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

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.

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Cilobradine, low, film-coated tablets; Drug: Placebo, film-coated tablets; Drug: Moxifloxacin, film-coated tablets; Drug: Cilobradine, high, film-coated tablets

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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

2. Age ≥21 and Age ≤55 years
3. BMI ≥18.5 and BMI < 30 kg/m2 (Body Mass Index)
4. Resting Heart rate (HR) (after 10 min. in the supine position) of equal or more than 60 bpm
5. Females: post-menopausal or those who have had a hysterectomy (plus a negative pregnancy test)
6. 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, ophthalmological, or hormonal disorders
2. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
3. History of relevant orthostatic hypotension, fainting spells or blackouts
4. Chronic or relevant acute infections
5. History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator
6. 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
7. 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
8. Participation in another trial with an investigational drug within two months prior to administration or during the trial
9. Smoker (more than 10 cigarettes or 3 cigars or 3 pipes/day)
10. Inability to refrain from smoking on trial days
11. Alcohol abuse
12. Drug abuse
13. Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
14. Excessive physical activities (within one week prior to administration or during the trial)

15. Any laboratory value outside the reference range that is of clinical relevance.

    Exclusion criteria specific for this study:

16. Subjects at increased risk for development of cardiac arrhythmia (e.g. family history of long QT syndrome or sudden cardiac death)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo, film-coated tablets
Active Comparator: Moxifloxacin	Drug: Moxifloxacin, film-coated tablets
Experimental: Cilobradine low	Drug: Cilobradine, low, film-coated tablets
Experimental: Cilobradine high	Drug: Cilobradine, high, film-coated tablets

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: January 1, 2004
• Primary Completion (Actual): May 1, 2004

Study Registration Dates

• First Submitted: October 13, 2014
• First Submitted That Met QC Criteria: October 13, 2014
• First Posted (Estimate): October 15, 2014

Study Record Updates

• Last Update Posted (Estimate): October 15, 2014
• Last Update Submitted That Met QC Criteria: October 13, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Moxifloxacin
• Other Study ID Numbers: 503.204