Parkinson Disease
Conditions
Brief summary
Primary objective: to assess the efficacy of pramipexole given two times daily compared to placebo. Secondary objectives: to assess the effects of pramipexole on mood, cognition, fatigue, impulse control, daytime sleepiness and nighttime sleep compared to placebo; to compare the tolerability among the treatment groups over 12 weeks
Interventions
DRUGPramipexole
DRUGPlacebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
31 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Potential subjects must meet all of the following inclusion criteria to be eligible for enrollment into this study: 1. Must be willing and able to give informed consent. 2. Must be over 30 years of age at Baseline. 3. Must have idiopathic Parkinson's disease of less than 7 years duration since diagnosis, characterized by 2 of the following 3 cardinal signs (signs need to be asymmetric): resting tremor, bradykinesia and rigidity. 4. Must have a Modified Hoehn and Yahr stage \<3. 5. Should be able to safely tolerate placebo for up to 12 weeks after Baseline. 6. Must have a negative urine pregnancy test at the Screening Visit and use an adequate contraceptive method throughout the study if a woman of child-bearing potential. Women who are surgically sterile (hysterectomy or tubal ligation) or whose last menstruation was 12 months or more prior to the Screening Visit are considered to be of non-child-bearing potential. Acceptable forms of contraception include oral, implanted, or injected contraceptives intrauterine devices in place for at least 3 months estrogen patch and adequate barrier methods in conjunction with spermicide. Abstinence is considered an acceptable contraceptive regimen. 7. Must be willing and able to comply with trial procedures. They must be sufficiently proficient in English to understand and complete study instruments.
Exclusion criteria
Individuals with any of the following characteristics will not be eligible for entry into this study: 1. Signs or symptoms suggesting other parkinsonian syndromes. 2. Use of medications that may cause secondary parkinsonism, including but not limited to: neuroleptics, metaclopramide, alphamethyldopa, flunarizine, methylphenidate, cinnarizine, reserpine, or amphetamines in the last 6 months prior to Baseline Visit. 3. Use of dopaminergic medications within the last 3 months or for longer than 6 months prior to Baseline Visit. 4. Presence of dementia by Diagnostic and Statistical Manual of Mental Disorders IV criteria (R06-1340) or a Mini Mental State Examination (R96-2656) (Appendix 10.1) score less than 26 at Screening Visit. 5. Presence of major depression, as determined by medical history. 6. Active epilepsy (i.e., occurrence of a seizure) within the past year prior to Baseline Visit. 7. Electro Convulsive Therapy in previous 90 days prior to Baseline Visit. 8. Myocardial infarction within previous 6 months prior to Baseline Visit. 9. Third degree atrioventricular block or sick sinus syndrome. 10. Congestive heart failure Class III or IV by New York Heart Association classification. 11. Symptomatic orthostatic hypotension at Screening Visit. 12. Stereotaxic brain surgery. 13. Clinically significant liver disease. 14. Clinically significant renal disease. 15. Any other clinically significant medical or psychiatric condition (e.g., angina, active neoplasm) that in the judgment of the investigator would interfere with the subjects ability to participate in the study or would jeopardize safe conduct of the study. 16. Breastfeeding. 17. Known hypersensitivity or intolerability to pramipexole. 18. Participating in other drug studies or receiving other experimental medications within 30 days of Baseline Visit. 19. History of drug or alcohol dependency within 6 months of baseline visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Unified Parkinson's Disease Rating Scale (UPDRS) Total Score | From baseline to week 12 | Total score ranges from zero (best) to 176 (worst), as the sum of Parts I (Mental questions), II (Activity of Daily Living questions), and III (Motor examination) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Modified Hoehn and Yahr Stage | From baseline to week 12 | Score ranges from best 0 (no signs of disease) to worst 5 (wheelchair bound or bedridden unless aided) |
| Epworth Sleepiness Scale | From baseline to week 12 | Total score ranges from zero (best) to 24 (worst); scale has 8 items, each rated from zero (no chance of dozing) to 3 (high chance of dozing) |
| Beck Depression Inventory II | From baseline to week 12 | Total score ranges from zero (best) to 63 (worst); scale has 21 items, each rated from zero (absent) to 3 (severe) |
Countries
United States
Participant flow
Pre-assignment details
There were 312 patients enrolled and 311 patients entered
Participants by arm
| Arm | Count |
|---|---|
| Placebo matching tablet | 77 |
| Mirapex (Pramipexole 0.5 mg Tid) Week 1: Pramipexole 0.125 mg tid, Week 2: Pramipexole 0.25 mg tid, Week 3: Pramipexole 0.5 mg tid, Week 4 to Week 12: Pramipexole 0.5 mg tid. After the initial 4 week titration period, each dosage group will maintain the specified dosage for an additional 8 weeks, to complete the 12 week double-blind period. | 80 |
| Mirapex (Pramipexole 0.5 mg Bid) Week 1: Pramipexole 0.125 mg bid, Week 2: Pramipexole 0.25 mg bid, Week 3: Pramipexole 0.5 mg bid, Week 4 to Week 12: Pramipexole 0.5 mg bid. After the initial 4 week titration period, each dosage group will maintain the specified dosage for an additional 8 weeks, to complete the 12 week double-blind period. | 81 |
| Mirapex (Pramipexole 0.75 mg Bid) Week 1: Pramipexole 0.125 mg bid, Week 2: Pramipexole 0.25 mg bid, Week 3: Pramipexole 0.5 mg bid, Week 4 to Week 12: Pramipexole 0.75 mg bid. After the initial 4 week titration period, each dosage group will maintain the specified dosage for an additional 8 weeks, to complete the 12 week double-blind period. | 73 |
| Total | 311 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 7 | 9 | 9 |
| Overall Study | Protocol Violation | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 2 | 2 |
| Overall Study | Worsening of disease under study | 2 | 0 | 0 | 0 |
| Overall Study | Worsening of other pre-existing disease | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | Mirapex (Pramipexole 0.5 mg Tid) | Mirapex (Pramipexole 0.5 mg Bid) | Mirapex (Pramipexole 0.75 mg Bid) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 60.7 years STANDARD_DEVIATION 11 | 63.7 years STANDARD_DEVIATION 9.8 | 61.6 years STANDARD_DEVIATION 10.2 | 63.1 years STANDARD_DEVIATION 9.9 | 62.3 years STANDARD_DEVIATION 10.2 |
| Sex: Female, Male Female | 19 Participants | 23 Participants | 30 Participants | 32 Participants | 104 Participants |
| Sex: Female, Male Male | 58 Participants | 57 Participants | 51 Participants | 41 Participants | 207 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 | 27 / 77 | 42 / 81 | 37 / 73 | 43 / 80 |
| serious Total, serious adverse events | 0 / 77 | 0 / 81 | 2 / 73 | 1 / 80 |
Outcome results
Primary
Unified Parkinson's Disease Rating Scale (UPDRS) Total Score
Total score ranges from zero (best) to 176 (worst), as the sum of Parts I (Mental questions), II (Activity of Daily Living questions), and III (Motor examination)
Time frame: From baseline to week 12
Population: Treated set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Unified Parkinson's Disease Rating Scale (UPDRS) Total Score | UPDRS at baseline | 28.97 units on a scale | Standard Deviation 11.82 |
| Placebo | Unified Parkinson's Disease Rating Scale (UPDRS) Total Score | UPDRS at week 12 | 28.19 units on a scale | Standard Deviation 12.94 |
| Mirapex (Pramipexole 0.5 mg Tid) | Unified Parkinson's Disease Rating Scale (UPDRS) Total Score | UPDRS at week 12 | 22.92 units on a scale | Standard Deviation 10.44 |
| Mirapex (Pramipexole 0.5 mg Tid) | Unified Parkinson's Disease Rating Scale (UPDRS) Total Score | UPDRS at baseline | 27.66 units on a scale | Standard Deviation 10.72 |
| Mirapex (Pramipexole 0.5 mg Bid) | Unified Parkinson's Disease Rating Scale (UPDRS) Total Score | UPDRS at baseline | 27.21 units on a scale | Standard Deviation 11.76 |
| Mirapex (Pramipexole 0.5 mg Bid) | Unified Parkinson's Disease Rating Scale (UPDRS) Total Score | UPDRS at week 12 | 22.96 units on a scale | Standard Deviation 11.94 |
| Mirapex (Pramipexole 0.75 mg Bid) | Unified Parkinson's Disease Rating Scale (UPDRS) Total Score | UPDRS at baseline | 27.77 units on a scale | Standard Deviation 9.18 |
| Mirapex (Pramipexole 0.75 mg Bid) | Unified Parkinson's Disease Rating Scale (UPDRS) Total Score | UPDRS at week 12 | 22.65 units on a scale | Standard Deviation 10.82 |
p-value: <0.000195% CI: [-6.53, -2.26]ANCOVA
p-value: <0.000195% CI: [-6.54, -2.28]ANCOVA
p-value: <0.000195% CI: [-6.91, -2.52]ANCOVA
Secondary
Beck Depression Inventory II
Total score ranges from zero (best) to 63 (worst); scale has 21 items, each rated from zero (absent) to 3 (severe)
Time frame: From baseline to week 12
Population: Treated set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Beck Depression Inventory II | Beck Depression Inventory II at baseline | 6.05 units on a scale | Standard Deviation 6.01 |
| Placebo | Beck Depression Inventory II | Beck Depression Inventory II at week 12 | 5.92 units on a scale | Standard Deviation 5.83 |
| Mirapex (Pramipexole 0.5 mg Tid) | Beck Depression Inventory II | Beck Depression Inventory II at week 12 | 5.70 units on a scale | Standard Deviation 5.14 |
| Mirapex (Pramipexole 0.5 mg Tid) | Beck Depression Inventory II | Beck Depression Inventory II at baseline | 6.66 units on a scale | Standard Deviation 5.36 |
| Mirapex (Pramipexole 0.5 mg Bid) | Beck Depression Inventory II | Beck Depression Inventory II at baseline | 6.96 units on a scale | Standard Deviation 5.14 |
| Mirapex (Pramipexole 0.5 mg Bid) | Beck Depression Inventory II | Beck Depression Inventory II at week 12 | 5.97 units on a scale | Standard Deviation 5.14 |
| Mirapex (Pramipexole 0.75 mg Bid) | Beck Depression Inventory II | Beck Depression Inventory II at baseline | 7.4 units on a scale | Standard Deviation 5.87 |
| Mirapex (Pramipexole 0.75 mg Bid) | Beck Depression Inventory II | Beck Depression Inventory II at week 12 | 6.54 units on a scale | Standard Deviation 5.19 |
p-value: 0.3995% CI: [-1.82, 0.71]ANCOVA
p-value: 0.3795% CI: [-1.84, 0.69]ANCOVA
p-value: 0.4895% CI: [-1.78, 0.84]ANCOVA
Secondary
Epworth Sleepiness Scale
Total score ranges from zero (best) to 24 (worst); scale has 8 items, each rated from zero (no chance of dozing) to 3 (high chance of dozing)
Time frame: From baseline to week 12
Population: Treated set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Epworth Sleepiness Scale | Epworth Sleepiness Scale at baseline | 5.29 units on a scale | Standard Deviation 3.47 |
| Placebo | Epworth Sleepiness Scale | Epworth Sleepiness Scale at week 12 | 5.09 units on a scale | Standard Deviation 3.33 |
| Mirapex (Pramipexole 0.5 mg Tid) | Epworth Sleepiness Scale | Epworth Sleepiness Scale at week 12 | 6.58 units on a scale | Standard Deviation 3.62 |
| Mirapex (Pramipexole 0.5 mg Tid) | Epworth Sleepiness Scale | Epworth Sleepiness Scale at baseline | 5.8 units on a scale | Standard Deviation 3.66 |
| Mirapex (Pramipexole 0.5 mg Bid) | Epworth Sleepiness Scale | Epworth Sleepiness Scale at baseline | 5.78 units on a scale | Standard Deviation 3.74 |
| Mirapex (Pramipexole 0.5 mg Bid) | Epworth Sleepiness Scale | Epworth Sleepiness Scale at week 12 | 6.44 units on a scale | Standard Deviation 4.21 |
| Mirapex (Pramipexole 0.75 mg Bid) | Epworth Sleepiness Scale | Epworth Sleepiness Scale at baseline | 6.34 units on a scale | Standard Deviation 4.35 |
| Mirapex (Pramipexole 0.75 mg Bid) | Epworth Sleepiness Scale | Epworth Sleepiness Scale at week 12 | 7.52 units on a scale | Standard Deviation 5.03 |
p-value: 0.01495% CI: [0.23, 2.04]ANCOVA
p-value: 0.0395% CI: [0.094, 1.9]ANCOVA
p-value: 0.001995% CI: [0.56, 2.43]ANCOVA
Secondary
Modified Hoehn and Yahr Stage
Score ranges from best 0 (no signs of disease) to worst 5 (wheelchair bound or bedridden unless aided)
Time frame: From baseline to week 12
Population: Treated set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Modified Hoehn and Yahr Stage | Modified Hoehn and Yahr Stage at baseline | 1.81 units on a scale | Standard Deviation 0.48 |
| Placebo | Modified Hoehn and Yahr Stage | Modified Hoehn and Yahr Stage at week 12 | 1.74 units on a scale | Standard Deviation 0.54 |
| Mirapex (Pramipexole 0.5 mg Tid) | Modified Hoehn and Yahr Stage | Modified Hoehn and Yahr Stage at week 12 | 1.68 units on a scale | Standard Deviation 0.52 |
| Mirapex (Pramipexole 0.5 mg Tid) | Modified Hoehn and Yahr Stage | Modified Hoehn and Yahr Stage at baseline | 1.74 units on a scale | Standard Deviation 0.5 |
| Mirapex (Pramipexole 0.5 mg Bid) | Modified Hoehn and Yahr Stage | Modified Hoehn and Yahr Stage at baseline | 1.72 units on a scale | Standard Deviation 0.5 |
| Mirapex (Pramipexole 0.5 mg Bid) | Modified Hoehn and Yahr Stage | Modified Hoehn and Yahr Stage at week 12 | 1.69 units on a scale | Standard Deviation 0.52 |
| Mirapex (Pramipexole 0.75 mg Bid) | Modified Hoehn and Yahr Stage | Modified Hoehn and Yahr Stage at baseline | 1.73 units on a scale | Standard Deviation 0.51 |
| Mirapex (Pramipexole 0.75 mg Bid) | Modified Hoehn and Yahr Stage | Modified Hoehn and Yahr Stage at week 12 | 1.62 units on a scale | Standard Deviation 0.56 |
95% CI: [0.431, 1.849]Regression, Logistic
95% CI: [0.424, 1.845]Regression, Logistic
95% CI: [0.317, 1.492]Regression, Logistic