In Vivo Specificity of KUC 7483 CL Co-administered With Bisoprolol, Propranolol, and Acipimox in Healthy Male Subjects

A Randomised, Open Label, Four-way Crossover Phase I Trial to Investigate the in Vivo Specificity of a Single Oral Dose of 320 mg KUC 7483 CL Co-administered With Bisoprolol (10 mg Daily), Propranolol (160 mg Daily), and Acipimox (500 mg Daily) Over 5 Days and a Single Inhalative Dose of 100 μg Salmeterol in Healthy Male Subjects

Study to compare the metabolic and electrolyte effects of a single oral dose of 320 mg ritobegron administered alone or with a pre- and comedication with bisoprolol, propranolol and acipimox. In addition, to compare the metabolic and electrolyte effects of a single dose of 320 mg ritobegron with those of a single inhalatory dose of 100 μg salmeterol

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Bisoprolol; Drug: Salmeterol; Drug: Propranolol; Drug: Acipimox; Drug: KUC 7483 CL

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male
• Age >= 30 and <= 60 years
• Body Mass Index (BMI) >= 18.5 and <= 29.9 kg/m2
• Signed and dated written informed consent in accordance with Good Clinical Practice and local legislation

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
• Alcohol abuse (> 60 g/day)
• 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, salmeterol and/or related drugs of these classes
• Congenital or documented acquired QT- prolongation, previous history of symptomatic arrhythmias
• Systolic BP < 115 mmHg
• Heart rate at rest of > 80 bpm or < 55 bpm
• Any screening ECG value outside of the reference range of clinical relevance including, but not limited to PR interval > 220 ms, QRS interval > 115 ms, QTcB > 420 ms, or QT (uncorrected) > 450 ms
• History of asthma or obstructive pulmonary disease.
• Psoriasis (own medical history or relative)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment B	Drug: Bisoprolol; Drug: KUC 7483 CL
Experimental: Treatment C	Drug: Propranolol; Drug: KUC 7483 CL
Experimental: Treatment A	Drug: KUC 7483 CL
Active Comparator: Treatment E	Drug: Salmeterol
Experimental: Treatment D	Drug: Acipimox; Drug: KUC 7483 CL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Absolute change from baseline in glucose	up to 24 hours after administration of study drug
Percentage change from baseline in glucose	up to 24 hours after administration of study drug
Absolute change from baseline in free fatty acids (FFA)	up to 24 hours after administration of study drug
Percentage change from baseline in FFA	up to 24 hours after administration of study drug
Absolute change from baseline in insulin	up to 24 hours after administration of study drug
Percentage change from baseline in insulin	up to 24 hours after administration of study drug
Absolute change from baseline in C-Peptide	up to 24 hours after administration of study drug
Percentage change from baseline in C-Peptide	up to 24 hours after administration of study drug
Absolute change from baseline in Potassium	up to 24 hours after administration of study drug
Percentage change from baseline in Potassium	up to 24 hours after administration of study drug
Absolute change from baseline in Magnesium	up to 24 hours after administration of study drug
Percentage change from baseline in Magnesium	up to 24 hours after administration of study drug
Absolute change from baseline in cAMP	up to 24 hours after administration of study drug
Percentage change from baseline in cAMP	up to 24 hours after administration of study drug

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of subjects with adverse events	up to 80 days
Number of subjects with clinically relevant changes in laboratory tests	up to 24 hours after administration of study drug
Number of subjects with clinically relevant changes in vital signs	up to 24 hours after administration of study drug
Number of subjects with clinically relevant findings in electrocardiogram	up to 24 hours after administration of study drug
Number of subjects with clinically relevant changes in physical examination	Baseline, within 10 days after last drug administration
Maximum measured concentration of the analyte in plasma	up to 24 hours after administration of study drug
Time from dosing to the maximum concentration of the analyte in plasma	up to 24 hours after administration of study drug
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 4 hours	up to 24 hours after administration of study drug

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): November 1, 2005

Study Registration Dates

• First Submitted: October 2, 2014
• First Submitted That Met QC Criteria: October 2, 2014
• First Posted (Estimate): October 6, 2014

Study Record Updates

• Last Update Posted (Estimate): October 6, 2014
• Last Update Submitted That Met QC Criteria: October 2, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Antimetabolites; Adrenergic Agonists; Hypolipidemic Agents; Lipid Regulating Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Propranolol; Salmeterol Xinafoate; Bisoprolol; Acipimox
• Other Study ID Numbers: 1207.26