A Study to Assess Safety and Tolerability of Oral AZD3241 in Patients With Parkinson's Disease

A Phase IIa, 12 Week, Multicentre, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study to Assess the Safety and Tolerability of Oral AZD3241 in Patients With Parkinson's Disease

This is a study where AZD3241 or placebo is given to patients with Parkinson's disease in a blinded and randomized assignment. The main objective is to see if safety and tolerability of the drug is acceptable.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: AZD3241 300 mg BID; Drug: AZD3241 600 mg BID; Drug: Placebo

Detailed Description

A Phase IIa, 12 Week, Multicentre, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study to Assess the Safety and Tolerability of Oral AZD3241 in Patients with Parkinson's Disease

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States
      • Research Site
  • California
    • Long Beach, California, United States
      • Research Site
  • Connecticut
    • New Haven, Connecticut, United States
      • Research Site
  • Florida
    • Atlantis, Florida, United States
      • Research Site
    • Boca Raton, Florida, United States
      • Research Site
    • Orlando, Florida, United States
      • Research Site
    • Sunrise, Florida, United States
      • Research Site
    • Tampa, Florida, United States
      • Research Site
  • Kansas
    • Kansas City, Kansas, United States
      • Research Site
  • Michigan
    • Bingham Farms, Michigan, United States
      • Research Site
  • Nebraska
    • Omaha, Nebraska, United States
      • Research Site
  • New Jersey
    • Lawrenceville, New Jersey, United States
      • Research Site
    • Marlton, New Jersey, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Each patient must be able and willing to provide signed and dated informed consent prior to the study.
• Female and male patients aged 30 to 80 years at the day of enrollment (Visit 1).
• Patients must meet the criteria for "Diagnosis of idiopathic Parkinson's disease" according to the UKPDS Brain Bank criteria (Hughes et al 1992).
• Have a modified Hoehn and Yahr stage 1-2.5.
• Having no treatment for Parkinson's disease and have no need to add anti-Parkinson's disease treatment during the 14 weeks of study OR are on stable anti-Parkinson's disease medication.

Exclusion Criteria:

• Diagnosis is unclear or a suspicion of other Parkinsonian syndromes exists, such as secondary Parkinsonism (caused by drugs, toxins, infectious agents, vascular disease, trauma, brain neoplasm), Parkinson-plus syndromes or heredodegenerative diseases.
• Have undergone surgery for the treatment of Parkinson's disease (eg, pallidotomy, deep brain stimulation, fetal tissue transplantation) or have undergone any other brain surgery at any time, even for non-Parkinson's disease conditions.
• Presence of dyskinesias, motor fluctuations, swallowing difficulties or loss of postural reflexes, defined as scoring 2 or more on item 30 of the UPDRS.
• Current/history of psychiatric diagnosis of acute psychotic disorder or other primary psychiatric diagnoses, i.e. bipolar disorder or MDD, or other psychiatric, neurological or behavioral disorders/symptoms that may interfere with conduct of study.
• Current significant major or unstable respiratory disease, heart disease, cerebrovascular disease, hematological disease, hepatic disease, renal disease, gastrointestinal (GI) disease, or other major disease as judged by the investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: AZD3241, 300 mg; AZD3241 300 mg BID	Drug: AZD3241 300 mg BID; The following dose escalation schedule will be used for 300 mg BID: 100 mg BID from Day 1 through Day 7. On Day 8, the patients will start maintenance treatment of 300 mg BID for the duration of the treatment period.
Active Comparator: AZD3241, 600 mg; AZD3241 600 mg BID	Drug: AZD3241 600 mg BID; The following dose escalation schedule will be used for 600 mg BID: 100 mg BID from Day 1 through Day 7 and 300 mg BID from Day 8 through Day 14. On Day 15, the patients will start maintenance treatment of 600 mg BID for the duration of the treatment period.
Placebo Comparator: Placebo; Placebo to AZD3241	Drug: Placebo; Placebo to AZD3241 BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in vital signs.	Vital signs: systolic and diastolic blood pressure and pulse including orthostatic challenge will be assessed. Change from baseline at each visit will be calculated as the visit value minus the baseline value for each vital sign: Blood Pressure, pulse rate (supine and standing), weight and oral temperature.	Screening (baseline), randomization, after 2, 4, 8 and 12 weeks of treatment and 2 weeks after termination of treatment (week 14)
Change from baseline in Physical Exam results.	Assessment of general appearance, skin, head and neck, lymph nodes, thyroid, abdomen, cardiovascular, respiratory, and neurological systems, including full palpation of thyroid gland.	Baseline and 2 weeks after termination of treatment (week 14)
Change from baseline in Suicidality as assessed by the Columbia-Suicide Severity Rating Scale (CSSRS).	Suicidality as assessed by the Columbia-Suicide Severity Rating Scale (CSSRS) The CSSRS assesses the suicidal behavior and suicidal ideation in patients. Occurrence of suicidal behavior is defined as having answered "yes" to a least 1 of the 4 suicidal behavior sub categories (actual attempt, interrupted attempt, aborted attempt, and preparatory acts or behavior) at any post randomization evaluation. Occurrence of suicidal ideation after randomization is defined as having answered "yes" to at least one of the suicidal ideation sub-categories (wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods [not plan] without intent to act, active suicidal ideation with some intent to act [without specific plan], and active suicidal ideation with specific plan and intent) at any post randomization evaluation.	screening (baseline), randomization, after 2, 4, 8 and 12 weeks of treatment and 2 weeks after termination of treatment (week 14)
Adverse events (AEs) including frequency and severity.		Screening, randomization, week 1, 2, 4, 8, 12, 14
Change from baseline in laboratory safety assessments.	Change from baseline at each visit will be calculated as the visit value minus the baseline value for each continuous clinical chemistry, hematology and urinalysis measurements. Abnormal or out-of-range values will be flagged.	Screening (baseline), randomization, after 2, 4, 8 and 12 weeks of treatment and 2 weeks after termination of treatment (week 14)
Change from baseline in 12-lead ECG.	Change from baseline at each visit will be calculated as the visit value minus the baseline value for each ECG parameter: heart rate, QRS duration, PR interval, RR interval, QT and calculated QTcF interval. Abnormal or out-of-range values will be flagged.	Screening (baseline), randomization, after 2, 4, 8 and 12 weeks of treatment and 2 weeks after termination of treatment (week 14)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK) of AZD3241 in the terms of Cmax, Cmin, and AUC0-t.	Blood samples (5 mL) for determination of AZD3241 concentration in plasma will be collected in accordance with the information in the Study Plan. PK analysis will be based on the PK analysis set. Plasma concentrations of AZD3241 will be determined and PK analyzed by a population PK model. PK analysis will be based on the PK analysis set and will include determination of observed Cmax, Cmin, and AUC0-t. Plasma drug concentrations of AZD3241 will be determined and PK analyzed by a population PK model. If the quality of the data does not allow a population PK analysis, plasma concentrations from all patients will be analyzed graphically and by descriptive statistics, as appropriate.	Randomization and after week 1, 2, 4, 8, and 12 weeks of treatment
Pharmacodynamic effect of AZD3241 in the terms of Myeloperoxidase (MPO) activity in plasma.		Screening (baseline), randomization, after, 4, 8 and 12 weeks of treatment and 2 weeks after termination of treatment (week 14)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Joel Posener, MSD, AZ Neuro

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: May 14, 2012
• First Submitted That Met QC Criteria: May 18, 2012
• First Posted (Estimate): May 22, 2012

Study Record Updates

• Last Update Posted (Estimate): July 19, 2013
• Last Update Submitted That Met QC Criteria: July 18, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: Safety; Tolerability; Parkinson's disease
• 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
• Other Study ID Numbers: D0490C00005; EudraCT number: 2012-001313-16