Parkinson Disease
Conditions
Keywords
Levodopa, Dyskinesia
Brief summary
This is a multicenter, randomized, three-arm, parallel-group, double-blind, placebo-controlled, study to evaluate the efficacy, safety and pharmacokinetics (PK) of pridopidine vs. placebo for the treatment of Levodopa Induced Dyskinesia (LID) in patients with Parkinson Disease.
Interventions
DRUGPridopidine
Oral capsule
DRUGPlacebo
Oral capsule
Sponsors
Prilenia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Provides signed informed consent form. * Has clinical diagnosis of Parkinson's Disease (PD). * Has Levodopa-induced dyskinesia (LID). * Patient and/or study partner must demonstrate ability to keep accurate home diary of PD symptoms. * Has stable anti-PD treatments for at least 28 days prior to start of study treatment and kept constant throughout study. * All routine and allowed prescription/non-prescription medications and/or nutritional supplements taken regularly must be at stable dosage for at least 28 days prior to start of study treatment and maintained throughout study.
Exclusion criteria
* Diagnosis of atypical Parkinsonism. * Treatment with dopamine blocking drugs. * History of surgical intervention related to PD, such as deep brain stimulation. * History of severe depression, psychosis or hallucinations within 6 months prior to screening; active suicidal ideation; or suicidal attempt within 5 years prior to screening. * History of certain cancers within 5 years prior to screening. * Significant cardiac event within 12 weeks prior to Baseline or history of certain cardiac arrhythmias. * History of epilepsy or seizures within 5 years prior to screening. * Females who are pregnant or breastfeeding. * Sexually active female patients who are not surgically sterile or at least 2 years postmenopausal prior to screening, and who do not agree to utilize a highly effective hormonal method of contraception in combination with a barrier method, from screening until at least 4 weeks after completion of study treatment. * Male patients not using highly effective contraception or not agreeing to continue highly effective contraception until at least 90 days after the completion of study treatment. * Treatment with any investigational product within 30 days of screening or plans to participate in another clinical study assessing any investigational product during the study. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Levodopa-induced Dyskinesia as Measured by UDysRS Score | Baseline; Visit 7 (at Week 16) planned. Since the study was terminated early due to the COVID-19 pandemic, analysis of the primary endpoint was done at Visit 5 (Week 8/10) in those patients who were on study drug at this visit. | Mean change from baseline (BL) in the sum of Parts 1, 3 and 4 of the Unified Dyskinesia Rating Scale (UdysRS), in the ON state. The UDysRS comprises 2 primary sections i.e. Historical \[Part 1 (ON-Dyskinesia) and Part 2 (OFF-Dystonia)\] and Objective \[Part 3 (Impairment) and Part 4 (Disability)\] assessment. ON-Dyskinesia are choreic and dystonic movements that occur when the Parkinson's disease (PD) medicine is working. Lower UDysRS values mean better patient outcome i.e. less dyskinesia. The UDysRS score for this study is calculated as sum of the parts, with scores of 0-44 for Part 1, 0-28 for Part 3 and 0-16 for Part 4. |
Countries
United States
Participant flow
Pre-assignment details
A total of 23 patients were randomized to pridopidine 100 mg BID (n=7), pridopidine 150 mg BID (n=8), or placebo (n=8). Of these, 5 patients randomized to 150 mg BID discontinued study drug during the titration period prematurely (i.e. did not reach the maintenance dose) and were therefore analyzed in the 100 mg BID group. The study was terminated early due to the COVID-19 pandemic.
Participants by arm
| Arm | Count |
|---|---|
| Pridopidine 100 mg BID Titration period of 2-week (original protocol) or 4-week (Amendment 1) duration, followed by 12-week maintenance treatment at a dose of 100 mg BID.
2-week titration: 3 days pridopidine 75 mg QD, then 4 days pridopidine 75 mg BID, then 1 week pridopidine 100 mg BID 4-week titration: 1 week pridopidine 75 mg every 48 h, then 1 week pridopidine 75 mg QD, then 1 week pridopidine 75 mg BID, then 1 week pridopidine 100 mg BID. | 12 |
| Pridopidine 150 mg BID Titration period of 2-week (original protocol) or 4-week (Amendment 1) duration, followed by 12-week maintenance treatment at a dose of 150 mg BID.
2-week titration: 3 days pridopidine 75 mg QD, then 4 days pridopidine 75 mg BID, then 1 week pridopidine 100 mg BID 4-week titration: 1 week pridopidine 75 mg every 48 h, then 1 week pridopidine 75 mg QD, then 1 week pridopidine 75 mg BID, then 1 week pridopidine 100 mg BID. | 3 |
| Placebo Titration period of 2-week (original protocol) or 4-week (Amendment 1) duration, followed by 12-week maintenance treatment, using pridopidine-matching placebo. | 8 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 | 2 |
| Overall Study | Not further specified | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 3 | 1 |
Baseline characteristics
| Characteristic | Pridopidine 100 mg BID | Total | Placebo | Pridopidine 150 mg BID |
|---|---|---|---|---|
| Age, Continuous | 69.0 years STANDARD_DEVIATION 7.5 | 66.3 years STANDARD_DEVIATION 9 | 64.0 years STANDARD_DEVIATION 9.7 | 61.3 years STANDARD_DEVIATION 12.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 19 Participants | 5 Participants | 3 Participants |
| Region of Enrollment United States | 12 participants | 23 participants | 8 participants | 3 participants |
| Sex: Female, Male Female | 7 Participants | 13 Participants | 5 Participants | 1 Participants |
| Sex: Female, Male Male | 5 Participants | 10 Participants | 3 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 3 | 0 / 8 |
| other Total, other adverse events | 10 / 12 | 3 / 3 | 7 / 8 |
| serious Total, serious adverse events | 0 / 12 | 0 / 3 | 1 / 8 |
Outcome results
Primary
Change From Baseline in Levodopa-induced Dyskinesia as Measured by UDysRS Score
Mean change from baseline (BL) in the sum of Parts 1, 3 and 4 of the Unified Dyskinesia Rating Scale (UdysRS), in the ON state. The UDysRS comprises 2 primary sections i.e. Historical \[Part 1 (ON-Dyskinesia) and Part 2 (OFF-Dystonia)\] and Objective \[Part 3 (Impairment) and Part 4 (Disability)\] assessment. ON-Dyskinesia are choreic and dystonic movements that occur when the Parkinson's disease (PD) medicine is working. Lower UDysRS values mean better patient outcome i.e. less dyskinesia. The UDysRS score for this study is calculated as sum of the parts, with scores of 0-44 for Part 1, 0-28 for Part 3 and 0-16 for Part 4.
Time frame: Baseline; Visit 7 (at Week 16) planned. Since the study was terminated early due to the COVID-19 pandemic, analysis of the primary endpoint was done at Visit 5 (Week 8/10) in those patients who were on study drug at this visit.
Population: The primary endpoint was analyzed for the population of patients randomized and on study drug at Visit 5 (Week 8/10). Of the 3 pridopidine patients included, 1 and 2 patients, respectively, received pridopidine 100 and 150 mg. Analysis of these data, separately for each pridopidine dose, is not meaningful or conclusive.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pridopidine Total | Change From Baseline in Levodopa-induced Dyskinesia as Measured by UDysRS Score | Change from baseline at Visit 5 | -17.3 score on a scale | Standard Deviation 6.03 |
| Pridopidine Total | Change From Baseline in Levodopa-induced Dyskinesia as Measured by UDysRS Score | Baseline | 32.0 score on a scale | Standard Deviation 10.44 |
| Pridopidine Total | Change From Baseline in Levodopa-induced Dyskinesia as Measured by UDysRS Score | Visit 5 | 14.7 score on a scale | Standard Deviation 5.13 |
| Placebo | Change From Baseline in Levodopa-induced Dyskinesia as Measured by UDysRS Score | Visit 5 | 26.1 score on a scale | Standard Deviation 11.02 |
| Placebo | Change From Baseline in Levodopa-induced Dyskinesia as Measured by UDysRS Score | Change from baseline at Visit 5 | -9.7 score on a scale | Standard Deviation 9.43 |
| Placebo | Change From Baseline in Levodopa-induced Dyskinesia as Measured by UDysRS Score | Baseline | 35.9 score on a scale | Standard Deviation 6.44 |