E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Idiopathic 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 | 18.0 |
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 |
primary objective is determining the efficacy of varenicline in reducing EDS in PD patients after 4 weeks of daily use. |
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E.2.2 | Secondary objectives of the trial |
As secondary objectives we investigate whether varenicline treatment improves nocturnal sleep quality and quality of life. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
- title: pharmacokinetic-pharmacodynamic relationships of varenicline in Parkinson's disease
- date: 26-04-2012
-version: 2.0
- objective: establish a pharmacokinetic-pharmacodynamic (PK-PD) model for the effects of varenicline plasma levels on neuro-cognitive function |
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E.3 | Principal inclusion criteria |
- idiopathic PD according to clinical diagnostic criteria UK PD Society Brain Bank
- receiving stable PD medications for at least four weeks before and throughout study
- suffering EDS, defined by a score of >10 on the Epworth Sleeping Scale (ESS)
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E.4 | Principal exclusion criteria |
- PD patients receiving medications with known central depressant effects (benzodiazepines, neuroleptics, anticholinergics)
- dementia defined by a Mini Mental State Examination (MMSE) <24
- depression defined by a Beck Depression Inventory (BDI) >16
- a known diagnosis of sleep apnea or narcolepsy
- current smoking or smoking cessation in past 6 months
- presence of contra-indications for treatment with varenicline, including:
known psychiatric diseases, alcohol or drug abuse, unstable angina, a history of cardiac disease or stroke in previous 6 months, severe renal failure (glomerular filtration rate ≤ 30 ml/min), insulin-dependent diabetes
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E.5 End points |
E.5.1 | Primary end point(s) |
the difference in severity of EDS as measured by the ESS at baseline and after four weeks treatment (varenicline vs placebo) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
after two times four weeks treatment (cross over design) |
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E.5.2 | Secondary end point(s) |
• the difference in nocturnal sleep disturbance on the SCales for Outcome of Parkinson’s Disease sleep (SCOPA- sleep) after four weeks treatment varenicline vs placebo
• the difference in overall sleep quality on the Pittsburgh Sleep Quality Inventory (PSQI) after four weeks treatment varenicline vs placebo
• the difference in fatigue on the Fatigue Severity Scale (FSS) after four weeks treatment varenicline vs placebo
• the difference in quality of life on the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) after four weeks treatment varenicline vs placebo
• the plasmaconcentrations of varenicline after first administration and in steady state condition (measured in subgroup only)
• the pharmacodynamic effects on central nervous system functioning of varenicline after first administration and in steady state condition through scores on the NeuroCart test battery (measured in subgroup only)
• the difference in sleep latency after first administration of varenicline and in steady state condition measured by the Maintenance of Wakefulness Test (MWT) (measured in subgroup only)
• the correlation of error scores on the Sustained Attention to Response Test (SART) as a part of the NeuroCart test battery and the mean time until sleep onset on the MWT (measured in subgroup only)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
after two times four weeks treatment (cross over design) |
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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 | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | Yes |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |