Pharmacokinetics of Salmeterol (Serevent®) After Inhalation With Metered Dose Inhaler (MDI) and Diskus® in Healthy Male Volunteers

• ClinicalTrials.gov Identifier: NCT02254226
• Recruitment Status: Completed
• First Posted: October 1, 2014
• Last Update Posted: October 1, 2014
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

Study Description

Brief Summary:

1. To compare the systemic drug exposure of 100 μg Serevent ® Diskus ® with that of 50 μg Serevent ® MDI with sufficient precision so that in combination with a second trial it can be demonstrated that the systemic drug exposure of a new formulation of salmeterol xinafoate is not superior to that of Serevent ® MDI
2. To test a system of ordered null hypotheses regarding the exposure of two dose levels of Serevent ® Diskus ® and Serevent ® MDI
3. To get data about the systemic drug exposure of 25 μg Serevent ® MDI and of 50 μg Serevent ® Diskus ®

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: Salmeterol Diskus low; Drug: Salmeterol Diskus high; Drug: Salmeterol MDI low; Drug: Salmeterol MDI high	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomised, Open-label Four-way Crossover Study to Evaluate Pharmacokinetics of Salmeterol (Serevent®) After Inhalation of a 25 μg and 50 μg Single Dose (Metered Dose Inhaler) and a 50 μg and 100 μg Single Dose (Diskus®) in Healthy Male Volunteers
• Study Start Date: November 2004
• Actual Primary Completion Date: January 2005

Arms and Interventions

Arm	Intervention/treatment
Experimental: Salmeterol MDI low	Drug: Salmeterol MDI low
Active Comparator: Salmeterol MDI high	Drug: Salmeterol MDI high
Experimental: Salmeterol Diskus low	Drug: Salmeterol Diskus low
Experimental: Salmeterol Diskus high	Drug: Salmeterol Diskus high

Outcome Measures

Primary Outcome Measures :

1. AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) [ Time Frame: Up to 6 hours after drug administration ]
2. Cmax (maximum measured concentration of the analyte in plasma) [ Time Frame: Up to 6 hours after drug administration ]

Secondary Outcome Measures :

1. AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point) [ Time Frame: Up to 6 hours after drug administration ]
2. AUCt1-t2 (Area under the concentration time curve of the analyte in plasma over the time interval t1 to t2) [ Time Frame: Up to 6 hours after inhalation ]
3. tmax (time from dosing to the maximum concentration of the analyte in plasma) [ Time Frame: Up to 6 hours after drug administration ]
4. λz (terminal rate constant in plasma) [ Time Frame: Up to 6 hours after drug administration ]
5. t½ (terminal half-life of the analyte in plasma) [ Time Frame: Up to 6 hours after drug administration ]
6. MRTinh (mean residence time of the analyte in the body after inhalational administration) [ Time Frame: Up to 6 hours after drug administration ]
7. CL/F (apparent clearance of the analyte in the plasma after extravascular administration) [ Time Frame: Up to 6 hours after drug administration ]
8. Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) [ Time Frame: Up to 6 hours after drug administration ]
9. Aet1-t2 (amount of analyte that was eliminated in urine from the time interval t1 to t2) [ Time Frame: Up to 6 hours after inhalation ]
10. fet1-t2 (fraction of administered drug excreted unchanged in urine from time point t1 to t2) [ Time Frame: Up to 6 hours after inhalation ]
11. CLR,t1-t2 (renal clearance of the analyte in plasma from the time point t1 to t2) [ Time Frame: Up to 6 hours after inhalation ]
12. Number of participants with abnormal findings in physical examination [ Time Frame: Up to 15 days after last drug administration ]
13. Number of participants with clinically significant changes in vital signs [ Time Frame: Up to 15 days after last drug administration ]
14. Number of participants with abnormal findings in ECG [ Time Frame: Up to 15 days after last drug administration ]
15. Number of participants with abnormal changes in clinical laboratory parameters [ Time Frame: Up to 15 days after last drug administration ]
16. Number of participants with adverse events [ Time Frame: Up to 15 days after last drug administration ]

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 50 Years (Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Healthy males 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 ECG (electrocardiogram) , clinical laboratory tests 1.1 No finding deviating from normal and of clinical relevance 1.2 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.

Exclusion Criteria:

1. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
2. Surgery of gastrointestinal tract (except appendectomy)
3. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
4. History of relevant orthostatic hypotension, fainting spells or blackouts.
5. Chronic or relevant acute infections
6. History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator
7. 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 administration or during the trial.
8. 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.
9. Participation in another trial with an investigational drug within 2 months prior to administration or during the trial.
10. Smoker (more than 10 cigarettes or three cigars or three pipes per day)
11. Inability to refrain from smoking on trial days
12. Alcohol abuse (more than 60 g/day)
13. Drug abuse
14. Blood donation (more than 100 mL within 4 weeks prior to administration or during the trial)
15. Excessive physical activities (within 1 week prior to administration or during the trial)
16. Any laboratory value outside the reference range that is of clinical relevance

17. Inability to comply with dietary regimen of study centre

    Exclusion criterion specific for this study:

18. Asthma or history of pulmonary hyperreactivity
19. Allergy / hypersensitivity to Lactose monohydrate
20. Hyperthyrosis
21. Allergic rhinitis in need of treatment
22. Cardiac arrhythmia
23. Paroxysmal tachycardia (> 100 beats per minute)
24. Aortic stenosis

Contacts and Locations

No Contacts or Locations Provided

More Information

Additional Information:

Related Info 

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT02254226
• Other Study ID Numbers: 1184.8
• First Posted: October 1, 2014
• Last Update Posted: October 1, 2014
• Last Verified: September 2014

Additional relevant MeSH terms:

Respiratory Aspiration; Respiration Disorders; Respiratory Tract Diseases; Pathologic Processes; Salmeterol Xinafoate; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action