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

Amphastar Pharmaceuticals

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Asthma

Treatments: Drug: E004 (epinephrine inhalation aerosol), 160 mcg; Drug: E004 (epinephrine inhalation aerosol), 90 mcg/actuation; Drug: E004 Placebo; Drug: E004 (epinephrine inhalation aerosol), 125 mcg; Drug: epinephrine inhalation aerosol, CFC propelled; Drug: E004 (epinephrine inhalation aerosol), 220 mcg

Study type: Interventional

Funder types: Industry

Identifiers

NCT01025648

API-E004-CL-A

Details and patient eligibility

About

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.

Enrollment: 9 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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9 participants in 6 patient groups, including a placebo group

T1 - E004 90 mcg/actuation

Experimental group

Description:

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

Treatment:

Drug: E004 (epinephrine inhalation aerosol), 90 mcg/actuation

T2 - E004 125 mcg/actuation

Experimental group

Description:

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

Treatment:

Drug: E004 (epinephrine inhalation aerosol), 125 mcg

T3 - 160 mcg/actuation

Experimental group

Description:

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

Treatment:

Drug: E004 (epinephrine inhalation aerosol), 160 mcg

T4 - 220 mcg/actuation

Experimental group

Description:

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

Treatment:

Drug: E004 (epinephrine inhalation aerosol), 220 mcg

A - Active control

Active Comparator group

Description:

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

Treatment:

Drug: epinephrine inhalation aerosol, CFC propelled

P, Placebo HFA

Placebo Comparator group

Description:

E004 placebo single treatment with 2 inhalations

Treatment:

Drug: E004 Placebo