HealthyPhase 1NCT01741519
Long-term PK and Safety/Tolerability Testing LDLL600 Against Esmolol in Healthy Volunteers
A Phase 1 study testing LDLL600 and Brevibloc in people with Healthy, run by AOP Orphan Pharmaceuticals AG at 1 site in Czechia.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- LDLL600 and Brevibloc
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteCzechia
- Study dates
- Dec 2012to Jan 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- Subjects with any condition which in the opinion of the investigator makes the subject unsuitable for inclusion.
- 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.
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- 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.
- Subjects with anomalies of the venous and arterial vessels of the forearms or systemic vascular diseases.
- Subjects with small and/or invisible and/or badly visible veins on both forearms.
- Pregnancy and/or breast-feeding.
- History of serious clinical illness that can impact fate of drugs.
- Use of organ toxic drugs within 3 months before the first dose. Any drug with a well-defined potential for toxicity to a major organ or system is to be considered here.
- Systemic multiple dose treatment with drugs altering hepatic metabolism or monoamineoxidase (MAO) inhibitors within 30 days before the first dose.
- Donation of 1) 400 mL of blood or more within 60 days, or 2) more than 150 mL of blood within 30 days, or 3) plasma or platelets within 14 days before the first dose.
- Regular use of medication except hormonal contraceptives or replacement therapy (HC or HRT) taken without significant changes for three months at least.
- Any systemic prescription drug treatment or systemic over-the-counter (OTC) drug treatment within 7 days before the first dose (except HC or HRT).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Single Centre Prospective, Randomized, Double Blind, Crossover, Pharmacokinetic, Safety and Tolerability Study to Compare Long-term Infusion Administration of LDLL600 Against Esmolol in Healthy Volunteers.
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).
Read the detailed description
12 subjects will be administered LDLL600 and Brevibloc in a double-blind, randomized, cross-over setting. PK, systemic cardiovascular and local tolerability and safety of 24-hour long infusions of three dose levels of both Investigational Medicinal Products (IMPs) during each treatment period will be assessed.
Each treatment period will consist of:
Dose level 1 (LOW) for 2 hours (h) Dose level 2 (MEDIUM)for 2 hours Dose level 3 (HIGH)for 2 hours PK and tolerability observation at dose level 3, 2 or 1 will be continued for 18 hours in order to end up with a total infusion period of 24 h Post-infusion follow-up (FU)for 6 hours after infusion termination
The duration of the wash-out period between treatment periods will be at least two days. Each subject, if confirmed eligible, will complete two treatment periods in total.
In case of poor tolerability, alternative dosing schemes will be followed.
- Conditions
- Healthy
- Being tested
- LDLL600, Brevibloc
- Keywords
- PK, PD, landiolol, esmolol, healthy volunteers phase I study
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LDLL600Drug
Also called Landiolol hydrochloride
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.
BreviblocDrug
Also called Esmolol
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Brevibloc |
What is being measured
The primary outcome is the main question the study is designed to answer.
PK
PK as measured by Cmax, Tmax, area under curve (AUC), residual area, T1/2, total body clearance (CL) and V
Measured: 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.
Measured: 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.
Measured: 24 h
Secondary outcomes (1)
Pharmacodynamics (PD)
PD as measured by ECG (HR, PQ, QRS, QT and QTc) and BP in mmHG.
Measured: 24 h
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2012 (estimated)
- Study startDec 2012
- Primary completionJan 2013
- Study completionJan 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- AOP Orphan Pharmaceuticals AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ivan Ulc, MD, Principal investigator, Cepha s.r.o
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01741519
- Sponsor's protocol ID
- AOP LDLL600.101
- Status last verified
- Apr 2015
- First submitted
- 3 Dec 2012
- Last updated
- 21 Apr 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Centre Prospective, Randomized, Double Blind, Crossover, Pharmacokinetic, Safety and Tolerability Study to Compare Long-term Infusion Administration of LDLL600 Against Esmolol in Healthy Volunteers.
- ClinicalTrials.gov ID
- NCT01741519
- Acronym / sponsor ID
- AOP LDLL600.101
- Conditions
- Healthy
- Keywords
- PK, PD, landiolol, esmolol, healthy volunteers phase I study
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- AOP Orphan Pharmaceuticals AGIndustry (pharma, biotech, devices)
- Study start
- Dec 2012
- Primary completion
- Jan 2013 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 5 Dec 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
12 subjects will be administered LDLL600 and Brevibloc in a double-blind, randomized, cross-over setting. PK, systemic cardiovascular and local tolerability and safety of 24-hour long infusions of three dose levels of both Investigational Medicinal Products (IMPs) during each treatment period will be assessed.
Each treatment period will consist of:
Dose level 1 (LOW) for 2 hours (h) Dose level 2 (MEDIUM)for 2 hours Dose level 3 (HIGH)for 2 hours PK and tolerability observation at dose level 3, 2 or 1 will be continued for 18 hours in order to end up with a total infusion period of 24 h Post-infusion follow-up (FU)for 6 hours after infusion termination
The duration of the wash-out period between treatment periods will be at least two days. Each subject, if confirmed eligible, will complete two treatment periods in total.
In case of poor tolerability, alternative dosing schemes will be followed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LDLL600 | Experimental | Drug: LDLL600Landiolol 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. |
| Brevibloc | Active comparator | Drug: BreviblocEsmolol, 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. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (25 listed)
- Subjects with any condition which in the opinion of the investigator makes the subject unsuitable for inclusion.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LDLL600Also: Landiolol hydrochlorideComparison of 3 different doses LDLL600 in long-term infusion. 54 PK samples, BP and ECG measurement time points, several local tolerability measurement time points. | Drug | LDLL600 |
| BreviblocAlso: EsmololComparison of 3 different doses Esmolol in long-term infusion. 54 PK samples, BP and ECG measurement time points, several local tolerability measurement time points. | Drug | Brevibloc |
Primary outcome
PK
Time frame: 24 h
PK as measured by Cmax, Tmax, area under curve (AUC), residual area, T1/2, total body clearance (CL) and V
Safety
Time frame: 24 h
Safety as measured by Adverse events, clinical chemistry, hematology, urinalysis, physical examination, ECG (HR, PQ, QRS, QT and QTc) and BP in mmHG.
Local Tolerability
Time frame: 24 h
Local tolerability as measured by signs and symptoms of inflammation judged by the clinical investigator on a 6-symptom, 4-point venous score.
1 secondary outcome
Pharmacodynamics (PD)
Time frame: 24 h
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2015.
- SponsorLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ivan Ulc, MD principal investigator
Cepha s.r.o
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LDLL600 and Brevibloc in people with Healthy, run by AOP Orphan Pharmaceuticals AG at 1 site in Czechia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PK (time frame: 24 h). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2015.