Study to Investigate the Effect of KUC 7483 CL on the QT/QTc Interval of the ECG in Comparison to Placebo and Moxifloxacin in Healthy Male and Female Volunteers

A Double-blinded, Randomised, Placebo Controlled, Five-way Crossover Study With One Positive Control (Open-label) (Moxifloxacin) to Assess the Influence of Oral Single Dose KUC 7483 BS (40 mg, 80 mg, 160 mg, 320 mg) on the QT/QTc Interval of the ECG in Healthy Male and Female Volunteers

Study to investigate the effect of Ritobegron CL (KUC 7483 CL) on the QT/QTc interval of the ECG in comparison to placebo and moxifloxacin

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: Moxifloxacin; Drug: Treatment A; Drug: Treatment B; Drug: Treatment C; Drug: Treatment D

• Study Type: Interventional
• Enrollment (Actual): 39
• 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: All

Description

Inclusion Criteria:

• Healthy males or females
• Age 30 to 60 years
• Body mass index (BMI) within 18.5 to 29.9 kg/m2
• In accordance with Good Clinical Practice (GCP) and the local legislation all volunteers are to have given their written informed consent prior to admission to the study

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
• 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, moxifloxacin and/or related drugs of these classes
• Previous tendon disease related to quinolone treatment
• Congenital or documented acquired QT- prolongation, previous history of symptomatic arrhythmias
• Heart rate at screening of > 80 bpm or < 45 bpm
• Any screening ECG value outside of the reference range of clinical relevance including, but not limited to Pulse rate (PR) interval > 220 ms, QRS interval > 115 ms, QTcB > 450 ms, or QT (uncorrected) > 470 ms

For Female Subjects:

• Pregnancy
• Positive pregnancy test
• No adequate contraception (adequate contraception e.g. sterilization, Intrauterine pessary (IUP), oral contraceptives)
• Inability to maintain this adequate contraception during the whole study period
• Lactation period

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo
Experimental: Treatment B	Drug: Treatment B; Other Names: Ritobegron Cl (KUC 7483 CL) tablets medium 1 dose
Experimental: Treatment C	Drug: Treatment C; Other Names: Ritobegron Cl (KUC 7483 CL) tablets medium 2 dose
Experimental: Treatment A	Drug: Treatment A; Ritobegron Cl (KUC 7483 CL) tablets low dose
Active Comparator: Moxifloxacin	Drug: Moxifloxacin
Experimental: Treatment D	Drug: Treatment D; Other Names: Ritobegron Cl (KUC 7483 CL) tablets high dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in mean time-matched QTcI	up to 2 hours following drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in mean time-matched QTcI		up to 8 hours following drug administration
Occurrence of uncorrected QT interval	QT interval <=500 ms, > 500 ms	up to 8 hours following drug administration
Occurrence of the QTcI interval	QTcI interval <= 450 ms, >450 ms, >480 ms or >500 ms	up to 8 hours following drug administration
Change from baseline of the QTcI interval	QTcI interval < 30 ms, ≤ 60 ms	up to 8 hours following drug administration
Change from baseline in Heart Rate (HR)	increase ≥25 % or decrease HR by ≥25 %	up to 6 hours following drug administration
Cmax (maximum measured concentration of the analyte in plasma)		up to 8 hours following drug administration
tmax (time from dosing to the maximum concentration of the analyte in plasma)		up to 8 hours following drug administration
AUC0-6 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours)		up to 6 hours following drug administration
AUC0-8 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 8 hours) for moxifloxacin		up to 8 hours following drug administration
Number of subjects with adverse events		up to 17 days after last drug administration
Number of subjects with abnormal changes in laboratory parameters		up to 17 days after last drug administration
Number of subjects with abnormal changes in 12-lead ECG		up to 17 days after last drug administration
Number of patients with clinically significant changes in vital signs	Blood pressure, pulse rate	up to 17 days after last drug administration
Assessment of tolerability by investigator on a 4-point scale		17 days after last drug administration

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: August 1, 2005
• Primary Completion (Actual): December 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 Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Antineoplastic Agents; Adrenergic Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Adrenergic beta-Agonists; Sympathomimetics; Mydriatics; Adrenergic beta-3 Receptor Agonists; Moxifloxacin; p-Hydroxyamphetamine; Ritobegron
• Other Study ID Numbers: 1207.22