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

NCT01603069 | Completed Phase 2

• 2 other identifiers: D0490C00005EudraCT number: 2012-001313-16
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 13

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.

Conditions

Parkinson's Disease

Keywords

Parkinson's disease; Safety; Tolerability

Outcome Measures

Primary Outcomes (6)

• 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)

• 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)

• 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)

• Adverse events (AEs) including frequency and severity.

  Screening, randomization, week 1, 2, 4, 8, 12, 14

• 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)

• 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)

Secondary Outcomes (2)

• Pharmacokinetics (PK) of AZD3241 in the terms of Cmax, Cmin, and AUC0-t.

  Randomization and after week 1, 2, 4, 8, and 12 weeks of treatment

• 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)

Study Arms (3)

AZD3241, 300 mg

ACTIVE COMPARATOR

AZD3241 300 mg BID

Drug: AZD3241 300 mg BID

AZD3241, 600 mg

ACTIVE COMPARATOR

AZD3241 600 mg BID

Drug: AZD3241 600 mg BID

Placebo

PLACEBO COMPARATOR

Placebo to AZD3241

Drug: Placebo

Interventions

AZD3241 300 mg BID DRUG

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, 300 mg

AZD3241 600 mg BID DRUG

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.

AZD3241, 600 mg

Placebo DRUG

Placebo to AZD3241 BID

Placebo

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (13)

Research Site

Birmingham, Alabama, United States

Location

Research Site

Long Beach, California, United States

Location

Research Site

New Haven, Connecticut, United States

Location

Research Site

Atlantis, Florida, United States

Location

Research Site

Boca Raton, Florida, United States

Location

Research Site

Orlando, Florida, United States

Location

Research Site

Sunrise, Florida, United States

Location

Research Site

Tampa, Florida, United States

Location

Research Site

Kansas City, Kansas, United States

Location

Research Site

Bingham Farms, Michigan, United States

Location

Research Site

Omaha, Nebraska, United States

Location

Research Site

Lawrenceville, New Jersey, United States

Location

Research Site

Marlton, New Jersey, United States

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

AZD3241; BID protein, human

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Joel Posener, MSD

  AZ Neuro

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2012
• First Posted: May 22, 2012
• Study Start: October 1, 2012
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: July 19, 2013

Record last verified: 2013-07

Locations

US (13)