Pharmacodynamic Effects, Safety and Tolerability of Cilobradine, to Healthy Male and Female Volunteers, With an Intra-individual Comparison to Moxifloxacin in a Subset of Volunteers

Study Overview
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Brief Summary
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Incidence of visual phenomena, heart rate at rest, safety (with particular emphasis on QT analysis of ECGs), and pharmacokinetic parameters

Official Title
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Pharmacodynamic Effects, Safety and Tolerability of 2 mg and 5 mg Cilobradine, Administered p.o. Once Daily Over 14 Days to Healthy Male and Female Volunteers in a Randomised, Placebo-controlled, Double Blind Study, With an Open-label Uncontrolled Intra-individual Comparison to 400 mg Moxifloxacin Single Dose in a Subset of Volunteers.

Conditions
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Healthy

Intervention / Treatment
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* Drug: Cilobradine, low, film-coated tablets
* Drug: Cilobradine, high, film-coated tablets
* Drug: Placebo, film-coated tablets
* Drug: Moxifloxacin, film-coated tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males and females 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 Electrocardiogram (ECG), clinical laboratory tests 1.1 No finding deviating from normal and of clinical relevance 1.2 No evidence of a clinically relevant concomitant disease Age ≥21 and Age ≤55 years BMI ≥18.5 and BMI < 30 kg/m2 (Body Mass Index) Resting Heart rate (HR) (after 10 min. in the supine position) of equal or more than 60 bpm Females: post-menopausal or those who have had a hysterectomy (plus a negative pregnancy test) 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: Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, ophthalmological, or hormonal disorders Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders History of relevant orthostatic hypotension, fainting spells or blackouts Chronic or 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 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial 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 Participation in another trial with an investigational drug within two months prior to administration or during the trial Smoker (more than 10 cigarettes or 3 cigars or 3 pipes/day) Inability to refrain from smoking on trial days Alcohol abuse Drug abuse Blood donation (more than 100 mL within four weeks prior to administration or during the trial) Excessive physical activities (within one week prior to administration or during the trial) Any laboratory value outside the reference range that is of clinical relevance. Exclusion criteria specific for this study: Subjects at increased risk for development of cardiac arrhythmia (e.g. family history of long QT syndrome or sudden cardiac death)

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 55 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: Cilobradine low<br> | Drug: Cilobradine, low, film-coated tablets<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo, film-coated tablets<br> <br> |
| Active Comparator: Moxifloxacin<br> | Drug: Moxifloxacin, film-coated tablets<br> <br> |
| Experimental: Cilobradine high<br> | Drug: Cilobradine, high, film-coated tablets<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of visual phenomena | Reported as adverse events | Up to 12 days after last scheduled study day | 
| Change in heart rate at rest |  | Pre dose, up to 12 hours after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator assessed tolerability on a 4 point scale |  | Up to 12 days after last scheduled study day | 
| Number of participants with abnormal findings in physical examination |  | Up to 12 days after last scheduled study day | 
| Number of participants with clinically significant changes in vital signs |  | Up to 12 days after last scheduled study day | 
| Number of participants with adverse events |  | Up to 12 days after last scheduled study day | 
| Characteristics of visual phenomena on a special questionnaire |  | Up to 12 days after last scheduled study day | 
| Number of participants with abnormal changes in clinical laboratory parameters |  | Up to 12 days after last scheduled study day | 
| Number of participants with abnormal findings in electrocardiogram (ECG) |  | Up to 12 days after last scheduled study day | 
| Area under the concentration-time curve of the analyte in plasma from zero time to 24 hours (AUC0-24) |  | Up to 24 hours after drug administration | 
| Maximum plasma concentration following the first dose (Cmax) |  | Up to 24 hours after drug administration | 
| Time from first dose to the maximum plasma concentration (tmax) |  | Up to 24 hours after drug administration | 
| Terminal half-life (t1/2) |  | Up to 24 hours after drug administration | 
| Mean residence time of the analyte in the body after oral administration (MRTpo) |  | Up to 24 hours after drug administration | 
| Apparent clearance of the analyte in plasma following extravascular administration (CL/F) |  | Up to 24 hours after drug administration | 
| Apparent volume of distribution during the terminal phase λz following extravascular administration (Vz/F) |  | Up to 24 hours after drug administration |