Dyskinesia, Parkinson's Disease
Conditions
Keywords
Parkinson's Disease, Dyskinesia, Dyskinesia associated with dopaminergic treatment
Brief summary
The purpose of this study is to test multiple doses of sarizotan to establish a dose with maximal safety and efficacy for treating treatment associated dyskinesia in Parkinson's disease participants.
Interventions
DRUGSarizotan
Sarizotan will be administered twice daily.
DRUGPlacebo
Placebo matching to sarizotan will be administered twice daily.
Sponsors
EMD Serono
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* The participant is an out-patient * The participant presents with a diagnosis of idiopathic Parkinson's disease * Prior therapy with all registered Parkinsonian medication is allowed
Exclusion criteria
* (For female participants) The participant is pregnant or lactating * The participant is participating in another clinical study or has done so within the past 30 days * The participant has received neurosurgical intervention related to Parkinson's disease * The participant has relevant renal impairment * The participant has relevant hepatic impairment * The participant is suffering from any dementia or psychiatric illness * The participant has a history of allergic asthma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Diary-Based On-Time Without Dyskinesia at Week 12 | Baseline, Week 12 | On-time without dyskinesia was defined as a period (in hours) when the participant had no symptoms of off-time and was not asleep; also, participant had no difficulty in performing voluntary movements (that is, without dyskinesia). Off-time was defined as a period (in hours) when participant experienced increased parkinsonian symptoms (e.g. immobility or inability to move with ease). On-time was recorded by participant in a participant diary. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Modified Abnormal Involuntary Movement Scale (AIMS) Score at Week 12 | Baseline, Week 12 | Modified AIMS was a 7-item investigator-assessed scale to assess severity of dyskinesia. Each item was rated on a 0 (none) to 4 (severe) scale. Modified AIMS score was sum of the all item scores and ranged from 0 to 28, where higher score indicated increased severity. Modified AIMS score in resting state as well as with activity is reported. |
| Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Items 32 and 33 Composite Score at Week 12 | Baseline, Week 12 | The UPDRS was an investigator-assessed rating tool to follow the longitudinal course of Parkinson's disease. Items 32 and 33 assessed duration of dyskinesia and disability due to dyskinesia, respectively. Both items were rated on a 0 to 4-point scale, where higher scores indicated higher duration of dyskinesia and more disability due to dyskinesia, respectively. The Items 32 and 33 composite score was sum of the individual item scores and ranged from 0 to 8, where higher score indicated more complications due to dyskinesia. |
| Change From Baseline in UPDRS Part III Total Score at Week 12 | Baseline, Week 12 | The UPDRS was an investigator-assessed rating tool to follow the longitudinal course of Parkinson's disease. UPDRS Part III total score was the sum of the 27 answers (rated on 0 to 4-point scale) related to motor examination, and ranged from 0-108. Higher scores indicated worse motor function. Change from baseline in UPDRS Part III total score, assessed during on-time (time when the participant has no parkinsonian symptoms) as well as off-time (time when the patient experiences increased parkinsonian symptoms), is reported. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo matched to sarizotan tablet orally twice daily up to Week 12. | 98 |
| Sarizotan 2 mg/Day Participants received sarizotan 2 mg/day (given in 2 divided daily doses) up to Week 12. | 101 |
| Sarizotan 4 mg/Day Participants received sarizotan 4 mg/day (given in 2 divided daily doses) up to Week 12. | 97 |
| Sarizotan 10 mg/Day Participants received sarizotan 10 mg/day (given in 2 divided daily doses) up to Week 12. | 102 |
| Total | 398 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 10 | 4 | 10 | 8 |
| Overall Study | Lack of Efficacy | 0 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Overall Study | Other | 1 | 1 | 2 | 0 |
| Overall Study | Protocol Violation | 3 | 5 | 4 | 4 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 | 4 |
Baseline characteristics
| Characteristic | Placebo | Sarizotan 2 mg/Day | Sarizotan 4 mg/Day | Sarizotan 10 mg/Day | Total |
|---|---|---|---|---|---|
| Age, Continuous | 63.1 years STANDARD_DEVIATION 8.3 | 63.4 years STANDARD_DEVIATION 9.2 | 63.2 years STANDARD_DEVIATION 9.7 | 62.9 years STANDARD_DEVIATION 8.7 | 63.2 years STANDARD_DEVIATION 9 |
| Sex: Female, Male Female | 48 Participants | 47 Participants | 37 Participants | 45 Participants | 177 Participants |
| Sex: Female, Male Male | 50 Participants | 54 Participants | 60 Participants | 57 Participants | 221 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 81 / 98 | 78 / 101 | 75 / 97 | 85 / 102 |
| serious Total, serious adverse events | 5 / 98 | 8 / 101 | 7 / 97 | 2 / 102 |
Outcome results
Primary
Change From Baseline in Diary-Based On-Time Without Dyskinesia at Week 12
On-time without dyskinesia was defined as a period (in hours) when the participant had no symptoms of off-time and was not asleep; also, participant had no difficulty in performing voluntary movements (that is, without dyskinesia). Off-time was defined as a period (in hours) when participant experienced increased parkinsonian symptoms (e.g. immobility or inability to move with ease). On-time was recorded by participant in a participant diary.
Time frame: Baseline, Week 12
Population: Modified intent-to-treat (ITT) population included all randomized participants who received at least one treatment dose and who had at least one follow-up visit assessment for an efficacy target outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Diary-Based On-Time Without Dyskinesia at Week 12 | 1.6 hours/day | Standard Deviation 3.3 |
| Sarizotan 2 mg/Day | Change From Baseline in Diary-Based On-Time Without Dyskinesia at Week 12 | 1.9 hours/day | Standard Deviation 3.8 |
| Sarizotan 4 mg/Day | Change From Baseline in Diary-Based On-Time Without Dyskinesia at Week 12 | 1.7 hours/day | Standard Deviation 3 |
| Sarizotan 10 mg/Day | Change From Baseline in Diary-Based On-Time Without Dyskinesia at Week 12 | 1.8 hours/day | Standard Deviation 3.1 |
Secondary
Change From Baseline in Modified Abnormal Involuntary Movement Scale (AIMS) Score at Week 12
Modified AIMS was a 7-item investigator-assessed scale to assess severity of dyskinesia. Each item was rated on a 0 (none) to 4 (severe) scale. Modified AIMS score was sum of the all item scores and ranged from 0 to 28, where higher score indicated increased severity. Modified AIMS score in resting state as well as with activity is reported.
Time frame: Baseline, Week 12
Population: Modified ITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Modified Abnormal Involuntary Movement Scale (AIMS) Score at Week 12 | Change at Week 12: Modified AIMS with Activity | -3.0 units on a scale | Standard Deviation 5.9 |
| Placebo | Change From Baseline in Modified Abnormal Involuntary Movement Scale (AIMS) Score at Week 12 | Change at Week 12: Modified AIMS at Rest | -2.7 units on a scale | Standard Deviation 5.7 |
| Sarizotan 2 mg/Day | Change From Baseline in Modified Abnormal Involuntary Movement Scale (AIMS) Score at Week 12 | Change at Week 12: Modified AIMS at Rest | -3.0 units on a scale | Standard Deviation 5.3 |
| Sarizotan 2 mg/Day | Change From Baseline in Modified Abnormal Involuntary Movement Scale (AIMS) Score at Week 12 | Change at Week 12: Modified AIMS with Activity | -3.3 units on a scale | Standard Deviation 5.6 |
| Sarizotan 4 mg/Day | Change From Baseline in Modified Abnormal Involuntary Movement Scale (AIMS) Score at Week 12 | Change at Week 12: Modified AIMS with Activity | -3.0 units on a scale | Standard Deviation 4.8 |
| Sarizotan 4 mg/Day | Change From Baseline in Modified Abnormal Involuntary Movement Scale (AIMS) Score at Week 12 | Change at Week 12: Modified AIMS at Rest | -2.7 units on a scale | Standard Deviation 4.1 |
| Sarizotan 10 mg/Day | Change From Baseline in Modified Abnormal Involuntary Movement Scale (AIMS) Score at Week 12 | Change at Week 12: Modified AIMS with Activity | -3.6 units on a scale | Standard Deviation 6 |
| Sarizotan 10 mg/Day | Change From Baseline in Modified Abnormal Involuntary Movement Scale (AIMS) Score at Week 12 | Change at Week 12: Modified AIMS at Rest | -3.7 units on a scale | Standard Deviation 5.5 |
Secondary
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Items 32 and 33 Composite Score at Week 12
The UPDRS was an investigator-assessed rating tool to follow the longitudinal course of Parkinson's disease. Items 32 and 33 assessed duration of dyskinesia and disability due to dyskinesia, respectively. Both items were rated on a 0 to 4-point scale, where higher scores indicated higher duration of dyskinesia and more disability due to dyskinesia, respectively. The Items 32 and 33 composite score was sum of the individual item scores and ranged from 0 to 8, where higher score indicated more complications due to dyskinesia.
Time frame: Baseline, Week 12
Population: Modified ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Items 32 and 33 Composite Score at Week 12 | -1.0 units on a scale | Standard Deviation 1.4 |
| Sarizotan 2 mg/Day | Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Items 32 and 33 Composite Score at Week 12 | -1.4 units on a scale | Standard Deviation 1.6 |
| Sarizotan 4 mg/Day | Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Items 32 and 33 Composite Score at Week 12 | -1.1 units on a scale | Standard Deviation 1.4 |
| Sarizotan 10 mg/Day | Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Items 32 and 33 Composite Score at Week 12 | -1.3 units on a scale | Standard Deviation 1.3 |
Secondary
Change From Baseline in UPDRS Part III Total Score at Week 12
The UPDRS was an investigator-assessed rating tool to follow the longitudinal course of Parkinson's disease. UPDRS Part III total score was the sum of the 27 answers (rated on 0 to 4-point scale) related to motor examination, and ranged from 0-108. Higher scores indicated worse motor function. Change from baseline in UPDRS Part III total score, assessed during on-time (time when the participant has no parkinsonian symptoms) as well as off-time (time when the patient experiences increased parkinsonian symptoms), is reported.
Time frame: Baseline, Week 12
Population: modified ITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in UPDRS Part III Total Score at Week 12 | Change at Week 12: UPDRS Part III On-Time | 0.3 units on a scale | Standard Deviation 6.8 |
| Placebo | Change From Baseline in UPDRS Part III Total Score at Week 12 | Change at Week 12: UPDRS Part III Off-Time | -3.0 units on a scale | Standard Deviation 8.7 |
| Sarizotan 2 mg/Day | Change From Baseline in UPDRS Part III Total Score at Week 12 | Change at Week 12: UPDRS Part III Off-Time | -1.1 units on a scale | Standard Deviation 8.7 |
| Sarizotan 2 mg/Day | Change From Baseline in UPDRS Part III Total Score at Week 12 | Change at Week 12: UPDRS Part III On-Time | -0.1 units on a scale | Standard Deviation 6.4 |
| Sarizotan 4 mg/Day | Change From Baseline in UPDRS Part III Total Score at Week 12 | Change at Week 12: UPDRS Part III Off-Time | -0.0 units on a scale | Standard Deviation 7.6 |
| Sarizotan 4 mg/Day | Change From Baseline in UPDRS Part III Total Score at Week 12 | Change at Week 12: UPDRS Part III On-Time | -0.1 units on a scale | Standard Deviation 6.8 |
| Sarizotan 10 mg/Day | Change From Baseline in UPDRS Part III Total Score at Week 12 | Change at Week 12: UPDRS Part III On-Time | -0.8 units on a scale | Standard Deviation 7.1 |
| Sarizotan 10 mg/Day | Change From Baseline in UPDRS Part III Total Score at Week 12 | Change at Week 12: UPDRS Part III Off-Time | -1.8 units on a scale | Standard Deviation 9 |