Back to resultsA Study to Assess Safety and Tolerability of Oral AZD3241 in Patients With Parkinson's Disease
Primary Purpose
Parkinson's Disease
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
AZD3241 300 mg BID
AZD3241 600 mg BID
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Parkinson's Disease focused on measuring Parkinson's disease, Safety, Tolerability
Eligibility Criteria
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.
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
AZD3241, 300 mg
AZD3241, 600 mg
Placebo
Arm Description
AZD3241 300 mg BID
AZD3241 600 mg BID
Placebo to AZD3241
Outcomes
Primary Outcome Measures
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.
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.
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.
Adverse events (AEs) including frequency and severity.
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.
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.
Secondary Outcome Measures
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.
Pharmacodynamic effect of AZD3241 in the terms of Myeloperoxidase (MPO) activity in plasma.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01603069
Brief Title
A Study to Assess Safety and Tolerability of Oral AZD3241 in Patients With Parkinson's Disease
Official Title
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
2. Study Status
Record Verification Date
July 2013
Overall Recruitment Status
Completed
Study Start Date
October 2012 (undefined)
Primary Completion Date
June 2013 (Actual)
Study Completion Date
June 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
5. Study Description
Brief Summary
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.
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson's Disease
Keywords
Parkinson's disease, Safety, Tolerability
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
51 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AZD3241, 300 mg
Arm Type
Active Comparator
Arm Description
AZD3241 300 mg BID
Arm Title
AZD3241, 600 mg
Arm Type
Active Comparator
Arm Description
AZD3241 600 mg BID
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo to AZD3241
Intervention Type
Drug
Intervention Name(s)
AZD3241 300 mg BID
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
AZD3241 600 mg BID
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo to AZD3241 BID
Primary Outcome Measure Information:
Title
Change from baseline in vital signs.
Description
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.
Time Frame
Screening (baseline), randomization, after 2, 4, 8 and 12 weeks of treatment and 2 weeks after termination of treatment (week 14)
Title
Change from baseline in Physical Exam results.
Description
Assessment of general appearance, skin, head and neck, lymph nodes, thyroid, abdomen, cardiovascular, respiratory, and neurological systems, including full palpation of thyroid gland.
Time Frame
Baseline and 2 weeks after termination of treatment (week 14)
Title
Change from baseline in Suicidality as assessed by the Columbia-Suicide Severity Rating Scale (CSSRS).
Description
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.
Time Frame
screening (baseline), randomization, after 2, 4, 8 and 12 weeks of treatment and 2 weeks after termination of treatment (week 14)
Title
Adverse events (AEs) including frequency and severity.
Time Frame
Screening, randomization, week 1, 2, 4, 8, 12, 14
Title
Change from baseline in laboratory safety assessments.
Description
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.
Time Frame
Screening (baseline), randomization, after 2, 4, 8 and 12 weeks of treatment and 2 weeks after termination of treatment (week 14)
Title
Change from baseline in 12-lead ECG.
Description
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.
Time Frame
Screening (baseline), randomization, after 2, 4, 8 and 12 weeks of treatment and 2 weeks after termination of treatment (week 14)
Secondary Outcome Measure Information:
Title
Pharmacokinetics (PK) of AZD3241 in the terms of Cmax, Cmin, and AUC0-t.
Description
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.
Time Frame
Randomization and after week 1, 2, 4, 8, and 12 weeks of treatment
Title
Pharmacodynamic effect of AZD3241 in the terms of Myeloperoxidase (MPO) activity in plasma.
Time Frame
Screening (baseline), randomization, after, 4, 8 and 12 weeks of treatment and 2 weeks after termination of treatment (week 14)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joel Posener, MSD
Organizational Affiliation
AZ Neuro
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Birmingham
State/Province
Alabama
Country
United States
Facility Name
Research Site
City
Long Beach
State/Province
California
Country
United States
Facility Name
Research Site
City
New Haven
State/Province
Connecticut
Country
United States
Facility Name
Research Site
City
Atlantis
State/Province
Florida
Country
United States
Facility Name
Research Site
City
Boca Raton
State/Province
Florida
Country
United States
Facility Name
Research Site
City
Orlando
State/Province
Florida
Country
United States
Facility Name
Research Site
City
Sunrise
State/Province
Florida
Country
United States
Facility Name
Research Site
City
Tampa
State/Province
Florida
Country
United States
Facility Name
Research Site
City
Kansas City
State/Province
Kansas
Country
United States
Facility Name
Research Site
City
Bingham Farms
State/Province
Michigan
Country
United States
Facility Name
Research Site
City
Omaha
State/Province
Nebraska
Country
United States
Facility Name
Research Site
City
Lawrenceville
State/Province
New Jersey
Country
United States
Facility Name
Research Site
City
Marlton
State/Province
New Jersey
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Study to Assess Safety and Tolerability of Oral AZD3241 in Patients With Parkinson's Disease
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