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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AOP Orphan Pharmaceuticals AG
ClinicalTrials.gov Identifier:
NCT01313143
First received: March 10, 2011
Last updated: July 18, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Healthy Volunteers
Pharmacokinetics/Dynamics Study
Drug: AOP200704
Drug: Esmolol hydrochloride, infusion
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by AOP Orphan Pharmaceuticals AG:

Primary Outcome Measures:
  • Pharmacokinetics/dynamics [ Time Frame: 9 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Local tolerability [ Time Frame: 9 hours ] [ Designated as safety issue: No ]

Enrollment: 16
Study Start Date: March 2011
Study Completion Date: January 2012
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AOP200704, infusion Drug: AOP200704
Comparison of AOP200704 with Esmolol
Active Comparator: Esmolol, infusion Drug: Esmolol hydrochloride, infusion
Comparison of AOP200704 with Esmolol

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

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01313143

Locations
Czech Republic
AOP contract research facility
Pilsen, Czech Republic, 32300
Sponsors and Collaborators
AOP Orphan Pharmaceuticals AG
Investigators
Principal Investigator: AOP Study Principal Investigator AOP Contract Clinical Research Facility
  More Information

Additional Information:
No publications provided

Responsible Party: AOP Orphan Pharmaceuticals AG
ClinicalTrials.gov Identifier: NCT01313143     History of Changes
Other Study ID Numbers: CPA368-10
Study First Received: March 10, 2011
Last Updated: July 18, 2012
Health Authority: Czech Republic: State Institute for Drug Control

Keywords provided by AOP Orphan Pharmaceuticals AG:
AOP200704, Esmolol, Pharmacokinetics, Pharmacodynamics

Additional relevant MeSH terms:
Esmolol
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 01, 2014