A Short Term Pharmacokinetic, Pharmacodynamic and Tolerability Study to Compare AOP200704 vs. Esmolol

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.

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Pharmacokinetics/Dynamics Study
• Intervention / Treatment: Drug: AOP200704; Drug: Esmolol hydrochloride, infusion

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czech Republic
  • Pilsen, Czech Republic, 32300
    • AOP contract research facility

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: AOP200704, infusion	Drug: AOP200704; Comparison of AOP200704 with Esmolol
ACTIVE_COMPARATOR: Esmolol, infusion	Drug: Esmolol hydrochloride, infusion; Comparison of AOP200704 with Esmolol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics/dynamics	9 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Local tolerability	9 hours

Collaborators and Investigators

• Sponsor: AOP Orphan Pharmaceuticals AG
• Investigators: Principal Investigator: AOP Study Principal Investigator, AOP Contract Clinical Research Facility

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (ACTUAL): May 1, 2011
• Study Completion (ACTUAL): January 1, 2012

Study Registration Dates

• First Submitted: March 10, 2011
• First Submitted That Met QC Criteria: March 10, 2011
• First Posted (ESTIMATE): March 11, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): July 19, 2012
• Last Update Submitted That Met QC Criteria: July 18, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: AOP200704, Esmolol, Pharmacokinetics, Pharmacodynamics
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Adrenergic beta-1 Receptor Antagonists; Esmolol
• Other Study ID Numbers: CPA368-10