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

Phase 2

Completed

Conditions: Sialorrhoea

Interventions: Drug: oxybutynin and clonidine oral solution treatment A
Drug: oxybutynin and clonidine oral solution treatment D
Drug: oxybutynin and clonidine oral solution treatment C
Drug: oxybutynin and clonidine oral solution treatment B

Registration Number: NCT01370811

Lead Sponsor: Orient Pharma Co., Ltd.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 24

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
oxybutynin and clonidine oral solution treatment A	oxybutynin and clonidine oral solution treatment A	Low dose oxybutynin and clonidine
oxybutynin and clonidine oral solution treatment D	oxybutynin and clonidine oral solution treatment D	Placebo
oxybutynin and clonidine oral solution treatment C	oxybutynin and clonidine oral solution treatment C	High dose oxybutynin and clonidine
oxybutynin and clonidine oral solution treatment B	oxybutynin and clonidine oral solution treatment B	Intermediate dose oxybutynin and clonidine

Primary Outcome Measures

Name	Time	Method
Saliva Secreted Rate	8 hours post-dose	Change from baseline, negative mean reduce secret rate from baseline, positive mean not reduce secretion.

Secondary Outcome Measures

Name	Time	Method
Numeric Rating Scale (NRS) Measurements of Subjective Judgment of Excessive Saliva Production	8 hours post-dose	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.
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	during the study treatment period and follow up period at least 23 days excluding the screening period.	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.