Clinical trial NCT01313143: A Short Term Pharmacokinetic, Pharmacodynamic and Tolerability Study to Compare AOP200704 vs. Esmolol
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Healthy Volunteers
Pharmacokinetics/Dynamics Study
Keywords: AOP200704, Esmolol, Pharmacokinetics, Pharmacodynamics
Lead sponsor: AOP Orphan Pharmaceuticals AG
Sponsor class: INDUSTRY
First posted: 2011-03-11
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Pharmacokinetics, pharmacodynamics and tolerability of AOP200704 infusion is compared to that of Esmolol by measurement of plasma concentrations of AOP200704, esmolol and their metabolites, by assessing the effect of both drugs on dobutamine-induced tachycardia, and by monitoring vital signs, ECG and adverse events.

Detailed description: 16 healthy volunteers of both sexes, age 18 to 45 years, will be enrolled. The mean dose necessary to suppress the Dobutamine induced heart rate increase of at least 30 bpm above baseline rate (maximum heart rate app. 110 bpm) by at least 20 bpm will be calculated for AOP200704 and Esmolol and the dose/efficacy relation of both agents to each other will be calculated for the steady state condition. For both drugs the time to reach a decrease of 10 bpm, 20 bpm and the maximum effect will be calculated. In addition the mean time to increase in 10 and 20 bpm and the time to reach maximum heart rate (increase of 30 bpm above baseline or more) after termination of infusion will also be assessed for both drugs. Blood pressure values will be compared for all above mentioned time points where heart rate is assessed for pharmacodynamics.The study will consist of a screening, cross-over 1, cross-over 2 and end-of-study visit.

Eligibility criteria: 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
* Caucasians
* Subjects without clinically relevant abnormalities
* Subjects 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
* No drug or alcohol abuse
* Non-smokers, ex smokers and mild smokers

Exclusion Criteria:

* 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, clinically relevant or 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.

Primary outcomes:
measure: Pharmacokinetics/dynamics
timeFrame: 9 hours
Secondary outcomes:
measure: Local tolerability
timeFrame: 9 hours
Other outcomes:
Locations:
city: Pilsen
country: Czech Republic
facility: AOP contract research facility
Study officials:
affiliation: AOP Contract Clinical Research Facility
name: AOP Study Principal Investigator
role: PRINCIPAL_INVESTIGATOR
References: