E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Levodopa induced dyskinesias within Parkinson's disease. |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061536 |
E.1.2 | Term | Parkinson's disease |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate that buspirone which is a serotonine (5HT1A) antagonist will reduce the levels of synaptic dopamine generated from the serotonergic terminals after L−dopa administration. This will be associated with a reduction in dyskinesia intensity in PD patients. |
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E.2.2 | Secondary objectives of the trial |
To elucidate more the role of dysregulated DA transmission from striatum for groups of patients with PD with different degrees of severity in LIDs through analysis with data already gained from our previous studies. This will be confirmed by functional Imaging with PET and 11C-PHNO targeting postsynaptic D2/3 receptors on a Buspirone+Levodopa vs Placebo+Levodopa acute challenge. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The inclusion/exclusion criteria include non-depressed, non-demented PD subjects with no other history of neurological or psychiatric illness and who are not receiving any medication with known direct action on the 5-HT system. All patients will have a clinical diagnosis of idiopathic Parkinson's disease according to UK Parkinson's Disease Society Brain Bank diagnostic criteria. The participants will be people above the age of 40 and under the age of 80.
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E.4 | Principal exclusion criteria |
Subjects that have developed dementia and/or Parkinson plus syndromes. Subjects with depression and/or anxiety disorders history will be excluded. Subjects with epilepsy and/or other neurological conditions will be excluded. Subjects with acute porphyria history will be excluded. Subjects that are receiving medication with known action on the 5-HT system. Subjects with a clinical history that Buspirone is contraindicated. Subject with a clinical history of acute intoxication with alcohol, hypnotics, analgesics, or antipsychotic drugs. Patients with severe renal or hepatic impairment. Women of child bearing potential will be provided with a beta human chorionic gonadotropin (b-HCG) pregnancy test (by urine dipstick method) on each visit prior to the administration of the Buspirone. An additional urine b-HCG pregnancy test will be performed on each PET visit. Positive results of this b-HCG test exclude potential participants from this study. Pregnant and breast feeding women are excluded from this study. Patients who recently took part in clinical studies or underwent medical procedures involving ionizing radiation will be excluded from participation in the PET part of the study if participation will lead to an ionising radiation exposure >10mSv in the past 12 months. Patients found to have contraindications to having an MRI scan (e.g, claustrophobia, metal implants).
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E.5 End points |
E.5.1 | Primary end point(s) |
We will assess/measure whether the severity of Levodopa-induced dyskinesias improves by the administration of Buspirone prior to Levodopa and we will compare this to placebo. We anticipate that Buspirone will be efficient in attenuating the Levodopa-induced dyskinesias in Parkinson's disease patients without counteracting Levodopa's main effects. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 17 |