NH004-2: Safety and Efficacy Study of NH004 Films for Relief of Sialorrhea Symptoms in Parkinson's Disease Patients

• Sponsor: NeuroHealing Pharmaceuticals Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00761137
• Collaborator: Michael J. Fox Foundation for Parkinson's Research (Other)
• Enrollment: 19
• Location: 1
• Arms: 4
• Duration (Months): 27
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Sialorrhea Secondary to Parkinson's Disease	Drug: 0.3 mg tropicamide; Drug: 1 mg tropicamide; Drug: 3 mg tropicamide; Drug: 0 mg tropicamide	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Mar 1, 2008
• Actual Primary Completion Date: Jun 1, 2010
• Actual Study Completion Date: Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tropicamide placebo 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; 0.3 mg tropicamide in intra-oral thin film; Other Names: NH004 ; Drug: 1 mg tropicamide; 1 mg tropicamide in intra-oral thin film; Other Names: NH004 ; Drug: 3 mg tropicamide; 3 mg tropicamide in intra-oral thin film; Other Names: NH004 ; Drug: 0 mg tropicamide; 0 mg tropicamide (placebo) in intra-oral thin film; Other Names: NH004 (placebo)
Experimental: Tropicamide 0.3 mg 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; 0.3 mg tropicamide in intra-oral thin film; Other Names: NH004 ; Drug: 1 mg tropicamide; 1 mg tropicamide in intra-oral thin film; Other Names: NH004 ; Drug: 3 mg tropicamide; 3 mg tropicamide in intra-oral thin film; Other Names: NH004 ; Drug: 0 mg tropicamide; 0 mg tropicamide (placebo) in intra-oral thin film; Other Names: NH004 (placebo)
Experimental: Tropicamide 1 mg 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; 0.3 mg tropicamide in intra-oral thin film; Other Names: NH004 ; Drug: 1 mg tropicamide; 1 mg tropicamide in intra-oral thin film; Other Names: NH004 ; Drug: 3 mg tropicamide; 3 mg tropicamide in intra-oral thin film; Other Names: NH004 ; Drug: 0 mg tropicamide; 0 mg tropicamide (placebo) in intra-oral thin film; Other Names: NH004 (placebo)
Experimental: Tropicamide 3 mg 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; 0.3 mg tropicamide in intra-oral thin film; Other Names: NH004 ; Drug: 1 mg tropicamide; 1 mg tropicamide in intra-oral thin film; Other Names: NH004 ; Drug: 3 mg tropicamide; 3 mg tropicamide in intra-oral thin film; Other Names: NH004 ; Drug: 0 mg tropicamide; 0 mg tropicamide (placebo) in intra-oral thin film; Other Names: NH004 (placebo)

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts 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 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	FLENI Hospital	Buenos Aires		Argentina

Sponsors and Collaborators

• NeuroHealing Pharmaceuticals Inc.
• Michael J. Fox Foundation for Parkinson's Research

Investigators

• Principal Investigator: Elkan R Gamzu, PhD, NeuroHealing Pharmaceuticals Inc.
• Principal Investigator: Marcelo Merello, MD, PhD, FLENI Hospital, Argentina

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: NeuroHealing Pharmaceuticals Inc.
• ClinicalTrials.gov Identifier: NCT00761137
• Other Study ID Numbers: NH004-2
• First Posted: Sep 29, 2008
• Last Update Posted: Oct 12, 2015
• Last Verified: Apr 1, 2013

• Keywords provided by NeuroHealing Pharmaceuticals Inc.: sialorrhea; drooling; excessive salivation; parkinson's disease
• Additional relevant MeSH terms: Sialorrhea; Parkinson Disease; Tropicamide

Study Results

Participant Flow

Pre-assignment Detail	Four interventions, subjects were randomly assigned to one of 16 sequences.

Arm/Group Title	All Participants
Arm/Group Description	subjects randomly received (blinded) each of the 4 doses at different visits - 0 mg, 0.3 mg, 1mg, 3 mg Drug: Tropicamide
Period Title: Overall Study
STARTED	19
Placebo	19
0.3 mg Tropicamide	19
1 mg Tropicamide	19
3 mg Tropicamide	19
COMPLETED	19
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	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.
Overall Participants	19
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67 (12)
Sex: Female, Male (Count of Participants)
Female	4 21.1%
Male	15 78.9%
Region of Enrollment (participants) [Number]
Argentina	19 100%

Outcome Measures

1. Primary Outcome

Title	Sialorrhea Visual Analogue Scale (VAS)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tropicamide - Placebo	Tropicamide - 0.3 mg	Tropicamide - 1 mg	Tropicamide 3 mg
Arm/Group Description	Each subject randomly received blinded a placebo thin film containing no active drug ingredient	Each subject randomly received blinded a thin film containing 0.3 mg active drug ingredient	Each subject randomly received blinded a thin film containing 1 mg active drug ingredient	Each subject randomly received blinded a thin film containing 3 mg active drug ingredient
Measure Participants	19	19	19	19
Mean (Standard Deviation) [cm on VAS]	-0.55 (0.54)	-1.08 (0.54)	-1.53 (0.52)	-0.81 (0.51)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tropicamide - Placebo, Tropicamide - 0.3 mg, Tropicamide - 1 mg, Tropicamide 3 mg
	Comments	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%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6
	Comments
	Method	ANOVA
	Comments

2. Secondary Outcome

Title	Percentage Change in Saliva Volume
Description	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

Outcome Measure Data

Analysis Population Description

Percentage saliva volume change was determined in the last seven (7) patients enrolled.

Arm/Group Title	Tropicamide - Placebo	Tropicamide - 0.3 mg	Tropicamide - 1 mg	Tropicamide 3 mg
Arm/Group Description	Each subject randomly received blinded a placebo thin film containing no active drug ingredient	Each subject randomly received blinded a thin film containing 0.3 mg active drug ingredient	Each subject randomly received blinded a thin film containing 1 mg active drug ingredient	Each subject randomly received blinded a thin film containing 3 mg active drug ingredient
Measure Participants	7	7	7	7
Median (95% Confidence Interval) [percentage change of saliva volume]	-5	-27	-33	-20

Adverse Events

Time Frame	1 month
Arm/Group Title	All Participants
Arm/Group Description	subjects received (blinded) each of the 4 doses at different visits - 0 mg, 0.3 mg, 1mg, 3 mg Drug: Tropicamide
All Cause Mortality
	All Participants
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	0/19 (0%)
Other (Not Including Serious) Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	0/19 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.