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

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT01025648
• Date of registration: 01/12/2009
• Primary sponsor: Amphastar Pharmaceuticals, Inc.
• Public title: Randomized, Placebo/Active Controlled Crossover, Dose-ranging Study for Initial Evaluation of Safety and Efficacy in Asthma Patients.
• Scientific title: Phase 1/2 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
• Date of first enrolment: December 2009
• Target sample size: 24
• Recruitment status: Withdrawn
• URL: http://clinicaltrials.gov/show/NCT01025648
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: Jim Shi, M.D., Ph.D.
• Affiliation: Amphastar Pharmaceuticals, Inc.

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Clinical diagnosis of intermittent, or mild-to-moderate persistent, asthma for at
least 6 months before Screening, and having used inhaled epinephrine or ß-agonist(s)
for asthma control;

2. Demonstrating a baseline forced expiratory volume in 1 second (FEV1) at 50-90 percent
of predicted normal at Screening;

3. 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;

4. Females of child-bearing potential must be non-pregnant, non-lactating, and
practicing a clinically acceptable form of birth control;

5. Demonstration of proficiency in the use of a MDI inhaler after training;

6. 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.



Age minimum: 18 Years
Age maximum: 55 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Asthma

Intervention(s)

Drug: epinephrine inhalation aerosol, 125 mcg

Drug: epinephrine inhalation aerosol, 160 mcg

Drug: epinephrine inhalation aerosol, 220 mcg

Drug: epinephrine inhalation aerosol, 90 mcg/actuation

Drug: epinephrine inhalation aerosol, CFC propelled

Drug: Placebo HFA

Primary Outcome(s)

The AUC of post-dose FEV1 percentage changes (?%) from the Pre-dose baseline. The primary analysis of the primary endpoint is the difference of ?% 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(s)

AUC of FEV1 volume post-dose changes (? Volume) from the Pre-dose baseline. [Time Frame: 306 minutes post dose]

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]

Dose response relationship of Epinephrine HFA-MDI, analyzed using efficacy data from all E004 doses. [Time Frame: 360 minutes post dose]

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]

Monitoring of adverse drug events (ADE) [Time Frame: Ongoing through End of Study]

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]

Response Rate of responders who demonstrate 12.0 percent or greater FEV1 changes from the Pre-dose baseline. [Time Frame: 360 minutes post dose]

The peak bronchodilator response (Fmax), defined as the maximum post-dose FEV1 percent change. [Time Frame: 360 minutes post dose]

The time to peak FEV1 effect (Tmax), defined as the time of Fmax. [Time Frame: 360 minutes post dose]

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]

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]

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]

Secondary ID(s)

API-E004-CL-A

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Armstrong Pharmaceuticals, Inc.