Safety, Tolerability and Pharmacokinetics of the Fixed Dose Combination of BI 1744 CL Plus BI 54903 XX Via Respimat® B Versus the Free Combination of BI 1744 CL Via Respimat® A and BI 54903 XX Via Respimat® B in Healthy Male and Female Volunteers

Boehringer Ingelheim

Status and phase

Completed

Phase 1

Conditions

Healthy

Treatments

Drug: Placebo

Drug: BI 1744 CL

Drug: BI 54903 XX

Drug: BI 1744 CL + BI 54903 XX FDC

Study type

Interventional

Funder types

Industry

Identifiers

NCT02220660

1256.2

Details and patient eligibility

About

The primary objective of this study was to compare the systemic exposure of BI 1744 BS and CD 1857 XX (the active metabolite of the pro-drug BI 54903 XX) at steady state following inhalation of the fixed dose combination (FDC) BI 1744 CL plus BI 54903 XX (as ethanolic solution for inhalation, EIS) with the systemic exposure following inhalation of the free dose combination of BI 1744 CL (as aqueous solution for inhalation, AIS) and BI 54903 XX (EIS), respectively, when administered once-daily via Respimat® Inhaler (Respimat® A for AIS and Respimat® B for EIS) for 14 days in healthy volunteers. Secondary objectives were: to compare exposure to BI 1744 BS and CD 1857 XX after a single dose of the BI 1744 CL/BI 54903 XX FDC and the free dose combination, respectively; to compare exposure to BI 54903 XX after a single dose and at steady state after multiple doses of the BI 1744 CL/BI 54903 XX fixed dose combination and the free dose combination, respectively; to compare the safety and tolerability of BI 1744 CL and BI 54903 XX when administered as BI 1744 CL/BI 54903 XX fixed dose combination and as the free dose combination, respectively.

Enrollment

32 patients

Sex

All

Ages

21 to 50 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Healthy males and females according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (Blood pressure (BP), Pulse rate (PR)), 12-lead Electrocardiogram (ECG), clinical laboratory tests
Age >= 21 and <= 50 years
BMI >= 18.5 and <= 29.9 kg/m2
Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation

Exclusion criteria

Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance
Any evidence of a clinically relevant concomitant disease
Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
Surgery of the gastrointestinal tract (except appendectomy)
Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
History of relevant orthostatic hypotension, fainting spells or blackouts
Chronic or relevant acute infections
History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
Intake of drugs with a long half-life (> 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial
Use of drugs which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial
Participation in another trial with an investigational drug within two months prior to administration or during the trial
Smoker (> 10 cigarettes or > 3 cigars or > 3 pipes/day)
Inability to refrain from smoking on trial days
alcohol abuse (more than 40 g/day)
Drug abuse
Blood donation (> 100 mL within four weeks prior to administration or during the trial)
Excessive physical activities (within one week prior to administration or during the trial)
Any laboratory value outside the reference range that is of clinical relevance
Inability to comply with dietary regimen of trial site

For female Subjects:

Pregnancy
Positive pregnancy test
No adequate contraception (adequate contraception e.g. sterilization, intrauterine pessary (IUP), oral contraceptives)
Inability to maintain this adequate contraception during the whole study period
Lactation period

Exclusion criteria specific for this study due to the known class side effect profile of ß2-mimetics and inhaled corticosteroids: