A prospective, randomized, double blinded, crossover, two-treatment, two-sequence, short term pharmacokinetic, pharmacodynamic and tolerability, single centre study to compare AOP200704 vs. Esmolol in healthy subjects.

• Conditions: healthy male and female volunteers, intended for the treatment of dobutamine-induced tachycardia; MedDRA version: 12.1Level: LLTClassification code 10040752Term: Sinus tachycardia

• Registration Number: EUCTR2010-023311-34-CZ
• Lead Sponsor: AOP Orphan Pharmaceuticals AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-12-21
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Male and female human subjects, age 18-45 years.
Body weight of at least 50 kg, maximum of 90 kg. Body-mass index 18.5 to 30.0 kg/m2.
Caucasian race.
Subjects without clinically relevant abnormalities as determined by baseline medical history, physical examination and vital signs (blood pressure, pulse rate and ear temperature) at screening.
Subjects without clinically relevant abnormalities as determined by blood count, coagulation tests, biochemistry, infectious disease screening (HIV, hepatitis B and hepatitis C), urinalysis, ECG, and 2D Echo at screening.
Subject is willing and able to undergo procedures required by this protocol and gave written informed consent.
Agreeing to not using any prescription and over the counter medications including vitamins and minerals for 7 days prior to study and during the course of the study (unless prescribed by the principal investigator for treatment of adverse events).
No history or presence of alcoholism.
No history of drug abuse (benzodiazepines, barbiturates, cocaine) for the last one month and other illegal drugs for the last 6 months.

Non-smokers, ex smokers and mild smokers will be included. Mild smokers are defined as someone smoking 9 cigarettes or less per day, ex smokers are individuals who completely stopped smoking for at least 3 months.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Subjects with any condition which in the opinion of the investigator makes the subject unsuitable for inclusion.
Subjects with history or presence of clinically relevant cardiovascular, renal, hepatic, ophthalmic, pulmonary, neurological, metabolic, hematological, gastrointestinal, endocrine, immunological, psychiatric or skin diseases.
Subjects with bradycardia (heart rate below 50 bpm), tachycardia (heart rate above 100 bpm), hypotension (systolic blood pressure below 100 mmHg, and/or diastolic blood pressure below 70 mm Hg) at screening, history of clinically relevant arrhythmias
Subjects with clinically relevant cardiac supraventricular or ventricular arrhythmias.
Subjects with atrioventricular block of grade II and III, sick sinus syndrome, sinoatrial block or congestive heart failure
Participation in a clinical drug study or bioequivalence study 60 days prior to present study.
History of malignancy or other serious diseases.
Any contraindication to blood sampling.
History of i.v. drug abuse.
Subjects with positive HIV tests, HBsAg or Hepatitis C tests or other acute, subacute or chronic infectious disease.
Known history of hypersensitivity to AOP200704, esmolol, dobutamine or related drugs.
Refusal to abstain from smoking or consumption of tobacco products 48 hours before drug administration and during the study period.
Refusal to abstain from alcohol, caffeine, or other xanthines, or grapefruit containing food or drinks for 72 hours before drug administration and during the study period.
Refusal to abstain from strenuous activities for 7 days before screening and end-of-study examinations, before and during each study period.
Found positive in breath alcohol test done at the time of screening and on the day of check-in for the study for each period.
Found positive in urine test for drug abuse done on the day of check-in for the study for each period.
Subjects with anomalies of the venous and arterial vessels of the forearms or systemic vascular diseases.
Subjects with small and/or invisible and/or badly visible veins on both forearms.
Pregnancy and/or breast-feeding.
History of serious clinical illness that can impact fate of drugs.
Use of organ toxic drugs within 3 months before study Period 1. [Any drug with a well-defined potential for toxicity to a major organ or system (for example chloramphenicol, which may cause bone marrow suppression) is to be considered here].
Systemic multiple dose treatment with drugs altering hepatic metabolism or monoaminooxidase (MAO) inhibitors within 30 days before study Period 1.
Donation of 1) 400 mL of blood or more within 60 days, or 2) more than 150 mL of blood within 30 days, or 3) plasma or platelets within 14 days before study Period 1.
Regular use of medication except hormonal contraceptives or replacement therapy (HC or HRT) taken without significant changes for three months at least.
Any systemic prescription drug treatment within 14 days before study Period 1 (except HC or HRT).
Any systemic over-the-counter (OTC) drug treatment within 7 days before study Period 1.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the short-term pharmacokinetics, pharmacodynamics and tolerability of Landiolol compared with Esmolol in Caucasians;Secondary Objective: To assess the pharmacodynamics and tolerability of Landiolol compared with Esmolol in Caucasians;Primary end point(s): To assess the pharmacokinetics in all completed subjects out of 16 enrolled.