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

NCT01652898 | Completed Phase 1

• 1 other identifier: AOP LDLA202.101
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Healthy

Keywords

PK

Outcome Measures

Primary Outcomes (3)

• PK as measured by Cmax, Tmax, AUC, residual area, T1/2, CL and V

  7 hours

• Local tolerability as measured by signs and symptoms of inflammation judged by the clinical investigator on a 6-symptom, 4-point venous score.

  7 hours

• Safety as measured by Adverse events, clinical chemistry, hematology, urinalysis, physical examination, ECG (HR, PQ (PR), QRS, QT and QTc) and BP in mmHg.

  7 hours

Secondary Outcomes (1)

• PD as measured by BP in mmHg and ECG parameters (HR, PQ, QRS, QT and QTc)

  7 hours

Study Arms (3)

Esmolol hydrochloride

ACTIVE COMPARATOR

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

ONO LDL50

ACTIVE COMPARATOR

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

AOP LDLA202

EXPERIMENTAL

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

Interventions

LDLA202 DRUG

Comparison of 3 different doses LDLA202, 40 PK samples, 40 BP and ECG measurement time points, 23 local tolerability measurement time points

AOP LDLA202

ONO LDL50 DRUG

Comparison of 3 different doses ONO LDL50, 40 PK samples, 40 BP and ECG measurement time points, 23 local tolerability measurement time points

ONO LDL50

Esmolol hydrochloride DRUG

Comparison of 3 different doses Esmolol, 40 PK samples, 40 BP and ECG measurement time points, 23 local tolerability measurement time points

Esmolol hydrochloride

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• AOP Orphan Pharmaceuticals AG: lead

Study Sites (1)

Cepha s.r.o

Pilsen, 323 00, Czechia

Location

Related Publications (1)

• Krumpl G, Ulc I, Trebs M, Kadlecova P, Hodisch J. Bolus application of landiolol and esmolol: comparison of the pharmacokinetic and pharmacodynamic profiles in a healthy Caucasian group. Eur J Clin Pharmacol. 2017 Apr;73(4):417-428. doi: 10.1007/s00228-016-2176-0. Epub 2017 Jan 13.

  PMID: 28091703 DERIVED

Related Links

• Sponsor

MeSH Terms

Interventions

esmolol

Study Officials

• Ivan Ulc, Dr. med.

  Cepha s.r.o

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2012
• First Posted: July 30, 2012
• Study Start: July 1, 2012
• Primary Completion: July 1, 2012
• Study Completion: August 1, 2012
• Last Updated: September 5, 2012

Record last verified: 2012-09

Locations

CZ (1)