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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

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Multiple System Atrophy, MSA
Interventions: Drug: AZD3241
Drug: Placebo

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations

124 subjects were screened, 22 of these were rescreened. A total of 61 subjects were assigned a treatment allocation through randomization. Two of ineligible subjects were never dispensed investigational product.

One ineligible randomized subject was discontinued prior to dosing and refused to supply further data.


Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

Protocol was administratively changed to allow reduction of sample size from 64 in this study population.

A total of 59 completed screening and were randomized, but only 58 completed randomization and were dosed with study medication.


Reporting Groups
  Description
Placebo Placebo to match AZD3241 dosed twice daily
AZD3241 300 mg AZD3241 300 mg dosed twice daily
AZD3241 600 mg AZD3241 600 mg dosed twice daily

Participant Flow for 3 periods

Period 1:   Dose Escalation Week 1
    Placebo   AZD3241 300 mg   AZD3241 600 mg
STARTED   19 [1]   19 [1]   20 [1] 
COMPLETED   17   16   18 
NOT COMPLETED   2   3   2 
Adverse Event                1                2                1 
Determined not eligible                1                1                1 
[1] Number randomized to treatment

Period 2:   Dose Escalation Week 2
    Placebo   AZD3241 300 mg   AZD3241 600 mg
STARTED   17   16   18 
COMPLETED   16   14   17 
NOT COMPLETED   1   2   1 
Protocol Violation                0                1                0 
Determined not eligible                1                1                1 

Period 3:   Treatment Weeks 3 to 12
    Placebo   AZD3241 300 mg   AZD3241 600 mg
STARTED   16   14   17 
COMPLETED   15   13   17 
NOT COMPLETED   1   1   0 
Adverse Event                1                1                0 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety population, includes only 58 of 59 randomized subjects, those taking at least 1 dose of investigational product

Reporting Groups
  Description
Placebo Placebo to match AZD3241 dosed twice daily
AZD3241 300 mg AZD3241 300 mg dosed twice daily
AZD3241 600 mg AZD3241 600 mg dosed twice daily
Total Total of all reporting groups

Baseline Measures
   Placebo   AZD3241 300 mg   AZD3241 600 mg   Total 
Overall Participants Analyzed 
[Units: Participants]
 19   19   20   58 
Age 
[Units: Years]
Mean (Standard Deviation)
 59.3  (7.9)   59.9  (6.1)   58.0  (8.5)   59  (7.5) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
       
Female      7  36.8%      5  26.3%      5  25.0%      17  29.3% 
Male      12  63.2%      14  73.7%      15  75.0%      41  70.7% 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of Participants
       
Hispanic or Latino      1   5.3%      0   0.0%      0   0.0%      1   1.7% 
Not Hispanic or Latino      16  84.2%      16  84.2%      18  90.0%      50  86.2% 
Unknown or Not Reported      2  10.5%      3  15.8%      2  10.0%      7  12.1% 
Race (NIH/OMB) 
[Units: Participants]
Count of Participants
       
American Indian or Alaska Native      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Asian      0   0.0%      1   5.3%      2  10.0%      3   5.2% 
Native Hawaiian or Other Pacific Islander      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Black or African American      1   5.3%      0   0.0%      0   0.0%      1   1.7% 
White      16  84.2%      15  78.9%      16  80.0%      47  81.0% 
More than one race      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Unknown or Not Reported      2  10.5%      3  15.8%      2  10.0%      7  12.1% 
Multiple System Atropy Subtype [1] 
[Units: Participants]
       
MSA - P   7   10   7   24 
MSA - C   12   9   13   34 
[1] Multiple System Atropy (MSA) Subtype, Parkinsonian (P) or Cerebellar (C)
Diagnostic Category [1] 
[Units: Participants]
       
Possible MSA   1   4   8   13 
Probable MSA   18   15   12   45 
[1] Diagnostic Category for Multiple System Atropy (MSA); Possible or Probable were the eligible categories
Genotype [1] 
[Units: Participants]
       
TSPO - High Affinity Binding   12   10   16   38 
TSPO - Mixed affinity binding   7   9   4   20 
TSPO- Low Affinity Binding   0   0   0   0 
[1] Translocator Protein binding (TSPO) : genotype (affinity for binding); Low Affinity Binding was exclusionary


  Outcome Measures

1.  Primary:   Striatum Brain Region: Change From Baseline in Microglia Activation Via Positron Emission Tomography(PET)   [ Time Frame: Baseline (pre randomization) and Week 12 ]

2.  Secondary:   Myeloperoxidase (MPO) Inhibition in Plasma (Change From Baseline), Specific Activity   [ Time Frame: Baseline (Day -1) and week 12 ]

3.  Other Pre-specified:   Exploratory Efficacy: Unified Multiple System Atropy Rating Scale, Change From Baseline (Total Score, Part 1 + Part 2)   [ Time Frame: Baseline to final treatment visit ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Biomarker samples were included if testing done within 6 months of collection, recommendation changed to 3 months of collection during study. Included based on 6 months as per protocol to include as many samples as possible.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Jamie Mullen MD
Organization: AstraZeneca Pharmaceuticals LP
e-mail: Clinicaltrialtransparency@astrazeneca.net



Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02388295     History of Changes
Other Study ID Numbers: D0490C00023
First Submitted: March 9, 2015
First Posted: March 17, 2015
Results First Submitted: June 23, 2017
Results First Posted: September 25, 2017
Last Update Posted: September 25, 2017