Long-term PK and Safety/Tolerability Testing LDLL600 Against Esmolol in Healthy Volunteers

NCT01741519 | Completed Phase 1

• 1 other identifier: AOP LDLL600.101
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The study will compare the pharmacokinetics (PK), safety and tolerability of long-term infusion of lyophilized landiolol (LDLL600) against esmolol (Brevibloc) by measurement of blood concentrations of landiolol, esmolol and their metabolites, and by monitoring systemic cardiovascular and local tolerability, blood pressure (BP), ECG including heart rate (HR) and adverse events (AEs).

Conditions

Healthy

Keywords

PK; PD; landiolol; esmolol; healthy volunteers phase I study

Outcome Measures

Primary Outcomes (3)

• PK

  PK as measured by Cmax, Tmax, area under curve (AUC), residual area, T1/2, total body clearance (CL) and V

  24 h

• Safety

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

  24 h

• Local Tolerability

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

  24 h

Secondary Outcomes (1)

• Pharmacodynamics (PD)

  24 h

Study Arms (2)

LDLL600

EXPERIMENTAL

Landiolol hydrochloride, intravenous infusion of 10, 20 and 40 µg/kg/min for 2 h each followed by 18 h long-term infusion of best tolerated dose.

Drug: LDLL600

Brevibloc

ACTIVE COMPARATOR

Esmolol, intravenous infusion of 50, 100 and 200 µg/kg/min for 2 h each followed by 18 h long-term infusion of best tolerated dose.

Drug: Brevibloc

Interventions

LDLL600 DRUG

Comparison of 3 different doses LDLL600 in long-term infusion. 54 PK samples, BP and ECG measurement time points, several local tolerability measurement time points.

Also known as: Landiolol hydrochloride

LDLL600

Brevibloc DRUG

Comparison of 3 different doses Esmolol in long-term infusion. 54 PK samples, BP and ECG measurement time points, several local tolerability measurement time points.

Also known as: Esmolol

Brevibloc

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.
• Body weight of at least 50 kg, maximum of 90 kg. Body-mass index 18.5 to 30.0 kg/m2.
• Caucasian race.
• 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 (except factors for thrombophlebitis), infectious disease screening (HIV, hepatitis B and hepatitis C), 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 or over the counter medications including vitamins and minerals for 7 days prior to study and during the course of the study (unless prescribed by the principal investigator for treatment of adverse events).
• No history or presence of alcoholism.
• No history of drug abuse (benzodiazepines, barbiturates, cocaine) for the last one month and other illegal drugs for the last 6 months.

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 the 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 landiolol, esmolol, or related drugs.
• 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.
• Found positive in breath alcohol test done at the time of screening and on the day of check-in for the study for each period.
• Found positive in urine test for drug abuse done on the day of check-in for the study for each period.

Sponsors & Collaborators

• AOP Orphan Pharmaceuticals AG: lead

Study Sites (1)

Cepha s.r.o

Pilsen, 323 00, Czechia

Location

Related Links

• Sponsor

MeSH Terms

Interventions

esmolol

Study Officials

• Ivan Ulc, MD

  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: December 3, 2012
• First Posted: December 5, 2012
• Study Start: December 1, 2012
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: April 21, 2015

Record last verified: 2015-04

Locations

CZ (1)