In Vivo Specificity of KUC 7483 CL Co-administered With Bisoprolol, Propranolol, and Acipimox in Healthy Male Subjects

Study Overview
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Brief Summary
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Study to compare the metabolic and electrolyte effects of a single oral dose of 320 mg ritobegron administered alone or with a pre- and comedication with bisoprolol, propranolol and acipimox. In addition, to compare the metabolic and electrolyte effects of a single dose of 320 mg ritobegron with those of a single inhalatory dose of 100 μg salmeterol

Official Title
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A Randomised, Open Label, Four-way Crossover Phase I Trial to Investigate the in Vivo Specificity of a Single Oral Dose of 320 mg KUC 7483 CL Co-administered With Bisoprolol (10 mg Daily), Propranolol (160 mg Daily), and Acipimox (500 mg Daily) Over 5 Days and a Single Inhalative Dose of 100 μg Salmeterol in Healthy Male Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: KUC 7483 CL
* Drug: Bisoprolol
* Drug: Propranolol
* Drug: Acipimox
* Drug: Salmeterol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male Age >= 30 and <= 60 years Body Mass Index (BMI) >= 18.5 and <= 29.9 kg/m2 Signed and dated written informed consent in accordance with Good Clinical Practice and local legislation Exclusion Criteria: Any finding of the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders, clinically relevant electrolyte disturbances Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders History of orthostatic hypotension, fainting spells or blackouts Chronic or clinically relevant acute infections History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator Intake of drugs with a long half-life (> 24:00 hours) within at least one month or less than ten half-lives of the respective drug before enrolment in the study or during the study Use of any drugs which might influence the results of the trial up to 7 days prior to enrolment in the study or during the study Participation in another trial with an investigational drug (within two months prior to administration or during the trial) Smoker (> 10 cigarettes or > 3 cigars of > 3 pipes/day) Inability to refrain from smoking on trial days Alcohol abuse (> 60 g/day) Drug abuse Blood donation (> 100 mL within four weeks prior to administration or during the trial) Any laboratory value outside the reference range if indicative of underlying disease or poor health Excessive physical activities within the last week before the trial or during the trial Hypersensitivity to treatment medication, salmeterol and/or related drugs of these classes Congenital or documented acquired QT- prolongation, previous history of symptomatic arrhythmias Systolic BP < 115 mmHg Heart rate at rest of > 80 bpm or < 55 bpm Any screening ECG value outside of the reference range of clinical relevance including, but not limited to PR interval > 220 ms, QRS interval > 115 ms, QTcB > 420 ms, or QT (uncorrected) > 450 ms History of asthma or obstructive pulmonary disease. Psoriasis (own medical history or relative)

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 60 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: Treatment A<br> | Drug: KUC 7483 CL<br> <br> |
| Experimental: Treatment B<br> | Drug: KUC 7483 CL<br> <br> Drug: Bisoprolol<br> <br> |
| Experimental: Treatment C<br> | Drug: KUC 7483 CL<br> <br> Drug: Propranolol<br> <br> |
| Experimental: Treatment D<br> | Drug: KUC 7483 CL<br> <br> Drug: Acipimox<br> <br> |
| Active Comparator: Treatment E<br> | Drug: Salmeterol<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute change from baseline in glucose |  | up to 24 hours after administration of study drug | 
| Percentage change from baseline in glucose |  | up to 24 hours after administration of study drug | 
| Absolute change from baseline in free fatty acids (FFA) |  | up to 24 hours after administration of study drug | 
| Percentage change from baseline in FFA |  | up to 24 hours after administration of study drug | 
| Absolute change from baseline in insulin |  | up to 24 hours after administration of study drug | 
| Percentage change from baseline in insulin |  | up to 24 hours after administration of study drug | 
| Absolute change from baseline in C-Peptide |  | up to 24 hours after administration of study drug | 
| Percentage change from baseline in C-Peptide |  | up to 24 hours after administration of study drug | 
| Absolute change from baseline in Potassium |  | up to 24 hours after administration of study drug | 
| Percentage change from baseline in Potassium |  | up to 24 hours after administration of study drug | 
| Absolute change from baseline in Magnesium |  | up to 24 hours after administration of study drug | 
| Percentage change from baseline in Magnesium |  | up to 24 hours after administration of study drug | 
| Absolute change from baseline in cAMP |  | up to 24 hours after administration of study drug | 
| Percentage change from baseline in cAMP |  | up to 24 hours after administration of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events |  | up to 80 days | 
| Number of subjects with clinically relevant changes in laboratory tests |  | up to 24 hours after administration of study drug | 
| Number of subjects with clinically relevant changes in vital signs |  | up to 24 hours after administration of study drug | 
| Number of subjects with clinically relevant findings in electrocardiogram |  | up to 24 hours after administration of study drug | 
| Number of subjects with clinically relevant changes in physical examination |  | Baseline, within 10 days after last drug administration | 
| Maximum measured concentration of the analyte in plasma |  | up to 24 hours after administration of study drug | 
| Time from dosing to the maximum concentration of the analyte in plasma |  | up to 24 hours after administration of study drug | 
| Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 4 hours |  | up to 24 hours after administration of study drug |