| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Early Parkinson's Disease |
|
| E.1.1.1 | Medical condition in easily understood language |
| Early Parkinson's Disease |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | HLT |
| E.1.2 | Classification code | 10034005 |
| E.1.2 | Term | Parkinson's disease and parkinsonism |
| E.1.2 | System Organ Class | 100000004852 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To determine the superiority of 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). |
|
| E.2.2 | Secondary objectives of the trial |
• To determine 12 weeks the superiority of P2B 0.6/0.75 mg as compared to pramipexole ER in the change of Epworth Sleepiness Scale (ESS) score.
• To determine the efficacy of P2B 0.6/0.75 mg as compared to its individual components in the change of Total PDQ39 score.
• To determine the efficacy of P2B 0.6/0.75 mg as compared to its individual components in the change of ADL UPDRS (part II) score.
• To determine the efficacy of P2B 0.6/0.75 mg as compared to its individual components in the change of motor UPDRS (part III) score.
• To determine the efficacy of P2B 0.6/0.75 mg as compared to its individual components in the CGI-S responder’s analysis (change from baseline ≥1 CGI-S points). |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subject is informed and given ample time and opportunity to think about his/her participation in this study and has given his/her written informed consent on an EC/IRB approved consent form.
2. Subject is willing and able to comply with all study requirements (protocol, clinic visits, procedures and medication administration).
3. Subject is male or female ≥35 years of age to ≤80 years of age at the time of enrollment
4. 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.
5. Subject with disease duration less than 3 years since diagnosis
6. Subject has a H&Y stage score of < 3.
7. Subject has a MMSE score ≥ 26.
8. Women of child-bearing potential (WOCBP)* must use a reliable method of contraception (e.g., oral contraceptive or long-term injectable or implantable hormonal contraceptive, double-barrier methods [such as condom plus diaphragm, condom plus spermicide foam, condom plus sponge], or intra-uterine devices) for the entire study duration, and must have a negative serum pregnancy test at Screening and negative urine pregnancy at baseline visit.
*WOCBP are defined as any female who has experienced menarche and who is NOT permanently sterile or postmenopaused. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause.
9. Subject was approved by a central Eligibility Monitoring Committee (EMC) based on suitability for the study, and his/her eligibility was confirmed by EMC signature on the Randomization Authorization Form (RAF). |
|
| E.4 | Principal exclusion criteria |
Subjects are not permitted to enroll in the study if any 1 of the following criteria is met.
1. Subject has previously participated in this study.
2. Subject has participated in another study of an investigational medicinal product (IMP) or a medical device within the last 30 days or is currently participating in another study of an IMP or medical device.
3. Subject has an atypical parkinsonian syndrome or secondary parkinsonism (e.g., due to drugs, toxins, metabolic disorders, encephalitis, cerebrovascular disease or degenerative disease).
4. Subject has a history of psychosis or hallucinations within the previous 12 months.
5. Subject has cognitive impairment in the judgment of the Investigator that excludes him/her from understanding consent or participating in the study.
6. 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.
7. 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.
8. 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.
9. Subject who is taking non-selective MAO inhibitors.
10. Subject who is taking potent CYP1A2 inhibitors, e,g, Ciprofloxacin
11. Subject who is taking antitussive agent dextromethorphan.
12. Subject who is taking analgesic agents such as tramadol, meperidine, methadone and propoxyphene.
13. Subject who is taking strong 3A4 inducers, e.g., St. John's Wort or cyclobenzaprine (tricyclic muscle relaxant).
14. Subject who is taking dopamine antagonists, such as the neuroleptics (phenothiazines, butyrophenones, thioxanthenes) or metoclopramide.
15. Subject has a history of alcohol or drug abuse or dependence within the prior 12 months, according to Investigator judgment, (alcohol intake is limited to 1 glass or shot per day during the whole study taken not less than 3 hours before or after dosing (see section 10.2).
16. Any relevant medical, surgical, or psychiatric condition, laboratory value, or concomitant medication which, in the opinion of the Investigator, makes the subject unsuitable for study entry or potentially unable to complete all aspects of the study.
17. Subject has severe renal impairment (creatinine clearance <30 mL/min) or on dialysis.
18. Subject has moderate (Child-Pugh categorization B, score 7-9) or severe (Child-Pugh categorization C, score 10-15) hepatic impairment.
19. Subject has a lifetime history of suicide attempt (including an active attempt, interrupted attempt or aborted attempt), or has suicidal ideation in the past 6 months as indicated by a positive response ('Yes') to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale (CSSRS) at Screening.
20. Subject has known hypersensitivity or intolerance to pramipexole or rasagiline or to any components or excipients of the test drug or placebo.
21. Subject who has a history of neuroleptic malignant syndrome.
22. Subject who is pregnant or breastfeeding.
23. Subject, who, for any reason, is judged by the Investigator or the eligibility monitoring committee (EMC) to be inappropriate for this study, including a subject who is unable to communicate or cooperate with the Investigator or who has/had a clinically significant illness or abnormal physical examination that may compromise safety of the subject during the trial or affect ability of the subject to adhere to study procedures. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Superiority of P2B001 0.6/0.75 mg as compared to its individual components in the change of total UPDRS score. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Week 12/Treatment termination visit. |
|
| E.5.2 | Secondary end point(s) |
1. Superiority of P2B001 as compared to pramipexole ER in the change of Epworth Sleepiness Scale (ESS) score.
2. Efficacy of P2B001 as compared to its individual components in the change of Total PDQ39 score.
3. Efficacy of P2B001 as compared to its individual components in the change of ADL UPDRS (part II) score.
4. Efficacy of P2B001 as compared to its individual components in the change of motor UPDRS (part III) score.
5. Efficacy of P2B001 as compared to its individual components in the CGI-S responder’s analysis (change from baseline ≥1 CGI-S points). |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Week 12/Treatment termination visit. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Individual components of P2B001 (pramipexole alone and rasagiline alone) |
|
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 18 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Canada |
| United States |
| France |
| Germany |
| Spain |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 8 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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