Parkinson's Disease
Conditions
Keywords
Parkinson's Disease, Rasagiline, Pramipexole
Brief summary
This study will evaluate an oral fixed-dose, once daily product that combines pramipexole and rasagiline for the treatment of early Parkinson's disease. Animal studies support the therapeutic advantage of combining low doses of rasagiline and pramipexole and suggest further improvement when both are administered in a sustained fashion. Both rasagiline and pramipexole are well known marketed drugs for Parkinson's disease with a good safety profile. combining the drugs in low doses and controlled release may provide better symptom management than the existing drugs alone or together.
Interventions
DRUGP2B001 once daily (pramipexole 0.6 mg / rasagiline 0.75 mg),
Fixed Dose Combination of pramipexole 0.6 mg and rasagiline 0.75 mg once daily
DRUGPlacebo
placebo
DRUGP2B001 once daily (pramipexole 0.3 mg / rasagiline 0.75 mg),
Fixed Dose Combination of pramipexole 0.3 mg and rasagiline 0.75 mg once daily
Sponsors
Pharma Two B Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
35 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subject is male or female ≥35 years of age to ≤75 years of age at the time of enrollment. * Subject has idiopathic Parkinson's disease consistent with the UK Brain Bank Criteria; must have bradykinesia with sequence effect and rest tremor or prominent motor asymmetry. * Subject with disease duration no longer than 3 years and 0 months. * Subject has a Hoehn & Yahr (H&Y) stage score of \< 3. * Subject has a MMSE score ≥ 26
Exclusion criteria
* Subject has an atypical parkinsonian syndrome or secondary parkinsonism (e.g., due to drugs, metabolic neurogenetic disorders, encephalitis, cerebrovascular disease or degenerative disease). * Subject has a history of psychosis or hallucinations within the previous 12 months. * Subject who is taking anticholinergic drugs. * 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. * 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. * Subject who is taking MAO inhibitors, potent CYP1A2 inhibitors, e,g, Ciprofloxacin, Dextromethorphan or antitussive agent, analgesic agents such as tramadol, meperidine, methadone and propoxyphene, strong 3A4 inducers, e.g., St. John's Wort or cyclobenzaprine (tricyclic muscle relaxant), dopamine antagonists, such as the neuroleptics (phenothiazines, butyrophenones, thioxanthenes) or metoclopramide. Probenecid, cimetidine, ranitidine, diltiazem, verapamil and quinidine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total UPDRS I, II, III Scores | Week 12 | Change from baseline to final visit (week 12) in total UPDRS score (defined as sum of parts I, II and III, scores (0-176). UPDRS- Unified Parkinson's Disease Rating Scale, minimum value is 0 points and maximum value is 176. High score mean worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| UPDRS ADL (Part II) | Week 12 | Change from baseline in individual UPDRS ADL (part II). Activity of daily Life UPDRS part II minimum is 0 point and max is 52 point (worse outcome) |
| CGI-S | 12 weeks | Change from baseline in individual Clinical Global Impression - Severity. Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness (Parkinson's Disease) at the time of assessment relative to the clinician's past experience with patients who have the same diagnosis as one of the following:. 1 is normal and 7 is the most extremely ill patients. A subject defined as a treatment responder when the improvement from baseline to the Week12 / Last Observed Value (LOV) was of at least 1 point or more. |
| UPDRS Motor (Part III) | 12 weeks | Change from baseline in individual UPDRS motor (part III). UPDRS- Unified Parkinson's Disease Rating Scale, part III motor . min is 0 and Max is 108 (Worse outcome) |
| PDQ39 | 12 weeks | Change from baseline in individual Parkinson's Disease Questionnaire - 39. Score 0-100 where 0 is indicative of no problem at all and 100 is the maximum level of problem. |
Countries
Israel, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| P2B001 Treatment A Fixed Dose Combination of pramipexole 0.6 mg and rasagiline 0.75 mg once daily.
P2B001 once daily (pramipexole 0.6 mg / rasagiline 0.75 mg), : Fixed Dose Combination of pramipexole 0.6 mg and rasagiline 0.75 mg once daily | 49 |
| P2B001 Treatment B Fixed Dose Combination of pramipexole 0.3 mg and rasagiline 0.75 mg once daily
P2B001 once daily (pramipexole 0.3 mg / rasagiline 0.75 mg), : Fixed Dose Combination of pramipexole 0.3 mg and rasagiline 0.75 mg once daily | 50 |
| Placebo Placebo once daily for 12 weeks.
Placebo: placebo | 50 |
| Total | 149 |
Baseline characteristics
| Characteristic | P2B001 Treatment A | P2B001 Treatment B | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 24 Participants | 27 Participants | 32 Participants | 83 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 23 Participants | 18 Participants | 66 Participants |
| Age, Continuous | 62 years STANDARD_DEVIATION 8 | 63 years STANDARD_DEVIATION 8 | 64 years STANDARD_DEVIATION 7 | 63 years STANDARD_DEVIATION 8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 4 Participants | 1 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 1 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 | 46 Participants | 43 Participants | 47 Participants | 136 Participants |
| Region of Enrollment Israel | 7 participants | 8 participants | 8 participants | 23 participants |
| Region of Enrollment United States | 42 participants | 42 participants | 42 participants | 126 participants |
| Sex: Female, Male Female | 14 Participants | 16 Participants | 19 Participants | 49 Participants |
| Sex: Female, Male Male | 35 Participants | 34 Participants | 31 Participants | 100 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 49 | 0 / 50 | 0 / 50 |
| other Total, other adverse events | 37 / 49 | 20 / 50 | 24 / 50 |
| serious Total, serious adverse events | 1 / 49 | 0 / 50 | 0 / 50 |
Outcome results
Primary
Total UPDRS I, II, III Scores
Change from baseline to final visit (week 12) in total UPDRS score (defined as sum of parts I, II and III, scores (0-176). UPDRS- Unified Parkinson's Disease Rating Scale, minimum value is 0 points and maximum value is 176. High score mean worse outcome.
Time frame: Week 12
Population: ITT analyis
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| P2B001 Treatment A | Total UPDRS I, II, III Scores | -5.97 units on a scale | Standard Error 0.94 |
| P2B001 Treatment B | Total UPDRS I, II, III Scores | -5.15 units on a scale | Standard Error 0.9 |
| Placebo | Total UPDRS I, II, III Scores | -1.31 units on a scale | Standard Error 0.88 |
p-value: 0.000495% CI: [-7.2, -2.13]MMRM
p-value: 0.002795% CI: [-6.32, -1.36]MMRM
Secondary
CGI-S
Change from baseline in individual Clinical Global Impression - Severity. Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness (Parkinson's Disease) at the time of assessment relative to the clinician's past experience with patients who have the same diagnosis as one of the following:. 1 is normal and 7 is the most extremely ill patients. A subject defined as a treatment responder when the improvement from baseline to the Week12 / Last Observed Value (LOV) was of at least 1 point or more.
Time frame: 12 weeks
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| P2B001 Treatment A | CGI-S | 13 Participants |
| P2B001 Treatment B | CGI-S | 9 Participants |
| Placebo | CGI-S | 3 Participants |
Comparison: A subject will be defined as a treatment responder in case that the improvement from baseline to the Week12 / Last Observed Value (LOV) in the CGI-S will be of 1 point or more. Baseline adjusted logistic regression (SAS® LOGISTIC procedure) stratified by GeoSite using the STRATA sub-command with the following effects: treatment group and baseline CGI-S measurement was used to test the between the active groups and placebo contrasts.p-value: 0.016595% CI: [1.47, 44.77]Regression, Logistic
p-value: 0.11195% CI: [0.72, 24.9]Regression, Logistic
Secondary
PDQ39
Change from baseline in individual Parkinson's Disease Questionnaire - 39. Score 0-100 where 0 is indicative of no problem at all and 100 is the maximum level of problem.
Time frame: 12 weeks
Population: ITT Analysis
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| P2B001 Treatment A | PDQ39 | -3.01 units on a scale | Standard Error 0.89 |
| P2B001 Treatment B | PDQ39 | -2.19 units on a scale | Standard Error 0.88 |
| Placebo | PDQ39 | 0.26 units on a scale | Standard Error 0.88 |
p-value: 0.009795% CI: [-5.72, -0.8]Mixed Models Analysis
p-value: 0.050995% CI: [-4.91, -0.012]Mixed Models Analysis
Secondary
UPDRS ADL (Part II)
Change from baseline in individual UPDRS ADL (part II). Activity of daily Life UPDRS part II minimum is 0 point and max is 52 point (worse outcome)
Time frame: Week 12
Population: ITT analysis
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| P2B001 Treatment A | UPDRS ADL (Part II) | -1.49 units on a scale | Standard Error 0.37 |
| P2B001 Treatment B | UPDRS ADL (Part II) | -1.06 units on a scale | Standard Error 0.36 |
| Placebo | UPDRS ADL (Part II) | 0.36 units on a scale | Standard Error 0.39 |
p-value: 0.000495% CI: [-2.86, -0.84]MMRM
p-value: 0.00595% CI: [-2.41, 0.44]MMRM
Secondary
UPDRS Motor (Part III)
Change from baseline in individual UPDRS motor (part III). UPDRS- Unified Parkinson's Disease Rating Scale, part III motor . min is 0 and Max is 108 (Worse outcome)
Time frame: 12 weeks
Population: ITT anlysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| P2B001 Treatment A | UPDRS Motor (Part III) | -4.43 units on a scale | Standard Error 0.74 |
| P2B001 Treatment B | UPDRS Motor (Part III) | -3.95 units on a scale | Standard Error 0.7 |
| Placebo | UPDRS Motor (Part III) | -1.62 units on a scale | Standard Error 0.69 |
p-value: 0.005895% CI: [-4.8, -0.83]MMRM
p-value: 0.019195% CI: [-4.26, -0.39]MMRM