcg/actuation
E004 Placebo
E004 (epinephrine inhalation aerosol), 125 mcg
E004 (epinephrine inhalation aerosol), 220 mcg
epinephrine inhalation aerosol, CFC propelled
E004 (epinephrine inhalation aerosol), 160 mcg
Sponsored by
Amphastar Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Asthma focused on measuring Mild to Moderate Asthma, Dyspnea, Wheezing, Status Asthmaticus

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Generally healthy, male and female adults aged 18 to 55 years at Screening.
  2. Clinical diagnosis of intermittent, or mild-to-moderate persistent, asthma for at least 6 months before Screening, and having used inhaled epinephrine or β-agonist(s) for asthma control;
  3. Demonstrating a baseline forced expiratory volume in 1 second (FEV1) at 50-90 percent of predicted normal at Screening;
  4. Demonstrating a 12.0 percent or greater airway reversibility in FEV1 within 30 min after inhaling 2 actuations of Epinephrine CFC-MDI (440 mcg Epinephrine base) at Screening;
  5. Females of child-bearing potential must be non-pregnant, non-lactating, and practicing a clinically acceptable form of birth control;
  6. Demonstration of proficiency in the use of a MDI inhaler after training;
  7. Having properly consented to participate in the trial.

Exclusion Criteria:

  1. A smoking history of 10 or more pack-years, or having smoked within 6 months prior to Screening;
  2. Upper respiratory tract infections within 2 wk, or lower respiratory tract infection within 4 wk, prior to Screening;
  3. Asthma exacerbations that required emergency care or hospitalized treatment, within 4 wk prior to Screening;
  4. Any current or recent respiratory conditions that, per investigator discretion, might significantly affect pharmacodynamic response to the study drugs, including cystic fibrosis, bronchiectasis, tuberculosis, emphysema, and other significant respiratory diseases besides asthma;
  5. Concurrent clinically significant cardiovascular, hematological, renal, neurologic, hepatic, endocrine (including diabetes), psychiatric, neoplastic or other illnesses that in the opinion of the investigator could impact on the conduct, safety and evaluation of the study;
  6. Known intolerance or hypersensitivity to any of the study MDI ingredients (i.e., Epinephrine, HFA-134a, CFC-12, CFC-114, polysorbate-80, ethanol, thymol, nitric acid and ascorbic acid);
  7. Use of prohibited drugs or failure to observe the drug washout restrictions;
  8. Having been on other investigational drug/device studies in the last 30 days prior to Screening.

Sites / Locations

  • Amphastar Site 0001
  • Amphastar Site 0003

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Active Comparator

Placebo Comparator

Arm Label

T1 - E004 90 mcg/actuation

T2 - E004 125 mcg/actuation

T3 - 160 mcg/actuation

T4 - 220 mcg/actuation

A - Active control

P, Placebo HFA

Arm Description

T1 - E004 (epinephrine inhalation aerosol) 90 mcg/actuation - treatment by 2 actuations of E004 at 90 mcg/actuation

E004 (epinephrine inhalation aerosol), 125 mcg, 2 actuations

E004 (epinephrine inhalation aerosol), 160 mcg - E004 (epinephrine inhalation aerosol), 160 mcg/ actuation, 2 actuations

E004 (epinephrine inhalation aerosol), 220 mcg - 220 mcg/actuation, 2 actuations

epinephrine inhalation aerosol, CFC propelled 220 mcg Epinephrine Inhalation Aerosol, CFC-MDI, 2 actuations

E004 placebo single treatment with 2 inhalations

Outcomes

Primary Outcome Measures

The AUC of post-dose FEV1 percentage changes (Δ%) from the Pre-dose baseline. The primary analysis of the primary endpoint is the difference of Δ% FEV1, compared between the E004 treatment arms (T1, T2, T3 and T4) and the Placebo control (Arm P).

Secondary Outcome Measures

Dose response relationship of Epinephrine HFA-MDI, analyzed using efficacy data from all E004 doses.
AUC of FEV1 volume post-dose changes (Δ Volume) from the Pre-dose baseline.
Time to onset of bronchodilator effect, determined by linear interpolation as the point where FEV1 first reaches 12.0 percent from the Pre-dose Baseline.
The peak bronchodilator response (Fmax), defined as the maximum post-dose FEV1 percent change.
The time to peak FEV1 effect (Tmax), defined as the time of Fmax.
Duration of effect, calculated as the total duration of bronchodilator effects when post-dose FEV1 reaches and stays 12.0 percent above the Pre-dose Baseline.
Response Rate of responders who demonstrate 12.0 percent or greater FEV1 changes from the Pre-dose baseline.
Vital signs, i.e., blood pressure and heart rate,at Screening baseline and 15(±5) min post dosing for reversibility
Vital signs, i.e., blood pressure (SBP/DBP) and heart rate (HR), at: Pre-dose baseline, and 15(±5) min and 360(±15) post-dose, at each Study Visit.
Post-dose 20(±5) min ECG recordings (Routine and QT, QTc analysis) at each Study Visit, compared to the Screening baseline recording.
Data for physical examinations, CBC, serum comprehensive metabolic panel, and urinalysis for all subjects, and urinary pregnancy test for women of child-bearing potential
Monitoring of adverse drug events (ADE)

Full Information

First Posted
December 1, 2009
Last Updated
May 14, 2018
Sponsor
Amphastar Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01025648
Brief Title
Randomized, Placebo/Active Crossover Dose-ranging Study for Safety and Efficacy in Asthma Patients.
Official Title
A Randomized, Double-blinded or Evaluator-blinded, Placebo and Active Controlled, Six-arm, Crossover, Single Dose, Dose-ranging Study, for Initial Evaluation of Safety and Efficacy in Asthma Patients
Study Type
Interventional

2. Study Status

Record Verification Date
May 2018
Overall Recruitment Status
Terminated
Why Stopped
Optimization of protocol
Study Start Date
December 2009 (undefined)
Primary Completion Date
December 2009 (Actual)
Study Completion Date
December 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amphastar Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The main objective of this study is to evaluate the efficacy and safety of the Armstrong's Epinephrine HFA-MDI (E004) formulation, in comparison to the Placebo (Placebo-HFA) and an Active Control (Epinephrine CFC-MDI), and to identify the optimum E004 dose strength(s) for the ensuing pivotal clinical trials. The study will be conducted in adult patients who have intermittent, or mild-to-moderate persistent, asthma, but are otherwise healthy. The bronchodilatory efficacy of E004, is evaluated in terms of post-dose area under the curves (AUC) of FEV1 changes (% and volumes), from the pre-dose baseline values, in comparison to the Placebo Control and the Active Control.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma
Keywords
Mild to Moderate Asthma, Dyspnea, Wheezing, Status Asthmaticus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
9 (Actual)

8. Arms, Groups, and Interventions

Arm Title
T1 - E004 90 mcg/actuation
Arm Type
Experimental
Arm Description
T1 - E004 (epinephrine inhalation aerosol) 90 mcg/actuation - treatment by 2 actuations of E004 at 90 mcg/actuation
Arm Title
T2 - E004 125 mcg/actuation
Arm Type
Experimental
Arm Description
E004 (epinephrine inhalation aerosol), 125 mcg, 2 actuations
Arm Title
T3 - 160 mcg/actuation
Arm Type
Experimental
Arm Description
E004 (epinephrine inhalation aerosol), 160 mcg - E004 (epinephrine inhalation aerosol), 160 mcg/ actuation, 2 actuations
Arm Title
T4 - 220 mcg/actuation
Arm Type
Experimental
Arm Description
E004 (epinephrine inhalation aerosol), 220 mcg - 220 mcg/actuation, 2 actuations
Arm Title
A - Active control
Arm Type
Active Comparator
Arm Description
epinephrine inhalation aerosol, CFC propelled 220 mcg Epinephrine Inhalation Aerosol, CFC-MDI, 2 actuations
Arm Title
P, Placebo HFA
Arm Type
Placebo Comparator
Arm Description
E004 placebo single treatment with 2 inhalations
Intervention Type
Drug
Intervention Name(s)
E004 (epinephrine inhalation aerosol), 90 mcg/actuation
Other Intervention Name(s)
Primatene Mist HFA
Intervention Description
E004 (epinephrine inhalation aerosol), 90 mcg/actuation, 2 actuations, single dose crossover, 1 -14 day washout period
Intervention Type
Drug
Intervention Name(s)
E004 Placebo
Intervention Description
E004 Placebo, 0 mcg epinephrine inhalation aerosol, 2 actuations, 1 -14 day washout period
Intervention Type
Drug
Intervention Name(s)
E004 (epinephrine inhalation aerosol), 125 mcg
Other Intervention Name(s)
Primatene Mist HFA
Intervention Description
E004 (epinephrine inhalation aerosol), 125 mcg/actuation, 2 actuations, single dose crossover, 1 - 14 day washout period
Intervention Type
Drug
Intervention Name(s)
E004 (epinephrine inhalation aerosol), 220 mcg
Other Intervention Name(s)
Primatene Mist HFA
Intervention Description
E004 (epinephrine inhalation aerosol), 220 mcg - 220 mcg/actuation, 2 actuations, single dose crossover, 1 - 14 days washout period
Intervention Type
Drug
Intervention Name(s)
epinephrine inhalation aerosol, CFC propelled
Other Intervention Name(s)
Primatene Mist
Intervention Description
epinephrine inhalation aerosol, 220 mcg/actuation, 2 actuations, single dose crossover, 1 - 14 day washout period
Intervention Type
Drug
Intervention Name(s)
E004 (epinephrine inhalation aerosol), 160 mcg
Other Intervention Name(s)
Primatene Mist HFA
Intervention Description
E004 (epinephrine inhalation aerosol), 160 mcg/actuation, 2 actuations, single dose crossover, 1 - 14 days washout period
Primary Outcome Measure Information:
Title
The AUC of post-dose FEV1 percentage changes (Δ%) from the Pre-dose baseline. The primary analysis of the primary endpoint is the difference of Δ% FEV1, compared between the E004 treatment arms (T1, T2, T3 and T4) and the Placebo control (Arm P).
Time Frame
360 minutes post-dose
Secondary Outcome Measure Information:
Title
Dose response relationship of Epinephrine HFA-MDI, analyzed using efficacy data from all E004 doses.
Time Frame
360 minutes post dose
Title
AUC of FEV1 volume post-dose changes (Δ Volume) from the Pre-dose baseline.
Time Frame
360 minutes post dose
Title
Time to onset of bronchodilator effect, determined by linear interpolation as the point where FEV1 first reaches 12.0 percent from the Pre-dose Baseline.
Time Frame
30 (±5) min post-dose
Title
The peak bronchodilator response (Fmax), defined as the maximum post-dose FEV1 percent change.
Time Frame
360 minutes post dose
Title
The time to peak FEV1 effect (Tmax), defined as the time of Fmax.
Time Frame
360 minutes post dose
Title
Duration of effect, calculated as the total duration of bronchodilator effects when post-dose FEV1 reaches and stays 12.0 percent above the Pre-dose Baseline.
Time Frame
360 minutes post dose
Title
Response Rate of responders who demonstrate 12.0 percent or greater FEV1 changes from the Pre-dose baseline.
Time Frame
360 minutes post dose
Title
Vital signs, i.e., blood pressure and heart rate,at Screening baseline and 15(±5) min post dosing for reversibility
Time Frame
screening and 15 minutes post dose
Title
Vital signs, i.e., blood pressure (SBP/DBP) and heart rate (HR), at: Pre-dose baseline, and 15(±5) min and 360(±15) post-dose, at each Study Visit.
Time Frame
360 minutes post dose
Title
Post-dose 20(±5) min ECG recordings (Routine and QT, QTc analysis) at each Study Visit, compared to the Screening baseline recording.
Time Frame
20 minutes post dose
Title
Data for physical examinations, CBC, serum comprehensive metabolic panel, and urinalysis for all subjects, and urinary pregnancy test for women of child-bearing potential
Time Frame
Screening and end of study
Title
Monitoring of adverse drug events (ADE)
Time Frame
Ongoing through End of Study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Generally healthy, male and female adults aged 18 to 55 years at Screening. Clinical diagnosis of intermittent, or mild-to-moderate persistent, asthma for at least 6 months before Screening, and having used inhaled epinephrine or β-agonist(s) for asthma control; Demonstrating a baseline forced expiratory volume in 1 second (FEV1) at 50-90 percent of predicted normal at Screening; Demonstrating a 12.0 percent or greater airway reversibility in FEV1 within 30 min after inhaling 2 actuations of Epinephrine CFC-MDI (440 mcg Epinephrine base) at Screening; Females of child-bearing potential must be non-pregnant, non-lactating, and practicing a clinically acceptable form of birth control; Demonstration of proficiency in the use of a MDI inhaler after training; Having properly consented to participate in the trial. Exclusion Criteria: A smoking history of 10 or more pack-years, or having smoked within 6 months prior to Screening; Upper respiratory tract infections within 2 wk, or lower respiratory tract infection within 4 wk, prior to Screening; Asthma exacerbations that required emergency care or hospitalized treatment, within 4 wk prior to Screening; Any current or recent respiratory conditions that, per investigator discretion, might significantly affect pharmacodynamic response to the study drugs, including cystic fibrosis, bronchiectasis, tuberculosis, emphysema, and other significant respiratory diseases besides asthma; Concurrent clinically significant cardiovascular, hematological, renal, neurologic, hepatic, endocrine (including diabetes), psychiatric, neoplastic or other illnesses that in the opinion of the investigator could impact on the conduct, safety and evaluation of the study; Known intolerance or hypersensitivity to any of the study MDI ingredients (i.e., Epinephrine, HFA-134a, CFC-12, CFC-114, polysorbate-80, ethanol, thymol, nitric acid and ascorbic acid); Use of prohibited drugs or failure to observe the drug washout restrictions; Having been on other investigational drug/device studies in the last 30 days prior to Screening.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jim Shi, M.D., Ph.D.
Organizational Affiliation
Amphastar Pharmaceuticals, Inc.
Official's Role
Study Chair
Facility Information:
Facility Name
Amphastar Site 0001
City
San Jose
State/Province
California
ZIP/Postal Code
95117
Country
United States
Facility Name
Amphastar Site 0003
City
Stockton
State/Province
California
ZIP/Postal Code
95207
Country
United States

12. IPD Sharing Statement

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Randomized, Placebo/Active Crossover Dose-ranging Study for Safety and Efficacy in Asthma Patients.

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