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Trial record 23 of 90 for:    "Brain Diseases" AND "Multiple System Atrophy"

AZD3241 PET MSA Trial, Phase 2, Randomized,12 Week Safety and Tolerability Trial With PET in MSA Patients

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ClinicalTrials.gov Identifier: NCT02388295
Recruitment Status : Completed
First Posted : March 17, 2015
Results First Posted : September 25, 2017
Last Update Posted : September 25, 2017
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE March 9, 2015
First Posted Date  ICMJE March 17, 2015
Results First Submitted Date  ICMJE June 23, 2017
Results First Posted Date  ICMJE September 25, 2017
Last Update Posted Date September 25, 2017
Actual Study Start Date  ICMJE April 27, 2015
Actual Primary Completion Date September 19, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 18, 2017)
Striatum Brain Region: Change From Baseline in Microglia Activation Via Positron Emission Tomography(PET) [ Time Frame: Baseline (pre randomization) and Week 12 ]
Striatum Brain region: Change from baseline in microglia activation via PET By [11C]PBR28 binding to translocator protein
Original Primary Outcome Measures  ICMJE
 (submitted: March 9, 2015)
  • Assessment of the safety and tolerability of AZD3241 in MSA subjects via Adverse Events [ Time Frame: From Screen up to 3 months ]
    The primary objectives of the study are to assess the safety, tolerability and effect on microglia activation of AZD3241 versus placebo in MSA subjects.
  • Assessment of the safety and tolerability of AZD3241 in MSA subjects via Vital Signs (blood pressure and pulse) as well as body temperature and weight. [ Time Frame: From Screen up to 3 months ]
    The primary objectives of the study are to assess the safety, tolerability and effect on microglia activation of AZD3241 versus placebo in MSA subjects.
  • Assessment of the safety and tolerability of AZD3241 in MSA Subjects via ECG. [ Time Frame: From Screen up to 3 months ]
    The primary objectives of this study are to assess the safety, tolerability and effect on microglia activation of AZD3241 versus placebo in MSA subjects.
  • Assessment of the safety and tolerability of AZD3241 in MSA subjects via clinical laboratory tests (chemistry, hematology and urinalysis) [ Time Frame: From Screen up to 3 months ]
    The primary objectives of the study are to assess the safety, tolerability and effect on microglia activation of AZD3241 versus placebo in MSA Subjects.
  • Assessment of the safety and tolerability of AZD3241 in MSA Subjects via neurological and psychiatric exams. [ Time Frame: From Screen up to 3 months ]
    The primary objectives of the study are to assess the safety, tolerability and effect on microglia activation of AZD3241 versus placebo in MSA subjects. A full neurological exam by a licensed neurologist as well as a brief neurological exam will be employed. This includes an assessment of motor and sensory skills, balance and coordination, mental status (the patient's level of awareness and interaction with the environment), reflexes, and functioning of the nerves. Psychiatric assessments include the Columbia Suicide Severity Rating Scale.
  • Assessment of the safety and tolerability of AZD3241 in MSA subjects via physical exams. [ Time Frame: From Screen up to 3 months ]
    The primary objectives of the study are to assess the safety, tolerability and effect on microglia activation of AZD3241 versus placebo in MSA subjects.
  • Assessment of the effect on microglia activiation of AZD3241 in MSA subjects via positron emission tomography (PET) imaging. [ Time Frame: From Screen up to 3 months ]
    The primary objectives of the study are to assess the safety, tolerability and effect of microglia activation of AZD3241 versus placebo in MSA subjects.
Change History Complete list of historical versions of study NCT02388295 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 18, 2017)
Myeloperoxidase (MPO) Inhibition in Plasma (Change From Baseline), Specific Activity [ Time Frame: Baseline (Day -1) and week 12 ]
Myeloperoxidase (MPO) inhibition in plasma (change from baseline), on samples collected and analyzed, specific activity (activity/protein)
Original Secondary Outcome Measures  ICMJE
 (submitted: March 9, 2015)
Assessment of the biomarker effects of AZD3241 versus placebo in MSA subjects via assay of myeloperoxidase activity. [ Time Frame: From Screen up to 3 months ]
A secondary objective is to determine the biomarker effects of AZD3241 in MSA subjects.
Current Other Pre-specified Outcome Measures
 (submitted: August 18, 2017)
Exploratory Efficacy: Unified Multiple System Atropy Rating Scale, Change From Baseline (Total Score, Part 1 + Part 2) [ Time Frame: Baseline to final treatment visit ]
Exploratory efficacy: Unified Multiple System Atropy Rating Scale, change from baseline (total Score, Part 1 + Part 2) : Score range 0 to 104, positive value indicates worsening symptoms
Original Other Pre-specified Outcome Measures
 (submitted: March 9, 2015)
  • Assessment of pharmacokinetics of AZD3241 in MSA subjects via assay of AZD3241 [ Time Frame: From Screen up to 3 months ]
    An exploratory objective is to determine the pharmacokinetics of AZD3241 in MSA subjects.
  • Assessment of the efficacy of AZD3241 in MSA subjects via administration of questionnaires, including the C-SSRS, UMSARs, COMPASS Select Scale, COMPASS Select Change Scale, MSA-QOL [ Time Frame: From Screen up to 3 months ]
    An exploratory objective is to determine the efficacy of AZD3241 versus placebo in MSA subjects.
 
Descriptive Information
Brief Title  ICMJE AZD3241 PET MSA Trial, Phase 2, Randomized,12 Week Safety and Tolerability Trial With PET in MSA Patients
Official Title  ICMJE A 12-Week, Multicenter, Randomized, Parallel-Group Study to Assess the Safety, Tolerability, Pharmacokinetics, Biomarker Effects, Efficacy, and Effect on Microglia Activation, as Measured by Positron Emission Tomography, of AZD3241 in Subjects With Multiple System Atrophy
Brief Summary AZD3241 myeloperoxidase (MPO) inhibitor trial is assessing safety and tolerability, randomized trial, in patients with Multiple System Atrophy.
Detailed Description Not Provided
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 Multiple System Atrophy, MSA
Intervention  ICMJE
  • Drug: AZD3241
    Drug: AZD3241 administered for 12 weeks orally as a tablet.
    Other Name: AZD3241 to match placebo administered for 12 weeks.
  • Drug: Placebo
    Placebo to match AZD3241 administered for 12 weeks orally as a tablet.
    Other Name: Placebo to match AZD3241 administered for 12 weeks.
Study Arms  ICMJE
  • Experimental: AZD3241
    Subjects will be randomized to one of the two doses of AZD3241 or placebo in a 1:1:1 ratio.
    Intervention: Drug: AZD3241
  • Placebo Comparator: Placebo to match AZD3241
    Subjects will be randomized to one of the two doses of AZD3241 or placebo in a 1:1:1 ratio.
    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: August 18, 2017)
59
Original Estimated Enrollment  ICMJE
 (submitted: March 9, 2015)
64
Actual Study Completion Date  ICMJE September 19, 2016
Actual Primary Completion Date September 19, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female, age 30-80 years, inclusive, at screen.
  2. Meet criteria for diagnosis of probable or possible MSA according to the consensus criteria (Gilman et al. 2008 ).
  3. "High-affinity binder" or "mixed-affinity binder" for TSPO, as confirmed by prospective genotyping of TSPO polymorphism during screen.
  4. Subjects must understand the nature of the study and must provide signed and dated written informed consent in accordance with local regulations before the conduct of any study-related procedures. The informed consent should reflect the protocol stipulations concerning the use of contraception.
  5. Medical treatment of MSA and co-morbid medical conditions must be stable for at least 30 days prior to screen and between screen and baseline.
  6. Written and oral fluency in the local language.
  7. Able and willing to participate in all scheduled evaluations, abide by all study restrictions, and complete all required tests and procedures.
  8. In the opinion of the investigator, the subject must be considered likely to comply with the study protocol and to have a high probability of completing the study.
  9. Able to swallow tablets whole.

Exclusion Criteria:

  1. Prior participation in any AZD3241 study.
  2. Magnetic resonance imaging (MRI) performed during screen not consistent with diagnosis of MSA.
  3. Received a PET scan within the last 12 months.
  4. Negative Allen test in both hands, unless the brachial artery is used for arterial cannulation.
  5. Subjects determined to be "low affinity binders" by TSPO genotyping.
  6. Claustrophobia that would contraindicate a brain MRI scan or brain PET scan.
  7. Pregnancy, lactation, or, if female of childbearing potential, positive serum β-hCG at screen or positive urine β-hCG at baseline (Day -1).
  8. Initiation or change in pharmacologic therapy for symptoms of MSA within 30 days prior to screen or between screen and baseline (Day -1).
  9. Significant neurological disease affecting the central nervous system (CNS), other than MSA
  10. History of brain surgery for parkinsonism.
  11. History of stem cell treatment.
  12. Seizure disorder, unless well controlled and for which treatment has been stable for at least 30 days prior to screen and between screen and baseline (Day -1).
  13. Presence of any clinically significant medical condition
  14. History or presence of thyroid disease.
  15. Any abnormal TSH or Free T4 test result at screen or baseline (Day -1).
  16. History or presence of gastrointestinal disorders or other disease known to interfere with absorption, distribution, metabolism or excretion of drugs
  17. History or presence of renal disease or impaired renal function.
  18. A QT interval corrected according to the Fridericia procedure (QTcF) interval measurement > 450 msec at screen (single ECG) or baseline (Day -1) (mean of three ECG measurements) or a family history of long-QT syndrome.
  19. Uncontrolled hypertension
  20. History or presence of diabetes, unless glucose levels have been well controlled and for which treatment has been stable for at least 30 days prior to screen and between screen and baseline (Day -1).
  21. History of cancer within the last 5 years, with the exception of nonmetastatic basal cell carcinoma of the skin.
  22. Any clinically important abnormality, as determined by the investigator, on physical examination or vital signs, ECG, or clinical laboratory test results other than abnormality due to a stable, well-controlled medical condition; or any abnormality that could be detrimental to the subject or could compromise the study.
  23. Use of potent inhibitors of CYP3A4, Use of potent inducers of CYP3A4 and/or Use of drugs mainly metabolized by CYP3A4
  24. Treatment with any investigational drug or device within 60 days or five half-lives prior to screen, whichever is longer, or between screen and baseline (Day -1).
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 Austria,   Finland,   France,   Italy,   Sweden,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02388295
Other Study ID Numbers  ICMJE D0490C00023
Has Data Monitoring Committee Yes
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 Not Provided
PRS Account AstraZeneca
Verification Date July 2017

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