SYN120 Study to Evaluate Its Safety, Tolerability and Efficacy in Parkinson's Disease Dementia (SYNAPSE) (SYNAPSE)

• ClinicalTrials.gov Identifier: NCT02258152
• Recruitment Status: Completed
• First Posted: October 7, 2014
• Results First Posted: April 19, 2019
• Last Update Posted: April 19, 2019
• Sponsor: Biotie Therapies Inc.
• Collaborators: Michael J. Fox Foundation for Parkinson's Research; Massachusetts General Hospital; Acorda Therapeutics
• Information provided by (Responsible Party): Biotie Therapies Inc.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Parkinson's Disease Dementia (PDD)
• Interventions: Drug: SYN120; Drug: Placebo
• Enrollment: 82

Participant Flow

Recruitment Details	This study was conducted in 18 study centers in the US. Combined, a total of 82 patients were randomized: 44 patients to treatment with placebo and 38 to treatment with SYN120, 100 mg QD (once a day). Of these patients, 72 (88%) completed the study.
Pre-assignment Details

Arm/Group Title	Placebo	SYN120
Arm/Group Description	Placebo: Placebo QD	SYN120: SYN120 Doses to be Administered: 20 mg QD (1 week titration), 50 mg QD (1 week titration), 100 mg QD (14 weeks of maintenance).
Period Title: Overall Study
Started	44	38
Completed	38	34
Not Completed	6	4

Baseline Characteristics

Arm/Group Title		Placebo	SYN120	Total
Arm/Group Description		Placebo: Placebo QD	SYN120: SYN120 Doses to be Administered: 20 mg QD (1 week titration), 50 mg QD (1 week titration), 100 mg QD (14 weeks of maintenance).	Total of all reporting groups
Overall Number of Baseline Participants		44	38	82
Baseline Analysis Population Description		The Safety Population (safety analysis set) consisted of patients who received a dose of placebo or SYN120; all 82 patients randomized in this study were included in the Safety Population.
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	44 participants	38 participants	82 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	3 6.8%	7 18.4%	10 12.2%
	>=65 years	41 93.2%	31 81.6%	72 87.8%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	44 participants	38 participants	82 participants
		74.13 (5.86)	72.13 (8.13)	73.21 (7.03)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	44 participants	38 participants	82 participants
	Female	3 6.8%	6 15.8%	9 11.0%
	Male	41 93.2%	32 84.2%	73 89.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	44 participants	38 participants	82 participants
	Hispanic or Latino	0 0.0%	0 0.0%	0 0.0%
	Not Hispanic or Latino	44 100.0%	37 97.4%	81 98.8%
	Unknown or Not Reported	0 0.0%	1 2.6%	1 1.2%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	44 participants	38 participants	82 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	1 2.3%	0 0.0%	1 1.2%
	White	43 97.7%	38 100.0%	81 98.8%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	44 participants	38 participants	82 participants
		44	38	82
Weight at Screening; Mean (Standard Deviation); Unit of measure: Kg
	Number Analyzed	44 participants	38 participants	82 participants
		81.03 (16.31)	76.54 (10.69)	78.95 (14.09)

Outcome Measures

1. Primary Outcome

Title	The Primary Efficacy Objective of This Study is to Assess the Efficacy of SYN120 on Cognition as Determined by the Cognitive Drug Research Computerized Cognition Battery (CDR) Continuity of Attention in Patients With Parkinson's Disease.
Description	To access the effect of SYN-120 for Continuity of Attention, a measure which reflects the ability to sustain attention and avoid error The Cognitive Drug Research Computerized Cognition Battery is a computerized neuropsychological test battery to assess cognitive tasks based on measures of Vigilance (1 - 180 seconds) and Choice Reaction Time (1 - 120 seconds). The stimuli are presented on a computer screen and the subjects respond by pressing either a "Yes" or "No" on a response box. It is a time measured test. The ability to keep mind on a single task over time. COA is calculated as (VIGACC*0.45) + (CRTACC*0.5) - where VIGACC is digit vigilance accuracy, CRTACC is choice reaction time accuracy. Higher COA scores represent greater sustained attention and avoidance of errors.
Time Frame	up to Week 16

Outcome Measure Data

Analysis Population Description

Protocol Deviation: No patient was discontinued from the study due to a protocol deviation and results based on the PP (per-protocol analysis set) population are similar to those from the mITT (modified intention-to-treat analysis set) population. Patients were not withdrawn from the study despite meeting withdrawal criteria.

Arm/Group Title	Placebo	SYN120
Arm/Group Description:	Placebo: Placebo QD	SYN120: SYN120 Doses to be Administered: 20 mg QD (1 week titration), 50 mg QD (1 week titration), 100 mg QD (14 weeks of maintenance).
Overall Number of Participants Analyzed	38	34
Mean (Standard Deviation); Unit of Measure: Seconds
Screening (1)	77.04 (15.56)	75.61 (21.39)
Screening (2)	80.97 (13.66)	80.70 (16.80)
Baseline	80.95 (11.45)	80.98 (13.01)
Week 8	78.83 (17.08)	77.68 (19.60)
Week 16	81.25 (12.36)	79.37 (15.90)
Change from Week 0 to 8	-1.88 (16.73)	-3.31 (12.22)
Change from Week 0 to 16	-0.35 (10.51)	-3.70 (12.86)

2. Secondary Outcome

Title	To Assess the Effects of SYN120 on Cognitive Drug Research Computerized Cognition Battery (CDR) Quality of Episodic Memory (QEM)
Description	To access the effects of SYN120 for Quality of Episodic Memory. QEM measures the ability to store, hold, and retrieve information of an episodic nature. The stimuli are presented on a computer screen and the subjects respond by pressing either a "Yes" or "No" on a response box. It is a time measured test. Quality of Episodic Memory is calculated as (DRECOACC + DRECNACC - 100) + (DPICOACC + DPICNACC - 100) +((IRCL - IRCLERR)*100 / 15) + ((DRCL - DRCLERR)*100 / 15), where DRECOACC is Word Recognition original stimuli accuracy (1 - 120 seconds), DRECNACC is word recognition new stimuli accuracy, DPICOACC is Picture Recognition original stimuli accuracy (1 - 120.5 seconds), DPICNACC is picture recognition new stimuli accuracy, IRCL is Immediate Word Recall (1 - 120.5 seconds), IRCLERR is immediate word recall errors, DRCL is Delayed Word Recall (1 - 120.5 seconds), and DRCLERR is delayed word recall errors. Higher QEM scores greater ability to retain memory.
Time Frame	up to Week 16

Outcome Measure Data

Analysis Population Description

Protocol Deviation: No patient was discontinued from the study due to a protocol deviation and results based on the PP (per-protocol analysis set) population are similar to those from the mITT (modified intention-to-treat analysis set) population. Patients were not withdrawn from the study despite meeting withdrawal criteria.

Arm/Group Title	Placebo	SYN120
Arm/Group Description:	Placebo: Placebo QD	SYN120: SYN120 Doses to be Administered: 20 mg QD (1 week titration), 50 mg QD (1 week titration), 100 mg QD (14 weeks of maintenance).
Overall Number of Participants Analyzed	38	34
Mean (Standard Deviation); Unit of Measure: Seconds
Screening (1)	107.66 (55.49)	116.14 (60.50)
Screening (2)	111.98 (55.62)	99.69 (30.11)
Baseline	117.70 (49.68)	114.13 (45.93)
Week 8	123.58 (52.03)	118.37 (61.95)
Week 16	112.43 (69.50)	118.20 (54.08)
Change from Week 0 to 8	5.89 (46.66)	4.25 (49.02)
Change from Week 0 to 16	-5.77 (55.41)	-0.08 (45.33)

Adverse Events

Time Frame	16 Weeks
Adverse Event Reporting Description	Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.
Arm/Group Title	Placebo		SYN120
Arm/Group Description	Placebo: Placebo QD		SYN120: SYN120 Doses to be Administered: 20 mg QD (1 week titration), 50 mg QD (1 week titration), 100 mg QD (14 weeks of maintenance).
All-Cause Mortality
	Placebo		SYN120
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/44 (0.00%)		1/38 (2.63%)
Serious Adverse Events
	Placebo		SYN120
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/44 (11.36%)		4/38 (10.53%)
Cardiac disorders
Cardiac Tamponade † 1	1/44 (2.27%)	1	0/38 (0.00%)	0
Gastrointestinal disorders
Pancreatitis † 1	0/44 (0.00%)	0	1/38 (2.63%)	1
Infections and infestations
Urinary Tract Infection † 1	0/44 (0.00%)	0	1/38 (2.63%)	1
Injury, poisoning and procedural complications
Contusion † 1	1/44 (2.27%)	1	0/38 (0.00%)	0
Fall † 1	1/44 (2.27%)	2	0/38 (0.00%)	0
Femoral Neck Fracture † 1	1/44 (2.27%)	1	1/38 (2.63%)	1
Procedural Pain † 1	1/44 (2.27%)	1	0/38 (0.00%)	0
Pulmonary Contusion † 1	1/44 (2.27%)	1	0/38 (0.00%)	0
Rib Fracture † 1	1/44 (2.27%)	2	0/38 (0.00%)	0
Metabolism and nutrition disorders
Failure to Thrive † 1	0/44 (0.00%)	0	1/38 (2.63%)	1
Hyponatraemia † 1	0/44 (0.00%)	0	1/38 (2.63%)	1
Musculoskeletal and connective tissue disorders
Musculoskeletal Chest Pain † 1	1/44 (2.27%)	1	0/38 (0.00%)	0
Nervous system disorders
Cerebrovascular Accident † 1	1/44 (2.27%)	1	0/38 (0.00%)	0
Embolic Stroke † 1	1/44 (2.27%)	1	0/38 (0.00%)	0
Parkinson's Disease † 1	0/44 (0.00%)	0	1/38 (2.63%)	1
Subarachnoid Haemorrhage † 1	1/44 (2.27%)	1	0/38 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Haemothorax † 1	1/44 (2.27%)	1	0/38 (0.00%)	0
1 Term from vocabulary, MedDRA 20.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo		SYN120
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/44 (77.27%)		28/38 (73.68%)
Gastrointestinal disorders
Diarrhoea † 1	0/44 (0.00%)	0	2/38 (5.26%)	2
Nausea † 1	3/44 (6.82%)	3	7/38 (18.42%)	9
Vomiting † 1	0/44 (0.00%)	0	3/38 (7.89%)	3
Infections and infestations
Urinary Tract Infection † 1	5/44 (11.36%)	5	7/38 (18.42%)	8
Injury, poisoning and procedural complications
Fall † 1	8/44 (18.18%)	12	5/38 (13.16%)	5
Investigations
Alanine Aminotransferase Increased † 1	0/44 (0.00%)	0	2/38 (5.26%)	2
Aspartate Aminotransferase Increased † 1	0/44 (0.00%)	0	2/38 (5.26%)	2
Haemoglobin Decreased † 1	2/44 (4.55%)	2	2/38 (5.26%)	2
Nervous system disorders
Cognitive Disorder † 1	3/44 (6.82%)	3	2/38 (5.26%)	4
Dizziness † 1	4/44 (9.09%)	5	2/38 (5.26%)	2
Psychiatric disorders
Anxiety † 1	1/44 (2.27%)	1	2/38 (5.26%)	4
Confusional State † 1	5/44 (11.36%)	5	4/38 (10.53%)	4
Hallucination, Visual † 1	2/44 (4.55%)	2	5/38 (13.16%)	5
Vascular disorders
Orthostatic Hypotension † 1	2/44 (4.55%)	2	2/38 (5.26%)	2
1 Term from vocabulary, MedDRA 20.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding the study results for a period up to 30 days from the date the communication is submitted to the sponsor. The sponsor shall have the right to defer proposed publication an additional 60 days from the end of the review period. The sponsor cannot require changes to the communication and cannot unilaterally extend the embargo.

Results Point of Contact

• Name/Title: Christopher Kenney, Senior Vice President - Medical Affairs
• Organization: Acorda Therapeutics
• Phone: 914-326-5775
• EMail: ckenney@acorda.com

• Responsible Party: Biotie Therapies Inc.
• ClinicalTrials.gov Identifier: NCT02258152
• Other Study ID Numbers: SYN120-CL03
• First Submitted: October 3, 2014
• First Posted: October 7, 2014
• Results First Submitted: September 14, 2018
• Results First Posted: April 19, 2019
• Last Update Posted: April 19, 2019