A Pharmacokinetic, Pharmacodynamic, Safety Study With AOP LDLA202, ONO LDL50 and Esmolol in Healthy Volunteers
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).
Drug: ONO LDL50
Drug: Esmolol hydrochloride
|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.|
- 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 ]
- 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 ]
|Study Start Date:||July 2012|
|Study Completion Date:||August 2012|
|Primary Completion Date:||July 2012 (Final data collection date for primary outcome measure)|
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
Comparison of 3 different doses LDLA202, 40 PK samples, 40 BP and ECG measurement time points, 23 local tolerability measurement time points
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01652898
|Pilsen, Czech Republic, 323 00|
|Principal Investigator:||Ivan Ulc, Dr. med.||Cepha s.r.o|