Efficacy, Tolerability and Safety of Azilect in Subjects With Progressive Supranuclear Palsy (PROSPERA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01187888
Recruitment Status : Terminated (IMP used off label by phys. in pat. with PSP. Thus no more eligible patients were available for the study(pre-treatm.with Rasagiline=exclusion criterion)
First Posted : August 24, 2010
Last Update Posted : April 24, 2013
Teva Pharmaceutical Industries
Ludwig-Maximilians - University of Munich
Information provided by (Responsible Party):
Prof. Dr. Stefan Lorenzl, Ludwig-Maximilians - University of Munich

Brief Summary:
The purpose of this study is to determine whether rasagiline is effective in the treatment of Progressive Supranuclear Palsy (PSP), a rapidly progressing disease with a symptomatology similar to Parkinson's Disease. The major aim of this study is the limitation or halting of the process of neurodegeneration and influence postural instability.

Condition or disease Intervention/treatment Phase
Progressive Supranuclear Palsy Drug: Rasagiline Drug: Sugar pill Phase 3

Detailed Description:
Progressive Supranuclear Palsy (PSP) is a rapidly progressing disease with a median survival after onset of symptoms of 5.8 years.PSP is characterized by early falls, vertical ophthalmoparesis, akinetic-rigid features, prominent bulbar dysfunction and fronto-subcortical dementia. So far there is no treatment for the disease as the negative outcomes of the vast majority of studies make it impossible to set standards. As the majority of patients experience severe falls and vertigo already in the early phase of the disease, the drug of desire would be able to slow disease progression with a special focus on postural instability and exert neuroprotective effects. The monoamino oxidase inhibitor Rasagiline might be able to influence progression of PSP.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 44 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Assess the Efficacy, Safety and Tolerability of Rasagiline in Subjects With Progressive Supranuclear Palsy (Phase III)
Study Start Date : January 2010
Actual Primary Completion Date : June 2012
Actual Study Completion Date : June 2012

Arm Intervention/treatment
Active Comparator: Rasagiline Drug: Rasagiline
tablet once daily 1 mg 1 year
Other Name: Azilect
Placebo Comparator: Sugar pill Drug: Sugar pill
tablet once daily one year
Other Name: Placebo

Primary Outcome Measures :
  1. Assessment of the need for additional L-DOPA therapy or the need to increase the dose of L-DOPA during the trial [ Time Frame: 1 year ]
    Since there is no established treatment regimen for Progressive Supranuclear Palsy (PSP) patients, the only well characterized medication is L-3,4-Dihydroxyphenylalanine (L-DOPA) therapy. Since this therapy may exert a small effect in PSP patients, begin with L-DOPA therapy or increase in L-DOPA therapy will be used in this trial as rescue medication.

  2. Reduction of the reported deterioration using the PSP rating scale [ Time Frame: 1 year ]
    To assess the efficacy of Rasagiline using the Progressive Supranuclear Palsy Rating Scale (PSPRS), aiming at a 33% reduction of the reported deterioration (Golbe et. al., 2007), i.e. a mean yearly increase of 6.5 instead of 9.7 points.

Secondary Outcome Measures :
  1. Reduction of gait disturbances and postural stability [ Time Frame: 1 year ]
  2. Adverse Event (AE) incidence [ Time Frame: 1 year ]
  3. Safety laboratory values (blood cell count, aspartate aminotransferase [AST], alanine aminotransferase [ALT], creatinine, Vitamin B12, folic acid, homocysteine and methylmalonic acid) [ Time Frame: 1 year ]
  4. Vital signs [ Time Frame: 1 year ]
  5. Number of subjects (%) who discontinue the study [ Time Frame: 1 year ]
  6. Number of subjects (%) who discontinue the study due to AEs [ Time Frame: 1 year ]

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Ages Eligible for Study:   50 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Clinical signs of Progressive Supranuclear Palsy (PSP). Diagnosis will be made for patients with clinical probable PSP (Litvan et al., 1996). Patients will be included with PSP stage </= II (Golbe et al., 1997), at least with a PSPRS < 40 (Golbe et al., 2007) and according to the diagnostic criteria resumed after the Neuroprotection and Natural History in Parkinson Plus Syndromes (NNIPPS) trial (Bensimon et al., 2009)
  • Patients, male or female, aged 50 to 80 years
  • Subjects whose clinical condition at the time of enrolment does not or requires a low [</= 500 mg /day] stable dose of L-3,4-Dihydroxyphenylalanine (L-DOPA) for at least 2 weeks prior to study entry
  • Capability and willingness to give written signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study

Exclusion Criteria:

  • No clinically probable PSP
  • No written informed consent possible
  • Age > 80 or < 50 years
  • Dementia (Mini-Mental State Examination [MMSE] </= 24)
  • Subjects with clinically significant psychiatric illness, including major depression
  • Subjects who have taken any experimental drugs within 60 days prior to baseline
  • Subjects who have used sympathomimetics (including over-the-counter remedies - nasal or oral), dextromethorphan, pethidine or St. John's wort within 7 days prior to baseline.
  • Loss of postural reflexes (no independent walking possible, inability to stand unassisted, wheelchair-bound)
  • Feeding tube / recommendation for a feeding tube
  • Unintelligible speech
  • History of brain disease (e.g. repeated strokes, cerebral tumour, hydrocephalus)
  • 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) exposure
  • Oculogyric crisis
  • Early severe autonomic failure
  • Systemic disorder affecting the brain
  • Women who are not postmenopausal (e.g. one year without menstrual periods) or surgically sterilized.
  • Known history of hypersensitivity to the investigational drug or to drugs with a similar chemical structure
  • Subjects who have used antidepressants, including selective serotonin re-uptake inhibitors, tricyclic and tetracyclic antidepressants (except amitriptyline <= 50 mg/day, trazodone < = 100 mg/day, citalopram < = 20 mg/ day, sertraline < = 100 mg/day and paroxetine < = 30 mg/day, escitalopram < = 10 mg/day) within 42 days prior to baseline
  • Subjects who have used any drugs known to have been involved in a drug interaction via inhibition of hepatic Cytochrome P450 1A2 (CYP 1A2) within 30 days prior to baseline (cimetidine, ciprofloxacin, clarithromycin, enoxacin, erythromycin, fluvoxamine, isoniazide, nalidixic acid, norfloxacin, troleandomycin, zileuton)
  • Subjects who have used Monoamine oxidase (MAO) inhibitors including reserpine and methyldopa within three months prior to baseline
  • Anti-emetic or antipsychotic medication with central dopamine antagonist activity (except quetiapine fumarate) within six months prior to baseline
  • Participation in a clinical trial within the last 30 days prior to study start
  • Unstable antiparkinsonian medication within 30 days before baseline
  • Previous use of Rasagiline or Selegiline
  • Subjects who have a clinically significant or unstable medical or surgical condition that may preclude safe and complete study participation (based on the investigator's judgment). Such conditions might include cardiovascular, vascular diseases, pulmonary, hepatic impairment (Child-Pugh score > 5), renal, or metabolic dis-eases or malignancies as determined by medical history, physical examination, laboratory tests, or ECG

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01187888

Department of Neurology and Palliative Care Klinikum der Universität München (Hospital of the University of Munich)
München, Germany, 81377
Sponsors and Collaborators
Prof. Dr. Stefan Lorenzl
Teva Pharmaceutical Industries
Ludwig-Maximilians - University of Munich
Principal Investigator: Stefan Lorenzl, PD Dr. Klinikum der Universität München (Hospital of the University of Munich)

Responsible Party: Prof. Dr. Stefan Lorenzl, Principal Investigator and Sponsor Delegated Person, Hospital of the University of Munich, Ludwig-Maximilians - University of Munich Identifier: NCT01187888     History of Changes
Other Study ID Numbers: 08P02
2008-007520-26 ( EudraCT Number )
First Posted: August 24, 2010    Key Record Dates
Last Update Posted: April 24, 2013
Last Verified: April 2013

Keywords provided by Prof. Dr. Stefan Lorenzl, Ludwig-Maximilians - University of Munich:
Progressive Supranuclear Palsy

Additional relevant MeSH terms:
Supranuclear Palsy, Progressive
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Movement Disorders
Ocular Motility Disorders
Cranial Nerve Diseases
Neurodegenerative Diseases
Eye Diseases
Monoamine Oxidase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Neuroprotective Agents
Protective Agents
Physiological Effects of Drugs