Double-blind, placebo-controlled, randomized, multicentre Phase II / III study to evaluate the efficacy and safety of Lisparin®, applied subcutaneously by means of a minipump in patients with advanced Parkinson’s Disease refractory to conventional oral therapy. - CALIPSO

• Register: EUCTR
• Last refreshed on: 8 August 2022
• Main ID: EUCTR2005-001006-12-DE
• Date of registration: 05/09/2006
• Prospective Registration: No
• Primary sponsor: Axxonis Pharma GmbH
• Public title: Double-blind, placebo-controlled, randomized, multicentre Phase II / III study to evaluate the efficacy and safety of Lisparin®, applied subcutaneously by means of a minipump in patients with advanced Parkinson’s Disease refractory to conventional oral therapy. - CALIPSO
• Scientific title: Double-blind, placebo-controlled, randomized, multicentre Phase II / III study to evaluate the efficacy and safety of Lisparin®, applied subcutaneously by means of a minipump in patients with advanced Parkinson’s Disease refractory to conventional oral therapy. - CALIPSO
• Date of first enrolment: 09/03/2006
• Target sample size: 60
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-001006-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Czech Republic, Germany, Italy

Key inclusion & exclusion criteria

Inclusion criteria:
• Male or Female patients
• Age 18 - 75 years
• Idiopathic Parkinson’s disease for at least 3 years (diagnosis based on the UK Brain Bank Criteria)
• Presence of motor fluctuations (wearing-off or other “OFF“ periods) and / or presence of troublesome dyskinesia, with a total daily minimum of at least 4 hours, despite optimized oral anti-parkinsonian therapy
• Stable levodopa intake, i.e. at least four doses of levodopa per day
• Stable dosing of all other anti-parkinsonian drugs, such as dopamine agonists, COMT- and MAO-B inhibitors, amantadine, or anticholin-ergics for a minimum of four weeks prior to inclusion.
• The following oral dopamine agonist drugs are allowed in this trial: pramipexol up to a total daily dose of 3,15mg, ropinirol up to a total daily dose of 24mg, cabergoline up to a total daily dose of 6mg or combinations
• Concomitant diseases are stable and well controlled
• Willingness and ability to comply with all trial requirements
• Written informed consent

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Non-idiopathic Parkinson’s disease (e.g. drug-induced or other forms of secondary or atypical parkinsonism such as MSA)
• Significant neurological symptoms not accounted for by Parkinson’s disease
• History or presence of dementia according to clinical impressions
• Mini-mental status examination (MMSE < 24)
• Presence of major depression according to DSM IV criteria (= 6 months)
• History or presence of epilepsy
• Presence of dopaminergic psychosis
• Unstable severe concomitant diseases (e.g. liver diseases, kidney diseases or clinically relevant cardiac or coronary dysfunction)
• Presence of heart valvular fibrosis or indication of significant valvular stenosis / insufficiency on echocardiogram
• History of syncope and/or severe or otherwise symptomatic orthostatic hypotension
• Present treatment with neuroleptics, including atypical neuroleptics
• Treatment with other CNS active drug therapy (e.g. sedatives, hypnotics, anti-depressants, anxiolytics) unless the dose has been stable for at least four weeks prior to the baseline visit
• Participation in another trial of an investigational drug within the last 28 days or current participation in another trial of an investigational drug
• Clinically significant laboratory abnormalities
• Previous neurosurgery for Parkinson’s disease
• Alcohol or drug abuse in the past three years
• Women of childbearing potential without adequate and effective form of birth control with a Pearl index <1% (e.g. abstinence, hormonal contraception, hormonal IUD)
• Pregnancy or lactation
• Known hypersensitivity to Lisurid, Ropinirole, Pramipexol, Cabergoline, or other ergoline substances.
• History of pleural effusion or fibrosis or acute pulmonary fibrosis.
• Raynaud-syndrome
• Known gastro-intestinal ulcers or bleedings
• Clinically significant liver failure (total bilirubin > 2.0 mg/dl or SGOT and/or SGPT greater than two times the upper limit of the reference range)
• Clinically relevant renal dysfunction (serum creatinine > 2.0 mg/dl)
• QTc interval > 470 msec at screening ECG
• Co-medication with drugs prolonging the QTc interval
• Other known risk factors for Torsades de Pointes arrhythmias (e.g. cardiac insufficiency NYHA II-IV, hypokalemia, hereditary long-QT-syndrome)


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with advanced Parkinson’s disease with motor fluctuations and “OFF” periods refractory to conventional treatment.
MedDRA version: 9.1 Level: LLT Classification code 10034006 Term: Parkinson's disease aggravated

Intervention(s)

Product Name: Lisparin
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Lisuride Hydrogenmaleate
CAS Number: 018016803
Other descriptive name: 3- (9,10- Didehydro- 6- methyl- 8?- ergolinyl)-1,1- diethylurea hydrogenmaleate
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration number: 2.0-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Subcutaneous use

Product Name: Pramipexol
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Pramipexol
CAS Number: 104632260
Other descriptive name: (S)- 2- Amino- 4,5,6,7- tetrahydro- 6- (propylamino)benzothiazol
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.35-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: Pramipexol
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Pramipexol
CAS Number: 104632260
Other descriptive name: (S)- 2- Amino- 4,5,6,7- tetrahydro- 6- (propylamino)benzothiazol
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.7-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: Cabergoline
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Cabergoline
CAS Number: 081409907
Other descriptive name: 1[(6- Allyl- 8ß- ergolinyl)carbonyl]- 1- [3- (dimethylamino)propyl]- 3- ethylurea
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1.0-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: Cabergoline
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Cabergoline
CAS Number: 081409907
Other descriptive name: 1[(6- Allyl- 8ß- erg

Primary Outcome(s)

Main Objective: To confirm superiority of Lisparin® applied as subcutaneous infusion compared to placebo in this indication.

Primary end point(s): Change from baseline B0 to T6 in total daily “OFF-time and ON-time with troublesome dyskinesia”, based upon patient diaries

Secondary Objective: To evaluate long-term efficacy, local tolerability and safety of Lisparin® applied as subcutaneous infusion compared to placebo.

Secondary ID(s)

CALIPSO

2005-001006-12-AT

Ethics review

Status: Approved
Approval date: 22/03/2006
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