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

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00694161
• Collaborator: (none)
• Enrollment: 35
• Locations: 6
• Arm: 1
• Duration (Months): 17
• Patients Per Site: 5.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Open-label, multicenter, international, single-treatment study designed to determine TTR stabilization as well as Fx-1006A safety and tolerability, and its effects on clinical outcomes in patients with V122I or wild-type TTR amyloid cardiomyopathy.

The study will be conducted in two parts. Part 1 will include a six-week dosing period during which all enrolled patients will self-administer oral Fx-1006A 20 mg soft gelatin capsules once daily for six weeks. At Week 6, blood samples will be collected from each patient to determine TTR stabilization. Patients who complete the Week 6 visit will continue taking daily oral Fx 1006A 20 mg for up to a total of 12 months during Part 2 of this study. If it is determined that a patient is not stabilized at Week 6 (based on TTR stabilization data), the patient will be discontinued from the study. Safety and clinical outcomes will be evaluated during Part 2 of this study.

Two whole blood samples for pharmacodynamic assessments (TTR stabilization) and pharmacokinetic assessments (Fx-1006A concentrations as well as calculated steady-state parameters) will be collected at Baseline and Week 6. At Months 6 and 12, two whole blood samples will be collected for pharmacodynamic assessments, and four whole blood samples (two samples per time point) will be collected for pharmacokinetic assessments to be utilized in population pharmacokinetic modeling.

Echocardiography, chest x-ray, cardiac MRI, and 24-hour Holter monitoring will be conducted at Baseline, and Months 6 and 12. Six-minute walk test and quality of life utilizing the Patient Global Assessment, KCCQ, and SF-36 will be assessed at Baseline, and Months 3, 6, and 12. NYHA Classification will be assessed at Baseline, Week 6, and Months 3, 6, and 12. Serum markers of troponin I and T, and NT-pro-BNP levels will be assessed at each study visit.

Safety and tolerability will be assessed throughout the study. Vital signs, 12-lead ECG, blood and urine samples for clinical laboratory tests (serum chemistry, hematology, coagulation panel, and urinalysis), AEs, and concomitant medications (including diuretic usage) will be assessed at each study visit. Abbreviated physical examinations will be conducted at Baseline, Weeks 2 and 6, and Months 3 and 6, and a complete physical examination will be conducted at Month 12.

Clinic visits will be conducted during Screening (Days -30 to -1) and Baseline (Day 0); procedures scheduled for the Baseline visit may be conducted over a period of one week to accommodate patient scheduling. All Baseline procedures must be completed prior to the first self-administered dose on Day 1. Day 1 will be defined as administration of the first dose of study medication, which patients will self-administer at home. During treatment, clinic visits will be conducted at Week 2 (± 2 days), Week 6 (± 1 week), Month 3 (± 1 week), Month 6 (± 2 weeks), and Month 12 (± 2 weeks). Procedures scheduled for the Month 6 and 12 visits may occur over one week during the visit window to accommodate patient scheduling. Monthly telephone contacts (± 1 week of the scheduled date) will be made during months in which no clinical site visits are scheduled (Months 4, 5, 7, 8, 9, 10, and 11) for assessment of AEs and concomitant medications. A final telephone contact to assess AEs and concomitant medication usage will be made 30 days after the last dose of study medication for each patient.

Patients who discontinue from the study at any time will have a final visit performed, including all safety assessments, at the time of discontinuation. Any patient discontinuing after the Month 6 visit will also have all exploratory assessments performed.

Condition or Disease	Intervention/Treatment	Phase
Cardiomyopathy	Drug: Fx-1006A	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Effects Of Fx-1006A On Transthyretin Stabilization And Clinical Outcome Measures In Patients With V122I Or Wild-Type TTR Amyloid Cardiomyopathy
• Study Start Date: Aug 1, 2008
• Actual Primary Completion Date: Jan 1, 2010
• Actual Study Completion Date: Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fx-1006A	Drug: Fx-1006A; Fx-1006A 20mg soft gelatin capsules once daily (at the same time each day) for 12 months

Outcome Measures

Primary Outcome Measures

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

   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.

Secondary Outcome Measures

1. Percentage of Participants With Stabilized Transthyretin (TTR Tetramer) at Month 6 and 12 [Month 6, Month 12]

   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.

Other Outcome Measures

1. Number of Participants With Treatment-Emergent Adverse Events (AEs) [Baseline up to 30 days after the last dose]

   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.

2. Number of Participants With Greater Than or Equal to (>=) Grade 3 Treatment-Emergent AEs [Baseline up to 30 days after the last dose]

   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.

3. Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings [Baseline up to Month 12]

   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.

4. Number of Participants Discontinuing From The Study Due to Clinically Significant Clinical or Laboratory Adverse Events (AEs) [Baseline up to Month 12]

5. Change From Baseline in Echocardiographic (ECHO) Parameters at Month 6 and 12 [Baseline, Month 6, Month 12]

   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).

6. Change From Baseline in Left Ventricular Mass (LVM) at Month 6 and 12 [Baseline, Month 6, Month 12]

   LVM was defined as increase in the mass of left ventricle, estimated by echocardiography. Increased LVM was associated with cardiovascular morbidity and mortality.

7. Change From Baseline in Left Ventricular Ejection Fraction at Month 6 and 12 [Baseline, Month 6, Month 12]

   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.

8. Change From Baseline in Doppler Data: E/A and E/e' Ratio at Month 6 and 12 [Baseline, Month 6, Month 12]

   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.

9. Change From Baseline in Doppler Data: Mitral Deceleration Time at Month 6 and 12 [Baseline, Month 6, Month 12]

   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.

10. Change From Baseline in Tissue Doppler- Septal and Lateral Velocity at Month 6 and 12 [Baseline, Month 6, Month 12]

    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.

11. Change From Baseline in Pericardial Effusion at Month 6 and 12 [Baseline, Month 6, Month 12]

    Pericardial effusion was the presence of an abnormal amount of fluid in the pericardial cavity, as determined by echocardiography.

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

    Valvular abnormalities were those abnormalities (thickening or regurgitation) that involved one or more valves of the heart, determined by echocardiography.

13. 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 [Baseline, Month 6, Month 12]

    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.

14. 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 [Baseline, Month 6, Month 12]

    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).

15. 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. [Baseline, Month 6, Month 12]

    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).

16. Change From Baseline in Left Ventricular Ejection Fraction and Right Ventricular Ejection Fraction at Month 6 and 12 [Baseline, Month 6, Month 12]

    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.

17. Change From Baseline in Left Ventricular Cardiac Output and Right Ventricular Cardiac Output at Month 6 and 12 [Baseline, Month 6, Month 12]

    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.

18. 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 [Baseline, Month 6, Month 12]

    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.

19. Change From Baseline in 4 Chamber Interatrial Septal Thickness at Month 6 and 12 [Baseline, Month 6, Month 12]

    Cardiac MRI was done to measure interatrial septal thickness in the 4 chamber view.

20. Change From Baseline in 4 Chamber Left Atrial Dimension and 4 Chamber Right Atrial Dimension at Month 6 and 12 [Baseline, Month 6, Month 12]

    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.

21. 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 [Baseline, Month 6, Month 12]

    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.

22. 24-Hour Average Heart Rate and Maximium/Minimum Heart Rate [Baseline, Month 6, Month 12]

    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.

23. Number of Participants With Complete Heart Block [Baseline, Month 6, Month 12]

    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.

24. Heart Rate Variability (HRV)- Standard Deviation (SD) Parameters [Baseline, Month 6, Month 12]

    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.

25. Heart Rate Variability- Percentage of Successive R-R Intervals With Greater Than 50 Msec Difference Between Normal Beats (pNN50) [Baseline, Month 6, Month 12]

    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.

26. Number of Participants With Change From Baseline in New York Heart Association (NYHA) Classification at Week 6, Month 3, 6 and 12 [Baseline, Week 6, Month 3, Month 6, Month 12]

    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).

27. Cardiothoracic (CT) Ratio [Baseline, Month 6, Month 12]

    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.

28. Number of Participants With Increased Interstitial Markings and Pleural Effusions [Baseline, Month 6, Month 12]

    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.

29. Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12 [Baseline, Month 3, Month 6, Month 12]

    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.

30. Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 [Baseline, Month 3, Month 6, Month 12]

    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.

31. Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 [Baseline, Month 3, Month 6, Month 12]

    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.

32. Change From Baseline in Troponin I and Troponin T at Week 2, 6, Month 3, 6 and 12 [Baseline, Week 2, Week 6, Month 3, Month 6, Month 12]

    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.

33. Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide(NT-proBNP) Levels at Week 2, 6, Month 3, 6 and 12 [Baseline, Week 2, Week 6, Month 3, Month 6, Month 12]

    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.

34. Change From Baseline in 6-Minute Walk Test (6MWT) at Month 3, 6 and 12 [Baseline, Month 3, Month 6, Month 12]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patient is > 40 years-old.

2. Patient participated in FoldRx Study Fx-001 (TRACS) OR Patient has documented TTR amyloid cardiomyopathy and NYHA Classification of I or II.

TTR amyloid cardiomyopathy is defined as:

1. Variant TTR amyloid cardiomyopathy as defined as: V122I genotype and presence of amyloid in cardiac biopsy tissue (as determined by congo red stain, alcin blue stain, or immunohistochemical TTR analysis), or

2. Variant TTR amyloid cardiomyopathy as defined as: V122I genotype, evidence of cardiac involvement by echocardiography with left ventricle wall thickness > 12 mm and presence of amyloid in non-cardiac biopsy tissue (as determined by congo red stain, alcin blue stain, or immunohistochemical TTR analysis), or

3. Wild-type TTR amyloid cardiomyopathy as defined as: normal TTR genotype and presence of TTR amyloid deposits in cardiac biopsy tissue (as determined by congo red stain and immunohistochemical TTR analysis), or

4. Wild-type TTR amyloid cardiomyopathy as defined as: normal TTR genotype, evidence of cardiac involvement by echocardiography with left ventricle wall thickness > 12 mm and presence of TTR amyloid deposits in non-cardiac biopsy tissue (as determined by congo red stain and immunohistochemical TTR analysis).

5. Patient's symptoms of congestive heart failure (CHF) have been optimally managed prior to baseline, as assessed by the Principal Investigator. Optimal CHF management includes stable drug regimen for ≥ 4 weeks prior to enrollment and stable dose of beta blocker for ≥ 3 months prior to enrollment.

6. If female, patient is post-menopausal. If male with a female partner of childbearing potential, willing to use an acceptable method of birth control for the duration of the study and for at least 3 months after the last dose of study medication.

7. Patient is, in the opinion of the Investigator, willing and able to comply with the study medication regimen and all other study requirements

Exclusion Criteria:

1. Chronic use of non-protocol approved non-steroidal anti-inflammatory drugs (NSAIDs), defined as greater than 3-4 times/month. The following NSAID are allowed: acetylsalicylic acid, etodolac, ibuprofen, indomethicin, ketoprofen, nabumetone, naproxen, nimesulide, piroxicam, and sulindac.

2. Patient has a TTR mutation other than V122I.

3. Patient has primary or secondary amyloidosis.

4. Patient has received prior liver or heart transplantation.

5. Patient with positive results for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (anti-HCV), and/or human immunodeficiency virus (HIV).

6. Patient has renal failure requiring dialysis.

7. Patient has moderate or severe hepatic impairment (assessed by Child-Pugh).

8. Patient has liver function test abnormalities: alanine transaminases (ALT) and/or aspartate transaminases (AST) > 2 times upper limit of normal (ULN) that, in the medical judgment of the Investigator, are due to reduced liver function or active liver disease.

9. Patient has prior non-amyloid cardiac disease, such as myocardial infarction due to obstructive coronary artery disease, active non-amyloid cardiomyopathy (i.e., symptomatic left ventricular dysfunction from any cause other than amyloid), or symptomatic valvular heart disease that significantly contribute to the patient's underlying cardiac signs or symptoms.

10. Patient has a co-morbidity anticipated to limit survival to less than 12 months.

11. Patient received an investigational drug/device in another clinical investigational study within 60 days before Baseline (Day 0).

12. Patient had active alcohol or substance abuse within 60 days before Baseline (Day 0).

13. Patient has a history of documented noncompliance.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Emory University School of Medicine	Atlanta	Georgia	United States	30322
2	University of Chicago	Chicago	Illinois	United States	60637
3	Johns Hopkins Hospital	Baltimore	Maryland	United States	21205
4	Harvard Vanguard Medical Associates	Boston	Massachusetts	United States	02215
5	Mayo Clinic	Rochester	Minnesota	United States	55905
6	Columbia University	New York	New York	United States	10032

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Jeff Packman, MBA, FoldRx Pharmaceuticals, Inc

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00694161
• Other Study ID Numbers: FX1B-201; B3461025
• First Posted: Jun 10, 2008
• Last Update Posted: Jan 11, 2013
• Last Verified: Jan 1, 2013

• Keywords provided by Pfizer: Transthyretin; TTR; ATTR; TTR amyloidosis; cardiomyopathy; V122I; wild-type TTR; SSA; Patients with V122I or wild-type TTR amyloid cardiomyopathy
• Additional relevant MeSH terms: Cardiomyopathies

Study Results

Participant Flow

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Period Title: Part 1 (up to Week 6)
STARTED	35
COMPLETED	35
NOT COMPLETED	0
Period Title: Part 1 (up to Week 6)
STARTED	35
COMPLETED	32
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Overall Participants	35
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	76.4 (4.7)
Sex: Female, Male (Count of Participants)
Female	3 8.6%
Male	32 91.4%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Stabilized Transthyretin (TTR Tetramer) at Week 6
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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	35
Number (95% Confidence Interval) [Percentage of participants]	97.1 277.4%

2. Secondary Outcome

Title	Percentage of Participants With Stabilized Transthyretin (TTR Tetramer) at Month 6 and 12
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	34
Month 6	88.2 252%
Month 12	87.5 250%

3. Other Pre-specified Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs)
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

Outcome Measure Data

Analysis Population Description

ITT population included all participants who received at least one dose of study medication.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	35
Number [Participants]	35 100%

4. Other Pre-specified Outcome

Title	Number of Participants With Greater Than or Equal to (>=) Grade 3 Treatment-Emergent AEs
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

Outcome Measure Data

Analysis Population Description

ITT population included all participants who received at least one dose of study medication.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	35
Grade 3 (severe)	18 51.4%
Grade 4 (life-threatening)	1 2.9%
Grade 5 (death)	2 5.7%

5. Other Pre-specified Outcome

Title	Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings
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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	34
Any ECHO abnormalities (n=34)	31 88.6%
Pericardial effusion (n=28)	6 17.1%
Valvular abnormalities- thickening (n=4)	4 11.4%
Valvular abnormalities- regurgitation (n=7)	6 17.1%
Abnormal regional wall motion (n=19)	10 28.6%
Inferior vena cava respiratory variation (n=14)	7 20%
Left ventricular posterior wall thickness (n=0)	NA NaN
Left ventricular septal thickness (n=0)	NA NaN
Right ventricular thickness (n=7)	6 17.1%
E/A ratio (n=8)	4 11.4%
E/e' prime lateral (n=13)	5 14.3%
E/e' prime septal (n=6)	5 14.3%
Ejection fraction (n=18)	11 31.4%
E deceleration time (n=16)	8 22.9%
Isovolumic relaxation time (n=16)	4 11.4%

6. Other Pre-specified Outcome

Title	Number of Participants Discontinuing From The Study Due to Clinically Significant Clinical or Laboratory Adverse Events (AEs)
Time Frame	Baseline up to Month 12

Outcome Measure Data

Analysis Population Description

ITT population included all participants who received at least one dose of study medication.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	35
Number [Participants]	1 2.9%

7. Other Pre-specified Outcome

Title	Change From Baseline in Echocardiographic (ECHO) Parameters at Month 6 and 12
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	34
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)

8. Other Pre-specified Outcome

Title	Change From Baseline in Left Ventricular Mass (LVM) at Month 6 and 12
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	34
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)

9. Other Pre-specified Outcome

Title	Change From Baseline in Left Ventricular Ejection Fraction at Month 6 and 12
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	34
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)

10. Other Pre-specified Outcome

Title	Change From Baseline in Doppler Data: E/A and E/e' Ratio at Month 6 and 12
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	26
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)

11. Other Pre-specified Outcome

Title	Change From Baseline in Doppler Data: Mitral Deceleration Time at Month 6 and 12
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	33
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)

12. Other Pre-specified Outcome

Title	Change From Baseline in Tissue Doppler- Septal and Lateral Velocity at Month 6 and 12
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	26
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)

13. Other Pre-specified Outcome

Title	Change From Baseline in Pericardial Effusion at Month 6 and 12
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

Outcome Measure Data

Analysis Population Description

Data for this pre-specified outcome measure was collected and reported in individual participant listings but not statistically summarized for analysis.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	0

14. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

Data for this pre-specified outcome measure was collected and reported in individual participant listings but not statistically summarized for analysis.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	0

15. Other Pre-specified Outcome

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
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	18
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)

16. Other Pre-specified Outcome

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
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	18
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)

17. Other Pre-specified Outcome

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.
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	18
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)

18. Other Pre-specified Outcome

Title	Change From Baseline in Left Ventricular Ejection Fraction and Right Ventricular Ejection Fraction at Month 6 and 12
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	18
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)

19. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

MRI data was collected and reported for cardiac output through the measure of stroke volume as given in outcome measure 17.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	0

20. Other Pre-specified Outcome

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
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	15
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)

21. Other Pre-specified Outcome

Title	Change From Baseline in 4 Chamber Interatrial Septal Thickness at Month 6 and 12
Description	Cardiac MRI was done to measure interatrial septal thickness in the 4 chamber view.
Time Frame	Baseline, Month 6, Month 12

Outcome Measure Data

Analysis Population Description

Data for this measure was not collected due to a change in the planned analysis.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	0

22. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

Data for this measure was not collected due to a change in the planned analysis.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	0

23. Other Pre-specified Outcome

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
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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	34
Atrial fibrillation/flutter: Baseline (n=33)	6 17.1%
Atrial fibrillation/flutter: Month 6 (n=27)	9 25.7%
Atrial fibrillation/flutter: Month 12 (n=22)	9 25.7%
Atrial tachycardia: Baseline (n=34)	14 40%
Atrial tachycardia: Month 6 (n=20)	0 0%
Atrial tachycardia: Month 12 (n=17)	0 0%
NSVT (<30 beats): Baseline (n=34)	20 57.1%
NSVT (<30 beats): Month 6 (n=13)	3 8.6%
NSVT (<30 beats): Month 12 (n=12)	5 14.3%
SVT (>= 30 beats): Baseline (n=34)	0 0%
SVT (>= 30 beats): Month 6 (n=33)	0 0%
SVT (>= 30 beats): Month 12 (n=30)	1 2.9%
Sinus pause: Baseline (n=34)	2 5.7%
Sinus pause: Month 6 (n=31)	4 11.4%
Sinus pause: Month 12 (n=28)	5 14.3%

24. Other Pre-specified Outcome

Title	24-Hour Average Heart Rate and Maximium/Minimum Heart Rate
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	34
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)

25. Other Pre-specified Outcome

Title	Number of Participants With Complete Heart Block
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

Outcome Measure Data

Analysis Population Description

No summary was prepared for this data as there were no reports of complete heart block.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	0

26. Other Pre-specified Outcome

Title	Heart Rate Variability (HRV)- Standard Deviation (SD) Parameters
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	33
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)

27. Other Pre-specified Outcome

Title	Heart Rate Variability- Percentage of Successive R-R Intervals With Greater Than 50 Msec Difference Between Normal Beats (pNN50)
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	30
Baseline (n=30)	19.7 (25.5)
Month 6 (n=26)	29.3 (32.7)
Month 12 (n=21)	23.6 (27.3)

28. Other Pre-specified Outcome

Title	Number of Participants With Change From Baseline in New York Heart Association (NYHA) Classification at Week 6, Month 3, 6 and 12
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	35
Baseline: Class I (n=35)	5 14.3%
Baseline: Class II (n=35)	28 80%
Baseline: Class III (n=35)	2 5.7%
Baseline: Class IV (n=35)	0 0%
Change at Month 3: improved (n=34)	5 14.3%
Change at Month 3: no change (n=34)	23 65.7%
Change at Month 3: worsened (n=34)	6 17.1%
Change at Month 6: improved (n=34)	1 2.9%
Change at Month 6: no change (n=34)	27 77.1%
Change at Month 6: worsened (n=34)	6 17.1%
Change at Month 12: improved (n=32)	4 11.4%
Change at Month 12: no change (n=32)	20 57.1%
Change at Month 12: worsened (n=32)	8 22.9%

29. Other Pre-specified Outcome

Title	Cardiothoracic (CT) Ratio
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

Outcome Measure Data

Analysis Population Description

ITT population included all participants who received at least one dose of study medication.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	35
Baseline	55.130 (6.075)
Month 6	56.620 (5.904)
Month 12	57.830 (5.366)

30. Other Pre-specified Outcome

Title	Number of Participants With Increased Interstitial Markings and Pleural Effusions
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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	35
Increased interstitial markings: Baseline	11 31.4%
Increased interstitial markings: Month 6	4 11.4%
Increased interstitial markings: Month 12	4 11.4%
Pleural effusion- right: Baseline	9 25.7%
Pleural effusion- right: Month 6	8 22.9%
Pleural effusion- right: Month 12	6 17.1%
Pleural effusion- left: Baseline	6 17.1%
Pleural effusion- left: Month 6	5 14.3%
Pleural effusion- left: Month 12	4 11.4%
Pleural effusion- bilateral: Baseline	6 17.1%
Pleural effusion- bilateral: Month 6	4 11.4%
Pleural effusion- bilateral: Month 12	3 8.6%

31. Other Pre-specified Outcome

Title	Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	34
Excellent: Baseline (n=33)	5 14.3%
Very good: Baseline (n=33)	14 40%
Good: Baseline (n=33)	12 34.3%
Fair: Baseline (n=33)	2 5.7%
Poor: Baseline (n=33)	0 0%
Markedly improved: Month 3 (n=34)	2 5.7%
Moderately improved: Month 3 (n=34)	7 20%
Mildly improved: Month 3 (n=34)	6 17.1%
Unchanged: Month 3 (n=34)	15 42.9%
Mildly worsened: Month 3 (n=34)	2 5.7%
Moderately worsened: Month 3 (n=34)	2 5.7%
Markedly worsened: Month 3 (n=34)	0 0%
Markedly improved: Month 6 (n=34)	3 8.6%
Moderately improved: Month 6 (n=34)	4 11.4%
Mildly improved: Month 6 (n=34)	3 8.6%
Unchanged: Month 6 (n=34)	16 45.7%
Mildly worsened: Month 6 (n=34)	8 22.9%
Moderately worsened: Month 6 (n=34)	0 0%
Markedly worsened: Month 6 (n=34)	0 0%
Markedly improved: Month 12 (n=32)	0 0%
Moderately improved: Month 12 (n=32)	5 14.3%
Mildly improved: Month 12 (n=32)	3 8.6%
Unchanged: Month 12 (n=32)	16 45.7%
Mildly worsened: Month 12 (n=32)	4 11.4%
Moderately worsened: Month 12 (n=32)	3 8.6%
Markedly worsened: Month 12 (n=32)	1 2.9%

32. Other Pre-specified Outcome

Title	Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	35
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)

33. Other Pre-specified Outcome

Title	Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	35
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)

34. Other Pre-specified Outcome

Title	Change From Baseline in Troponin I and Troponin T at Week 2, 6, Month 3, 6 and 12
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	35
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)

35. Other Pre-specified Outcome

Title	Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide(NT-proBNP) Levels at Week 2, 6, Month 3, 6 and 12
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	35
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)

36. Other Pre-specified Outcome

Title	Change From Baseline in 6-Minute Walk Test (6MWT) at Month 3, 6 and 12
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Tafamidis
Arm/Group Description	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.
Measure Participants	34
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)

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Tafamidis
Arm/Group Description	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.
All Cause Mortality
	Tafamidis
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Tafamidis
	Affected / at Risk (%)	# Events
Total	15/35 (42.9%)
Cardiac disorders
Cardiac failure congestive	9/35 (25.7%)
Atrial fibrillation	3/35 (8.6%)
Cardiac failure	2/35 (5.7%)
Supraventricular tachycardia	1/35 (2.9%)
Ventricular tachycardia	1/35 (2.9%)
Immune system disorders
Amyloidosis	1/35 (2.9%)
Infections and infestations
Cellulitis	1/35 (2.9%)
Escherichia sepsis	1/35 (2.9%)
Pneumonia	1/35 (2.9%)
Injury, poisoning and procedural complications
Fall	3/35 (8.6%)
Pelvic fracture	1/35 (2.9%)
Metabolism and nutrition disorders
Dehydration	1/35 (2.9%)
Hypokalaemia	1/35 (2.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Glioblastoma multiforme	1/35 (2.9%)
Nervous system disorders
Syncope	2/35 (5.7%)
Cerebrovascular accident	1/35 (2.9%)
Coordination abnormal	1/35 (2.9%)
Haemorrhagic stroke	1/35 (2.9%)
Metabolic encephalopathy	1/35 (2.9%)
Renal and urinary disorders
Renal failure acute	1/35 (2.9%)
Renal impairment	1/35 (2.9%)
Vascular disorders
Haemorrhage	1/35 (2.9%)
Other (Not Including Serious) Adverse Events
	Tafamidis
	Affected / at Risk (%)	# Events
Total	34/35 (97.1%)
Blood and lymphatic system disorders
Anaemia	1/35 (2.9%)
Cardiac disorders
Atrial fibrillation	4/35 (11.4%)
Cardiac failure congestive	3/35 (8.6%)
Cardiac failure	2/35 (5.7%)
Atrial tachycardia	1/35 (2.9%)
Bradycardia	1/35 (2.9%)
Bundle branch block right	1/35 (2.9%)
Palpitations	1/35 (2.9%)
Sinus arrhythmia	1/35 (2.9%)
Ventricular tachycardia	1/35 (2.9%)
Bundle branch block	1/35 (2.9%)
Congenital, familial and genetic disorders
Colour blindness	1/35 (2.9%)
Eye disorders
Corneal disorder	1/35 (2.9%)
Vitreous floaters	1/35 (2.9%)
Gastrointestinal disorders
Diarrhoea	7/35 (20%)
Constipation	5/35 (14.3%)
Nausea	5/35 (14.3%)
Abdominal pain upper	3/35 (8.6%)
Flatulence	3/35 (8.6%)
Dry mouth	2/35 (5.7%)
Vomiting	2/35 (5.7%)
Abdominal pain	1/35 (2.9%)
Cheilitis	1/35 (2.9%)
Faecal incontinence	1/35 (2.9%)
Inguinal hernia	1/35 (2.9%)
General disorders
Fatigue	8/35 (22.9%)
Oedema peripheral	6/35 (17.1%)
Asthenia	3/35 (8.6%)
Oedema	3/35 (8.6%)
Thirst	3/35 (8.6%)
Catheter related complication	1/35 (2.9%)
Chest discomfort	1/35 (2.9%)
Chest pain	1/35 (2.9%)
Hernia	1/35 (2.9%)
Hot flush	1/35 (2.9%)
Localised oedema	1/35 (2.9%)
Pain	1/35 (2.9%)
Pyrexia	1/35 (2.9%)
Hepatobiliary disorders
Hepatomegaly	4/35 (11.4%)
Immune system disorders
Seasonal allergy	3/35 (8.6%)
Infections and infestations
Upper respiratory tract infection	6/35 (17.1%)
Urinary tract infection	3/35 (8.6%)
Influenza	2/35 (5.7%)
Nasopharyngitis	2/35 (5.7%)
Bronchitis	1/35 (2.9%)
Cellulitis	1/35 (2.9%)
Furuncle	1/35 (2.9%)
Infection	1/35 (2.9%)
Lower respiratory tract infection	1/35 (2.9%)
Nail infection	1/35 (2.9%)
Injury, poisoning and procedural complications
Contusion	2/35 (5.7%)
Excoriation	2/35 (5.7%)
Fall	2/35 (5.7%)
Joint injury	2/35 (5.7%)
Skin laceration	2/35 (5.7%)
Joint sprain	1/35 (2.9%)
Laceration	1/35 (2.9%)
Post procedural haematuria	1/35 (2.9%)
Tooth injury	1/35 (2.9%)
Investigations
Weight decreased	6/35 (17.1%)
Work increased	5/35 (14.3%)
Alanine aminotransferase increased	2/35 (5.7%)
Aspartate aminotransferase increased	2/35 (5.7%)
Blood cholesterol increased	2/35 (5.7%)
Blood thyroid stimulating hormone increased	2/35 (5.7%)
Aspiration pleural cavity	1/35 (2.9%)
Blood creatinine increased	1/35 (2.9%)
Blood pressure decreased	1/35 (2.9%)
Blood thyroid stimulating hormone decreased	1/35 (2.9%)
Blood urine present	1/35 (2.9%)
Blood natriuretic peptide increased	1/35 (2.9%)
Ejection fraction decreased	1/35 (2.9%)
Gamma-glutamyltransferase increased	1/35 (2.9%)
Heart rate increased	1/35 (2.9%)
International normalised ratio increased	1/35 (2.9%)
Urine output increased	1/35 (2.9%)
Venous pressure jugular increased	1/35 (2.9%)
Metabolism and nutrition disorders
Anorexia	2/35 (5.7%)
Decreased appetite	2/35 (5.7%)
Fluid overload	2/35 (5.7%)
Gout	2/35 (5.7%)
Fluid retention	1/35 (2.9%)
Hyperkalaemia	1/35 (2.9%)
Hypochloraemia	1/35 (2.9%)
Hyponatraemia	1/35 (2.9%)
Musculoskeletal and connective tissue disorders
Back pain	3/35 (8.6%)
Pain in extremity	3/35 (8.6%)
Muscle spasms	2/35 (5.7%)
Arthralgia	1/35 (2.9%)
Finger deformity	1/35 (2.9%)
Joint swelling	1/35 (2.9%)
Muscle twitching	1/35 (2.9%)
Musculoskeletal discomfort	1/35 (2.9%)
Musculoskeletal pain	1/35 (2.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	1/35 (2.9%)
Benign neoplasm	1/35 (2.9%)
Lentigo	1/35 (2.9%)
Prostate cancer	1/35 (2.9%)
Nervous system disorders
Dizziness	7/35 (20%)
Dizziness postural	6/35 (17.1%)
Balance disorder	5/35 (14.3%)
Aguesia	3/35 (8.6%)
Tremor	2/35 (5.7%)
Amnesia	1/35 (2.9%)
Disturbance in attention	1/35 (2.9%)
Headache	1/35 (2.9%)
Loss of consciousness	1/35 (2.9%)
Memory impairment	1/35 (2.9%)
Migraine	1/35 (2.9%)
Neuralgia	1/35 (2.9%)
Neuropathy	1/35 (2.9%)
Neuropathy peripheral	1/35 (2.9%)
Restless legs syndrome	1/35 (2.9%)
Somnolence	1/35 (2.9%)
Syncope	1/35 (2.9%)
Psychiatric disorders
Insomnia	3/35 (8.6%)
Confusional state	2/35 (5.7%)
Depression	2/35 (5.7%)
Anxiety	1/35 (2.9%)
Nervousness	1/35 (2.9%)
Panic attack	1/35 (2.9%)
Renal and urinary disorders
Haematuria	2/35 (5.7%)
Dysuria	1/35 (2.9%)
Pollakiuria	1/35 (2.9%)
Urinary incontinence	1/35 (2.9%)
Reproductive system and breast disorders
Nipple pain	2/35 (5.7%)
Gynaecomastia	1/35 (2.9%)
Scrotal oedema	1/35 (2.9%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	11/35 (31.4%)
Dyspnoea exertional	6/35 (17.1%)
Epistaxis	3/35 (8.6%)
Rhinorrhoea	3/35 (8.6%)
Cough	2/35 (5.7%)
Pleural effusion	2/35 (5.7%)
Sinus congestion	2/35 (5.7%)
Dysphonia	1/35 (2.9%)
Postnasal drip	1/35 (2.9%)
Productive cough	1/35 (2.9%)
Pulmonary congestion	1/35 (2.9%)
Rales	1/35 (2.9%)
Skin and subcutaneous tissue disorders
Pruritus	3/35 (8.6%)
Rash	3/35 (8.6%)
Skin ulcer	3/35 (8.6%)
Blister	1/35 (2.9%)
Ingrowing nail	1/35 (2.9%)
Rash maculo-papular	1/35 (2.9%)
Skin discolouration	1/35 (2.9%)
Skin exfoliation	1/35 (2.9%)
Skin lesion	1/35 (2.9%)
Surgical and medical procedures
Foot operation	1/35 (2.9%)
Implantable defibrillator insertion	1/35 (2.9%)
Mole excision	1/35 (2.9%)
Tooth extraction	1/35 (2.9%)
Vascular disorders
Hypotension	1/35 (2.9%)
Varicose vein	1/35 (2.9%)

Limitations/Caveats

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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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.