Trial record 18 of 26 for:    PARKINSON DISEASE 12

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01603069
First received: May 14, 2012
Last updated: July 18, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Parkinson's Disease
Drug: AZD3241 300 mg BID
Drug: AZD3241 600 mg BID
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
  • 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) ] [ Designated as safety issue: Yes ]

    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) ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: Randomization and after week 1, 2, 4, 8, and 12 weeks of treatment ] [ Designated as safety issue: No ]

    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) ] [ Designated as safety issue: No ]

Enrollment: 51
Study Start Date: October 2012
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

  Eligibility

Ages Eligible for Study:   30 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01603069

Locations
United States, Alabama
Research Site
Birmingham, Alabama, United States
United States, California
Research Site
Long Beach, California, United States
United States, Connecticut
Research Site
New Haven, Connecticut, United States
United States, Florida
Research Site
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
United States, Kansas
Research Site
Kansas City, Kansas, United States
United States, Michigan
Research Site
Bingham Farms, Michigan, United States
United States, Nebraska
Research Site
Omaha, Nebraska, United States
United States, New Jersey
Research Site
Lawrenceville, New Jersey, United States
Research Site
Marlton, New Jersey, United States
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Joel   Posener, MSD AZ Neuro
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01603069     History of Changes
Other Study ID Numbers: D0490C00005, EudraCT number: 2012-001313-16
Study First Received: May 14, 2012
Last Updated: July 18, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by AstraZeneca:
Parkinson's disease
Safety
Tolerability

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases

ClinicalTrials.gov processed this record on September 18, 2014