Bioavailability of Two Sustained-release Theophylline Products in Healthy Males

Study Overview
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Brief Summary
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Study to compare the bioavailability of 350 mg Bronchoretard® - a sustained-release theophylline (anhydrous) product with respect to the reference product, Theo Dur® 300 mg theophylline anhydrous (sustained-release product) by comparing the rate and extent of absorption of theophylline based on both single and multiple-dose profiles.

Official Title
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A Study to Compare the Bioavailability of Two Sustained-release Theophylline Products

Conditions
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Healthy

Intervention / Treatment
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* Drug: anhydrous theophylline, 350 mg
* Drug: anhydrous theophylline, 300 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy, non-smoking male subjects between 18 and 45 years of age Body weight within 10% of the ideal weight according to the Body Mass Index (BMI) Normal health based on medical history and findings within the range of clinical acceptability, in respect of the physical examination (including electrocardiogram and vital signs) and special investigations Ability to comprehend and willingness to sign both statements of informed consent (for screening and study-specific procedures) Exclusion Criteria: History of serious systemic or organ disease A major illness during the 3 months before commencement of the study-related procedures Significant physical or organ abnormality History of hypersensitivity to theophylline or other xanthine derivatives Use of any medication within 2 weeks before the first administration of study medication Participation in another study with an experimental drug within 8 weeks before the first administration of study medication Treatment within the previous 3 months with any drug with a well-defined potential for adversely affecting a major organ or system (for example chloramphenicol, which may cause bone marrow suppression) Donation of blood during the 8 weeks before the first administration of study medication History of, or current compulsive alcohol abuse (> 10 drinks per week), of regular exposure to other substance of abuse Positive testing for HIV and hepatitis B antigens within the previous 3 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: anhydrous theophylline, 350 mg<br> | Drug: anhydrous theophylline, 350 mg<br> <br> * Other names: Bronchoretard®;|
| Active Comparator: anhydrous theophylline, 300 mg<br> | Drug: anhydrous theophylline, 300 mg<br> <br> * Other names: Theo-Dur®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum concentration (Cmax) |  | up to 36 hours after first drug administration | 
| Area under the plasma concentration versus time data pairs, with extrapolation to infinity (AUDC) |  | up to 36 hours after first drug administration | 
| Area under the plasma concentration versus time data pairs at steady state (AUDss) |  | up to 12 hours after last administration of study drug | 
| Percent peak-to-trough fluctuation (%PTF) |  | up to 12 hours after last administration of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to maximum concentration (Tmax) |  | up to 36 hours after first drug administration | 
| Apparent terminal half-life (t1/2.z) |  | up to 36 hours after first drug administration | 
| Area under the plasma concentration versus time data pairs [AUD(0-tlast)], also indicated by AUD, where tlast is the time of the last quantifiable concentration |  | up to 36 hours after first drug administration | 
| Ratio of Cmax and AUDC (Cmax/AUDC) |  | up to 36 hours after first drug administration | 
| Total mean time in the system (MTvsys) |  | up to 36 hours after first drug administration | 
| Maximum concentration at steady state (Cmax,ss) |  | up to 12 hours after last administration of study drug | 
| Minimum concentration at steady state (Cmin,ss) |  | up to 12 hours after last administration of study drug | 
| Plateau time (T75%Cmax) |  | up to 12 hours after last administration of study drug |