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

Measure Type Primary
Measure Title Percentage of Participants With Stabilized Transthyretin (TTR Tetramer) at Week 6
Measure Description TTR tetramer was assessed using a validated immunoturbidimetric assay. The Fraction of Initial (FOI) is the ratio of the measured TTR tetramer concentration after denaturation to the measured TTR tetramer concentration before denaturation. TTR tetramer stabilization is based on the difference between the on-treatment FOI and the baseline FOI expressed as a percentage of the baseline FOI.
Time Frame Week 6  
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  
Percentage of Participants With Stabilized Transthyretin (TTR Tetramer) at Week 6  
[units: Percentage of participants]
Number ( 95% Confidence Interval )
  97.1  
  ( 85.1 to 99.9 )  

No statistical analysis provided for Percentage of Participants With Stabilized Transthyretin (TTR Tetramer) at Week 6



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

Measure Type Secondary
Measure Title Percentage of Participants With Stabilized Transthyretin (TTR Tetramer) at Month 6 and 12
Measure Description TTR tetramer was assessed using a validated immunoturbidimetric assay. The Fraction of Initial (FOI) is the ratio of the measured TTR tetramer concentration after denaturation to the measured TTR tetramer concentration before denaturation. TTR tetramer stabilization is based on the difference between the on-treatment FOI and the baseline FOI expressed as a percentage of the baseline FOI.
Time Frame 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.
ITT population included all participants who received at least one dose of study medication. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

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]
  34  
Percentage of Participants With Stabilized Transthyretin (TTR Tetramer) at Month 6 and 12  
[units: Percentage of participants]
Number ( 95% Confidence Interval )
 
Month 6     88.2  
  ( 72.5 to 96.7 )  
Month 12     87.5  
  ( 71.0 to 96.5 )  

No statistical analysis provided for Percentage of Participants With Stabilized Transthyretin (TTR Tetramer) at Month 6 and 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 ]

Measure Type Other Pre-specified
Measure Title Number of Participants With Treatment-Emergent Adverse Events (AEs)
Measure Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Time Frame Baseline up to 30 days after the last dose  
Safety Issue Yes  

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.
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 Treatment-Emergent Adverse Events (AEs)  
[units: Participants]
  35  

No statistical analysis provided for Number of Participants With Treatment-Emergent Adverse Events (AEs)



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 ]

Measure Type Other Pre-specified
Measure Title Number of Participants With Greater Than or Equal to (>=) Grade 3 Treatment-Emergent AEs
Measure Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. On the basis of intensity, grade 3 was referred as severe, grade 4 as life-threatening and grade 5 as death.
Time Frame Baseline up to 30 days after the last dose  
Safety Issue Yes  

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.
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 Greater Than or Equal to (>=) Grade 3 Treatment-Emergent AEs  
[units: Participants]
 
Grade 3 (severe)     18  
Grade 4 (life-threatening)     1  
Grade 5 (death)     2  

No statistical analysis provided for Number of Participants With Greater Than or Equal to (>=) Grade 3 Treatment-Emergent AEs



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

Measure Type Other Pre-specified
Measure Title Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings
Measure Description ECHO:investigator assessed test to assess cardiac function.ECHO abnormality criteria:any/valvular abnormality,pericardial effusion,abnormal regional wall motion,inferior vena cava respiratory variation,posterior left ventricular wall/septal thickness>=13 millimeter(mm),right ventricular thickness>=7mm,ejection fraction <50%, ratio of early (E) diastolic transmitral flow and atrial(A) contraction velocity (E/A)>=2, ratio of ‘E’to lateral/septal mitral annular velocity (e’) (E/e’prime lateral>15, E/e’prime septal>15), E deceleration time<=150 millisecond(msec),Isovolumic relaxation time<=70msec.
Time Frame Baseline up to Month 12  
Safety Issue Yes  

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.
ITT population. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. The ‘n’ for any post-dose incidence included participants with baseline values that were not abnormal(that is treatment-emergent abnormalities).

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]
  34  
Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings  
[units: Participants]
 
Any ECHO abnormalities (n=34)     31  
Pericardial effusion (n=28)     6  
Valvular abnormalities- thickening (n=4)     4  
Valvular abnormalities- regurgitation (n=7)     6  
Abnormal regional wall motion (n=19)     10  
Inferior vena cava respiratory variation (n=14)     7  
Left ventricular posterior wall thickness (n=0)     NA [1]
Left ventricular septal thickness (n=0)     NA [1]
Right ventricular thickness (n=7)     6  
E/A ratio (n=8)     4  
E/e' prime lateral (n=13)     5  
E/e' prime septal (n=6)     5  
Ejection fraction (n=18)     11  
E deceleration time (n=16)     8  
Isovolumic relaxation time (n=16)     4  
[1] Data not analyzed since no participant were eligible for analysis.

No statistical analysis provided for Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings



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 ]

Measure Type Other Pre-specified
Measure Title Number of Participants Discontinuing From The Study Due to Clinically Significant Clinical or Laboratory Adverse Events (AEs)
Measure Description No text entered.
Time Frame Baseline up to Month 12  
Safety Issue Yes  

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.
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 Discontinuing From The Study Due to Clinically Significant Clinical or Laboratory Adverse Events (AEs)  
[units: Participants]
  1  

No statistical analysis provided for Number of Participants Discontinuing From The Study Due to Clinically Significant Clinical or Laboratory Adverse Events (AEs)



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

Measure Type Other Pre-specified
Measure Title Change From Baseline in Echocardiographic (ECHO) Parameters at Month 6 and 12
Measure Description Echocardiography was used to measure interventricular septal thickness (IVST), posterior left ventricular wall thickness (PLVWT), right ventricular wall thickness (RVWT), left atrial diameter (LAD): anterior-posterior (ant-post), medio-lateral, superior-inferior (sup-inf) and left ventricular end diastolic diameter (LVEDD).
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.
ITT population included all participants who received at least one dose of study medication. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. Here 'n' signifies those participants who were evaluable for specific timepoints.

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]
  34  
Change From Baseline in Echocardiographic (ECHO) Parameters at Month 6 and 12  
[units: millimeter (mm)]
Mean ± Standard Deviation
 
IVST: Baseline (n=34)     20.71  ± 3.58  
IVST: Change at Month 6 (n=33)     -0.64  ± 2.41  
IVST: Change at Month 12 (n=30)     0.87  ± 2.52  
PLVWT: Baseline (n=34)     20.20  ± 3.37  
PLVWT: Change at Month 6 (n=33)     -0.50  ± 3.83  
PLVWT: Change at Month 12 (n=30)     -0.00  ± 2.11  
RVWT: Baseline (n=27)     9.21  ± 2.34  
RVWT: Change at Month 6 (n=21)     -0.47  ± 2.47  
RVWT: Change at Month 12 (n=20)     0.26  ± 2.25  
LAD (ant-post): Baseline (n=34)     45.00  ± 6.14  
LAD (ant-post): Change at Month 6 (n=33)     -0.40  ± 4.33  
LAD (ant-post): Change at Month 12 (n=30)     -0.30  ± 4.19  
LAD (medio-lateral): Baseline (n=34)     44.10  ± 5.56  
LAD (medio-lateral): Change at Month 6 (n=32)     0.70  ± 5.17  
LAD (medio-lateral): Change at Month 12 (n=30)     -0.90  ± 6.41  
LAD (sup-inf): Baseline (n=34)     61.50  ± 8.43  
LAD (sup-inf): Change at Month 6 (n=32)     3.00  ± 5.90  
LAD (sup-inf): Change at Month 12 (n=30)     0.80  ± 6.29  
LVEDD: Baseline (n=34)     37.94  ± 5.19  
LVEDD: Change at Month 6 (n=33)     0.45  ± 3.49  
LVEDD: Change at Month 12 (n=30)     0.10  ± 3.41  

No statistical analysis provided for Change From Baseline in Echocardiographic (ECHO) Parameters at Month 6 and 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 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in Left Ventricular Mass (LVM) at Month 6 and 12
Measure Description LVM was defined as increase in the mass of left ventricle, estimated by echocardiography. Increased LVM was associated with cardiovascular morbidity and mortality.
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.
ITT population included all participants who received at least one dose of study medication. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. Here 'n' signifies those participants who were evaluable for specific timepoints.

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]
  34  
Change From Baseline in Left Ventricular Mass (LVM) at Month 6 and 12  
[units: Gram]
Mean ± Standard Deviation
 
Baseline (n=34)     372.50  ± 123.96  
Change at Month 6 (n=33)     -19.76  ± 54.38  
Change at Month 12 (n=30)     13.73  ± 77.12  

No statistical analysis provided for Change From Baseline in Left Ventricular Mass (LVM) at Month 6 and 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 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in Left Ventricular Ejection Fraction at Month 6 and 12
Measure Description Left ventricular ejection fraction (LVEF) was the fraction of the end-diastolic volume (EDV) that is ejected out of left ventricle with each contraction, estimated by echocardiography. EDV is the volume of blood within a ventricle immediately before a contraction.
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.
ITT population included all participants who received at least one dose of study medication. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. Here 'n' signifies those participants who were evaluable for specific timepoints.

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]
  34  
Change From Baseline in Left Ventricular Ejection Fraction at Month 6 and 12  
[units: Percentage of EDV]
Mean ± Standard Deviation
 
Baseline (n=34)     46.8  ± 14.1  
Change at Month 6 (n=33)     -0.4  ± 10.3  
Change at Month 12 (n=30)     -3.7  ± 10.4  

No statistical analysis provided for Change From Baseline in Left Ventricular Ejection Fraction at Month 6 and 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 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in Doppler Data: E/A and E/e' Ratio at Month 6 and 12
Measure Description Doppler echocardiography was a procedure which used ultrasound technology to examine the heart. Ratio of early (E) diastolic transmitral flow velocity and atrial (A) contraction velocity (E/A) and ratio of the early (E) diastolic transmitral flow velocity to the mitral annular velocity (e’) (E/e') were estimated.
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.
ITT population included all participants who received at least one dose of study medication. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. Here 'n' signifies those participants who were evaluable for specific timepoints.

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]
  26  
Change From Baseline in Doppler Data: E/A and E/e' Ratio at Month 6 and 12  
[units: Ratio]
Mean ± Standard Deviation
 
E/A ratio: Baseline (n=19)     2.516  ± 1.084  
E/A ratio: Change at Month 6 (n=12)     0.425  ± 1.117  
E/A ratio: Change at Month 12 (n=9)     0.544  ± 0.575  
E/e’ ratio: Baseline (n=26)     16.240  ± 9.089  
E/e’ ratio: Change at Month 6 (n=15)     2.217  ± 3.166  
E/e’ ratio: Change at Month 12 (n=14)     -0.717  ± 5.681  

No statistical analysis provided for Change From Baseline in Doppler Data: E/A and E/e' Ratio at Month 6 and 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 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in Doppler Data: Mitral Deceleration Time at Month 6 and 12
Measure Description Doppler echocardiography was a procedure which used ultrasound technology to examine the heart. The mitral deceleration time was the time taken from the maximum E wave to baseline. E wave arises due to early diastolic filling.
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.
ITT population included all participants who received at least one dose of study medication. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. Here 'n' signifies those participants who were evaluable for specific timepoints.

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]
  33  
Change From Baseline in Doppler Data: Mitral Deceleration Time at Month 6 and 12  
[units: msec]
Mean ± Standard Deviation
 
Baseline (n=33)     152.9  ± 35.3  
Change at Month 6 (n=27)     1.0  ± 37.5  
Change at Month 12 (n=27)     -7.1  ± 32.6  

No statistical analysis provided for Change From Baseline in Doppler Data: Mitral Deceleration Time at Month 6 and 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 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in Tissue Doppler- Septal and Lateral Velocity at Month 6 and 12
Measure Description Tissue Doppler used doppler principles to measure the annular velocities at the lateral and septal areas of the mitral annulus. s’: systolic velocity during ejection, e’: early diastolic mitral annular velocity, a’: late diastolic mitral annular velocity.
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.
ITT population included all participants who received at least one dose of study medication. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. Here 'n' signifies those participants who were evaluable for specific categories.

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]
  26  
Change From Baseline in Tissue Doppler- Septal and Lateral Velocity at Month 6 and 12  
[units: centimeter/second (cm/sec)]
Mean ± Standard Deviation
 
Septal s’: Baseline (n=23)     3.70  ± 1.31  
Septal s’: Change at Month 6 (n=16)     -0.57  ± 0.73  
Septal s’: Change at Month 12 (n=14)     -0.69  ± 0.77  
Septal e’: Baseline (n=23)     3.67  ± 1.60  
Septal e’: Change at Month 6 (n=17)     -0.09  ± 1.12  
Septal e’: Change at Month 12 (n=14)     -0.33  ± 1.32  
Septal a’: Baseline (n=16)     2.51  ± 1.60  
Septal a’: Change at Month 6 (n=6)     -0.40  ± 0.43  
Septal a’: Change at Month 12 (n=6)     -0.42  ± 0.72  
Lateral s’: Baseline (n=24)     4.53  ± 1.59  
Lateral s’: Change at Month 6 (n=14)     -0.50  ± 1.16  
Lateral s’: Change at Month 12 (n=13)     -0.73  ± 1.22  
Lateral e’: Baseline (n=26)     5.09  ± 2.00  
Lateral e’: Change at Month 6 (n=16)     -0.76  ± 0.80  
Lateral e’: Change at Month 12 (n=14)     0.05  ± 0.88  
Lateral a’: Baseline (n=17)     3.16  ± 1.94  
Lateral a’: Change at Month 6 (n=7)     -0.41  ± 0.60  
Lateral a’: Change at Month 12 (n=9)     0.06  ± 1.03  

No statistical analysis provided for Change From Baseline in Tissue Doppler- Septal and Lateral Velocity at Month 6 and 12



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

Measure Type Other Pre-specified
Measure Title Change From Baseline in Pericardial Effusion at Month 6 and 12
Measure Description Pericardial effusion was the presence of an abnormal amount of fluid in the pericardial cavity, as determined by echocardiography.
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.
Data for this pre-specified outcome measure was collected and reported in individual participant listings but not statistically summarized for analysis.

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]
  0  
Change From Baseline in Pericardial Effusion at Month 6 and 12      

No statistical analysis provided for Change From Baseline in Pericardial Effusion at Month 6 and 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 ]

Measure Type Other Pre-specified
Measure Title Number of Participants With Change From Baseline in Valvular Abnormalities at Month 6 and 12
Measure Description Valvular abnormalities were those abnormalities (thickening or regurgitation) that involved one or more valves of the heart, determined by echocardiography.
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.
Data for this pre-specified outcome measure was collected and reported in individual participant listings but not statistically summarized for analysis.

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]
  0  
Number of Participants With Change From Baseline in Valvular Abnormalities at Month 6 and 12      

No statistical analysis provided for Number of Participants With Change From Baseline in Valvular Abnormalities at Month 6 and 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 ]

Measure Type Other Pre-specified
Measure Title 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
Measure Description Cardiac Magnetic Resonance Imaging (MRI) was done to measure the thickness of left ventricular anteroseptal (LVAS) wall, left ventricular inferolateral (LVIL) wall and right ventricular end diastolic free (RVEDF) wall.
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.
ITT population included all participants who received at least one dose of study medication. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. Here 'n' signifies those participants who were evaluable for specific timepoints.

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]
  18  
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  
[units: mm]
Mean ± Standard Deviation
 
LVAS wall thickness: Baseline (n=18)     15.808  ± 3.603  
LVAS wall thickness: Change at Month 6 (n=18)     0.810  ± 3.447  
LVAS wall thickness: Change at Month 12 (n=15)     0.813  ± 3.099  
LVIL wall thickness: Baseline (n=18)     15.405  ± 4.616  
LVIL wall thickness: Change at Month 6 (n=18)     -1.472  ± 4.333  
LVIL wall thickness: Change at Month 12 (n=15)     1.182  ± 4.782  
RVEDF wall thickness: Baseline (n=17)     10.871  ± 14.001  
RVEDF wall thickness: Change at Month 6 (n=17)     -4.501  ± 14.734  
RVEDF wall thickness: Change at Month 12 (n=15)     -1.577  ± 4.722  

No statistical analysis provided for 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



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 ]

Measure Type Other Pre-specified
Measure Title 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
Measure Description Cardiac MRI was done to measure LVM, mass of left ventricular (LV) myocardium with amyloidosis, mass of LV myocardium with fibrosis/scar and right ventricular end diastolic mass (RVEDM).
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.
ITT population included all participants who received at least one dose of study medication. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. Here 'n' signifies those participants who were evaluable for specific timepoints.

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]
  18  
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  
[units: Gram]
Mean ± Standard Deviation
 
LVM: Baseline (n=18)     221.599  ± 63.680  
LVM: Change at Month 6 (n=18)     0.557  ± 24.901  
LVM: Change at Month 12 (n=15)     0.119  ± 20.027  
LV Amyloidosis: Baseline (n=15)     63.963  ± 25.614  
LV Amyloidosis : Change at Month 6 (n=14)     -13.854  ± 23.921  
LV Amyloidosis: Change at Month 12 (n=9)     -4.346  ± 38.364  
LV Fibrosis/Scar: Baseline (n=15)     87.746  ± 60.297  
LV Fibrosis/Scar: Change at Month 6 (n=14)     -30.496  ± 52.176  
LV Fibrosis/Scar: Change at Month 12 (n=9)     -20.238  ± 64.487  
RVEDM: Baseline (n=18)     65.999  ± 20.296  
RVEDM: Change at Month 6 (n=18)     -4.377  ± 20.648  
RVEDM: Change at Month 12 (n=15)     0.215  ± 18.038  

No statistical analysis provided for 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



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 ]

Measure Type Other Pre-specified
Measure Title 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.
Measure Description Cardiac MRI was done to measure left ventricle end diastolic volume (LVEDV), left ventricle end systolic volume (LVESV), left ventricle stroke volume (LVSV), right ventricle end diastolic volume (RVEDV), right ventricle end systolic volume (RVESV) and right ventricle stroke volume (RVSV).
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.
ITT population included all participants who received at least one dose of study medication. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. Here 'n' signifies those participants who were evaluable for specific timepoints.

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]
  18  
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.  
[units: mL]
Mean ± Standard Deviation
 
LVEDV: Baseline (n=18)     166.673  ± 40.417  
LVEDV: Change at Month 6 (n=18)     -0.922  ± 21.164  
LVEDV: Change at Month 12 (n=15)     -1.606  ± 20.323  
LVESV: Baseline (n=18)     84.651  ± 29.271  
LVESV: Change at Month 6 (n=18)     3.727  ± 20.963  
LVESV: Change at Month 12 (n=15)     6.479  ± 16.810  
LVSV: Baseline (n=18)     82.022  ± 19.866  
LVSV: Change at Month 6 (n=18)     -4.651  ± 21.391  
LVSV: Change at Month 12 (n=15)     -8.083  ± 15.614  
RVEDV: Baseline (n=18)     175.124  ± 67.977  
RVEDV: Change at Month 6 (n=18)     -4.836  ± 37.879  
RVEDV: Change at Month 12 (n=15)     19.540  ± 39.413  
RVESV: Baseline (n=18)     104.662  ± 48.775  
RVESV: Change at Month 6 (n=18)     -1.727  ± 21.438  
RVESV: Change at Month 12 (n=15)     26.250  ± 30.858  
RVSV: Baseline (n=18)     70.478  ± 26.364  
RVSV: Change at Month 6 (n=18)     -3.125  ± 26.125  
RVSV: Change at Month 12 (n=15)     -6.730  ± 33.975  

No statistical analysis provided for 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.



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 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in Left Ventricular Ejection Fraction and Right Ventricular Ejection Fraction at Month 6 and 12
Measure Description Cardiac MRI was done to measure: left ventricular ejection fraction (LVEF) was the fraction of the EDV that is ejected out of left ventricle with each contraction and right ventricular ejection fraction (RVEF) was the fraction of the EDV that is ejected out of right ventricle with each contraction. EDV is the volume of blood within a ventricle immediately before a contraction.
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.
ITT population included all participants who received at least one dose of study medication. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. Here 'n' signifies those participants who were evaluable for specific timepoints.

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]
  18  
Change From Baseline in Left Ventricular Ejection Fraction and Right Ventricular Ejection Fraction at Month 6 and 12  
[units: Percentage of EDV]
Mean ± Standard Deviation
 
LVEF: Baseline (n=18)     50.176  ± 9.183  
LVEF: Change at Month 6 (n=18)     -2.713  ± 13.362  
LVEF: Change at Month 12 (n=14)     -3.511  ± 9.063  
RVEF: Baseline (n=18)     42.323  ± 11.949  
RVEF: Change at Month 6 (n=18)     -1.756  ± 10.381  
RVEF: Change at Month 12 (n=15)     -7.381  ± 12.040  

No statistical analysis provided for Change From Baseline in Left Ventricular Ejection Fraction and Right Ventricular Ejection Fraction at Month 6 and 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 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in Left Ventricular Cardiac Output and Right Ventricular Cardiac Output at Month 6 and 12
Measure Description Cardiac MRI was done to measure cardiac output, which was the volume of blood being pumped by the heart, in particular by the left or right ventricle in the time interval of one minute.
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.
MRI data was collected and reported for cardiac output through the measure of stroke volume as given in outcome measure 17.

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]
  0  
Change From Baseline in Left Ventricular Cardiac Output and Right Ventricular Cardiac Output at Month 6 and 12      

No statistical analysis provided for Change From Baseline in Left Ventricular Cardiac Output and Right Ventricular Cardiac Output at Month 6 and 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 ]

Measure Type Other Pre-specified
Measure Title 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
Measure Description Cardiac MRI was done to measure percentage of LV myocardial mass with amyloidosis and LV myocardial mass with fibrosis/scar. LV myocardial mass with amyloidosis or fibrosis/scar was calculated from the product of the myocardial volume and specific gravity of heart muscle, in participants with amyloidosis or fibrosis/scar, respectively.
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.
ITT population included all participants who received at least one dose of study medication. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. Here 'n' signifies those participants who were evaluable for specific timepoints.

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]
  15  
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  
[units: Percentage of LVM]
Mean ± Standard Deviation
 
LV Amyloidosis: Baseline (n=15)     29.069  ± 11.111  
LV Amyloidosis: Change at Month 6 (n=14)     -8.200  ± 14.115  
LV Amyloidosis: Change at Month 12 (n=9)     -7.017  ± 13.660  
LV Fibrosis/Scar: Baseline (n=15)     36.513  ± 17.789  
LV Fibrosis/Scar: Change at Month 6 (n=14)     -10.126  ± 26.397  
LV Fibrosis/Scar: Change at Month 12 (n=9)     -8.268  ± 24.884  

No statistical analysis provided for 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



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 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in 4 Chamber Interatrial Septal Thickness at Month 6 and 12
Measure Description Cardiac MRI was done to measure interatrial septal thickness in the 4 chamber view.
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.
Data for this measure was not collected due to a change in the planned analysis.

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]
  0  
Change From Baseline in 4 Chamber Interatrial Septal Thickness at Month 6 and 12      

No statistical analysis provided for Change From Baseline in 4 Chamber Interatrial Septal Thickness at Month 6 and 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 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in 4 Chamber Left Atrial Dimension and 4 Chamber Right Atrial Dimension at Month 6 and 12
Measure Description Cardiac MRI was done to measure the left and right atrial dimensions which have diagnostic and prognostic significance in cardiology, in the 4 chamber view.
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.
Data for this measure was not collected due to a change in the planned analysis.

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]
  0  
Change From Baseline in 4 Chamber Left Atrial Dimension and 4 Chamber Right Atrial Dimension at Month 6 and 12      

No statistical analysis provided for Change From Baseline in 4 Chamber Left Atrial Dimension and 4 Chamber Right Atrial Dimension at Month 6 and 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 ]

Measure Type Other Pre-specified
Measure Title 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
Measure Description Holter monitor was a machine that recorded the heart rhythms. Holter monitoring abnormalities of atrial fibrillation/flutter (rapid, irregular heart rhythm), atrial tachycardia (rapid cardiac rate), non-sustained ventricular tachycardia (NSVT)<30 beats, sustained ventricular tachycardia (SVT) >=30 beats and sinus pause (transient interruption in the sinus rhythm) were recorded.
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.
ITT population. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. The ‘n’ for any post-dose incidence included participants with baseline values that were not abnormal(that is treatment-emergent abnormalities).

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]
  34  
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  
[units: Participants]
 
Atrial fibrillation/flutter: Baseline (n=33)     6  
Atrial fibrillation/flutter: Month 6 (n=27)     9  
Atrial fibrillation/flutter: Month 12 (n=22)     9  
Atrial tachycardia: Baseline (n=34)     14  
Atrial tachycardia: Month 6 (n=20)     0  
Atrial tachycardia: Month 12 (n=17)     0  
NSVT (<30 beats): Baseline (n=34)     20  
NSVT (<30 beats): Month 6 (n=13)     3  
NSVT (<30 beats): Month 12 (n=12)     5  
SVT (>= 30 beats): Baseline (n=34)     0  
SVT (>= 30 beats): Month 6 (n=33)     0  
SVT (>= 30 beats): Month 12 (n=30)     1  
Sinus pause: Baseline (n=34)     2  
Sinus pause: Month 6 (n=31)     4  
Sinus pause: Month 12 (n=28)     5  

No statistical analysis provided for 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



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

Measure Type Other Pre-specified
Measure Title 24-Hour Average Heart Rate and Maximium/Minimum Heart Rate
Measure Description Holter monitor was a machine that recorded the heart rhythms. 24-hour average heart rate and maximium/minimum heart rate was recorded using Holter monitoring.
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.
ITT population included all participants who received at least one dose of study medication. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. Here 'n' signifies those participants who were evaluable for specific timepoints.

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]
  34  
24-Hour Average Heart Rate and Maximium/Minimum Heart Rate  
[units: beats per minute (bpm)]
Mean ± Standard Deviation
 
24-hour average heart rate: Baseline (n=34)     74.7  ± 7.8  
24-hour average heart rate: Month 6 (n=33)     73.0  ± 7.2  
24-hour average heart rate: Month 12 (n=30)     76.6  ± 9.0  
Maximum Heart Rate: Baseline (n=34)     111.7  ± 22.3  
Maximum Heart Rate: Month 6 (n=33)     112.3  ± 17.0  
Maximum Heart Rate: Month 12 (n=30)     121.9  ± 20.4  
Minimum Heart Rate: Baseline (n=34)     56.6  ± 8.0  
Minimum Heart Rate: Month 6: (n=33)     53.1  ± 11.5  
Minimum Heart Rate Month 12: (n=30)     55.3  ± 10.1  

No statistical analysis provided for 24-Hour Average Heart Rate and Maximium/Minimum Heart Rate



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

Measure Type Other Pre-specified
Measure Title Number of Participants With Complete Heart Block
Measure Description Complete heart block is the third-degree atrioventricular block in which the impulse generated in the sinoatrial node in the atrium does not propagate to the ventricles.
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.
No summary was prepared for this data as there were no reports of complete heart block.

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]
  0  
Number of Participants With Complete Heart Block      

No statistical analysis provided for Number of Participants With Complete Heart Block



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

Measure Type Other Pre-specified
Measure Title Heart Rate Variability (HRV)- Standard Deviation (SD) Parameters
Measure Description Holter monitor was a machine that recorded the heart rhythms. HRV time-domain indices were summarized for root-mean-square of successive differences [RMS SD] of the R-R intervals (R-R is the interval between successive Rs in the ECG wave) between normal beats (NN), magid standard deviation (Magid SD) of normal to normal R-R intervals and Kleiger standard deviation of normal to normal R-R intervals (Kleiger SD). The term ‘NN’ is used in place of ‘R-R’ when the processed beats are normal beats.
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.
ITT population included all participants who received at least one dose of study medication. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. Here 'n' signifies those participants who were evaluable for specific timepoints.

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]
  33  
Heart Rate Variability (HRV)- Standard Deviation (SD) Parameters  
[units: msec]
Mean ± Standard Deviation
 
HRV- RMS SD: Baseline (n=30)     75.9  ± 71.0  
HRV- RMS SD: Month 6 (n=26)     88.1  ± 71.0  
HRV- RMS SD: Month 12 (n=21)     91.7  ± 72.1  
HRV- Magid SD: Baseline (n=31)     58.3  ± 42.1  
HRV- Magid SD: Month 6 (n=33)     82.6  ± 55.5  
HRV- Magid SD: Month 12 (n=30)     78.6  ± 50.1  
HRV- Kleiger SD: Baseline (n=31)     100.3  ± 49.1  
HRV- Kleiger SD: Month 6 (n=33)     123.9  ± 52.8  
HRV- Kleiger SD: Month 12 (n=30)     120.3  ± 48.7  

No statistical analysis provided for Heart Rate Variability (HRV)- Standard Deviation (SD) Parameters



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 ]

Measure Type Other Pre-specified
Measure Title Heart Rate Variability- Percentage of Successive R-R Intervals With Greater Than 50 Msec Difference Between Normal Beats (pNN50)
Measure Description Holter monitor was a machine that recorded the heart rhythms. The term ‘NN’ was used in place of ‘R-R’ when the processed beats are normal beats. The percentage of successive R-R intervals with greater than 50 msec difference between normal beats was derived by dividing NN50 by the total number of NN intervals (pNN50), where NN50 was the number of interval differences of successive NN intervals greater than 50 msec.
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.
ITT population included all participants who received at least one dose of study medication. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. Here 'n' signifies those participants who were evaluable for specific timepoints.

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]
  30  
Heart Rate Variability- Percentage of Successive R-R Intervals With Greater Than 50 Msec Difference Between Normal Beats (pNN50)  
[units: Percentage of intervals]
Mean ± Standard Deviation
 
Baseline (n=30)     19.7  ± 25.5  
Month 6 (n=26)     29.3  ± 32.7  
Month 12 (n=21)     23.6  ± 27.3  

No statistical analysis provided for Heart Rate Variability- Percentage of Successive R-R Intervals With Greater Than 50 Msec Difference Between Normal Beats (pNN50)



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 ]

Measure Type Other Pre-specified
Measure Title Number of Participants With Change From Baseline in New York Heart Association (NYHA) Classification at Week 6, Month 3, 6 and 12
Measure Description NYHA: classified as ‘class I’ (participants with cardiac disease but without resulting limitations of physical activity), ‘class II’ (participants with cardiac disease resulting in slight limitation of physical activity), ‘class III’ (participants with cardiac disease resulting in marked limitation of physical activity), ‘class IV’ (participants with cardiac disease resulting in inability to carry on any physical activity without discomfort). Participants with change from baseline were classified as ‘improved' (positive change), ‘no change’ or ‘worsened' (negative change).
Time Frame Baseline, Week 6, Month 3, 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.
ITT population included all participants who received at least one dose of study medication. Data at Week 6 was collected but was not summarized due to a change in the planned analysis. Here 'n' signifies those participants who were evaluable for specific timepoints.

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 Change From Baseline in New York Heart Association (NYHA) Classification at Week 6, Month 3, 6 and 12  
[units: Participants]
 
Baseline: Class I (n=35)     5  
Baseline: Class II (n=35)     28  
Baseline: Class III (n=35)     2  
Baseline: Class IV (n=35)     0  
Change at Month 3: improved (n=34)     5  
Change at Month 3: no change (n=34)     23  
Change at Month 3: worsened (n=34)     6  
Change at Month 6: improved (n=34)     1  
Change at Month 6: no change (n=34)     27  
Change at Month 6: worsened (n=34)     6  
Change at Month 12: improved (n=32)     4  
Change at Month 12: no change (n=32)     20  
Change at Month 12: worsened (n=32)     8  

No statistical analysis provided for Number of Participants With Change From Baseline in New York Heart Association (NYHA) Classification at Week 6, Month 3, 6 and 12



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

Measure Type Other Pre-specified
Measure Title Cardiothoracic (CT) Ratio
Measure Description Cardiothoracic ratio was defined as the transverse diameter of the heart, compared with that of the thoracic cage, used to help determine enlargement of the heart.
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.
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  
Cardiothoracic (CT) Ratio  
[units: Ratio]
Mean ± Standard Deviation
 
Baseline     55.130  ± 6.075  
Month 6     56.620  ± 5.904  
Month 12     57.830  ± 5.366  

No statistical analysis provided for Cardiothoracic (CT) Ratio



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

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 ]

Measure Type Other Pre-specified
Measure Title Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12
Measure Description Participant’s overall quality of life was measured by the PtGA. At baseline participants answered to question: "in general, how do you feel today?" - on a 5-point scale from '1' (excellent) to '5' (poor). At each follow-up visit, participant’s answered to question: “How do you feel today as compared to when we talked with you at your last clinic visit for this study?” on a 7-point scale- '1' markedly improved, '2' moderately improved, '3' mildly improved, '4' unchanged, '5' mildly worsened, '6' moderately worsened, '7' markedly worsened.
Time Frame Baseline, Month 3, 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.
ITT population included all participants who received at least one dose of study medication. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. Here 'n' signifies those participants who were evaluable for specific timepoints.

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]
  34  
Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12  
[units: Participants]
 
Excellent: Baseline (n=33)     5  
Very good: Baseline (n=33)     14  
Good: Baseline (n=33)     12  
Fair: Baseline (n=33)     2  
Poor: Baseline (n=33)     0  
Markedly improved: Month 3 (n=34)     2  
Moderately improved: Month 3 (n=34)     7  
Mildly improved: Month 3 (n=34)     6  
Unchanged: Month 3 (n=34)     15  
Mildly worsened: Month 3 (n=34)     2  
Moderately worsened: Month 3 (n=34)     2  
Markedly worsened: Month 3 (n=34)     0  
Markedly improved: Month 6 (n=34)     3  
Moderately improved: Month 6 (n=34)     4  
Mildly improved: Month 6 (n=34)     3  
Unchanged: Month 6 (n=34)     16  
Mildly worsened: Month 6 (n=34)     8  
Moderately worsened: Month 6 (n=34)     0  
Markedly worsened: Month 6 (n=34)     0  
Markedly improved: Month 12 (n=32)     0  
Moderately improved: Month 12 (n=32)     5  
Mildly improved: Month 12 (n=32)     3  
Unchanged: Month 12 (n=32)     16  
Mildly worsened: Month 12 (n=32)     4  
Moderately worsened: Month 12 (n=32)     3  
Markedly worsened: Month 12 (n=32)     1  

No statistical analysis provided for Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 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 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12
Measure Description KCCQ was a 23-item heart failure specific questionnaire quantified in to following 10 summary scores: physical limitation, symptom frequency, symptom severity, and symptom stability, total symptoms, quality of life, social interference, self-efficacy, overall summary and clinical summary. Total score ranged from 0 to 100, where higher scores indicated better functioning, fewer symptoms, and better disease specific quality of life. Summary scores were scaled to range from 0 to 100, with higher scores representing greater disability.
Time Frame Baseline, Month 3, 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.
ITT population included all participants who received at least one dose of study medication. Here 'n' signifies those participants who were evaluable for specific timepoints.

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  
Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12  
[units: Units on a scale]
Mean ± Standard Deviation
 
Physical limitations: Baseline (n=35)     72.9  ± 20.8  
Physical limitations: Change at Month 3 (n=33)     -2.7  ± 15.0  
Physical limitations: Change at Month 6 (n=34)     -0.4  ± 13.6  
Physical limitations: Change at Month 12 (n=31)     -8.1  ± 18.8  
Symptom stability: Baseline (n=35)     55.7  ± 13.7  
Symptom stability: Change at Month 3 (n=34)     3.7  ± 27.6  
Symptom stability: Change at Month 6 (n=34)     -5.9  ± 25.4  
Symptom stability: Change at Month 12 (n=31)     0.0  ± 22.4  
Symptom frequency: Baseline (n=35)     73.8  ± 22.2  
Symptom frequency: Change at Month 3 (n=34)     -1.8  ± 18.5  
Symptom frequency: Change at Month 6 (n=34)     -2.5  ± 15.9  
Symptom frequency: Change at Month 12 (n=31)     -6.0  ± 18.2  
Symptom burden: Baseline (n=35)     76.9  ± 18.1  
Symptom burden: Change at Month 3 (n=34)     -4.0  ± 18.3  
Symptom burden: Change at Month 6 (n=34)     -4.7  ± 15.2  
Symptom burden: Change at Month 12 (n=31)     -8.6  ± 19.2  
Total symptom: Baseline (n=35)     75.4  ± 19.2  
Total symptom: Change at Month 3 (n=34)     -2.9  ± 16.9  
Total symptom: Change at Month 6 (n=34)     -3.6  ± 14.3  
Total symptom: Change at Month 12 (n=31)     -7.3  ± 18.2  
Self-efficacy: Baseline (n=35)     85.7  ± 19.0  
Self-efficacy: Change at Month 3 (n=33)     1.9  ± 14.7  
Self-efficacy: Change at Month 6 (n=34)     1.1  ± 13.5  
Self-efficacy: Change at Month 12 (n=31)     1.6  ± 16.7  
Quality of life: Baseline (n=35)     66.9  ± 19.2  
Quality of life: Change at Month 3 (n=34)     1.0  ± 18.2  
Quality of life: Change at Month 6 (n=34)     -0.2  ± 14.4  
Quality of life: Change at Month 12 (n=31)     -4.0  ± 20.4  
Social limitation: Baseline (n=33)     69.3  ± 25.4  
Social limitation: Change at Month 3 (n=30)     -0.6  ± 19.6  
Social limitation: Change at Month 6 (n=31)     -2.4  ± 22.6  
Social limitation: Change at Month 12 (n=27)     -9.2  ± 25.2  
Overall summary: Baseline (n=35)     71.4  ± 18.8  
Overall summary: Change at Month 3 (n=34)     -0.8  ± 14.9  
Overall summary: Change at Month 6 (n=34)     -1.5  ± 12.4  
Overall summary: Change at Month 12 (n=31)     -6.9  ± 18.0  
Clinical summary: Baseline (n=35)     74.1  ± 18.9  
Clinical summary: Change at Month 3 (n=34)     -2.0  ± 15.9  
Clinical summary: Change at Month 6 (n=34)     -2.0  ± 11.9  
Clinical summary: Change at Month 12 (n=31)     -7.7  ± 17.9  

No statistical analysis provided for Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 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 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12
Measure Description SF-36 was standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. Scores for the 8 domains range from 0-100, where higher scores were better (100=highest level of functioning) and reported as 2 summary scores; Mental Component Score (MCS) and Physical Component Score (PCS). The score for a section was an average of the individual question scores, which were scaled 0-100, where higher scores were better.
Time Frame Baseline, Month 3, 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.
ITT population included all participants who received at least one dose of study medication. Here 'n' signifies those participants who were evaluable for specific timepoints. Data was collected at Month 3 but not statistically summarized as planned.

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  
Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12  
[units: Units on a scale]
Mean ± Standard Deviation
 
PCS: Baseline (n=33)     41.0  ± 9.69  
PCS: Change at Month 6 (n=32)     -1.4  ± 5.87  
PCS: Change at Month 12 (n=29)     -2.4  ± 7.58  
MCS: Baseline (n=33)     52.7  ± 9.51  
MCS: Change at Month 6 (n=32)     0.3  ± 8.40  
MCS: Change at Month 12 (n=29)     -2.0  ± 9.56  
Physical functioning: Baseline (n=34)     37.7  ± 11.28  
Physical functioning: Change at Month 6 (n=33)     -0.7  ± 6.89  
Physical functioning: Change at Month 12 (n=29)     -2.0  ± 7.34  
Role-physical: Baseline (n=35)     42.3  ± 10.84  
Role-physical: Change at Month 6 (n=34)     -1.4  ± 7.12  
Role-physical: Change at Month 12 (n=30)     -3.5  ± 9.29  
Bodily pain: Baseline (n=35)     53.2  ± 9.57  
Bodily pain: Change at Month 6 (n=34)     -4.0  ± 8.74  
Bodily pain: Change at Month 12 (n=30)     -3.2  ± 11.81  
General health: Baseline (n=35)     41.5  ± 9.33  
General health: Change at Month 6 (n=34)     0.7  ± 9.23  
General health: Change at Month 12 (n=30)     -1.6  ± 8.44  
Vitality: Baseline (n=34)     50.6  ± 8.11  
Vitality: Change at Month 6 (n=33)     -0.1  ± 6.83  
Vitality: Change at Month 12 (n=30)     -2.2  ± 7.83  
Social functioning: Baseline (n=35)     48.4  ± 9.84  
Social functioning: Change at Month 6 (n=34)     -2.9  ± 9.23  
Social functioning: Change at Month 12 (n=30)     -3.6  ± 11.40  
Role-emotional: Baseline (n=35)     45.2  ± 11.71  
Role-emotional: Change at Month 6 (n=34)     0.6  ± 12.26  
Role-emotional: Change at Month 12 (n=30)     -3.0  ± 12.53  
Mental health: Baseline (n=34)     53.3  ± 8.50  
Mental health: Change at Month 6 (n=33)     0.3  ± 5.01  
Mental health: Change at Month 12 (n=30)     -1.1  ± 7.50  

No statistical analysis provided for Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 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 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in Troponin I and Troponin T at Week 2, 6, Month 3, 6 and 12
Measure Description Troponin I and troponin T were the cardiac markers. Troponin I and troponin T were part of the troponin complex, where troponin I was bound to actin in thin myofilaments and troponin T was bound to tropomyosin. Higher level of these markers was indicative of heart damage.
Time Frame Baseline, Week 2, Week 6, Month 3, 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.
ITT population included all participants who received at least one dose of study medication. Here 'n' signifies those participants who were evaluable for specific timepoints.

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  
Change From Baseline in Troponin I and Troponin T at Week 2, 6, Month 3, 6 and 12  
[units: nanogram/milliliter (ng/mL)]
Mean ± Standard Deviation
 
Troponin I: Baseline (n=33)     0.135  ± 0.080  
Troponin I: Change at Week 2 (n=35)     0.003  ± 0.060  
Troponin I: Change at Week 6 (n=35)     -0.000  ± 0.055  
Troponin I: Change at Month 3 (n=34)     0.008  ± 0.057  
Troponin I: Change at Month 6 (n=34)     -0.016  ± 0.051  
Troponin I: Change at Month 12 (n=32)     0.016  ± 0.064  
Troponin T: Baseline (n=33)     0.044  ± 0.037  
Troponin T: Change at Week 2 (n=35)     0.001  ± 0.025  
Troponin T: Change at Week 6 (n=35)     0.006  ± 0.020  
Troponin T: Change at Month 3 (n=34)     0.008  ± 0.021  
Troponin T: Change at Month 6 (n=33)     0.002  ± 0.020  
Troponin T: Change at Month 12 (n=32)     0.012  ± 0.023  

No statistical analysis provided for Change From Baseline in Troponin I and Troponin T at Week 2, 6, Month 3, 6 and 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 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide(NT-proBNP) Levels at Week 2, 6, Month 3, 6 and 12
Measure Description NT-proBNP was a cardiac marker which had the prognostic value for participants with heart failure or left ventricular dysfunction. Higher level of the marker was indicative of heart damage.
Time Frame Baseline, Week 2, Week 6, Month 3, 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.
ITT population included all participants who received at least one dose of study medication. Here 'n' signifies those participants who were evaluable for specific timepoints.

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  
Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide(NT-proBNP) Levels at Week 2, 6, Month 3, 6 and 12  
[units: picogram/mL (pg/mL)]
Mean ± Standard Deviation
 
Baseline (n=33)     4934.2  ± 4324.9  
Change at Week 2 (n=35)     -1.6  ± 1349.1  
Change at Week 6 (n=35)     295.0  ± 1632.0  
Change at Month 3 (n=34)     102.8  ± 1998.0  
Change at Month 6 (n=33)     111.6  ± 2032.4  
Change at Month 12 (n=31)     958.2  ± 3178.0  

No statistical analysis provided for Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide(NT-proBNP) Levels at Week 2, 6, Month 3, 6 and 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 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in 6-Minute Walk Test (6MWT) at Month 3, 6 and 12
Measure Description 6MWT was used to assess the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed. Continuous pulse oximetry was conducted during the test for safety.. The distance walked in 6 minutes was categorized as: Level 1: <300 meter, Level 2: 300-374.9 meter, Level 3: 375-449.9 meter, Level 4: >=450 meter.
Time Frame Baseline, Month 3, 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.
ITT population included all participants who received at least one dose of study medication. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. Here 'n' signifies those participants who were evaluable for specific timepoints.

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]
  34  
Change From Baseline in 6-Minute Walk Test (6MWT) at Month 3, 6 and 12  
[units: meters]
Mean ± Standard Deviation
 
Distance walked: Baseline (n=34)     354.5  ± 126.0  
Distance walked: Change at Month 3 (n=31)     -4.6  ± 63.1  
Distance walked: Change at Month 6 (n=33)     3.9  ± 58.2  
Distance walked: Change at Month 12 (n=28)     -11.2  ± 76.4  

No statistical analysis provided for Change From Baseline in 6-Minute Walk Test (6MWT) at Month 3, 6 and 12




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide 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
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.


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