The Effects Of Fx-1006A On Transthyretin Stabilization And Clinical Outcome Measures In Patients With V122I Or Wild-Type TTR Amyloid Cardiomyopathy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00694161
First received: June 6, 2008
Last updated: January 4, 2013
Last verified: January 2013
Results First Received: November 16, 2012  
Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Cardiomyopathy
Intervention: Drug: Fx-1006A

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Tafamidis Participants with variant transthyretin (TTR) genotype (valine replaced at position 122 by isoleucine or V122I) and wild-type TTR genotype received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1 and participants who achieved TTR stabilization at Week 6 continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Participant Flow for 2 periods

Period 1:   Part 1 (up to Week 6)
    Tafamidis  
STARTED     35  
COMPLETED     35  
NOT COMPLETED     0  

Period 2:   Part 2 (After Week 6 up to Month 12)
    Tafamidis  
STARTED     35  
COMPLETED     32  
NOT COMPLETED     3  
Adverse Event                 1  
Physician Decision                 1  
Death                 1  



  Baseline Characteristics
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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.
No text entered.

Reporting Groups
  Description
Tafamidis Participants with variant transthyretin (TTR) genotype (valine replaced at position 122 by isoleucine or V122I) and wild-type TTR genotype received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1 and participants who achieved TTR stabilization at Week 6 continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Baseline Measures
    Tafamidis  
Number of Participants  
[units: participants]
  35  
Age  
[units: Years]
Mean ± Standard Deviation
  76.4  ± 4.7  
Gender  
[units: Participants]
 
Female     3  
Male     32  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Participants With Stabilized Transthyretin (TTR Tetramer) at Week 6   [ Time Frame: Week 6 ]

2.  Secondary:   Percentage of Participants With Stabilized Transthyretin (TTR Tetramer) at Month 6 and 12   [ Time Frame: Month 6, Month 12 ]

3.  Other Pre-specified:   Number of Participants With Treatment-Emergent Adverse Events (AEs)   [ Time Frame: Baseline up to 30 days after the last dose ]

4.  Other Pre-specified:   Number of Participants With Greater Than or Equal to (>=) Grade 3 Treatment-Emergent AEs   [ Time Frame: Baseline up to 30 days after the last dose ]

5.  Other Pre-specified:   Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings   [ Time Frame: Baseline up to Month 12 ]

6.  Other Pre-specified:   Number of Participants Discontinuing From The Study Due to Clinically Significant Clinical or Laboratory Adverse Events (AEs)   [ Time Frame: Baseline up to Month 12 ]

7.  Other Pre-specified:   Change From Baseline in Echocardiographic (ECHO) Parameters at Month 6 and 12   [ Time Frame: Baseline, Month 6, Month 12 ]

8.  Other Pre-specified:   Change From Baseline in Left Ventricular Mass (LVM) at Month 6 and 12   [ Time Frame: Baseline, Month 6, Month 12 ]

9.  Other Pre-specified:   Change From Baseline in Left Ventricular Ejection Fraction at Month 6 and 12   [ Time Frame: Baseline, Month 6, Month 12 ]

10.  Other Pre-specified:   Change From Baseline in Doppler Data: E/A and E/e' Ratio at Month 6 and 12   [ Time Frame: Baseline, Month 6, Month 12 ]

11.  Other Pre-specified:   Change From Baseline in Doppler Data: Mitral Deceleration Time at Month 6 and 12   [ Time Frame: Baseline, Month 6, Month 12 ]

12.  Other Pre-specified:   Change From Baseline in Tissue Doppler- Septal and Lateral Velocity at Month 6 and 12   [ Time Frame: Baseline, Month 6, Month 12 ]

13.  Other Pre-specified:   Change From Baseline in Pericardial Effusion at Month 6 and 12   [ Time Frame: Baseline, Month 6, Month 12 ]

14.  Other Pre-specified:   Number of Participants With Change From Baseline in Valvular Abnormalities at Month 6 and 12   [ Time Frame: Baseline, Month 6, Month 12 ]

15.  Other Pre-specified:   Change From Baseline in Left Ventricular Anteroseptal, Left Ventricular Inferolateral Wall Thickness and Right Ventricular End Diastolic Free Wall Thickness at Month 6 and 12   [ Time Frame: Baseline, Month 6, Month 12 ]

16.  Other Pre-specified:   Change From Baseline in Left Ventricular Mass, Mass of Left Ventricular Myocardium With Amyloidosis, Mass of Left Ventricular Myocardium With Fibrosis/Scar and Right Ventricular End Diastolic Mass at Month 6 and 12   [ Time Frame: Baseline, Month 6, Month 12 ]

17.  Other Pre-specified:   Change From Baseline in Left Ventricle End Diastolic Volume, Left Ventricle End Systolic Volume, Left Ventricle Stroke Volume, Right Ventricle End Diastolic Volume, Right Ventricle End Systolic Volume, Right Ventricle Stroke Volume at Month 6 and 12.   [ Time Frame: Baseline, Month 6, Month 12 ]

18.  Other Pre-specified:   Change From Baseline in Left Ventricular Ejection Fraction and Right Ventricular Ejection Fraction at Month 6 and 12   [ Time Frame: Baseline, Month 6, Month 12 ]

19.  Other Pre-specified:   Change From Baseline in Left Ventricular Cardiac Output and Right Ventricular Cardiac Output at Month 6 and 12   [ Time Frame: Baseline, Month 6, Month 12 ]

20.  Other Pre-specified:   Change From Baseline in Percentage of Left Ventricular Myocardial Mass With Amyloidosis and Left Ventricular Myocardial Mass With Fibrosis/Scar at Month 6 and 12   [ Time Frame: Baseline, Month 6, Month 12 ]

21.  Other Pre-specified:   Change From Baseline in 4 Chamber Interatrial Septal Thickness at Month 6 and 12   [ Time Frame: Baseline, Month 6, Month 12 ]

22.  Other Pre-specified:   Change From Baseline in 4 Chamber Left Atrial Dimension and 4 Chamber Right Atrial Dimension at Month 6 and 12   [ Time Frame: Baseline, Month 6, Month 12 ]

23.  Other Pre-specified:   Number of Participants With Atrial Fibrillation/Flutter, Atrial Tachycardia, Non-Sustained Ventricular Tachycardia (NSVT) Beats), Sustained Ventricular Tachycardia (SVT), Sinus Pause at Month 6 and 12   [ Time Frame: Baseline, Month 6, Month 12 ]

24.  Other Pre-specified:   24-Hour Average Heart Rate and Maximium/Minimum Heart Rate   [ Time Frame: Baseline, Month 6, Month 12 ]

25.  Other Pre-specified:   Number of Participants With Complete Heart Block   [ Time Frame: Baseline, Month 6, Month 12 ]

26.  Other Pre-specified:   Heart Rate Variability (HRV)- Standard Deviation (SD) Parameters   [ Time Frame: Baseline, Month 6, Month 12 ]

27.  Other Pre-specified:   Heart Rate Variability- Percentage of Successive R-R Intervals With Greater Than 50 Msec Difference Between Normal Beats (pNN50)   [ Time Frame: Baseline, Month 6, Month 12 ]

28.  Other Pre-specified:   Number of Participants With Change From Baseline in New York Heart Association (NYHA) Classification at Week 6, Month 3, 6 and 12   [ Time Frame: Baseline, Week 6, Month 3, Month 6, Month 12 ]

29.  Other Pre-specified:   Cardiothoracic (CT) Ratio   [ Time Frame: Baseline, Month 6, Month 12 ]

30.  Other Pre-specified:   Number of Participants With Increased Interstitial Markings and Pleural Effusions   [ Time Frame: Baseline, Month 6, Month 12 ]
  Hide Outcome Measure 30

Measure Type Other Pre-specified
Measure Title Number of Participants With Increased Interstitial Markings and Pleural Effusions
Measure Description Chest x-ray was done to record the presence of increased interstitial markings (a large number of interstitial markings was indicative of abnormality in the lung) and pleural effusion, which was defined as accumulation of fluid between the layers of tissue that line the lungs and chest cavity.
Time Frame Baseline, Month 6, Month 12  
Safety Issue No  

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.
Intent to Treat (ITT) population included all participants who received at least one dose of study medication.

Reporting Groups
  Description
Tafamidis Participants with variant transthyretin (TTR) genotype (valine replaced at position 122 by isoleucine or V122I) and wild-type TTR genotype received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1 and participants who achieved TTR stabilization at Week 6 continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  35  
Number of Participants With Increased Interstitial Markings and Pleural Effusions  
[units: Participants]
 
Increased interstitial markings: Baseline     11  
Increased interstitial markings: Month 6     4  
Increased interstitial markings: Month 12     4  
Pleural effusion- right: Baseline     9  
Pleural effusion- right: Month 6     8  
Pleural effusion- right: Month 12     6  
Pleural effusion- left: Baseline     6  
Pleural effusion- left: Month 6     5  
Pleural effusion- left: Month 12     4  
Pleural effusion- bilateral: Baseline     6  
Pleural effusion- bilateral: Month 6     4  
Pleural effusion- bilateral: Month 12     3  

No statistical analysis provided for Number of Participants With Increased Interstitial Markings and Pleural Effusions



31.  Other Pre-specified:   Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12   [ Time Frame: Baseline, Month 3, Month 6, Month 12 ]

32.  Other Pre-specified:   Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12   [ Time Frame: Baseline, Month 3, Month 6, Month 12 ]

33.  Other Pre-specified:   Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12   [ Time Frame: Baseline, Month 3, Month 6, Month 12 ]

34.  Other Pre-specified:   Change From Baseline in Troponin I and Troponin T at Week 2, 6, Month 3, 6 and 12   [ Time Frame: Baseline, Week 2, Week 6, Month 3, Month 6, Month 12 ]

35.  Other Pre-specified:   Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide(NT-proBNP) Levels at Week 2, 6, Month 3, 6 and 12   [ Time Frame: Baseline, Week 2, Week 6, Month 3, Month 6, Month 12 ]

36.  Other Pre-specified:   Change From Baseline in 6-Minute Walk Test (6MWT) at Month 3, 6 and 12   [ Time Frame: Baseline, Month 3, Month 6, Month 12 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
Results for Holter monitoring parameters, increased interstitial markings, pleural effusions, PtGA and cardiothoracic ratio are presented as absolute values at specified time points and not as change from baseline as planned.


  More Information
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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 less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
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.


Results Point of Contact:  
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com


No publications provided


Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00694161     History of Changes
Other Study ID Numbers: FX1B-201, B3461025
Study First Received: June 6, 2008
Results First Received: November 16, 2012
Last Updated: January 4, 2013
Health Authority: United States: Food and Drug Administration