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

Phase 2

Completed

• Conditions: Sialorrhea Secondary to Parkinson's Disease
• Interventions: Drug: 0.3 mg tropicamide; Drug: 1 mg tropicamide; Drug: 3 mg tropicamide; Drug: 0 mg tropicamide

• Registration Number: NCT00761137
• Lead Sponsor: NeuroHealing Pharmaceuticals Inc.

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.

Study Timeline

• Study Start: 2008-03
• Study First Submitted: 2008-09-25
• Study First Submitted QC: 2008-09-26
• Study First Posted: 2008-09-29
• Primary Completion: 2010-06
• Study Completion: 2010-06
• Results First Submitted: 2011-08-05
• Status Verified: 2013-04
• Results First Submitted QC: 2015-09-22
• Last Update Submitted: 2015-09-22
• Results First Posted: 2015-10-12
• Last Update Posted: 2015-10-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

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 exclusion criteria number 4 within the last week.
6. Patients with hypersensitivity to atropine or other anticholinergic drugs.
7. Patients who have experienced adverse effects as a result of taking anticholinergic drugs.
8. Patients taking hypnotic or other sleep inducing drugs.
9. Patients with severe urinary or gastrointestinal symptoms.
10. Patients with significant dental/oral pathology.
11. Patients with severe dysautonomia.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Tropicamide 0.3 mg	1 mg tropicamide	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
Tropicamide 0.3 mg	0 mg tropicamide	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
Tropicamide 1 mg	1 mg tropicamide	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
Tropicamide 1 mg	0 mg tropicamide	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
Tropicamide 3 mg	0.3 mg tropicamide	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
Tropicamide 3 mg	3 mg tropicamide	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
Tropicamide 3 mg	1 mg tropicamide	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
Tropicamide placebo	0.3 mg tropicamide	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
Tropicamide placebo	0 mg tropicamide	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
Tropicamide placebo	3 mg tropicamide	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
Tropicamide placebo	1 mg tropicamide	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
Tropicamide 0.3 mg	0.3 mg tropicamide	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
Tropicamide 0.3 mg	3 mg tropicamide	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
Tropicamide 1 mg	0.3 mg tropicamide	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
Tropicamide 1 mg	3 mg tropicamide	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
Tropicamide 3 mg	0 mg tropicamide	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

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

FLENI Hospital; 🇦🇷 Buenos Aires, Argentina