Sialorrhoea
Conditions
Keywords
oxybutynin, clonidine, OC Oral Solution, sialorrhoea, Parkinson's disease
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.
Interventions
DRUGoxybutynin and clonidine oral solution treatment A
DRUGoxybutynin and clonidine oral solution treatment B
DRUGoxybutynin and clonidine oral solution treatment C
DRUGoxybutynin and clonidine oral solution treatment D
Placebo
Sponsors
Orient Pharma Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Saliva Secreted Rate | 8 hours post-dose | Change from baseline, negative mean reduce secret rate from baseline, positive mean not reduce secretion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
This single center Phase II study was initated on 02 Aug 2011. First patient was screened on 25 Aug 2011. All the study patients were recruited from medical clinic and the patient recruitment ended on 23 Aug 2012.The last study patient completed study on 19 Sep 2012.
Pre-assignment details
After informed consent process, investigators screened 35 patients and successfully randomized 24 patients to receive study treatments. The other 11 patients were screening failure since they failed to meet study required inclusion and/or exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Sequence 1 Treatment A→Treatment B→Treatment D→Treatment C | 6 |
| Sequence 2 Treatment B→Treatment C→Treatment A→Treatment D | 6 |
| Sequence 3 Treatment C→Treatment D→Treatment B→Treatment A | 6 |
| Sequence 4 Treatment D→Treatment A→Treatment C→Treatment B | 6 |
| Total | 24 |
Baseline characteristics
| Characteristic | Sequence 2 | Sequence 3 | Sequence 1 | Sequence 4 | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 3 Participants | 4 Participants | 2 Participants | 11 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 3 Participants | 2 Participants | 4 Participants | 13 Participants |
| Age, Continuous | 64 years STANDARD_DEVIATION 6.5 | 62 years STANDARD_DEVIATION 7.45 | 64 years STANDARD_DEVIATION 6.46 | 62.8 years STANDARD_DEVIATION 7 | 63 years STANDARD_DEVIATION 7.62 |
| Region of Enrollment United States | 6 participants | 6 participants | 6 participants | 6 participants | 24 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 7 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 4 Participants | 5 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 24 | 6 / 24 | 5 / 24 | 4 / 23 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 23 |
Outcome results
Primary
Saliva Secreted Rate
Change from baseline, negative mean reduce secret rate from baseline, positive mean not reduce secretion.
Time frame: 8 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OC Oral Solution Treatment B | Saliva Secreted Rate | -6.508 percentage of change from baseline | Standard Deviation 0.165 |
| OC Oral Solution Treatment C | Saliva Secreted Rate | -34.512 percentage of change from baseline | Standard Deviation 0.147 |
| OC Oral Solution Treatment D | Saliva Secreted Rate | 83.695 percentage of change from baseline | Standard Deviation 0.281 |
| OC Oral Solution Treatment A | Saliva Secreted Rate | 7.414 percentage of change from baseline | Standard Deviation 0.175 |
Secondary
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.
Time frame: during the study treatment period and follow up period at least 23 days excluding the screening period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OC Oral Solution Treatment B | 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 | 6 Treatment Emergent Adverse Events |
| OC Oral Solution Treatment C | 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 | 6 Treatment Emergent Adverse Events |
| OC Oral Solution Treatment D | 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 | 5 Treatment Emergent Adverse Events |
| OC Oral Solution Treatment A | 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 | 4 Treatment Emergent Adverse Events |
Secondary
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.
Time frame: 8 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OC Oral Solution Treatment B | Numeric Rating Scale (NRS) Measurements of Subjective Judgment of Excessive Saliva Production | -0.8 score on a scale | Standard Deviation 1.74 |
| OC Oral Solution Treatment C | Numeric Rating Scale (NRS) Measurements of Subjective Judgment of Excessive Saliva Production | -1.2 score on a scale | Standard Deviation 1.71 |
| OC Oral Solution Treatment D | Numeric Rating Scale (NRS) Measurements of Subjective Judgment of Excessive Saliva Production | -1.6 score on a scale | Standard Deviation 1.74 |
| OC Oral Solution Treatment A | Numeric Rating Scale (NRS) Measurements of Subjective Judgment of Excessive Saliva Production | -1.1 score on a scale | Standard Deviation 1.83 |