Safety, Tolerability and Efficacy of Two Doses of Once Daily P2B001 in Subjects With Early Parkinson's Disease

A Phase 2B, Twelve-week Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study, To Determine the Safety, Tolerability and Efficacy of Two Doses of Once Daily P2B001 in Subjects With Early Parkinson's Disease

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.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: Placebo; Drug: P2B001 once daily (pramipexole 0.6 mg / rasagiline 0.75 mg),; Drug: P2B001 once daily (pramipexole 0.3 mg / rasagiline 0.75 mg),

• Study Type: Interventional
• Enrollment (Actual): 149
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Israel
  • Haifa, Israel
    • P2B001 Site Rambam Israel
  • Pethch Tikva, Israel
    • P2B001 Site Belinson
  • Ramat Gan, Israel
    • P2B001 Site Sheba Medical Center
  • Rishon LeZion, Israel
    • P2B001 Site Asaf Harofe
  • Tel Aviv, Israel
    • P2B001 Site Sourasky Medical Center
• United States
  • Alabama
    • Birmingham, Alabama, United States
      • P2B001 Site Birmingham
  • California
    • Los Angeles, California, United States
      • P2B001 Site Los Angeles
  • Colorado
    • Aurora, Colorado, United States
      • P2B001 Site Aurora
  • Connecticut
    • Manchester, Connecticut, United States
      • P2B001 Manchester
    • New Haven, Connecticut, United States
      • P2B001 Site New Haven
  • Florida
    • Boca Raton, Florida, United States
      • P2B001 Site Boca Raton
    • Port Charlotte, Florida, United States
      • P2B001 Site Port Charlotte
    • Tampa, Florida, United States
      • P2B001 Site Tampa
  • Georgia
    • Augusta, Georgia, United States
      • P2B001 Site Augusta
  • Illinois
    • Chicago, Illinois, United States, 60612
      • P2B001 site Chicago
  • Kansas
    • Kansas City, Kansas, United States
      • P2B001 Site Kansas City
  • Massachusetts
    • Boston, Massachusetts, United States
      • P2B001 Site Boston
  • Michigan
    • West Bloomfield, Michigan, United States
      • P2B001 Site west Bloomfield
  • Minnesota
    • Golden Valley, Minnesota, United States
      • P2B001 Site Golden Valley
  • New Jersey
    • Camden, New Jersey, United States
      • P2B001 Site Camden
    • New Brunswick, New Jersey, United States
      • P2B001 Site New Brunswick
  • New York
    • Commack, New York, United States
      • P2B001 site Commack
    • New York, New York, United States
      • P2B001 Site New York
  • North Carolina
    • Durham, North Carolina, United States
      • P2B001 Site Durham
  • Ohio
    • Cincinnati, Ohio, United States
      • P2B001 Site Cincinnati
    • Toledo, Ohio, United States
      • P2B001 Site Toledo
  • Oklahoma
    • Tulsa, Oklahoma, United States
      • P2B001 Site Tulsa
  • Texas
    • Houston, Texas, United States
      • P2B001 Site Houston
  • Virginia
    • Roanoke, Virginia, United States
      • P2B001 Site Roanoke

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo once daily for 12 weeks.	Drug: Placebo; placebo
Experimental: 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.	Drug: 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
Experimental: 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	Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Week 12
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.	12 weeks
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)	12 weeks
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.	12 weeks

Collaborators and Investigators

• Sponsor: Pharma Two B Ltd.
• Investigators: Study Director: pninit litman, Ph.D, Pharma Two B Ltd.

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: October 15, 2013
• First Submitted That Met QC Criteria: October 18, 2013
• First Posted (Estimate): October 24, 2013

Study Record Updates

• Last Update Posted (Actual): April 7, 2023
• Last Update Submitted That Met QC Criteria: March 15, 2023
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Keywords: Parkinson's Disease, Rasagiline, Pramipexole
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Neuroprotective Agents; Protective Agents; Dopamine Agonists; Dopamine Agents; Monoamine Oxidase Inhibitors; Antioxidants; Antiparkinson Agents; Anti-Dyskinesia Agents; Rasagiline; Pramipexole
• Other Study ID Numbers: P2B001/001