Relative Bioavailability of Tiotropium and Salmeterol After Inhalation of a Fixed Combined Dose Compared to Monocomponents in Healthy Male Volunteers

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Serevent® Diskus®; Drug: Tiotropium/Salmeterol; Drug: Spiriva®

Study type: Interventional

Funder types: Industry

Identifiers

NCT02254174

1184.11

Details and patient eligibility

About

Assessment of the relative bioavailability of a fixed dose combination of tiotropium and salmeterol compared to a free dose combination of the marketed products of tiotropium and salmeterol (Spiriva® and Serevent® Diskus®).

Assessment of the relative bioavailability of a fixed dose combination of tiotropium and salmeterol compared to tiotropium and salmeterol administered as individual mono substances from the marketed products.

Assessment of safety and tolerability of the fixed combination of tiotropium and salmeterol in a PE (Polyethylene) capsule administered via the HandiHaler® 2

Enrollment: 36 patients

Sex: Male

Ages: 21 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Healthy male based upon a complete medical history, including the physical examination, regarding vital signs (blood pressure (BP), pulse rate (PR)), 12-lead ECG (electrocardiogram) measurement, and clinical laboratory tests. There is no finding deviating from normal and of clinical relevance.

   There is no evidence of a clinically relevant concomitant disease

2. Age ≥21 and ≤50 years

3. BMI ≥18.5 and <30 kg/m2 (Body Mass Index)

4. Signed and dated written informed consent prior to admission to the study in accordance with GCP (Good Clinical Practice) and the local legislation

Exclusion criteria

1. Any finding of the medical examination (including BP, PR, and ECG measurements) deviating from normal and of clinical relevance

2. Evidence of a clinically relevant concomitant disease

3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders

4. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders

5. History of relevant orthostatic hypotension, fainting spells or blackouts

6. Chronic or relevant acute infections

7. History of relevant allergy/hypersensitivity (including allergy to the drug or its excipients) as judged clinically relevant by the investigator

8. Intake of drugs with a long half-life (>24 hours) within at least 1 month or less than 10 half-lives of the respective drug prior to randomisation

9. 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 enrolment in the study or during the study

10. Participation in another trial with an investigational drug within 2 months prior to randomisation

11. Smoker (>10 cigarettes or >3 cigars or >3 pipes/day)

12. Inability to refrain from smoking on trial days as judged by the investigator

13. Alcohol abuse (more than 40 g alcohol a day)

14. Drug abuse

15. Blood donation (more than 100 mL blood within 4 weeks prior to randomisation or during the trial)

16. Excessive physical activities within 1 week prior to randomisation or during the trial

17. Any laboratory value outside the reference range that is of clinical relevance

18. Inability to comply with dietary regimen of the study centre

    The following exclusion criteria are specific for this study due to the known class side effect profile of ß2-mimetics:

19. Asthma or history of pulmonary hyperreactivity

20. Hyperthyrosis

21. Allergic rhinitis in need of treatment

22. Clinically relevant cardiac arrhythmia

23. Paroxysmal tachycardia (>100 beats per minute)

    The following exclusion criteria are specific for this study due to the known class side effect profile of tiotropium:

24. Hypersensitivity to tiotropium and/or related drugs of this class

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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36 participants in 4 patient groups

Tiotropium/Salmeterol

Experimental group

Treatment:

Drug: Tiotropium/Salmeterol

Serevent® Diskus®

Active Comparator group

Treatment:

Drug: Serevent® Diskus®

Spiriva®

Active Comparator group

Treatment:

Drug: Spiriva®

Spiriva® and Serevent® Diskus®

Active Comparator group

Treatment:

Drug: Serevent® Diskus®

Drug: Spiriva®