A randomized, double-blind, double-dummy, safety crossover trial comparing cumulative doses up to 96 microg of formoterol delivered via an HFA-134a-propelled pMDI vs. same cumulative doses of formoterol DPI and placebo in asthmatic patients.
BACKGROUND
Formoterol's effects on the cardiovascular system are well known, but whether these effects are altered by the reformulation of inhalers to replace CFC propellants with HFA propellants is not.


OBJECTIVE
To evaluate the effect of cumulative doses up to 96 microg of formoterol delivered via an HFA-134a-propelled pMDI, on cardiac safety and the QTc interval, compared the same cumulative doses delivered via a DPI, in adult patients with moderate-to-severe asthma.


METHODS
This study was a multicenter, double-blind, double-dummy, placebo-controlled, three-period, crossover trial in which 22 patients with moderate-to-severe asthma received cumulative doses up to 96 microg of formoterol (12 + 12 + 24 + 48 microg) delivered via a pMDI or a dry power inhaler (DPI). Vital signs and fourteen 12-lead ECG measurements were taken at each clinic visit and at 5-10 days after the final drug administration.


RESULTS
An increase from baseline in QTc interval was observed with all formoterol treatment arms in a dose-dependent manner. The maximum increases were 56.3, 62.6 and 25.0 ms for the formoterol pMDI, formoterol DPI and placebo treatments, respectively. Heart rate was increased by 10.7, 14.9 and 6.5 bpm in the pMDI, DPI and placebo groups, respectively. Both formoterol treatments were also associated with a decrease in diastolic blood pressure compared with placebo.


CONCLUSIONS
With respect to cardiovascular safety parameters, the administration of formoterol via a pMDI device is comparable to its delivery via a DPI.
Molimard
M
M
Département de Pharmacologie, CHU de Bordeaux, Université Victor Segalen, Bordeaux, France. mathieu_molimard@pharmaco.u-bordeaux2.fr
Guenolé
E
E
Duvauchelle
T
T
Vicaut
E
E
Lefrançois
G
G
D000328:Adult; D000335:Aerosol Propellants; D001249:Asthma / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography; D004983:Ethanolamines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D000068759:Formoterol Fumarate; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006845:Hydrocarbons, Fluorinated; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D011188:Potassium / Q000097:blood; D011208:Powders
D000335:Aerosol Propellants; D001786:Blood Glucose; D001993:Bronchodilator Agents; D004983:Ethanolamines; D006845:Hydrocarbons, Fluorinated; D011208:Powders; D011188:Potassium; D000068759:Formoterol Fumarate