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

• ClinicalTrials.gov Identifier: NCT01603069
• Recruitment Status: Completed
• First Posted: May 22, 2012
• Last Update Posted: July 19, 2013
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: May 14, 2012
• First Posted Date: May 22, 2012
• Last Update Posted Date: July 19, 2013
• Study Start Date: October 2012
• Actual Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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. ]

Current Secondary Outcome Measures (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 (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: 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
• 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: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Parkinson's Disease

Intervention

• 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

• 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

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 18, 2013): 51
• Original Estimated Enrollment (submitted: May 18, 2012): 50
• Actual Study Completion Date: June 2013
• Actual Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 30 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01603069
• Other Study ID Numbers: D0490C00005; EudraCT number: 2012-001313-16
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: AstraZeneca
• Original Responsible Party: Same as current
• Current Study Sponsor: AstraZeneca
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Joel Posener, MSD; AZ Neuro

• PRS Account: AstraZeneca
• Verification Date: July 2013