Investigation of the Effect on the QT/QTc Interval After Multiple Dose Oral Administration (100 and 200 mg Bid) of CG5503 PR in a Randomised, Double-blind, Double-dummy Placebo- and Moxifloxacin-controlled 4- Way Cross-over Phase I Study in 48 Healthy Male and Female Volunteers

Grünenthal GmbH1 个研究点分布在 1 个国家目标入组 48 人开始时间: 2003年3月最近更新: 2019年5月17日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Grünenthal GmbH
入组人数: 48
试验地点: 1
主要终点: The mean of corrected QT interval (QTc) differences on Day 3 at 3 to 7 hours to matched time points on Day 0 of the respective treatment period

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The effect of multiple oral administration of two doses of CG5503 PR (prolonged release) compared to placebo on the electrical activity of the heart were investigated. The rationale to perform this study was to exclude any effect of CG5503 on the heart rhythm. This study was a randomised, double-blind, double-dummy, placebo- and moxifloxacin-controlled, 4-way cross-over study. Participants were given a combination of either CG5503 PR and placebo (medication with inactive ingredients which looks like the study drug) or moxifloxacin and placebo. Moxifloxacin was used as a positive control. It has consistently shown that it has an effect on the heart rhythm.

Within 14 days prior to the first dosing, participants had a physical examination, a 12-lead electrocardiogram (ECG) was recorded and haematological, serological, biochemical, and urine analyses took place. A blood sample for optional genotyping of genes responsible for long QT syndrome was taken. During each dosing session, the participants were confined in the evening before baseline assessments were performed and stayed in the clinic until 48 hours after the last dosing. Study medication was administered on Day 1 and 2 in the morning (0.5 hours after breakfast) and in the evening (1.5 hours after dinner), and on Day 3 in the morning (0.5 hours after breakfast). Dosing was separated by at least 7 days between the last dosing of each period and the first dosing of next period. Interim analysis of ECG-data were performed after completion of 24 participants (group 1) with possible subsequent adjustment of sample size for group 2.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Crossover
主要目的: Treatment
盲法: Double (Participant, Investigator)

入排标准

年龄范围: 45 Years 至 65 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 是

入选标准

•Male or female Caucasian participants aged 45-65 years;
•Body mass index (BMI) between 19 and 27 kilograms/square meter inclusive;
•Participants must be in good health as determined by medical history, physical examination, 12-lead electrocardiogram , vital signs, and clinical laboratory parameters (serum/urine biochemistry, serology and haematology). Electrocardiogram (ECG) parameters and vitals signs must be in the ranges given in exclusion criteria 3-8 and 11-14, respectively) Minor deviations of laboratory values from the normal range may be accepted (except potassium and magnesium), if judged by the investigator to have no clinical relevance and if not considered to interfere with the study objectives.
•Negative human immunodeficiency virus (HIV) 1/2 -antibodies, hepatitis B surface (HBs)-antigen, hepatitis B core (HBc)-antibodies and hepatitis C virus (HCV)-antibodies at the prestudy medical examination;
•Negative blood beta-human chorionic gonadotropine (HCG)-test for women of child bearing potential;
•Participants giving written consent to participate within this study;
•Participants giving written consent for blood sampling to be genotyped for genes responsible for long QT syndrome (KCNQ1, human ether-a-go-go-related gene (HERG), SCN5A, KCNE1, KCNE2, KCNJ2).

排除标准

•Regular use of any medication within four weeks prior to commencement of the study (self-medication or prescription except for hormonal contraception and HRT);
•Smoker more than 5 cigarettes per day;
•No regular sinus rhythm;
•ECG interval: QRS complex above 100 millisecond;
•ECG interval: PQ above 200 milliseconds;
•ECG interval: RR above 1333 milliseconds;
•QT/QTc intervals above 450 milliseconds;
•Known family history of sudden cardiac death and arrhythmias;
•Diseases and functional disorders of the gastrointestinal tract, liver, cardiovascular system or kidneys;
•Malignancy;
•History of orthostatic hypotension;
•Resting pulse rate below 45 beats/min or above 90 beats per minute;
•Systolic blood pressure above 160 mmHg or below 100 mmHg;
•Diastolic blood pressure above 95 mmHg or below 50 mmHg;
•History of drug allergy;
•Bronchial asthma;
•Participation in another clinical trial within the last three months before starting this study (exception: characterisation of metaboliser status);
•Blood donation (more than 100 milliliters) in the last three months before the start of the study;
•History or evidence of alcohol or drug abuse;
•Positive drug abuse screening test;
•Extremely unbalanced diet (in the opinion of the investigator);
•Excessive consumption of food or beverages containing caffeine (more than 1000 milliliters of coffee per day or other equivalent amounts of caffeine);
•Known or suspected of not being able to comply with the study protocol;
•Not able to communicate meaningfully with the investigator and staff;
•Neurotic personality, psychiatric illness, or suicide risk;
•History of seizures;
•Known hypersensitivity to opioids or quinolones;
•Pregnancy (for female participants);

研究组 & 干预措施

CG5503 PR 100 mg twice daily (tapentadol hydrochloride)

Experimental

Each participant received a morning and an evening dose of 100 mg CG5503 PR on days 1 and 2 and a morning dose on Day 3 (each dose: 1 tablet CG5503 PR and 1 placebo-tablet, matching CG5503 PR); additionally at each dosing each participant received 2 placebo-capsules, matching moxifloxacin 400 mg.