Early Parkinson's Disease, Parkinson Disease
Conditions
Keywords
Parkinson disease, early Parkinson's Disease, Parkinson's diagnosis, Parkinson's tretment, Parkinson's medications
Brief summary
P2B001 is an investigational drug that comprised of low doses of two drugs, pramipexole and rasagiline, which are both approved drugs and routinely used in standard therapy for Parkinson's disease. The two drugs work in two different mechanisms that help each other, so there is a reason to believe that their combined activity will be better than each individual drug, and that lower doses can be used without losing the therapeutic effect. Thus, the development of P2B001 is intended to provide a combination of low doses of these two drugs, in an improved formulation, that is hoped to be more effective in controlling Parkinson's disease symptoms and with less side effects than each of the drugs taken alone or the current available commercial drugs taken together. In a previously completed clinical trial a significant improvement in Parkinson's disease symptoms was seen in patients treated with P2B001 compared to patients that were treated with placebo. In this phase 3 study , the safety and efficacy of P2B001 will be assessed by comparing P2B001 to its individual components pramipexole and rasagiline. This will be done by monitoring the motor and non-motor symptoms, evaluating responses participants provide on questionnaires relating to Parkinson's disease and quality of life that will be completed on every visit. In addition, this study will also compare P2B001 to a marketed drug of pramipexole ER. Approximately 525 patients will participate in this research study and the participation in this study will last between 14 to 18 weeks.
Detailed description
A total of 525 eligible subjects with early untreated Parkinson's disease (PD), will be randomized to 4 treatment groups. Each subject will participate in the study for approximately 18 weeks including a 30 day screening period, 12 week treatment period, and 2 weeks follow-up period. Subjects will be requested to take one capsule and 1-3 tablets of study drug by mouth with a glass of water every day for 13 weeks. The study requires seven visits to the clinic one every 2-4 weeks.
Interventions
DRUGP2B001 0.6/0.75 mg
Fixed low dose extended release combination capsule of pramipexole and rasagiline
DRUGRasagiline 0.75 mg
Rasagiline 0.75 mg oral extended release capsule, component
DRUGPramipexole 0.6 mg
Pramipexole 0.6 mg oral extended release capsule, component
DRUGMarketed Pramipexole ER
Marketed Pramipexole ER titrated to optimal dose of 1.5, 3 or 4.5 mg tablet
Sponsors
Pharma Two B Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
double blind study
Intervention model description
4 arms
Eligibility
Sex/Gender
ALL
Age
35 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Subject has Parkinson's disease consistent with the UK Brain Bank Criteria and must have bradykinesia with sequence effect. If rest tremor does not exist must have prominent asymmetry of motor function. 2. Subject with disease duration less than 3 years since diagnosis. 3. Subject has a H&Y stage score of \< 3. 4. Subject has a MMSE score ≥ 26.
Exclusion criteria
1. Subject has an atypical parkinsonian syndrome or secondary parkinsonism 2. Subject has previous exposure to levodopa or a dopamine agonist for longer than 4 weeks; if previous exposure was less than 4 weeks then it must not be within 2 months prior to the baseline visit. 3. Subject has previous exposure to a MAO-B inhibitor for longer than 4 weeks; if previous exposure was less than 4 weeks then it must not be within 3 months prior to the baseline visit. 4. Subject who has taken anticholinergic drugs for PD or amantadine for longer than 4 weeks; if previous exposure was less than 4 weeks then it must not be within 1 month prior to the baseline visit. 5. Subject has moderate (Child-Pugh categorization B, score 7-9) or severe (Child-Pugh categorization C, score 10-15) hepatic impairment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Total Unified Parkinson's Disease Rating Scale (UPDRS) Score (Defined as Sum of Parts II and III, Scores (0-160). | baseline to week 12 | Differences between P2B 0.6/0.75 mg as compared to its individual components in the change of total UPDRS score (defined as sum of parts II and III, scores (0-160). UPDRS- Unified Parkinson's Disease Rating Scale, minimum value is 0 points and maximum value is 160. High score mean worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Epworth Sleepiness Scale (ESS) Score. | baseline to week 12 | Differences between P2B 0.6/0.75 mg as compared to pramipexole ER tablets in the change of Epworth Sleepiness Scale (ESS) score. Scale is 0-24 , when 24 is worse outcome |
| Change From Baseline to Week 12 in Total UPDRS III Motor | baseline to week 12 | Differences between P2B 0.6/0.75 mg as compared to its individual components in the change of Motor UPDRS score (UPDRS Part III ). UPDRS- Unified Parkinson's Disease Rating Scale, part III motor . min is 0 and Max is 108 (Worse outcome) |
| Change From Baseline to Week 12 in Total UPDRS II ADL | Baseline to week 12 | Differences between of P2B 0.6/0.75 mg as compared to its individual components in the change of ADL UPDRS score (UPDRS part II) Activity of daily Life UPDRS part II minimum is 0 point and max is 52 point (worse outcome) |
| Change From Baseline to End of Week 12 Visit in ADL Subscale of PDQ39 | Baseline to week 12 | The efficacy of P2B 0.6/0.75 mg as compared to Pramipexole ER tablet titrated to optimal dose. ADL PDQ39- Activity of daily life part in Parkinson's Disease Questionaries' 39 Score 0-100 when 100 is the worse outcome |
Countries
Canada, Germany, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| P2B001 Fixed dose combination once daily capsule of pramipexole and rasagiline
P2B001: Fixed dose once daily combination capsule of pramipexole and rasagiline | 157 |
| Rasagiline Capsule rasagiline Once daily capsule
Rasagiline: Rasagiline oral capsule | 154 |
| Pramipexole Capsule Pramipexole once daily capsule
Pramipexole: Pramipexole low dose oral capsule | 156 |
| Pramipexole Extended Release pramipexole ER tablet titrated to optimal dose of 1.5, 3.0 or 4.5mg
Pramipexole ER: Pramipexole ER titrated to optimal dose | 77 |
| Total | 544 |
Baseline characteristics
| Characteristic | P2B001 | Rasagiline Capsule | Pramipexole Capsule | Pramipexole Extended Release | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 78 Participants | 83 Participants | 79 Participants | 36 Participants | 276 Participants |
| Age, Categorical Between 18 and 65 years | 79 Participants | 71 Participants | 77 Participants | 41 Participants | 268 Participants |
| Age, Continuous | 63 Years STANDARD_DEVIATION 9 | 65 Years STANDARD_DEVIATION 1 | 64 Years STANDARD_DEVIATION 9 | 63 Years STANDARD_DEVIATION 9 | 64 Years STANDARD_DEVIATION 6 |
| Epworth Sleepiness Score | 5.5 units on a scale STANDARD_DEVIATION 4 | 5.7 units on a scale STANDARD_DEVIATION 4.3 | 6.2 units on a scale STANDARD_DEVIATION 4 | 6.1 units on a scale STANDARD_DEVIATION 4.1 | 5.8 units on a scale STANDARD_DEVIATION 4.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 5 Participants | 1 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 2 Participants | 2 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) White | 150 Participants | 145 Participants | 147 Participants | 74 Participants | 516 Participants |
| Region of Enrollment Canada | 1 participants | 0 participants | 1 participants | 0 participants | 2 participants |
| Region of Enrollment Germany | 29 participants | 29 participants | 30 participants | 15 participants | 103 participants |
| Region of Enrollment Spain | 18 participants | 16 participants | 17 participants | 8 participants | 59 participants |
| Region of Enrollment United States | 109 participants | 109 participants | 108 participants | 54 participants | 380 participants |
| Sex: Female, Male Female | 51 Participants | 48 Participants | 52 Participants | 24 Participants | 175 Participants |
| Sex: Female, Male Male | 106 Participants | 106 Participants | 104 Participants | 53 Participants | 369 Participants |
| Total UPDRS | 30.7 units on a scale STANDARD_DEVIATION 9.9 | 31.3 units on a scale STANDARD_DEVIATION 10.2 | 31.3 units on a scale STANDARD_DEVIATION 11 | 28.8 units on a scale STANDARD_DEVIATION 10 | 30.8 units on a scale STANDARD_DEVIATION 10.3 |
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 | 0 / 150 | 0 / 147 | 0 / 148 | 0 / 74 |
| other Total, other adverse events | 78 / 150 | 52 / 147 | 86 / 148 | 54 / 74 |
| serious Total, serious adverse events | 3 / 150 | 2 / 147 | 3 / 148 | 0 / 74 |
Outcome results
Primary
Change in Total Unified Parkinson's Disease Rating Scale (UPDRS) Score (Defined as Sum of Parts II and III, Scores (0-160).
Differences between P2B 0.6/0.75 mg as compared to its individual components in the change of total UPDRS score (defined as sum of parts II and III, scores (0-160). UPDRS- Unified Parkinson's Disease Rating Scale, minimum value is 0 points and maximum value is 160. High score mean worse outcome.
Time frame: baseline to week 12
Population: mITT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| P2B001 | Change in Total Unified Parkinson's Disease Rating Scale (UPDRS) Score (Defined as Sum of Parts II and III, Scores (0-160). | -7.98 score on a scale | Standard Error 0.6 |
| Rasagiline Capsule | Change in Total Unified Parkinson's Disease Rating Scale (UPDRS) Score (Defined as Sum of Parts II and III, Scores (0-160). | -4.69 score on a scale | Standard Error 0.61 |
| Pramipexole Capsule | Change in Total Unified Parkinson's Disease Rating Scale (UPDRS) Score (Defined as Sum of Parts II and III, Scores (0-160). | -5.32 score on a scale | Standard Error 0.61 |
| Pramipexole Extended Release | Change in Total Unified Parkinson's Disease Rating Scale (UPDRS) Score (Defined as Sum of Parts II and III, Scores (0-160). | -8.35 score on a scale | Standard Error 0.86 |
p-value: 0.001895% CI: [-4.33, -1]MMRM
p-value: 0.000195% CI: [-4.96, -1.63]MMRM
Secondary
Change From Baseline to End of Week 12 Visit in ADL Subscale of PDQ39
The efficacy of P2B 0.6/0.75 mg as compared to Pramipexole ER tablet titrated to optimal dose. ADL PDQ39- Activity of daily life part in Parkinson's Disease Questionaries' 39 Score 0-100 when 100 is the worse outcome
Time frame: Baseline to week 12
Population: mITT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| P2B001 | Change From Baseline to End of Week 12 Visit in ADL Subscale of PDQ39 | -5.30 score on a scale | Standard Error 0.89 |
| Rasagiline Capsule | Change From Baseline to End of Week 12 Visit in ADL Subscale of PDQ39 | -2.04 score on a scale | Standard Error 0.92 |
| Pramipexole Capsule | Change From Baseline to End of Week 12 Visit in ADL Subscale of PDQ39 | -3.40 score on a scale | Standard Error 0.9 |
| Pramipexole Extended Release | Change From Baseline to End of Week 12 Visit in ADL Subscale of PDQ39 | -3.12 score on a scale | Standard Error 1.27 |
p-value: 0.158995% CI: [-5.21, 0.85]MMRM
Secondary
Change From Baseline to Week 12 in Total UPDRS II ADL
Differences between of P2B 0.6/0.75 mg as compared to its individual components in the change of ADL UPDRS score (UPDRS part II) Activity of daily Life UPDRS part II minimum is 0 point and max is 52 point (worse outcome)
Time frame: Baseline to week 12
Population: mITT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| P2B001 | Change From Baseline to Week 12 in Total UPDRS II ADL | -2.14 score on a scale | Standard Error 0.22 |
| Rasagiline Capsule | Change From Baseline to Week 12 in Total UPDRS II ADL | -0.62 score on a scale | Standard Error 0.22 |
| Pramipexole Capsule | Change From Baseline to Week 12 in Total UPDRS II ADL | -0.97 score on a scale | Standard Error 0.22 |
| Pramipexole Extended Release | Change From Baseline to Week 12 in Total UPDRS II ADL | -2.02 score on a scale | Standard Error 0.31 |
p-value: 0.000195% CI: [-1.77, -0.57]MMRM
p-value: <0.000195% CI: [-2.13, -0.92]MMRM
Secondary
Change From Baseline to Week 12 in Total UPDRS III Motor
Differences between P2B 0.6/0.75 mg as compared to its individual components in the change of Motor UPDRS score (UPDRS Part III ). UPDRS- Unified Parkinson's Disease Rating Scale, part III motor . min is 0 and Max is 108 (Worse outcome)
Time frame: baseline to week 12
Population: mITT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| P2B001 | Change From Baseline to Week 12 in Total UPDRS III Motor | -5.82 score on a scale | Standard Error 0.47 |
| Rasagiline Capsule | Change From Baseline to Week 12 in Total UPDRS III Motor | -4.07 score on a scale | Standard Error 0.48 |
| Pramipexole Capsule | Change From Baseline to Week 12 in Total UPDRS III Motor | -4.30 score on a scale | Standard Error 0.48 |
| Pramipexole Extended Release | Change From Baseline to Week 12 in Total UPDRS III Motor | -6.36 score on a scale | Standard Error 0.68 |
p-value: 0.023195% CI: [-2.84, -0.21]MMRM
p-value: 0.009295% CI: [-3.06, -0.43]MMRM
Secondary
Change in Epworth Sleepiness Scale (ESS) Score.
Differences between P2B 0.6/0.75 mg as compared to pramipexole ER tablets in the change of Epworth Sleepiness Scale (ESS) score. Scale is 0-24 , when 24 is worse outcome
Time frame: baseline to week 12
Population: mITT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| P2B001 | Change in Epworth Sleepiness Scale (ESS) Score. | -0.33 score on a scale | Standard Error 0.25 |
| Rasagiline Capsule | Change in Epworth Sleepiness Scale (ESS) Score. | -0.81 score on a scale | Standard Error 0.26 |
| Pramipexole Capsule | Change in Epworth Sleepiness Scale (ESS) Score. | 0.39 score on a scale | Standard Error 0.25 |
| Pramipexole Extended Release | Change in Epworth Sleepiness Scale (ESS) Score. | 2.33 score on a scale | Standard Error 0.36 |
p-value: <0.000195% CI: [-3.5, -1.81]MMRM
p-value: <0.0595% CI: [-3.5, -1.81]MMRM