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

Parkinson's Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01603069
• Other study ID #: D0490C00005
• Secondary ID: EudraCT number:
• Status: Completed
• Phase: Phase 2
• First received: May 14, 2012
• Last updated: July 18, 2013
• Start date: October 2012
• Est. completion date: June 2013

Study information

• Verified date: July 2013
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 80 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Parkinson Disease
• 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.
• 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
Placebo to AZD3241 BID

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Yes
Primary	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)	Yes
Primary	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)	Yes
Primary	Adverse events (AEs) including frequency and severity.		Screening, randomization, week 1, 2, 4, 8, 12, 14	Yes
Primary	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)	Yes
Primary	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)	Yes
Secondary	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	No
Secondary	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)	No