Trial Outcomes & Findings for SYN120 Study to Evaluate Its Safety, Tolerability and Efficacy in Parkinson's Disease Dementia (SYNAPSE) (NCT NCT02258152)

Last Updated: 2019-04-19

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

82 participants

Primary outcome timeframe

up to Week 16

Results posted on

2019-04-19

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Placebo Placebo: Placebo QD	SYN120 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 Study STARTED	44	38
Overall Study COMPLETED	38	34
Overall Study NOT COMPLETED	6	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=44 Participants Placebo: Placebo QD	SYN120 n=38 Participants 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 n=82 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants
Age, Categorical >=65 years	41 Participants n=5 Participants	31 Participants n=7 Participants	72 Participants n=5 Participants
Age, Continuous	74.13 years STANDARD_DEVIATION 5.86 • n=5 Participants	72.13 years STANDARD_DEVIATION 8.13 • n=7 Participants	73.21 years STANDARD_DEVIATION 7.03 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	41 Participants n=5 Participants	32 Participants n=7 Participants	73 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	44 Participants n=5 Participants	37 Participants n=7 Participants	81 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	43 Participants n=5 Participants	38 Participants n=7 Participants	81 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	44 participants n=5 Participants	38 participants n=7 Participants	82 participants n=5 Participants
Weight at Screening	81.03 kg STANDARD_DEVIATION 16.31 • n=5 Participants	76.54 kg STANDARD_DEVIATION 10.69 • n=7 Participants	78.95 kg STANDARD_DEVIATION 14.09 • n=5 Participants

PRIMARY outcome

Timeframe: up to Week 16

Population: 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.

Outcome measures

Outcome measures
Measure	Placebo n=38 Participants Placebo: Placebo QD	SYN120 n=34 Participants 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).
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. Screening (1)	77.04 Seconds Standard Deviation 15.56	75.61 Seconds Standard Deviation 21.39
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. Screening (2)	80.97 Seconds Standard Deviation 13.66	80.70 Seconds Standard Deviation 16.80
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. Baseline	80.95 Seconds Standard Deviation 11.45	80.98 Seconds Standard Deviation 13.01
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. Week 8	78.83 Seconds Standard Deviation 17.08	77.68 Seconds Standard Deviation 19.60
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. Week 16	81.25 Seconds Standard Deviation 12.36	79.37 Seconds Standard Deviation 15.90
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. Change from Week 0 to 8	-1.88 Seconds Standard Deviation 16.73	-3.31 Seconds Standard Deviation 12.22
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. Change from Week 0 to 16	-0.35 Seconds Standard Deviation 10.51	-3.70 Seconds Standard Deviation 12.86

SECONDARY outcome

Timeframe: up to Week 16

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.

Outcome measures

Outcome measures
Measure	Placebo n=38 Participants Placebo: Placebo QD	SYN120 n=34 Participants 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).
To Assess the Effects of SYN120 on Cognitive Drug Research Computerized Cognition Battery (CDR) Quality of Episodic Memory (QEM) Screening (1)	107.66 Seconds Standard Deviation 55.49	116.14 Seconds Standard Deviation 60.50
To Assess the Effects of SYN120 on Cognitive Drug Research Computerized Cognition Battery (CDR) Quality of Episodic Memory (QEM) Screening (2)	111.98 Seconds Standard Deviation 55.62	99.69 Seconds Standard Deviation 30.11
To Assess the Effects of SYN120 on Cognitive Drug Research Computerized Cognition Battery (CDR) Quality of Episodic Memory (QEM) Baseline	117.70 Seconds Standard Deviation 49.68	114.13 Seconds Standard Deviation 45.93
To Assess the Effects of SYN120 on Cognitive Drug Research Computerized Cognition Battery (CDR) Quality of Episodic Memory (QEM) Week 8	123.58 Seconds Standard Deviation 52.03	118.37 Seconds Standard Deviation 61.95
To Assess the Effects of SYN120 on Cognitive Drug Research Computerized Cognition Battery (CDR) Quality of Episodic Memory (QEM) Week 16	112.43 Seconds Standard Deviation 69.50	118.20 Seconds Standard Deviation 54.08
To Assess the Effects of SYN120 on Cognitive Drug Research Computerized Cognition Battery (CDR) Quality of Episodic Memory (QEM) Change from Week 0 to 8	5.89 Seconds Standard Deviation 46.66	4.25 Seconds Standard Deviation 49.02
To Assess the Effects of SYN120 on Cognitive Drug Research Computerized Cognition Battery (CDR) Quality of Episodic Memory (QEM) Change from Week 0 to 16	-5.77 Seconds Standard Deviation 55.41	-0.08 Seconds Standard Deviation 45.33

Adverse Events

Placebo

Serious events: 5 serious events

Other events: 34 other events

Deaths: 0 deaths

SYN120

Serious events: 4 serious events

Other events: 28 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=44 participants at risk Placebo: Placebo QD	SYN120 n=38 participants at risk 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).
Gastrointestinal disorders Diarrhoea	0.00% 0/44 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.	5.3% 2/38 • Number of events 2 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.
Gastrointestinal disorders Nausea	6.8% 3/44 • Number of events 3 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.	18.4% 7/38 • Number of events 9 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.
Gastrointestinal disorders Vomiting	0.00% 0/44 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.	7.9% 3/38 • Number of events 3 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.
Infections and infestations Urinary Tract Infection	11.4% 5/44 • Number of events 5 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.	18.4% 7/38 • Number of events 8 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.
Injury, poisoning and procedural complications Fall	18.2% 8/44 • Number of events 12 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.	13.2% 5/38 • Number of events 5 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.
Investigations Alanine Aminotransferase Increased	0.00% 0/44 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.	5.3% 2/38 • Number of events 2 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.
Investigations Aspartate Aminotransferase Increased	0.00% 0/44 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.	5.3% 2/38 • Number of events 2 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.
Investigations Haemoglobin Decreased	4.5% 2/44 • Number of events 2 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.	5.3% 2/38 • Number of events 2 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.
Nervous system disorders Cognitive Disorder	6.8% 3/44 • Number of events 3 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.	5.3% 2/38 • Number of events 4 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.
Nervous system disorders Dizziness	9.1% 4/44 • Number of events 5 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.	5.3% 2/38 • Number of events 2 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.
Psychiatric disorders Anxiety	2.3% 1/44 • Number of events 1 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.	5.3% 2/38 • Number of events 4 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.
Psychiatric disorders Confusional State	11.4% 5/44 • Number of events 5 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.	10.5% 4/38 • Number of events 4 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.
Psychiatric disorders Hallucination, Visual	4.5% 2/44 • Number of events 2 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.	13.2% 5/38 • Number of events 5 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.
Vascular disorders Orthostatic Hypotension	4.5% 2/44 • Number of events 2 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.	5.3% 2/38 • Number of events 2 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.

Additional Information

Christopher Kenney, Senior Vice President - Medical Affairs

Acorda Therapeutics

Phone: 914-326-5775

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=44 participants at risk Placebo: Placebo QD	SYN120 n=38 participants at risk 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).
Cardiac disorders Cardiac Tamponade	2.3% 1/44 • Number of events 1 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.	0.00% 0/38 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.
Gastrointestinal disorders Pancreatitis	0.00% 0/44 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.	2.6% 1/38 • Number of events 1 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.
Infections and infestations Urinary Tract Infection	0.00% 0/44 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.	2.6% 1/38 • Number of events 1 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.
Injury, poisoning and procedural complications Contusion	2.3% 1/44 • Number of events 1 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.	0.00% 0/38 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.
Injury, poisoning and procedural complications Fall	2.3% 1/44 • Number of events 2 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.	0.00% 0/38 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.
Injury, poisoning and procedural complications Femoral Neck Fracture	2.3% 1/44 • Number of events 1 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.	2.6% 1/38 • Number of events 1 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.
Injury, poisoning and procedural complications Procedural Pain	2.3% 1/44 • Number of events 1 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.	0.00% 0/38 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.
Injury, poisoning and procedural complications Pulmonary Contusion	2.3% 1/44 • Number of events 1 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.	0.00% 0/38 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.
Injury, poisoning and procedural complications Rib Fracture	2.3% 1/44 • Number of events 2 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.	0.00% 0/38 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.
Metabolism and nutrition disorders Failure to Thrive	0.00% 0/44 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.	2.6% 1/38 • Number of events 1 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/44 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.	2.6% 1/38 • Number of events 1 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.
Musculoskeletal and connective tissue disorders Musculoskeletal Chest Pain	2.3% 1/44 • Number of events 1 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.	0.00% 0/38 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.
Nervous system disorders Cerebrovascular Accident	2.3% 1/44 • Number of events 1 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.	0.00% 0/38 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.
Nervous system disorders Embolic Stroke	2.3% 1/44 • Number of events 1 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.	0.00% 0/38 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.
Nervous system disorders Parkinson's Disease	0.00% 0/44 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.	2.6% 1/38 • Number of events 1 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.
Nervous system disorders Subarachnoid Haemorrhage	2.3% 1/44 • Number of events 1 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.	0.00% 0/38 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.
Respiratory, thoracic and mediastinal disorders Haemothorax	2.3% 1/44 • Number of events 1 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.	0.00% 0/38 • 16 Weeks Safety evaluation was based on the Safety Population which included all 82 patients enrolled into the study.