Study to Investigate the Effect of KUC 7483 CL on the QT/QTc Interval of the ECG in Comparison to Placebo and Moxifloxacin in Healthy Male and Female Volunteers

Study Overview
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Brief Summary
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Study to investigate the effect of Ritobegron CL (KUC 7483 CL) on the QT/QTc interval of the ECG in comparison to placebo and moxifloxacin

Official Title
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A Double-blinded, Randomised, Placebo Controlled, Five-way Crossover Study With One Positive Control (Open-label) (Moxifloxacin) to Assess the Influence of Oral Single Dose KUC 7483 BS (40 mg, 80 mg, 160 mg, 320 mg) on the QT/QTc Interval of the ECG in Healthy Male and Female Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: Treatment A
* Drug: Treatment B
* Drug: Treatment C
* Drug: Treatment D
* Drug: Placebo
* Drug: Moxifloxacin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males or females Age 30 to 60 years Body mass index (BMI) within 18.5 to 29.9 kg/m2 In accordance with Good Clinical Practice (GCP) and the local legislation all volunteers are to have given their written informed consent prior to admission to the study 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 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, moxifloxacin and/or related drugs of these classes Previous tendon disease related to quinolone treatment Congenital or documented acquired QT- prolongation, previous history of symptomatic arrhythmias Heart rate at screening of > 80 bpm or < 45 bpm Any screening ECG value outside of the reference range of clinical relevance including, but not limited to Pulse rate (PR) interval > 220 ms, QRS interval > 115 ms, QTcB > 450 ms, or QT (uncorrected) > 470 ms For Female Subjects: Pregnancy Positive pregnancy test No adequate contraception (adequate contraception e.g. sterilization, Intrauterine pessary (IUP), oral contraceptives) Inability to maintain this adequate contraception during the whole study period Lactation period

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A<br> | Drug: Treatment A<br>* Ritobegron Cl (KUC 7483 CL) tablets low dose<br>|
| Experimental: Treatment B<br> | Drug: Treatment B<br> <br> * Other names: Ritobegron Cl (KUC 7483 CL) tablets medium 1 dose;|
| Experimental: Treatment C<br> | Drug: Treatment C<br> <br> * Other names: Ritobegron Cl (KUC 7483 CL) tablets medium 2 dose;|
| Experimental: Treatment D<br> | Drug: Treatment D<br> <br> * Other names: Ritobegron Cl (KUC 7483 CL) tablets high dose;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |
| Active Comparator: Moxifloxacin<br> | Drug: Moxifloxacin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in mean time-matched QTcI |  | up to 2 hours following drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in mean time-matched QTcI |  | up to 8 hours following drug administration | 
| Occurrence of uncorrected QT interval | QT interval <=500 ms, > 500 ms | up to 8 hours following drug administration | 
| Occurrence of the QTcI interval | QTcI interval <= 450 ms, >450 ms, >480 ms or >500 ms | up to 8 hours following drug administration | 
| Change from baseline of the QTcI interval | QTcI interval < 30 ms, ≤ 60 ms | up to 8 hours following drug administration | 
| Change from baseline in Heart Rate (HR) | increase ≥25 % or decrease HR by ≥25 % | up to 6 hours following drug administration | 
| Cmax (maximum measured concentration of the analyte in plasma) |  | up to 8 hours following drug administration | 
| tmax (time from dosing to the maximum concentration of the analyte in plasma) |  | up to 8 hours following drug administration | 
| AUC0-6 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours) |  | up to 6 hours following drug administration | 
| AUC0-8 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 8 hours) for moxifloxacin |  | up to 8 hours following drug administration | 
| Number of subjects with adverse events |  | up to 17 days after last drug administration | 
| Number of subjects with abnormal changes in laboratory parameters |  | up to 17 days after last drug administration | 
| Number of subjects with abnormal changes in 12-lead ECG |  | up to 17 days after last drug administration | 
| Number of patients with clinically significant changes in vital signs | Blood pressure, pulse rate | up to 17 days after last drug administration | 
| Assessment of tolerability by investigator on a 4-point scale |  | 17 days after last drug administration |