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

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

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.

Study Overview

• Status: Completed
• Conditions: Sialorrhoea
• Intervention / Treatment: Drug: oxybutynin and clonidine oral solution treatment D; Drug: oxybutynin and clonidine oral solution treatment C; Drug: oxybutynin and clonidine oral solution treatment A; Drug: oxybutynin and clonidine oral solution treatment B

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Bingham Farms, Michigan, United States, 48025
      • Quest Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: oxybutynin and clonidine oral solution treatment D; Placebo	Drug: oxybutynin and clonidine oral solution treatment D; Placebo; Other Names: Placebo
Experimental: oxybutynin and clonidine oral solution treatment C; High dose oxybutynin and clonidine	Drug: oxybutynin and clonidine oral solution treatment C; Other Names: OP-014
Experimental: oxybutynin and clonidine oral solution treatment A; Low dose oxybutynin and clonidine	Drug: oxybutynin and clonidine oral solution treatment A; Other Names: OP-014
Experimental: oxybutynin and clonidine oral solution treatment B; Intermediate dose oxybutynin and clonidine	Drug: oxybutynin and clonidine oral solution treatment B; 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.

Collaborators and Investigators

• Sponsor: Orient Pharma Co., Ltd.
• Investigators: Study Director: Chi-Tai Chang, PhD, Orient Pharma Co., Ltd.; Principal Investigator: Aaron L Ellenbogen, DO, MPH, Quest Research Institute

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: June 8, 2011
• First Submitted That Met QC Criteria: June 8, 2011
• First Posted (Estimate): June 10, 2011

Study Record Updates

• Last Update Posted (Actual): April 10, 2023
• Last Update Submitted That Met QC Criteria: March 15, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: oxybutynin; Parkinson's disease; clonidine; OC Oral Solution; sialorrhoea
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stomatognathic Diseases; Mouth Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Salivary Gland Diseases; Parkinson Disease; Sialorrhea; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Anti-Infective Agents; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Urological Agents; Analgesics; Sensory System Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympatholytics; Anti-Infective Agents, Urinary; Renal Agents; Oxybutynin; Pharmaceutical Solutions; Clonidine; Mandelic Acids
• Other Study ID Numbers: OP-014-201