HealthyPhase 1NCT01652898
A Pharmacokinetic, Pharmacodynamic, Safety Study With AOP LDLA202, ONO LDL50 and Esmolol in Healthy Volunteers
A Phase 1 study testing LDLA202, ONO LDL50 and Esmolol hydrochloride in people with Healthy, run by AOP Orphan Pharmaceuticals AG at 1 site in Czechia.
Trial 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… 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?
- LDLA202, ONO LDL50 and Esmolol hydrochloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteCzechia
- Study dates
- Jul 2012to Aug 2012
- 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, 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
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).
Read the 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.
- Conditions
- Healthy
- Being tested
- LDLA202, ONO LDL50, Esmolol hydrochloride
- Keywords
- PK
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LDLA202Drug
Comparison of 3 different doses LDLA202, 40 PK samples, 40 BP and ECG measurement time points, 23 local tolerability measurement time points
ONO LDL50Drug
Comparison of 3 different doses ONO LDL50, 40 PK samples, 40 BP and ECG measurement time points, 23 local tolerability measurement time points
Esmolol hydrochlorideDrug
Comparison of 3 different doses Esmolol, 40 PK samples, 40 BP and ECG measurement time points, 23 local tolerability measurement time points
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: Drug: LDLA202 |
What is being measured
The primary outcome is the main question the study is designed to answer.
PK as measured by Cmax, Tmax, AUC, residual area, T1/2, CL and V
Measured: 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.
Measured: 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.
Measured: 7 hours
Secondary outcomes (1)
PD as measured by BP in mmHg and ECG parameters (HR, PQ, QRS, QT and QTc)
Measured: 7 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2012 (estimated)
- Study startJul 2012
- Primary completionJul 2012
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- AOP Orphan Pharmaceuticals AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ivan Ulc, Dr. med., Principal investigator, Cepha s.r.o
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01652898
- Sponsor's protocol ID
- AOP LDLA202.101
- Status last verified
- Sep 2012
- First submitted
- 19 Jul 2012
- Last updated
- 5 Sep 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 28091703
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01652898
- Acronym / sponsor ID
- AOP LDLA202.101
- Conditions
- Healthy
- Keywords
- PK
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- AOP Orphan Pharmaceuticals AGIndustry (pharma, biotech, devices)
- Study start
- Jul 2012
- Primary completion
- Jul 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 30 Jul 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 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).
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Esmolol hydrochloride | Active comparator | Drug: Esmolol hydrochlorideEsmolol 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 |
| ONO LDL50 | Active comparator | Drug: ONO LDL50ONO 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 |
| AOP LDLA202 | Experimental | Drug: LDLA202AOP 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 |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (15 listed)
- 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.
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 |
|---|---|---|
| LDLA202Comparison of 3 different doses LDLA202, 40 PK samples, 40 BP and ECG measurement time points, 23 local tolerability measurement time points | Drug | AOP LDLA202 |
| ONO LDL50Comparison of 3 different doses ONO LDL50, 40 PK samples, 40 BP and ECG measurement time points, 23 local tolerability measurement time points | Drug | ONO LDL50 |
| Esmolol hydrochlorideComparison of 3 different doses Esmolol, 40 PK samples, 40 BP and ECG measurement time points, 23 local tolerability measurement time points | Drug | Esmolol hydrochloride |
Primary outcome
PK as measured by Cmax, Tmax, AUC, residual area, T1/2, CL and V
Time frame: 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.
Time frame: 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.
Time frame: 7 hours
1 secondary outcome
PD as measured by BP in mmHg and ECG parameters (HR, PQ, QRS, QT and QTc)
Time frame: 7 hours
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 5 Sep 2012.
- Derived from this study: PubMed 28091703Krumpl 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.
- 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, Dr. med. 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 LDLA202, ONO LDL50 and Esmolol hydrochloride 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 7 inclusion and 15 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 5 Sep 2012. 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 as measured by Cmax, Tmax, AUC, residual area, T1/2, CL and V (time frame: 7 hours). 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?
On the ClinicalTrials.gov record for NCT01652898, which also lists 1 linked publication.
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 5 Sep 2012.