A Pharmacokinetic, Pharmacodynamic, Safety Study With AOP LDLA202, ONO LDL50 and Esmolol in Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AOP Orphan Pharmaceuticals AG
ClinicalTrials.gov Identifier:
NCT01652898
First received: July 19, 2012
Last updated: September 4, 2012
Last verified: September 2012
  Purpose

The study consists of a Pilot Phase (to assess safety and the local tolerability of highest AOP LDLA202 dose versus placebo) and a Main Treatment Phase (to compare PK, PD and safety and tolerability of AOP LDLA202, ONO LDL50 and esmolol bolus administrations by measurement of blood concentrations of landiolol, esmolol and their metabolites, and by monitoring ECG, blood pressure and adverse events).


Condition Intervention Phase
Healthy
Drug: LDLA202
Drug: ONO LDL50
Drug: Esmolol hydrochloride
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Single Centre Prospective, Randomized, Double Blind, Crossover, Three-treatment Periods PK, PD, Safety and Tolerability Study to Compare Bolus Administration of AOP LDLA202, ONO LDL50 and Esmolol in Healthy Volunteers After a Pilot Phase of AOP LDLA202 Safety and Local Tolerability Assessment.

Resource links provided by NLM:


Further study details as provided by AOP Orphan Pharmaceuticals AG:

Primary Outcome Measures:
  • PK as measured by Cmax, Tmax, AUC, residual area, T1/2, CL and V [ Time Frame: 7 hours ] [ Designated as safety issue: No ]
  • Local tolerability as measured by signs and symptoms of inflammation judged by the clinical investigator on a 6-symptom, 4-point venous score. [ Time Frame: 7 hours ] [ Designated as safety issue: No ]
  • Safety as measured by Adverse events, clinical chemistry, hematology, urinalysis, physical examination, ECG (HR, PQ (PR), QRS, QT and QTc) and BP in mmHg. [ Time Frame: 7 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • PD as measured by BP in mmHg and ECG parameters (HR, PQ, QRS, QT and QTc) [ Time Frame: 7 hours ] [ Designated as safety issue: No ]

Enrollment: 12
Study Start Date: July 2012
Study Completion Date: August 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Esmolol hydrochloride
Esmolol hydrochloride administered as intravenous bolus injection at low (0,5mg/kg), medium (1mg/kg) and high dose (1,5mg/kg) in 15/30/45 seconds once per subject
Drug: Esmolol hydrochloride
Comparison of 3 different doses Esmolol, 40 PK samples, 40 BP and ECG measurement time points, 23 local tolerability measurement time points
Active Comparator: ONO LDL50
ONO LDL50 administered as intravenous bolus injection at low (0,1mg/kg), medium (0,2mg/kg) and high dose (0,3mg/kg) in 15/30/45 seconds once per subject
Drug: ONO LDL50
Comparison of 3 different doses ONO LDL50, 40 PK samples, 40 BP and ECG measurement time points, 23 local tolerability measurement time points
Experimental: AOP LDLA202
AOP LDLA202 administered as intravenous bolus injection at low (0,1mg/kg), medium (0,2mg/kg) and high dose (0,3mg/kg) in 15/30/45 seconds once per subject
Drug: LDLA202
Comparison of 3 different doses LDLA202, 40 PK samples, 40 BP and ECG measurement time points, 23 local tolerability measurement time points

Detailed Description:

A single centre prospective, randomized, double blind study consisting of a local safety Pilot Phase and a triple-cross-over Main Study Phase.

In the pilot phase, 3 subjects will be administered a bolus with AOP LDLA202 vs. placebo (0.9% saline) simultaneously (same vein on the other body side). Following treatment of the first subject per cohort and assuming no safety concerns arise, second and third subjects will be treated in safety intervals of at least 3 hours between doses in individual subjects. On Day 3 after dosing a safety follow-up assessment will be done and all adverse events will be reported to the sponsor's medical monitor. Assuming no safety concerns arise, the sponsor's medical monitor will give green light for conduct of the Main Treatment Phase in writing.

In the main phase, 12 subjects will be treated with AOP LDLA202, ONO LDL50 and esmolol. Three doses per subject and day (=treatment period), all administered via big superficial veins, are planned with at least 1 hour observation period after each bolus injection. Each subject, if confirmed eligible, will complete three treatment periods in total in the main phase of the study.

ECG, blood pressure, local tolerability and adverse events will be monitored.

  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, Caucasians
  • Body weight of at least 50 kg, maximum of 90 kg. Body-mass index 18.5 to 30.0 kg/m2.
  • Subjects without clinically relevant abnormalities as determined by baseline medical history, physical examination, blood pressure, heart rate and ear temperature at screening.
  • Subjects without clinically relevant abnormalities as determined by blood count, coagulation tests, biochemistry, infectious disease screening, 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
  • No history or presence of alcoholism or drug abuse

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, 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 any IMP.
  • 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.
  • Subjects with anomalies of the venous and arterial vessels of the forearms or systemic vascular diseases.
  • Pregnancy and/or breast-feeding.
  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: NCT01652898

Locations
Czech Republic
Cepha s.r.o
Pilsen, Czech Republic, 323 00
Sponsors and Collaborators
AOP Orphan Pharmaceuticals AG
Investigators
Principal Investigator: Ivan Ulc, Dr. med. Cepha s.r.o
  More Information

Additional Information:
No publications provided

Responsible Party: AOP Orphan Pharmaceuticals AG
ClinicalTrials.gov Identifier: NCT01652898     History of Changes
Other Study ID Numbers: AOP LDLA202.101
Study First Received: July 19, 2012
Last Updated: September 4, 2012
Health Authority: Czech Republic: State Institute for Drug Control

Keywords provided by AOP Orphan Pharmaceuticals AG:
PK

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 October 02, 2014