Clinical trial NCT02264002: Pharmacodynamic Effects, Safety and Tolerability of Cilobradine, Compared to Metoprolol Succinate and Placebo in Healthy Volunteers
Official title: Pharmacodynamic Effects, Safety and Tolerability of 0.25 mg, 0.5 mg, 1 mg and 2 mg Cilobradine, Compared to 190 mg Metoprolol Succinate and Placebo, Administered p.o. Once Daily Over 14 Days to Healthy Volunteers in a Randomised, Placebo-controlled, Partly Double Blind Study, With a 4 mg/14 mg and 10 mg/20 mg Cilobradine Single Dose Versus Placebo Substudy (Double Blind, Three-fold Cross-over)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-10-15
Enrollment: 119
Sex: ALL
Minimum age (years): 21
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Pharmacodynamic effects on heart rate (HR) at rest and during exercise and on flicker fusion frequency (FFF), FFF method evaluation

Safety, tolerability and pharmacokinetics of cilobradine


Eligibility criteria: Inclusion Criteria:

* All participants in the study should be healthy males and females. Volunteers will

  * be 21 to 55 years of age
  * have a Body Mass Index (BMI) of 19.9 to 29.9 kg/m2 and
  * have a resting heart rate (HR) (after 10 min. in the supine position) of more than 55 beats per minute (bpm)
* Only post-menopausal females, or those who had had a hysterectomy, could participate. All females had to have a negative pregnancy test
* In accordance with good clinical practice (GCP) and the local legislation all volunteers had to give their written informed consent prior to admission to the study

Exclusion Criteria:

* Any finding of the medical examination (including BP, HR and ECG) deviating from normal and of clinical relevance
* Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
* Diseases of the central nervous system 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 ten half-lives of the respective drug before enrolment in the study
* Use of any drugs which might influence the results of the trial within two weeks prior to administration or during the trial
* Participation in another trial with an investigational drug (≤ 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)
* Excessive physical activities (within the last week before the study)
* Any laboratory value outside the reference range of clinical relevance

Not necessarily clinically relevant abnormalities, but specific Exclusion criteria for the drugs under study or for the study:

* Consumption of more than 2 cups of coffee or black tea, or cola drinks, per day during the last 6 weeks. However, subjects may participate if abstinence from the before mentioned beverages is well tolerated during an interval of at least 2 weeks between screening and first treatment
* ECG: PQ interval \> 210 ms
* HR at rest \< 55 bpm
* Systolic BP \< 115 mmHg
* Colour vision test abnormal. However, subjects may participate if they are able to perform the flicker fusion test without difficulty
* Psoriasis (own medical history or relative)
* Relevant ophthalmological disease
* History of asthma or obstructive pulmonary disease
* History (including childhood) of traumatic injury to the head or brain
* History (including childhood) of reduced seizure threshold
* The following subjects will not be allowed to participate in the study

  * Any subject involved in professional transportation of human subjects
  * Any subject involved in operating dangerous machinery

Primary outcomes:
measure: Changes in heart rate at rest
timeFrame: Pre-dose, up to day 20 after first drug administration
measure: Changes in heart rate during exercise
timeFrame: Pre-dose, up to day 20 after first drug administration
measure: Changes in flicker fusion frequency test (FFF)
timeFrame: Pre-dose, up to day 20 after first drug administration
Secondary outcomes:
measure: Number of patients with clinically relevant changes in laboratory tests
timeFrame: Pre-dose, up to 12 days after last drug administration
measure: Number of patients with clinically relevant changes in vital signs (blood pressure, heart rate)
timeFrame: Pre-dose, up to 12 days after last drug administration
measure: Number of patients with clinically relevant changes in 12-lead ECG
timeFrame: Pre-dose, up to 12 days after last drug administration
measure: Number of patients with adverse events
timeFrame: Up to 12 days after last drug administration
measure: Assessment of global tolerability by the investigator
timeFrame: Up to 12 days after last drug administration
measure: Changes in peripheral FFF
timeFrame: Pre-dose, up to day 20 after first drug administration
measure: Area under the concentration-time curve of the analytes in plasma (AUC)
timeFrame: Up to day 20 after start of first drug administration
measure: Maximum measured concentration of the analytes in plasma (Cmax)
timeFrame: Up to day 20 after start of first drug administration
measure: Time from dosing to the maximum concentration of the analytes in plasma (tmax)
timeFrame: Up to day 20 after start of first drug administration
measure: Terminal half-life of the analytes in plasma (t½)
timeFrame: Up to day 20 after start of first drug administration
measure: Mean residence time of the analytes in the body after oral administration (MRTpo)
timeFrame: Up to day 20 after start of first drug administration
measure: Total clearance of the analytes in plasma following extravascular administration (CL/F)
timeFrame: Up to day 20 after start of first drug administration
measure: Apparent volume of distribution of the analytes during the terminal phase λz following extravascular administration (Vz/F)
timeFrame: Up to day 20 after start of first drug administration
Other outcomes:
Locations:
Study officials:
References: