Sialorrhea Secondary to Parkinson's Disease
Conditions
Keywords
sialorrhea, drooling, excessive salivation, parkinson's disease
Brief summary
The primary goal of the study is to evaluate the safety and potential efficacy of intra-oral dissolvable NH004 films to improve the short-term symptoms of sialorrhea (drooling) in Parkinson's disease (PD) patients.
Detailed description
NH004 contains the anticholinergic agent tropicamide and is delivered in a convenient product form (intra-oral dissolvable thin films) designed for the management of sialorrhea. This study is a double blind, placebo-controlled, crossover study of the safety and potential efficacy of three doses of of NH004 films for the short-term relief of the symptoms of sialorrhea in Parkinson's disease patients. A total of up to 36 Parkinson's disease patients will be enrolled in the study in two Phases. Phase A will include 12 patients and Phase B up to 24 patients. There will be an interim analysis after conclusion of Phase A. In both phases patients will be randomized into one of four groups. Each group will have a distinctive sequence for receiving intra-oral dissolvable films of 0.3 mg, 1 mg, 3 mg of NH004, or placebo during four visits.
Interventions
DRUG0.3 mg tropicamide
0.3 mg tropicamide in intra-oral thin film
DRUG1 mg tropicamide
1 mg tropicamide in intra-oral thin film
DRUG3 mg tropicamide
3 mg tropicamide in intra-oral thin film
DRUG0 mg tropicamide
0 mg tropicamide (placebo) in intra-oral thin film
Sponsors
Michael J. Fox Foundation for Parkinson's Research
NeuroHealing Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Patients with idiopathic Parkinson's disease, according to the United Kingdom Brain Bank criteria. 2. Patients complaining of drooling, with a score of at least 3 in the FLENI Sialorrhea scale. 3. Patient is between 50 and 80 years of age, inclusive. 4. Male or non-pregnant female. Females of child-bearing potential will be required to have undergone a pregnancy test with negative results prior to entry to the study and agree to use contraceptive measures for the duration of the study. 5. Patients must have used the same medication and dose for PD for the last month. No changes in the medication for PD are expected during the study. 6. Patients who can reasonable be expected to be on on-state for the duration of the testing procedures. 7. Patients who have a stable response to levodopa for PD.
Exclusion criteria
1. Pregnant women or women who may become pregnant. 2. Patients with a diagnosis of depression, schizophrenia or with obvious symptoms of these diseases. 3. Patients with Mini-Mental State Examination (MMSE) score equal to or lower than 26. 4. Patients who are receiving the following drugs: tricyclic antidepressants, Monoamine Oxidase Inhibitors (MAOI's), neuroleptics (antipsychotics), or anticholinergics. 5. Patients who have taken any of the drugs mentioned in
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sialorrhea Visual Analogue Scale (VAS) | Before and 120 min after treatment administration | Saliva buccal assessment was evaluated by an VAS scale before, and 15, 30, 45, 60, 90, and 120 min after treatment administration. Subjects were asked to rate how much saliva they perceived in their buccal cavity on an unmarked 0 to 10 cm line, higher scores meaning greater perceived buccal saliva levels. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change in Saliva Volume | Before and 75 minutes after treatment administration | Saliva volume was measured at baseline and 75 minutes after treatment administration. Volumes were measured by using cotton rolls placed near each Stenton duct and below the tongue for 5 minutes; cotton rolls were centrifuged and the volume of saliva determined. |
Countries
Argentina
Participant flow
Pre-assignment details
Four interventions, subjects were randomly assigned to one of 16 sequences.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants This study was a double-blind, randomized, placebo controlled, two-phased, Latin-square crossover study. Subjects received three single-doses of tropicamide or placebo in random order, with a 7-day washout period. | 19 |
| Total | 19 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 67 years STANDARD_DEVIATION 12 |
| Region of Enrollment Argentina | 19 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 19 |
| serious Total, serious adverse events | 0 / 19 |
Outcome results
Primary
Sialorrhea Visual Analogue Scale (VAS)
Saliva buccal assessment was evaluated by an VAS scale before, and 15, 30, 45, 60, 90, and 120 min after treatment administration. Subjects were asked to rate how much saliva they perceived in their buccal cavity on an unmarked 0 to 10 cm line, higher scores meaning greater perceived buccal saliva levels.
Time frame: Before and 120 min after treatment administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tropicamide - Placebo | Sialorrhea Visual Analogue Scale (VAS) | -0.55 cm on VAS | Standard Deviation 0.54 |
| Tropicamide - 0.3 mg | Sialorrhea Visual Analogue Scale (VAS) | -1.08 cm on VAS | Standard Deviation 0.54 |
| Tropicamide - 1 mg | Sialorrhea Visual Analogue Scale (VAS) | -1.53 cm on VAS | Standard Deviation 0.52 |
| Tropicamide 3 mg | Sialorrhea Visual Analogue Scale (VAS) | -0.81 cm on VAS | Standard Deviation 0.51 |
Comparison: Primary outcome was analyzed by a mixed-effects ANOVA model employing subject as a random factor as well as visit and treatment as fixed factors. Intention-to-treat (ITT) sample was analyzed. Unweighted means and their 95% Confidence Interval (CI) are reported, which represent treatment group means adjusted for the effect of visit and removing the intra-subject variability. For all analyses, significance level was set at 5%.p-value: 0.6ANOVA
Secondary
Percentage Change in Saliva Volume
Saliva volume was measured at baseline and 75 minutes after treatment administration. Volumes were measured by using cotton rolls placed near each Stenton duct and below the tongue for 5 minutes; cotton rolls were centrifuged and the volume of saliva determined.
Time frame: Before and 75 minutes after treatment administration
Population: Percentage saliva volume change was determined in the last seven (7) patients enrolled.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tropicamide - Placebo | Percentage Change in Saliva Volume | -5 percentage change of saliva volume |
| Tropicamide - 0.3 mg | Percentage Change in Saliva Volume | -27 percentage change of saliva volume |
| Tropicamide - 1 mg | Percentage Change in Saliva Volume | -33 percentage change of saliva volume |
| Tropicamide 3 mg | Percentage Change in Saliva Volume | -20 percentage change of saliva volume |