Safety and Efficacy Study of NH004 Films for Relief of Sialorrhea Symptoms in Parkinson's Disease Patients

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Two-Phase, Double Blind, Placebo-Controlled, Randomized, Crossover Study of the Safety and Efficacy of Intra-Oral NH004 Films for the Short-Term Relief of Sialorrhea Symptoms in Parkinson's Disease Patients

Conditions
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Sialorrhea Secondary to Parkinson's Disease

Intervention / Treatment
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* Drug: 0.3 mg tropicamide
* Drug: 1 mg tropicamide
* Drug: 3 mg tropicamide
* Drug: 0 mg tropicamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with idiopathic Parkinson's disease, according to the United Kingdom Brain Bank criteria. Patients complaining of drooling, with a score of at least 3 in the FLENI Sialorrhea scale. Patient is between 50 and 80 years of age, inclusive. 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. 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. Patients who can reasonable be expected to be on on-state for the duration of the testing procedures. Patients who have a stable response to levodopa for PD. Exclusion Criteria: Pregnant women or women who may become pregnant. Patients with a diagnosis of depression, schizophrenia or with obvious symptoms of these diseases. Patients with Mini-Mental State Examination (MMSE) score equal to or lower than 26. Patients who are receiving the following drugs: tricyclic antidepressants, Monoamine Oxidase Inhibitors (MAOI's), neuroleptics (antipsychotics), or anticholinergics. Patients who have taken any of the drugs mentioned in exclusion criteria number 4 within the last week. Patients with hypersensitivity to atropine or other anticholinergic drugs. Patients who have experienced adverse effects as a result of taking anticholinergic drugs. Patients taking hypnotic or other sleep inducing drugs. Patients with severe urinary or gastrointestinal symptoms. Patients with significant dental/oral pathology. Patients with severe dysautonomia.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tropicamide placebo<br>subject received (blinded) each of the 4 drug doses at different visits - 0 mg tropicamide, 0.3 mg tropicamide, 1 mg tropicamide, 3 mg tropicamide | Drug: 0.3 mg tropicamide<br>* 0.3 mg tropicamide in intra-oral thin film<br>* Other names: NH004;Drug: 1 mg tropicamide<br>* 1 mg tropicamide in intra-oral thin film<br>* Other names: NH004;Drug: 3 mg tropicamide<br>* 3 mg tropicamide in intra-oral thin film<br>* Other names: NH004;Drug: 0 mg tropicamide<br>* 0 mg tropicamide (placebo) in intra-oral thin film<br>* Other names: NH004 (placebo);|
| Experimental: Tropicamide 0.3 mg<br>subject received (blinded) each of the 4 drug doses at different visits - 0.3 mg tropicamide, 1 mg tropicamide, 3 mg tropicamide, 0 mg tropicamide | Drug: 0.3 mg tropicamide<br>* 0.3 mg tropicamide in intra-oral thin film<br>* Other names: NH004;Drug: 1 mg tropicamide<br>* 1 mg tropicamide in intra-oral thin film<br>* Other names: NH004;Drug: 3 mg tropicamide<br>* 3 mg tropicamide in intra-oral thin film<br>* Other names: NH004;Drug: 0 mg tropicamide<br>* 0 mg tropicamide (placebo) in intra-oral thin film<br>* Other names: NH004 (placebo);|
| Experimental: Tropicamide 1 mg<br>subject received (blinded) each of the 4 drug doses at different visits - 1 mg tropicamide, 3 mg tropicamide, 0 mg tropicamide, 0.3 mg tropicamide | Drug: 0.3 mg tropicamide<br>* 0.3 mg tropicamide in intra-oral thin film<br>* Other names: NH004;Drug: 1 mg tropicamide<br>* 1 mg tropicamide in intra-oral thin film<br>* Other names: NH004;Drug: 3 mg tropicamide<br>* 3 mg tropicamide in intra-oral thin film<br>* Other names: NH004;Drug: 0 mg tropicamide<br>* 0 mg tropicamide (placebo) in intra-oral thin film<br>* Other names: NH004 (placebo);|
| Experimental: Tropicamide 3 mg<br>subject received (blinded) each of the 4 drug doses at different visits - 3 mg tropicamide, 0 mg tropicamide, 0.3 mg tropicamide, 1 mg tropicamide | Drug: 0.3 mg tropicamide<br>* 0.3 mg tropicamide in intra-oral thin film<br>* Other names: NH004;Drug: 1 mg tropicamide<br>* 1 mg tropicamide in intra-oral thin film<br>* Other names: NH004;Drug: 3 mg tropicamide<br>* 3 mg tropicamide in intra-oral thin film<br>* Other names: NH004;Drug: 0 mg tropicamide<br>* 0 mg tropicamide (placebo) in intra-oral thin film<br>* Other names: NH004 (placebo);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Before and 120 min after treatment administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Before and 75 minutes after treatment administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sialorrhea, drooling, excessive salivation, parkinson's disease