A Relative Efficacy and Safety Study of OC Oral Solution for Sialorrhoea in Patients With Parkinson's Disease

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether OC (oxybutynin and clonidine) oral solution is effective in reducing saliva secretion in patients suffering from Parkinson's Disease with excessive salivation.

Detailed Description
-----------------
Sialorrhea is excessive flow of saliva associated with its unintentional loss from the mouth, commonly known as drooling. Sialorrhea may result from any combination of hypersecretion, problems swallowing or sensorimotor problems containing saliva in the mouth. It is commonly found in people with neurological dysfunction such as Parkinson's Disease, leading to social isolation and embarrassment. In general, treatment options are limited because of the underlying chronic disease. The objective of the proposed low-dose, new combination drug, OC Oral solution is to develop a new treatment option that can be used to titrate saliva secretion rates to a level that is low enough to prevent unintentional loss (i.e. drooling) but not so low as to cause an uncomfortably dry mouth.

Official Title
-----------------
A Phase II, Double-blind, Randomized, Placebo-controlled 4-way Crossover Study to Evaluate the Relative Efficacy and Safety of OC Oral Solution (Oxybutynin and Clonidine) for Sialorrhoea in Patients With Parkinson's Disease

Conditions
-----------------
Sialorrhoea

Intervention / Treatment
-----------------
* Drug: oxybutynin and clonidine oral solution treatment A
* Drug: oxybutynin and clonidine oral solution treatment B
* Drug: oxybutynin and clonidine oral solution treatment C
* Drug: oxybutynin and clonidine oral solution treatment D


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of Parkinson's Disease for at least 2 years Patients with a score of ≥2 on the salivation section of UPDRS, item 6 Patients Hoehn and Yahr stage must be ≤4 under stable anti-Parkinson therapy throughout the study Able and willing to comply with the study procedures Able to provide and provision of a written informed consent Exclusion Criteria: Female who is pregnant/lactating or planning to be pregnant Must not have a form of drug-induced or atypical parkinsonism or parkinsonism with swallow problems due to other etiology Have current uncontrolled hypertension, symptomatic postural hypotension, active Raynaud's disease or other peripheral vascular occlusive disease Have a history or presence of hyperthyroidism, congestive heart failure, coronary heart disease, cardiac arrhythmias, tachycardia or severe bradycardia resulting from either sick sinus syndrome or AV block of 2nd or 3rd degree Have a history of narrow angle glaucoma or shallow anterior chamber Have a history or presence of gastrointestinal obstruction, including paralytic ileus and intestinal atony or gastrointestinal motility disorders, toxic megacolon or severe ulcerative colitis Have a history or presence of bladder outflow obstruction or urinary retention Patients with hepatic or renal impairment Male with QTc > 430 ms or female with QTc > 450 ms ECG results at screening Concomitant use of α2-agonist, anticholinergic medication or other medications that affect ACh levels Have a history of alcohol or substance abuse Any condition, including the presence of laboratory abnormalities, which places the patient at unacceptable risk to participate in the study or confounds the ability to interpret data from the study Have a history of hypersensitivity to the investigational medicinal product or any of the excipients or to medicinal products with similar chemical structures Have received treatment with any other investigational medicinal product in the last 6 weeks before administration of the first dose in this clinical study Have received treatment with any medicinal product known to have a well-defined potential for toxicity to a major organ in the previous 3 months Have a positive result of the human immunodeficiency virus (HIV) 1 and 2 test Have problems to understand the protocol requirements, instructions and study related restrictions, the nature, scope and possible consequences of the clinical study Are unlikely to comply with the protocol requirements, instructions and study related restrictions Patient is the Investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the clinical study Vulnerable subjects Have any concurrent disease or condition that, in the opinion of the Investigator, would make the patient unsuitable for participation in the clinical study Donation of 500 ml or more of blood within the last 8 weeks before start of the study and for at least 4 weeks after study completion Have previously been enrolled in this clinical study Vulnerable subjects

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: oxybutynin and clonidine oral solution treatment D<br>Placebo | Drug: oxybutynin and clonidine oral solution treatment D<br>* Placebo<br>* Other names: Placebo;|
| Experimental: oxybutynin and clonidine oral solution treatment C<br>High dose oxybutynin and clonidine | Drug: oxybutynin and clonidine oral solution treatment C<br> <br> * Other names: OP-014;|
| Experimental: oxybutynin and clonidine oral solution treatment A<br>Low dose oxybutynin and clonidine | Drug: oxybutynin and clonidine oral solution treatment A<br> <br> * Other names: OP-014;|
| Experimental: oxybutynin and clonidine oral solution treatment B<br>Intermediate dose oxybutynin and clonidine | Drug: oxybutynin and clonidine oral solution treatment B<br> <br> * Other names: OP-014;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Saliva Secreted Rate | Change from baseline, negative mean reduce secret rate from baseline, positive mean not reduce secretion. | 8 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numeric Rating Scale (NRS) Measurements of Subjective Judgment of Excessive Saliva Production | Evaluation of change from baseline the subjective assessment of saliva production after administration of a single dose of different combinations of oxybutynin and clonidine (OC Oral solution) in patients suffering from Parkinson's disease with excessive salivation. Compare with baseline the number of rate scale was more production with baseline or reduce from baseline. The min and max of the score is 0 and 10, the total range is 0 10, and higher value is represented more worse outcome. | 8 hours post-dose | 
| Evaluation of the Safety and Tolerability of Different Combinations of Oxybutynin and Clonidine (OC Oral Solution) in Patients Suffering From Parkinson's Disease With Excessive Salivation | Evaluation of the safety and tolerability of different combinations of oxybutynin and clonidine (OC Oral solution) in patients suffering from Parkinson's disease with excessive salivation. Calculate the treatment Emergent Adverse Events number during the study treatment period and follow up period up to at least 23 days excluding the screening period. | during the study treatment period and follow up period at least 23 days excluding the screening period. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
oxybutynin, clonidine, OC Oral Solution, sialorrhoea, Parkinson's disease