Pharmacokinetics of Salmeterol Via HandiHaler® in Healthy Male Volunteers

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Salmeterol capsule - low; Drug: Salmeterol via Serevent® Diskus®; Drug: Salmeterol capsule - high

• Registration Number: NCT02254187
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

The objective of this study is to investigate if the systemic drug exposure of at least 25 μg and perhaps 50 μg salmeterol presented as inhalation powder in PE capsules and administered via HandiHaler® 2 does not exceed that of 50 μg Serevent® Diskus® and to investigate safety and tolerability of salmeterol presented as inhalation powder in PE capsules and administered via HandiHaler® 2

Detailed Description

Not available

Study Timeline

• Study Start: 2005-09
• Primary Completion: 2005-10
• Status Verified: 2014-09
• Study First Submitted: 2014-09-29
• Study First Submitted QC: 2014-09-29
• Last Update Submitted: 2014-09-29
• Study First Posted: 2014-10-01
• Last Update Posted: 2014-10-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 30

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 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 Good Clinical Practice (GCP) and the local legislation

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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 randomization

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 randomization

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

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 60 g alcohol a day)

14. Drug abuse

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

16. Excessive physical activities within 1 week prior to randomization 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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Salmeterol capsule via Handihaler - low	Salmeterol capsule - low	-
Salmeterol via Serevent® Diskus®	Salmeterol via Serevent® Diskus®	-
Salmeterol capsule via Handihaler - high	Salmeterol capsule - high	-

Primary Outcome Measures

Name	Time	Method
AUC0-∞ (area under the concentration-time curve of salmeterol in blood plasma over the time interval from 0 extrapolated to infinity)	up to 8 hours after drug administration
Cmax (maximum measured concentration of salmeterol in blood plasma)	up to 8 hours after drug administration

Secondary Outcome Measures

Name	Time	Method
Number of patients with abnormal changes in laboratory parameters	up to 14 days following the last drug administration
Number of patients with clinically significant changes in vital signs	up to 14 days following the last drug administration	Blood Pressure, Pulse Rate
Assessment of tolerability by investigator on a 4-point scale	14 days following the last drug administration
AUC0-tz (area under the concentration-time curve of salmeterol in plasma over the time interval from 0 to the time of the last quantifiable data point)	up to 8 hours after drug administration
Number of patients with clinically significant changes in 12-lead ECG parameters	up to 14 days following the last drug administration
Number of patients with adverse events	up to 14 days following the last drug administration
t½ (terminal half-life of salmeterol in plasma)	up to 8 hours after drug administration
AUCt1-t2 (area under the concentration time curve of salmeterol in plasma over the time interval t1 to t2)	up to 8 hours after drug administration
tmax (time from dosing to the maximum concentration of salmeterol in plasma)	up to 8 hours after drug administration
MRTih (mean residence time of salmeterol in the body after inhalational administration)	up to 8 hours after drug administration
λz (terminal rate constant in plasma)	up to 8 hours after drug administration
CL/F (apparent clearance of salmeterol in the plasma after extravascular administration)	up to 8 hours after drug administration
Vz/F (apparent volume of distribution during the terminal phase (λz) following an extravascular dose)	up to 8 hours after drug administration