Clinical Efficacy, Safety and Tolerability of P2B001 in Early Parkinson's Disease

• Register: EUCTR
• Last refreshed on: 23 November 2020
• Main ID: EUCTR2017-001420-21-ES
• Date of registration: 15/03/2018
• Prospective Registration: Yes
• Primary sponsor: Pharma Two B Ltd
• Public title: Clinical Efficacy, Safety and Tolerability of P2B001 in Early Parkinson's Disease
• Scientific title: A Phase 3, Twelve-week, Multi-Center, Multinational, Randomized, Double-Blind, Double-Dummy, Parallel Group Study to Determine the Efficacy, Safety and Tolerability of P2B001 Once Daily Compared to its Individual Components in Subjects With Early Parkinson’s Disease and to a Calibration Arm of Pramipexole ER.
• Date of first enrolment: 13/06/2018
• Target sample size: 525
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001420-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: yes; Other: yes; Other specify the comparator: Individual components of P2B001 (pramipexole alone and rasagiline alone); Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Canada, France, Germany, Spain, United States

Contacts

• Name: Hadas Friedmann
• Affiliation: Pharma Two B Ltd

• Name: Hadas Friedmann
• Affiliation: Pharma Two B Ltd

Key inclusion & exclusion criteria

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 <76 year 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.
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), and must have a negative serum pregnancy test at Screening and negative urine pregnancy at baseline visit.
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).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 262
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 263

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 with a medical history of infection with human immunodeficiency virus, hepatitis C and/or hepatitis B.
24. Subject, who, for any reason, is judged by the Investigator or the eligibility monitoring committee (EMC) to be inappropria

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Early Parkinson's Disease
MedDRA version: 20.0 Level: HLT Classification code 10034005 Term: Parkinson's disease and parkinsonism System Organ Class: 100000004852

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Code: P2B001
Pharmaceutical Form: Capsule
INN or Proposed INN: PRAMIPEXOLE DIHYDROCHLORIDE
CAS Number: 191217-81-9
Other descriptive name: PRAMIPEXOLE DIHYDROCHLORIDE MONOHYDRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.6-
INN or Proposed INN: Rasagiline mesylate
CAS Number: 161735-79-1
Other descriptive name: RASAGILINE MESILATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.75-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Product Name: Pramipexole dihydrochloride
Pharmaceutical Form: Capsule
INN or Proposed INN: PRAMIPEXOLE DIHYDROCHLORIDE
CAS Number: 191217-81-9
Other descriptive name: PRAMIPEXOLE DIHYDROCHLORIDE MONOHYDRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.6-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Product Name: Rasagiline
Pharmaceutical Form: Capsule
INN or Proposed INN: Rasagiline mesylate
CAS Number: 161735-79-1
Other descriptive name: RASAGILINE MESILATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.75-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Trade Name: Pramipexole dihydrochloride extended-release tablets
Product Name: Pramipexole dihydrochloride extended-release tablets
Pharmaceutical Form: Tablet
INN or Proposed INN: PRAMIPEXOLE DIHYDROCHLORIDE
CAS Number: 191217-81-9
Other descriptive name: PRAMIPEXOLE DIHYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 0.375-4.5
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

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.

Main Objective: 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).

Secondary Objective: • 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).

Timepoint(s) of evaluation of this end point: Week 12/Treatment termination visit.

Secondary Outcome(s)

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).

Timepoint(s) of evaluation of this end point: Week 12/Treatment termination visit.

Secondary ID(s)

P2B001/003

2017-001420-21-DE

Source(s) of Monetary Support

Pharma Two B Ltd

Ethics review

Status: Approved
Approval date: 15/05/2018
Contact: