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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01603069
Recruitment Status : Completed
First Posted : May 22, 2012
Last Update Posted : July 19, 2013
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE May 14, 2012
First Posted Date  ICMJE May 22, 2012
Last Update Posted Date July 19, 2013
Study Start Date  ICMJE October 2012
Actual Primary Completion Date June 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 20, 2012)
  • Change from baseline in vital signs. [ Time Frame: Screening (baseline), randomization, after 2, 4, 8 and 12 weeks of treatment and 2 weeks after termination of treatment (week 14) ]
    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. [ Time Frame: Baseline and 2 weeks after termination of treatment (week 14) ]
    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). [ Time Frame: screening (baseline), randomization, after 2, 4, 8 and 12 weeks of treatment and 2 weeks after termination of treatment (week 14) ]
    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. [ Time Frame: Screening, randomization, week 1, 2, 4, 8, 12, 14 ]
  • Change from baseline in laboratory safety assessments. [ Time Frame: Screening (baseline), randomization, after 2, 4, 8 and 12 weeks of treatment and 2 weeks after termination of treatment (week 14) ]
    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. [ Time Frame: Screening (baseline), randomization, after 2, 4, 8 and 12 weeks of treatment and 2 weeks after termination of treatment (week 14) ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 18, 2012)
  • Number of patients with Adverse Events (AEs) and Serious Adverse Events (SAEs). [ Time Frame: Up to 14 weeks ]
  • Change from baseline in Vital signs (systolic and diastolic blood pressure and pulse) including orthostatic challenge, clinical laboratory tests, and ECG. [ Time Frame: From baseline up to 14 weeks. ]
  • Change from baseline in Physical Exam results. [ Time Frame: Baseline and 14 weeks. ]
    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). [ Time Frame: From baseline up to 14 weeks. ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 20, 2012)
  • Pharmacokinetics (PK) of AZD3241 in the terms of Cmax, Cmin, and AUC0-t. [ Time Frame: Randomization and after week 1, 2, 4, 8, and 12 weeks of treatment ]
    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. [ Time Frame: Screening (baseline), randomization, after, 4, 8 and 12 weeks of treatment and 2 weeks after termination of treatment (week 14) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 18, 2012)
  • Change from baseline in Population PK model parameter estimates, including exposures, derived from plasma concentrations of AZD3241. [ Time Frame: Randomization and after 2, 4, 8 and 12 weeks of treatment. ]
  • Change from baseline in Myeloperoxidase (MPO) activity in plasma as an evaluation of pharmacodynamics. [ Time Frame: From baseline up to 14 weeks. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Assess Safety and Tolerability of Oral AZD3241 in Patients With Parkinson's Disease
Official Title  ICMJE 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
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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Parkinson's Disease
Intervention  ICMJE
  • 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.
  • 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.
  • Drug: Placebo
    Placebo to AZD3241 BID
Study Arms  ICMJE
  • Active Comparator: AZD3241, 300 mg
    AZD3241 300 mg BID
    Intervention: Drug: AZD3241 300 mg BID
  • Active Comparator: AZD3241, 600 mg
    AZD3241 600 mg BID
    Intervention: Drug: AZD3241 600 mg BID
  • Placebo Comparator: Placebo
    Placebo to AZD3241
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 18, 2013)
51
Original Estimated Enrollment  ICMJE
 (submitted: May 18, 2012)
50
Actual Study Completion Date  ICMJE June 2013
Actual Primary Completion Date June 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01603069
Other Study ID Numbers  ICMJE D0490C00005
EudraCT number: 2012-001313-16
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Joel Posener, MSD AZ Neuro
PRS Account AstraZeneca
Verification Date July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP