Parkinson's Disease Dementia (PDD)
Conditions
Keywords
PDD, Parkinson's Disease Dementia, patients taking a cholinesterase inhibitor.
Brief summary
The purpose of this study placebo-controlled, randomized, double-blind study is to assess the safety and efficacy of SYN120 in patients with Parkinson's disease dementia (PDD) already treated with a stable dose of a cholinesterase inhibitor.
Detailed description
This study includes a Screening Period of up to 6 weeks, a 16 week Treatment Period, and a 2 week Safety Follow Up Period. Final eligibility will be determined at the Baseline Visit. Eligible patients will be randomized to receive placebo or SYN120 100 mg once a day (QD).
Interventions
DRUGSYN120
SYN120 Doses to be Administered: 20 mg QD (1 week titration), 50 mg QD (1 week titration), 100 mg QD (14 weeks of maintenance).
DRUGPlacebo
Placebo QD
Sponsors
Michael J. Fox Foundation for Parkinson's Research
Massachusetts General Hospital
Acorda Therapeutics
Biotie Therapies Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Parkinson's Disease Dementia * Patient has a routine caregiver * Taking a stable cholinesterase inhibitor. * Patient has a Montreal Cognitive Assessment (MoCA) 10-23 inclusive
Exclusion criteria
* History of any significant neurologic or psychiatric disease other than PD * Any other condition or clinically significant abnormal findings that would make the patient unsuitable for the study * Unpredictable motor fluctuations that would interfere with administering assessments
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | up to Week 16 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Assess the Effects of SYN120 on Cognitive Drug Research Computerized Cognition Battery (CDR) Quality of Episodic Memory (QEM) | 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. |
Countries
United States
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.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo: Placebo QD | 44 |
| 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). | 38 |
| Total | 82 |
Baseline characteristics
| Characteristic | Placebo | SYN120 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 41 Participants | 31 Participants | 72 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 7 Participants | 10 Participants |
| Age, Continuous | 74.13 years STANDARD_DEVIATION 5.86 | 72.13 years STANDARD_DEVIATION 8.13 | 73.21 years STANDARD_DEVIATION 7.03 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 44 Participants | 37 Participants | 81 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 43 Participants | 38 Participants | 81 Participants |
| Region of Enrollment United States | 44 participants | 38 participants | 82 participants |
| Sex: Female, Male Female | 3 Participants | 6 Participants | 9 Participants |
| Sex: Female, Male Male | 41 Participants | 32 Participants | 73 Participants |
| Weight at Screening | 81.03 kg STANDARD_DEVIATION 16.31 | 76.54 kg STANDARD_DEVIATION 10.69 | 78.95 kg STANDARD_DEVIATION 14.09 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 44 | 1 / 38 |
| other Total, other adverse events | 34 / 44 | 28 / 38 |
| serious Total, serious adverse events | 5 / 44 | 4 / 38 |
Outcome results
Primary
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.
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
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| SYN120 | 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 | -3.70 Seconds | Standard Deviation 12.86 |
| SYN120 | 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) | 75.61 Seconds | Standard Deviation 21.39 |
| SYN120 | 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) | 80.70 Seconds | Standard Deviation 16.8 |
| SYN120 | 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 | 80.98 Seconds | Standard Deviation 13.01 |
| SYN120 | 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 | 77.68 Seconds | Standard Deviation 19.6 |
| SYN120 | 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 | 79.37 Seconds | Standard Deviation 15.9 |
| SYN120 | 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 | -3.31 Seconds | Standard Deviation 12.22 |
Secondary
To Assess the Effects of SYN120 on Cognitive Drug Research Computerized Cognition Battery (CDR) Quality of Episodic Memory (QEM)
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
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 69.5 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| SYN120 | 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 | -0.08 Seconds | Standard Deviation 45.33 |
| SYN120 | To Assess the Effects of SYN120 on Cognitive Drug Research Computerized Cognition Battery (CDR) Quality of Episodic Memory (QEM) | Screening (1) | 116.14 Seconds | Standard Deviation 60.5 |
| SYN120 | To Assess the Effects of SYN120 on Cognitive Drug Research Computerized Cognition Battery (CDR) Quality of Episodic Memory (QEM) | Screening (2) | 99.69 Seconds | Standard Deviation 30.11 |
| SYN120 | To Assess the Effects of SYN120 on Cognitive Drug Research Computerized Cognition Battery (CDR) Quality of Episodic Memory (QEM) | Baseline | 114.13 Seconds | Standard Deviation 45.93 |
| SYN120 | To Assess the Effects of SYN120 on Cognitive Drug Research Computerized Cognition Battery (CDR) Quality of Episodic Memory (QEM) | Week 8 | 118.37 Seconds | Standard Deviation 61.95 |
| SYN120 | 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 | 4.25 Seconds | Standard Deviation 49.02 |
| SYN120 | To Assess the Effects of SYN120 on Cognitive Drug Research Computerized Cognition Battery (CDR) Quality of Episodic Memory (QEM) | Week 16 | 118.20 Seconds | Standard Deviation 54.08 |