E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Sialorrhoea associated with Parkinson's Disease |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059812 |
E.1.2 | Term | Sialorrhoea |
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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 determine whether adding oxybutynin to a dose of clonidine that has a demonstrable inhibitory effect on saliva secretion rates produces an additional inhibitory effect.
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E.2.2 | Secondary objectives of the trial |
• To determine the dose-response relationship for clonidine and saliva secretion rates in Parkinson’s disease patients. • To determine the dose-response relationship for a fixed dose of clonidine in combination with a range of doses of oxybutynin and saliva excretion rates in Parkinson’s disease patients. • To determine the ratio of oxybutynin:clonidine doses that produce the maximum inhibitory effect on saliva secretion rates. • To evaluate the safety profile of clonidine alone and in combination with oxybutynin in PD patients. • To determine the PK profile of clonidine alone, and of clonidine and oxybutynin when these drugs are co-administered, in PD patients. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The patient has Parkinson’s disease, with a score of >2 on the salivation section of UPDRS. 2. The patients’ anti-Parkinsonian medication is anticipated to remain constant (in terms of drugs, doses and timing) throughout the study period. 3. The patient is aged 18 to 75 years. 4. The patient is capable of giving informed consent and complying with the restrictions and requirements of the protocol. 5. The patient is available to complete the study. 6. The patient is registered with a General Practitioner (GP). 7. A signed and dated consent form has been obtained from the patient in accordance with ICH GCP. |
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E.4 | Principal exclusion criteria |
1. As a result of the medical screening process, the study physician considers the patient unfit for the study. 2. The patient is taking anticholinergic or α2 agonist medication. 3. The patient is taking medication that affects acetyl choline levels e.g. tricyclic antidepressants. 4. The patient has a history or presence of bladder outflow obstruction. 5. The patient has a hypersensitivity to oxybutynin or any component. 6. The patient has a hypersensitivity to clonidine hydrochloride or any component. 7. The patient has a history or presence of Myasthenia gravis. 8. The patient has a history of narrow angle glaucoma or shallow anterior chamber. 9. The patient has a history or presence of gastrointestinal obstruction including paralytic ileus and intestinal atony or gastrointestinal motility disorders. 10. The patient has a history or presence of toxic megacolon or severe ulcerative colitis. 11. The patient has documented autonomic neuropathy, hepatic or renal impairment, 12. The patient has presence of any clinically significant abnormality, in the opinion of the Investigator, on ECGs (including patients with baseline QTc > 430 msecs - males, > 450 msecs female) at screening. 13. The patient has a history or presence of severe bradyarrhythmia resulting from either sick sinus syndrome or AV block of 2nd or 3rd degree. 14. The patient has a history or presence of hyperthyroidism, congestive heart failure, coronary heart disease, cardiac arrhythmias, tachycardia, current uncontrolled hypertension, significant postural hypotension or urinary retention. 15. The patient has current active depression, Raynaud’s disease or other peripheral vascular occlusive disease. 16. The patient has a history of drug or other allergy that contraindicates his/her participation. 17. The patient has participated in a study with a new molecular entity within 4 months, or any other drug trial within 3 months of dosing with the investigational product or placebo. 18. The patient has donated a unit of blood (450 mL) in the 3 months prior to dosing or intends to donate in the month after the last scheduled study visit. 19. The subject has a history of drug abuse. 20. The patient, if a pre menopausal female, is pregnant or at risk of becoming pregnant. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Saliva excretion rates as determined by Saxon tests - Vital signs (lying and standing blood pressure and heart rate). - Continuously monitored blood pressure and heart rate |
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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 | No |
E.6.4 | Safety | Yes |
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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
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 | Information not present in EudraCT |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |