Pharmacodynamic Effects, Safety and Tolerability of Cilobradine, Compared to Metoprolol Succinate and Placebo in Healthy Volunteers

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Cilobradine high dose 2; Drug: Placebo; Drug: Cilobradine high dose 1; Drug: Cilobradine medium dose; Drug: Cilobradine low dose 1; Drug: Cilobradine low dose 2; Drug: Metoprolol succinate tablets

Study type: Interventional

Funder types: Industry

Identifiers

NCT02264002

503.203

Details and patient eligibility

About

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

Enrollment: 119 patients

Sex: All

Ages: 21 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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119 participants in 7 patient groups, including a placebo group

Cilobradine low dose 1

Experimental group

Treatment:

Drug: Cilobradine low dose 1

Cilobradine low dose 2

Experimental group

Treatment:

Drug: Cilobradine low dose 2

Cilobradine medium dose

Experimental group

Treatment:

Drug: Cilobradine medium dose

Cilobradine high dose 1

Experimental group

Treatment:

Drug: Cilobradine high dose 1

Cilobradine high dose 2

Experimental group

Treatment:

Drug: Cilobradine high dose 2

Metoprolol succinate

Active Comparator group

Description:

1 tablet on day 1, day 2 followed by two tablets from day 3 to day 14

Treatment:

Drug: Metoprolol succinate tablets

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo