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The Effects of Fx-1006A on Transthyretin Stabilization and Clinical Outcome Measures in Patients With Non-V30M Transthyretin Amyloidosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00630864
First received: February 27, 2008
Last updated: January 9, 2013
Last verified: January 2013
Results First Received: November 16, 2012  
Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Transthyretin-associated Amyloidosis With Polyneuropathy
Intervention: Drug: Fx-1006A

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

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

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Participant Flow for 2 periods

Period 1:   Part 1 (up to Week 6)
    Tafamidis  
STARTED     21  
COMPLETED     20  
NOT COMPLETED     1  
Adverse Event                 1  

Period 2:   Part 2 (After Week 6 up to Month 12)
    Tafamidis  
STARTED     20  
COMPLETED     18  
NOT COMPLETED     2  
Liver transplant                 2  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Baseline Measures
    Tafamidis  
Number of Participants  
[units: participants]
  21  
Age  
[units: years]
Mean ± Standard Deviation
  63.10  ± 9.86  
Gender  
[units: participants]
 
Female     8  
Male     13  



  Outcome Measures
  Hide All Outcome Measures

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

Measure Type Primary
Measure Title Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer at Week 6
Measure Description TTR tetramer was assessed using a validated immunoturbidimetric assay. The Fraction of Initial (FOI) is the ratio of the measured TTR tetramer concentration after denaturation to the measured TTR tetramer concentration before denaturation. TTR tetramer stabilization is based on the difference between the on-treatment FOI and the baseline FOI expressed as a percentage of the baseline FOI.
Time Frame Week 6  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) population included all participants who received at least 1 dose of study medication. Here ‘N’ (Number of participants analyzed) signifies those participants who were evaluable for this measure.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  19  
Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer at Week 6  
[units: percentage of participants]
Number ( 95% Confidence Interval )
  94.7  
  ( 74.0 to 99.9 )  

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



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

Measure Type Secondary
Measure Title Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer at Month 6 and 12
Measure Description TTR tetramer was assessed using a validated immunoturbidimetric assay. The FOI is the ratio of the measured TTR tetramer concentration after denaturation to the measured TTR tetramer concentration before denaturation. TTR tetramer stabilization is based on the difference between the on-treatment FOI and the baseline FOI expressed as a percentage of the baseline FOI.
Time Frame Month 6, Month 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who received at least 1 dose of study medication. Here ‘N’ (Number of participants analyzed) signifies those participants who were evaluable for this measure.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  18  
Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer at Month 6 and 12  
[units: percentage of participants]
Number ( 95% Confidence Interval )
 
Month 6 (n= 18)     100.0  
  ( 81.5 to 100.0 )  
Month 12 (n= 17)     100.0  
  ( 80.5 to 100.0 )  

No statistical analysis provided for Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer at Month 6 and 12



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

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

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who received at least 1 dose of study medication.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  21  
Number of Participants With Treatment-Emergent Adverse Events (AEs)  
[units: participants]
  17  

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



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

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

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who received at least 1 dose of study medication.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  21  
Number of Participants With Greater Than or Equal to Grade 3 Treatment-Emergent Adverse Events  
[units: participants]
  3  

No statistical analysis provided for Number of Participants With Greater Than or Equal to Grade 3 Treatment-Emergent Adverse Events



5.  Other Pre-specified:   Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings   [ Time Frame: Day 1 up to Month 12 ]

Measure Type Other Pre-specified
Measure Title Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings
Measure Description ECHO: investigator assessed test to assess cardiac function. ECHO abnormality criteria: any abnormality, valvular abnormality, pericardial effusion, abnormal regional wall motion, inferior vena cava respiratory variation, posterior (P) left ventricular (LV) wall/septal (S) thickness, right ventricular thickness, ejection fraction, ratio of early (E) diastolic transmitral flow and atrial(A) contraction velocity (E/A), ratio of ‘E’to lateral/septal mitral annular velocity (e') (E/e'prime lateral, E/e'prime septal), E deceleration time (DT), isovolumic relaxation time (IVRT).
Time Frame Day 1 up to Month 12  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population. The ‘n’ for any post-dose incidence included participants with baseline values that were not abnormal (that is treatment-emergent abnormalities). Abnormalities at early termination were excluded from the analysis.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  21  
Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings  
[units: participants]
 
Any ECHO abnormalities (n= 19)     12  
Pericardial effusion (n= 19)     2  
Valvular abnormalities- thickening (n= 5)     3  
Valvular abnormalities - regurgitation (n= 9)     2  
Abnormal regional wall motion (n= 11)     2  
Inferior vena cava respiratory variation (n= 13)     0  
LV P wall thickness >=13 millimeter (mm) (n= 3)     2  
LV S thickness >=13 mm (n= 3)     1  
Right ventricular thickness >=7 mm (n= 13)     6  
E/A ratio >=2 (n= 16)     3  
E/e'prime Lateral >15 (n= 15)     3  
E/e'prime Septal >15 (n= 10)     2  
Ejection fraction < 50 percent (%) (n= 17)     2  
EDT <= 150 milliseconds (msec) (n= 14)     1  
IVRT <=70 msec (n= 13)     2  

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



6.  Other Pre-specified:   Number of Participants With Clinically Significant Treatment-Emergent Electrocardiogram (ECG) Findings   [ Time Frame: Day 1 up to Month 12 ]

Measure Type Other Pre-specified
Measure Title Number of Participants With Clinically Significant Treatment-Emergent Electrocardiogram (ECG) Findings
Measure Description ECG: investigator assessed test to assess cardiac function. ECG abnormality criteria: any abnormality, arrhythmia, rhythm, conduction, morphology, myocardial infarction, ST segment, T waves and abnormal U waves.
Time Frame Day 1 up to Month 12  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population. The ‘n’ for any post-dose incidence included participants with baseline values that were not abnormal (that is treatment-emergent abnormalities). Abnormalities at early termination were excluded from the analysis.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  21  
Number of Participants With Clinically Significant Treatment-Emergent Electrocardiogram (ECG) Findings  
[units: participants]
 
Any ECG abnormalities (n= 21)     9  
Arrhythmia (n= 18)     8  
Rhythm (n= 18)     1  
Conduction (n= 8)     2  
Morphology (n= 20)     0  
Myocardial infarction (n= 18)     0  
ST segment (n= 20)     1  
T waves (n=18)     1  
Abnormal U waves (n= 21)     0  

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



7.  Other Pre-specified:   Number of Participants With Clinically Significant Treatment-Emergent Holter Monitoring Findings   [ Time Frame: Day 1 up to Month 12 ]

Measure Type Other Pre-specified
Measure Title Number of Participants With Clinically Significant Treatment-Emergent Holter Monitoring Findings
Measure Description Holter monitoring recorded heart rhythm. Holter monitoring abnormality criteria: any abnormality, atrial fibrillation/flutter, atrial tachycardia, non-sustained ventricular tachycardia (VT), sustained VT and sinus pause.
Time Frame Day 1 up to Month 12  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population. The ‘n’ for any post-dose incidence included participants with baseline values that were not abnormal (that is treatment-emergent abnormalities). Abnormalities at early termination were excluded from the analysis.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  21  
Number of Participants With Clinically Significant Treatment-Emergent Holter Monitoring Findings  
[units: participants]
 
Any Holter monitoring abnormalities (n= 19)     9  
Atrial fibrillation/flutter (n= 18)     1  
Atrial tachycardia (n= 9)     4  
Non-sustained VT <30 beats (n= 11)     4  
Sustained VT >=30 beats (n= 19)     0  
Sinus pause (n= 18)     1  

No statistical analysis provided for Number of Participants With Clinically Significant Treatment-Emergent Holter Monitoring Findings



8.  Other Pre-specified:   Number of Participants Who Discontinued Due to Clinical or Laboratory Adverse Events   [ Time Frame: Baseline up to Month 12 ]

Measure Type Other Pre-specified
Measure Title Number of Participants Who Discontinued Due to Clinical or Laboratory Adverse Events
Measure Description No text entered.
Time Frame Baseline up to Month 12  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who received at least 1 dose of study medication.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  21  
Number of Participants Who Discontinued Due to Clinical or Laboratory Adverse Events  
[units: participants]
  1  

No statistical analysis provided for Number of Participants Who Discontinued Due to Clinical or Laboratory Adverse Events



9.  Other Pre-specified:   Change From Baseline in the Neuropathy Impairment Score (NIS) at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in the Neuropathy Impairment Score (NIS) at Month 6, Month 12
Measure Description NIS assessed cranial nerves(nerve 3,6; facial, palate and tongue weakness),muscle weakness (respiratory; neck, elbow(E), wrist(W), finger(F), hip, knee(K) flexion; shoulder, thumb abduction; brachioradialis; E, W, hip, K extension; F spread; toe, dorsal and plantar ankle flexors; toe extensors); score: 0-4, higher score=more weakness, reflexes(biceps and triceps brachii; brachioradialis; quadriceps femoris; triceps surae), index F and great toe sensation(touch pressure, pin-prick, vibration, joint position)score:0=normal,1=decreased or 2=absent. Total score=0-244, higher score=more impairment.
Time Frame Baseline, Month 6, Month 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were analyzed for the specific category.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  21  
Change From Baseline in the Neuropathy Impairment Score (NIS) at Month 6, Month 12  
[units: units on a scale]
Mean ± Standard Deviation
 
Baseline (n= 21)     48.70  ± 44.31  
Change at Month 6 (n= 17)     2.00  ± 9.52  
Change at Month 12 (n= 18)     5.30  ± 12.62  

No statistical analysis provided for Change From Baseline in the Neuropathy Impairment Score (NIS) at Month 6, Month 12



10.  Other Pre-specified:   Change From Baseline in the Neuropathy Impairment Score-Lower Limb (NIS-LL) at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in the Neuropathy Impairment Score-Lower Limb (NIS-LL) at Month 6, Month 12
Measure Description NIS-LL: assessed muscle weakness, reflexes and sensation; scored separately for left and right limbs. Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) are scored on 0 to 4 scale, higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae) and sensation (touch pressure, pin-prick, vibration, joint position) were scored 0 = normal, 1= decreased, or 2 = absent. Total possible NIS-LL score range 0-88, higher score=greater impairment.
Time Frame Baseline, Month 6, Month 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were analyzed for the specific category.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  21  
Change From Baseline in the Neuropathy Impairment Score-Lower Limb (NIS-LL) at Month 6, Month 12  
[units: units on a scale]
Mean ± Standard Deviation
 
Baseline (n= 21)     27.60  ± 24.67  
Change at Month 6 (n= 19)     -0.50  ± 5.73  
Change at Month 12 (n= 18)     2.70  ± 6.21  

No statistical analysis provided for Change From Baseline in the Neuropathy Impairment Score-Lower Limb (NIS-LL) at Month 6, Month 12



11.  Other Pre-specified:   Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 6, Month 12   [ Time Frame: Month 6, Month 12 ]

Measure Type Other Pre-specified
Measure Title Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 6, Month 12
Measure Description Response to treatment was indicated by either improvement (decrease from baseline) or stabilization (change from baseline of 0 to less than [<] 2) in Neuropathy Impairment Score- Lower Limb (NIS-LL) score, based on mean of 2 scores in 1 week period. NIS-LL: assessed muscle weakness, reflexes, sensation. Each item scored separately for left, right limbs. Components of muscle weakness scored on 0(normal) to 4(paralysis) scale, higher score=greater weakness. Components of reflexes, sensation scored 0=normal, 1=decreased, or 2=absent. Total NIS-LL score range 0-88, higher score=greater impairment.
Time Frame Month 6, Month 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Data on NIS-LL was reported in individual participant listings but responder status was not statistically summarized.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  0  
Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 6, Month 12      

No statistical analysis provided for Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 6, Month 12



12.  Other Pre-specified:   Change From Baseline in Total Quality of Life (TQOL) Score at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in Total Quality of Life (TQOL) Score at Month 6, Month 12
Measure Description TQOL= sum of all Norfolk Quality of Life–Diabetic Neuropathy (Norfolk QOL-DN) items,a 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on QOL of participants with DN; Item 1 to 7: related to symptoms and presence of symptom was assessed as 1 and absence was assessed as 0. Item 8-35: related to activities of daily living and scored on a 5-point Likert scale, where 0= no problem and 4= severe problem (except item 32, where -2= much better, 0=about the same, 2=much worse). Total TQOL score=-2 to 138;higher score=worse quality of life.
Time Frame Baseline, Month 6, Month 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were analyzed for the specific category.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  21  
Change From Baseline in Total Quality of Life (TQOL) Score at Month 6, Month 12  
[units: units on a scale]
Mean ± Standard Deviation
 
Baseline (n= 21)     47.80  ± 35.14  
Change at Month 6 (n= 19)     -4.30  ± 13.25  
Change at Month 12 (n= 18)     0.10  ± 18.01  

No statistical analysis provided for Change From Baseline in Total Quality of Life (TQOL) Score at Month 6, Month 12



13.  Other Pre-specified:   Change From Baseline in Norfolk Quality of Life – Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in Norfolk Quality of Life – Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, Month 12
Measure Description Norfolk QOL-DN:35-item participant-rated questionnaire to assess impact of DN on QOL; Item 1-7: scored as 1=symptom present, 0=symptom absent. Item 8-35: scored on 5-point Likert scale:0=no problem, 4=severe problem(except item 32: -2=much better, 0=about same, 2=much worse).Norfolk QOL-DN summarized in 5 domains (score range): physical functioning/large fiber neuropathy(-2 to 58), activities of daily living(ADLs) (0 to 20), symptom(0 to 32), small fiber neuropathy(0 to 16), autonomic neuropathy(0 to 12);higher score=greater impairment, for each. Total score=-2 to 138 (higher score=worse QOL).
Time Frame Baseline, Month 6, Month 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were analyzed for the specific category.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  21  
Change From Baseline in Norfolk Quality of Life – Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, Month 12  
[units: units on a scale]
Mean ± Standard Deviation
 
Physical (P)functioning/large fiber:Baseline(n=21)     25.60  ± 18.50  
P functioning/large fiber: Change at Month 6(n=19)     -2.60  ± 8.66  
P functioning/large fiber:Change at Month 12(n=18)     -1.40  ± 11.71  
ADLs: Baseline (n=21)     7.30  ± 7.01  
ADLs: Change at Month 6 (n=19)     0.10  ± 3.07  
ADLs: Change at Month 12 (n=18)     0.90  ± 2.58  
Symptoms: Baseline (n=21)     9.00  ± 7.50  
Symptoms: Change at Month 6 (n=19)     -0.90  ± 3.05  
Symptoms: Change at Month 12 (n=18)     -0.10  ± 4.28  
Small fiber neuropathy (SFN): Baseline (n=21)     3.90  ± 4.92  
SFN: Change at Month 6 (n=19)     -0.30  ± 2.54  
SFN: Change at Month 12 (n=18)     0.70  ± 3.22  
Autonomic neuropathy (AN): Baseline (n=21))     2.00  ± 1.96  
AN: Change at Month 6 (n=19)     -0.50  ± 1.61  
AN: Change at Month 12 (n=18)     -0.10  ± 1.13  

No statistical analysis provided for Change From Baseline in Norfolk Quality of Life – Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, Month 12



14.  Other Pre-specified:   Change From Baseline in Nerve Conduction Studies (NCS) at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in Nerve Conduction Studies (NCS) at Month 6, Month 12
Measure Description NCS: quantitative measures of peripheral nerve dysfunction consists of 5 attributes: peroneal nerve (PN) motor distal latency, PN compound muscle action potential, PN motor conduction velocity, tibial nerve distal motor latency, sural nerve sensory nerve action potential. Normal deviates (Z-score) summated into composite score (higher score=worsened nerve fiber function). Z-score is the defined position of the result in normal probability distribution with a mean of 0 and standard deviation (std) of 1 and describes how far a score is (in std) from the mean.
Time Frame Baseline, Month 6, Month 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were analyzed for the specific category.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  21  
Change From Baseline in Nerve Conduction Studies (NCS) at Month 6, Month 12  
[units: Z-score]
Mean ± Standard Deviation
 
Baseline (n= 21)     6.10  ± 5.90  
Change at Month 6 (n= 19)     0.60  ± 2.69  
Change at Month 12 (n= 18)     0.20  ± 3.30  

No statistical analysis provided for Change From Baseline in Nerve Conduction Studies (NCS) at Month 6, Month 12



15.  Other Pre-specified:   Change From Baseline in Heart Rate Response to Deep Breathing (HRDB) at Month 6 and Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in Heart Rate Response to Deep Breathing (HRDB) at Month 6 and Month 12
Measure Description HRDB test was used to evaluate the cardio-vagal response. Participant took a series of 8 deep breaths and average heart rate difference was measured and compared to normative data. The main factor affecting HRDB is age, with older patients showing less heart rate variability. R-R (time between two consecutive R waves in the electrocardiogram) response to deep breathing was reported as the normal deviates (Z-score), the defined position of the result in normal probability distribution with a mean of 0 and standard deviation (std) of 1 and describes how far a score is (in std) from the mean.
Time Frame Baseline, Month 6, Month 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who received at least 1 dose of study medication. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants who were analyzed for the specific category.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  12  
Change From Baseline in Heart Rate Response to Deep Breathing (HRDB) at Month 6 and Month 12  
[units: Z-score]
Mean ± Standard Deviation
 
Baseline (n= 12)     -0.70  ± 2.17  
Change at Month 6 (n= 6)     0.00  ± 2.26  
Change at Month 12 (n= 7)     -0.1  ± 1.36  

No statistical analysis provided for Change From Baseline in Heart Rate Response to Deep Breathing (HRDB) at Month 6 and Month 12



16.  Other Pre-specified:   Change From Baseline in Modified Body Mass Index (mBMI) at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in Modified Body Mass Index (mBMI) at Month 6, Month 12
Measure Description BMI was calculated by weight divided by height squared and measured as kilogram per square meter (kg/m^2). mBMI was calculated by multiplying BMI by serum albumin levels [gram/liter (g/L)]. mBMI was measured as kg/m^2*g/L. A progressive decline in mBMI indicated worsening of disease severity.
Time Frame Baseline, Month 6, Month 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who received at least 1 dose of study medication. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants who were analyzed for the specific category.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  20  
Change From Baseline in Modified Body Mass Index (mBMI) at Month 6, Month 12  
[units: kg/m^2*g/L]
Mean ± Standard Deviation
 
Baseline (n= 20)     1052.50  ± 206.66  
Change at Month 6 (n= 17)     -22.40  ± 77.01  
Change at Month 12 (n= 16)     16.60  ± 89.33  

No statistical analysis provided for Change From Baseline in Modified Body Mass Index (mBMI) at Month 6, Month 12



17.  Other Pre-specified:   Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12
Measure Description SF-36 is a 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 and two total scores (physical component summary [PCS] and mental component summary [MCS]. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).
Time Frame Baseline, Month 6, Month 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were analyzed for the specific category.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  21  
Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12  
[units: units on a scale]
Mean ± Standard Deviation
 
PCS: Baseline (n= 21)     36.20  ± 11.90  
PCS: Change at Month 6 (n= 18)     1.60  ± 7.25  
PCS: Change at Month 12 (n= 18)     -0.40  ± 8.47  
MCS: Baseline (n= 21)     47.00  ± 10.96  
MCS: Change at Month 6 (n= 18)     -1.70  ± 10.02  
MCS: Change at Month 12 (n= 18)     3.00  ± 11.11  
Physical functioning: Baseline (n= 21)     33.20  ± 14.68  
Physical functioning: Change at Month 6 (n= 19)     0.90  ± 7.50  
Physical functioning: Change at Month 12 (n= 18)     -0.10  ± 10.84  
Role-physical: Baseline (n= 21)     38.90  ± 13.80  
Role-physical: Change at Month 6 (n= 19)     -1.80  ± 10.42  
Role-physical: Change at Month 12 (n= 18)     -3.80  ± 12.91  
Bodily pain: Baseline (n= 21)     45.50  ± 11.27  
Bodily pain: Change at Month 6 (n= 19)     0.80  ± 9.42  
Bodily pain: Change at Month 12 (n= 18)     1.50  ± 10.11  
General health: Baseline (n= 21)     36.00  ± 9.47  
General health: Change at Month 6 (n= 19)     2.70  ± 9.97  
General health: Change at Month 12 (n= 18)     4.00  ± 10.33  
Vitality: Baseline (n= 21)     43.30  ± 11.83  
Vitality: Change at Month 6 (n= 18)     1.20  ± 7.95  
Vitality: Change at Month 12 (n= 18)     3.10  ± 9.93  
Social functioning: Baseline (n= 21)     41.80  ± 11.16  
Social functioning: Change at Month 6 (n= 19)     2.00  ± 11.09  
Social functioning: Change at Month 12 (n= 18)     3.00  ± 11.72  
Role-emotional: Baseline (n= 21)     41.60  ± 14.82  
Role-emotional: Change at Month 6 (n= 19)     -1.20  ± 7.45  
Role-emotional: Change at Month 12 (n= 18)     0.40  ± 12.43  
Mental health: Baseline (n= 21)     46.90  ± 10.11  
Mental health: Change at Month 6 (n= 18)     -3.80  ± 11.47  
Mental health: Change at Month 12 (n= 18)     2.00  ± 12.44  

No statistical analysis provided for Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12



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

Measure Type Other Pre-specified
Measure Title Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 12
Measure Description Echocardiography was used to measure interventricular septal thickness (IVST), posterior left ventricular wall thickness (PLVWT), right ventricular wall thickness (RVWT), left atrial diameter (LAD): anterior-posterior (ant-post), medio-lateral, superior-inferior (sup-inf) and left ventricular end diastolic diameter (LVED), relative LV wall thickness (RLVWT).
Time Frame Baseline, Month 6, Month 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were analyzed for the specific category.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  21  
Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 12  
[units: millimeter (mm)]
Mean ± Standard Deviation
 
IVST: Baseline (n=19)     15.24  ± 2.77  
IVST: Change at Month 6 (n=15)     0.57  ± 2.10  
IVST: Change at Month 12 (n=14)     1.04  ± 2.04  
PLVWT: Baseline (n=19)     14.60  ± 2.59  
PLVWT: Change at Month 6 (n=15)     0.30  ± 1.98  
PLVWT: Change at Month 12 (n=14)     0.70  ± 1.73  
RVWT: Baseline (n=17)     6.09  ± 2.01  
RVWT: Change at Month 6 (n=8)     1.12  ± 1.72  
RVWT: Change at Month 12 (n=12)     1.08  ± 1.29  
LAD (ant-post): Baseline (n=21)     36.30  ± 6.20  
LAD (ant-post): Change at Month 6 (n=17)     1.50  ± 4.57  
LAD (ant-post): Change at Month 12 (n=16)     1.60  ± 3.52  
LAD (medio-lateral): Baseline (n=16)     37.40  ± 4.80  
LAD (medio-lateral): Change at Month 6 (n=7)     4.30  ± 6.90  
LAD (medio-lateral): Change at Month 12 (n=9)     1.90  ± 4.20  
LAD (sup-inf): Baseline (n=16)     48.30  ± 9.88  
LAD (sup-inf): Change at Month 6 (n= 8)     3.10  ± 5.03  
LAD (sup-inf): Change at Month 6 (n= 9)     4.20  ± 6.46  
LVED: Baseline (n= 19)     39.66  ± 4.84  
LVED: Change at Month 6 (n= 15)     -1.03  ± 3.88  
LVED: Change at Month 12 (n= 14)     0.11  ± 3.42  
RLVWT: Baseline (n=19)     0.75  ± 0.19  
RLVWT: Change at Month 6 (n= 15)     0.05  ± 0.16  
RLVWT: Change at Month 12 (n= 14)     0.03  ± 0.12  

No statistical analysis provided for Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 12



19.  Other Pre-specified:   Change From Baseline in Left Atrial Volume at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in Left Atrial Volume at Month 6, Month 12
Measure Description Left atrial volume was measured by echocardiography.
Time Frame Baseline, Month 6, Month 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who received at least 1 dose of study medication. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants who were analyzed for the specific category.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  15  
Change From Baseline in Left Atrial Volume at Month 6, Month 12  
[units: cubic centimeter (cc)]
Mean ± Standard Deviation
 
Baseline (n= 15)     51.50  ± 23.81  
Change at Month 6 (n= 6)     12.30  ± 17.20  
Change at Month 12 (n= 9)     1.90  ± 18.90  

No statistical analysis provided for Change From Baseline in Left Atrial Volume at Month 6, Month 12



20.  Other Pre-specified:   Change From Baseline in Left Ventricular (LV) End Systolic Volume, Left Ventricle (LV) Stroke Volume at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in Left Ventricular (LV) End Systolic Volume, Left Ventricle (LV) Stroke Volume at Month 6, Month 12
Measure Description Cardiac MRI was done to measure left ventricular (LV) end systolic volume, left ventricle (LV) stroke volume.
Time Frame Baseline, Month 6, Month 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who received at least 1 dose of study medication. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants who were analyzed for the specific category.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  11  
Change From Baseline in Left Ventricular (LV) End Systolic Volume, Left Ventricle (LV) Stroke Volume at Month 6, Month 12  
[units: milliliter (mL)]
Mean ± Standard Deviation
 
LV end systolic volume: Baseline (n= 11)     30.4  ± 13.93  
LV end systolic volume: Change at Month 6 (n= 6)     3.50  ± 7.79  
LV end systolic volume: Change at Month 12 (n= 6)     4.70  ± 3.01  
LV stroke volume: Baseline (n= 11)     43.10  ± 13.26  
LV stroke volume: Change at Month 6 (n= 6)     -2.50  ± 15.23  
LV stroke volume: Change at Month 12 (n= 6)     3.70  ± 10.69  

No statistical analysis provided for Change From Baseline in Left Ventricular (LV) End Systolic Volume, Left Ventricle (LV) Stroke Volume at Month 6, Month 12



21.  Other Pre-specified:   Change From Baseline in Fractional Shortening at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in Fractional Shortening at Month 6, Month 12
Measure Description Fractional shortening (FS) is the fraction of any diastolic dimension that is lost in systole. Percent of FS was calculated as difference between end-diastolic dimension (EDD) and end-systolic dimension (EDS) divided by EDD.
Time Frame Baseline, Month 6, Month 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were analyzed for the specific category.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  21  
Change From Baseline in Fractional Shortening at Month 6, Month 12  
[units: percentage of EDD]
Mean ± Standard Deviation
 
Baseline (n= 18)     31.20  ± 5.68  
Change at Month 6 (n= 14)     -1.10  ± 5.91  
Change at Month 12 (n= 14)     -0.90  ± 6.24  

No statistical analysis provided for Change From Baseline in Fractional Shortening at Month 6, Month 12



22.  Other Pre-specified:   Change From Baseline in Left Ventricular (LV) Ejection Fraction at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in Left Ventricular (LV) Ejection Fraction at Month 6, Month 12
Measure Description Cardiac MRI was done to measure left ventricular ejection fraction (LVEF) which was the fraction of the end-diastolic volume (EDV) that was ejected out of left ventricle with each contraction.
Time Frame Baseline, Month 6, Month 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were analyzed for the specific category.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  21  
Change From Baseline in Left Ventricular (LV) Ejection Fraction at Month 6, Month 12  
[units: percentage of EDV]
Mean ± Standard Deviation
 
Baseline (n= 21)     60.30  ± 9.96  
Change at Month 6 (n= 18)     -3.80  ± 7.73  
Change at Month 12 (n=18)     -2.20  ± 5.37  

No statistical analysis provided for Change From Baseline in Left Ventricular (LV) Ejection Fraction at Month 6, Month 12



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

Measure Type Other Pre-specified
Measure Title Change From Baseline in Left Ventricular Mass (LVM) at Month 6, Month 12
Measure Description LV mass was calculated from the product of the myocardial volume and specific gravity of heart muscle, estimated by echocardiography. Increased LVM was associated with cardiovascular morbidity and mortality.
Time Frame Baseline, Month 6, Month 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who received at least 1 dose of study medication. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants who were analyzed for the specific category.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  19  
Change From Baseline in Left Ventricular Mass (LVM) at Month 6, Month 12  
[units: gram]
Mean ± Standard Deviation
 
Baseline: (n= 19)     230.84  ± 62.54  
Change at Month 6 (n= 15)     1.11  ± 46.53  
Change at Month 12 (n= 14)     20.91  ± 35.07  

No statistical analysis provided for Change From Baseline in Left Ventricular Mass (LVM) at Month 6, Month 12



24.  Other Pre-specified:   Change From Baseline in Isovolumetric Relaxation Time (IVRT), Mitral Deceleration Time at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in Isovolumetric Relaxation Time (IVRT), Mitral Deceleration Time at Month 6, Month 12
Measure Description Doppler echocardiography was a procedure which used ultrasound technology to examine the heart. IVRT is the time between the closure of the aortic valve and the opening of the mitral valve. Mitral deceleration time (MDT) was the time taken from the maximum E point wave to baseline. E wave arises due to early diastolic filling.
Time Frame Baseline, Month 6, Month 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who received at least 1 dose of study medication. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants who were analyzed for the specific category.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  18  
Change From Baseline in Isovolumetric Relaxation Time (IVRT), Mitral Deceleration Time at Month 6, Month 12  
[units: msec]
Mean ± Standard Deviation
 
IVRT: Baseline (n= 10)     84.10  ± 17.51  
IVRT: Change at Month 6 (n= 3)     2.70  ± 20.03  
IVRT: Change at Month 12 (n= 8)     -4.00  ± 25.63  
MDT: Baseline (n= 18)     164.00  ± 35.59  
MDT: Change at Month 6 (n= 14)     1.90  ± 28.17  
MDT: Change at Month 12 (n= 15)     11.90  ± 29.45  

No statistical analysis provided for Change From Baseline in Isovolumetric Relaxation Time (IVRT), Mitral Deceleration Time at Month 6, Month 12



25.  Other Pre-specified:   Change From Baseline in Aortic Annulus Diameter at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in Aortic Annulus Diameter at Month 6, Month 12
Measure Description The diameter at the base of the aortic root, the basal ring, is also called the aortic annulus diameter.
Time Frame Baseline, Month 6, Month 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were analyzed for the specific category.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  21  
Change From Baseline in Aortic Annulus Diameter at Month 6, Month 12  
[units: centimeter (cm)]
Mean ± Standard Deviation
 
Baseline (n= 21)     2.045  ± 0.184  
Change at Month 6 (n= 17)     -0.009  ± 0.160  
Change at Month 12 (n= 16)     -0.041  ± 0.108  

No statistical analysis provided for Change From Baseline in Aortic Annulus Diameter at Month 6, Month 12



26.  Other Pre-specified:   Change From Baseline in Tricuspid Peak Velocity at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in Tricuspid Peak Velocity at Month 6, Month 12
Measure Description Tricuspid peak velocity was measured by echocardiography.
Time Frame Baseline, Month 6, Month 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who received at least 1 dose of study medication. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants who were analyzed for the specific category.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  11  
Change From Baseline in Tricuspid Peak Velocity at Month 6, Month 12  
[units: meter per second (m/sec)]
Mean ± Standard Deviation
 
Baseline (n= 11)     26.80  ± 8.62  
Change at Month 6 (n= 9)     0.90  ± 4.86  
Change at Month 12 (n= 8)     2.10  ± 9.25  

No statistical analysis provided for Change From Baseline in Tricuspid Peak Velocity at Month 6, Month 12



27.  Other Pre-specified:   Change From Baseline in Tricuspid Pulmonary Artery Systolic Pressure (PASP) at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in Tricuspid Pulmonary Artery Systolic Pressure (PASP) at Month 6, Month 12
Measure Description Systolic right ventricular pressure can be estimated on echocardiography by adding right atrial pressure (RAP) to the trans-tricuspid gradient derived from the tricuspid regurgitation velocity.
Time Frame Baseline, Month 6, Month 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who received at least 1 dose of study medication. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants who were analyzed for the specific category.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  11  
Change From Baseline in Tricuspid Pulmonary Artery Systolic Pressure (PASP) at Month 6, Month 12  
[units: millimeter of mercury (mmHg)]
Mean ± Standard Deviation
 
Baseline (n= 11)     35.50  ± 11.55  
Change at Month 6 (n= 6)     3.80  ± 7.81  
Change at Month 12 (n= 7)     2.10  ± 13.08  

No statistical analysis provided for Change From Baseline in Tricuspid Pulmonary Artery Systolic Pressure (PASP) at Month 6, Month 12



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

Measure Type Other Pre-specified
Measure Title Change From Baseline in Doppler Data at Month 6, Month 12
Measure Description Doppler echocardiography was a procedure which used ultrasound technology to examine the heart. Doppler principle was used to measure the mitral peak early (E) diastolic transmitral flow, mitral peak atrial (A) contraction velocity and annular velocities at the lateral and septal areas of the mitral annulus. s': systolic velocity during ejection, e': early diastolic mitral annular velocity, a': late diastolic mitral annular velocity.
Time Frame Baseline, Month 6, Month 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who received at least 1 dose of study medication. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants who were analyzed for the specific category.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  18  
Change From Baseline in Doppler Data at Month 6, Month 12  
[units: centimeter per second (cm/sec)]
Mean ± Standard Deviation
 
Mitral Peak A: Baseline (n= 18)     59.00  ± 23.77  
Mitral Peak A: Change at Month 6 (n= 13)     -0.50  ± 16.01  
Mitral Peak A: Change at Month 12 (n= 15)     -3.70  ± 15.43  
Mitral Peak E: Baseline (n= 19)     74.10  ± 15.58  
Mitral Peak E: Change at Month 6 (n= 15)     4.70  ± 10.28  
Mitral Peak E: Change at Month 12 (n= 16)     5.10  ± 13.75  
Septal s': Baseline (n= 16)     4.72  ± 1.64  
Septal s': Change at Month 6 (n= 12)     0.43  ± 0.51  
Septal s': Change at Month 12 (n= 8)     -0.33  ± 0.90  
Septal e': Baseline (n= 16)     4.54  ± 1.88  
Septal e': Change at Month 6 (n= 12)     1.25  ± 2.29  
Septal e': Change at Month 12 (n= 8)     0.04  ± 0.61  
Septal a': Baseline (n= 15)     4.66  ± 2.67  
Septal a': Change at Month 6 (n= 11)     0.53  ± 1.39  
Septal a': Change at Month 12 (n= 8)     -0.10  ± 1.74  
Lateral s': Baseline (n= 16)     6.71  ± 2.97  
Lateral s': Change at Month 6 (n= 10)     0.55  ± 1.41  
Lateral s': Change at Month 12 (n= 7)     0.19  ± 1.20  
Lateral e': Baseline (n= 16)     6.91  ± 2.90  
Lateral e': Change at Month 6 (n= 11)     0.65  ± 1.27  
Lateral e': Change at Month 12 (n= 7)     0.16  ± 1.42  
Lateral a': Baseline (n= 15)     5.93  ± 3.38  
Lateral a': Change at Month 6 (n= 10)     0.31  ± 2.69  
Lateral a': Change at Month 12 (n= 6)     -0.45  ± 2.94  

No statistical analysis provided for Change From Baseline in Doppler Data at Month 6, Month 12



29.  Other Pre-specified:   Change From Baseline in e:e’ Lateral Ratio , Ratio of Peak Mitral Early Diastolic and Atrial Contraction Velocity (E/A Ratio) at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in e:e’ Lateral Ratio , Ratio of Peak Mitral Early Diastolic and Atrial Contraction Velocity (E/A Ratio) at Month 6, Month 12
Measure Description Doppler echocardiography was a procedure which used ultrasound technology to examine the heart. Ratio of early (E) diastolic transmitral flow velocity and atrial (A) contraction velocity (E/A) and ratio of the early (E) diastolic transmitral flow velocity to the mitral annular velocity (e’) (E/e’) were estimated.
Time Frame Baseline, Month 6, Month 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who received at least 1 dose of study medication. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants who were analyzed for the specific category.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  18  
Change From Baseline in e:e’ Lateral Ratio , Ratio of Peak Mitral Early Diastolic and Atrial Contraction Velocity (E/A Ratio) at Month 6, Month 12  
[units: ratio]
Mean ± Standard Deviation
 
e:e’ Lateral: Baseline (n= 16)     13.148  ± 7.781  
e:e’ Lateral: Change at Month 6 (n= 10)     -0.145  ± 3.227  
e:e’ Lateral: Change at Month 12 (n= 7)     -0.243  ± 5.245  
E/A: Baseline (n= 18)     1.463  ± 0.667  
E/A: Change at Month 6 (n= 13)     0.175  ± 0.565  
E/A: Change at Month 12 (n= 15)     0.185  ± 0.658  

No statistical analysis provided for Change From Baseline in e:e’ Lateral Ratio , Ratio of Peak Mitral Early Diastolic and Atrial Contraction Velocity (E/A Ratio) at Month 6, Month 12



30.  Other Pre-specified:   Change From Baseline in Left Ventricular (LV) Mass/Voltage Ratio at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in Left Ventricular (LV) Mass/Voltage Ratio at Month 6, Month 12
Measure Description LV mass was calculated from the product of the myocardial volume and specific gravity of heart muscle, estimated by echocardiography. QRS score (the sum of QRS voltages in the peripheral leads) was used as an index of “electrical” LV mass.
Time Frame Baseline, Month 6, Month 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who received at least 1 dose of study medication. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants who were analyzed for the specific category.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  19  
Change From Baseline in Left Ventricular (LV) Mass/Voltage Ratio at Month 6, Month 12  
[units: gram/millivolt]
Mean ± Standard Deviation
 
Baseline (n= 19)     5.495  ± 2.149  
Change at Month 6 (n= 14)     0.028  ± 1.479  
Change at Month 12 (n= 14)     0.878  ± 1.437  

No statistical analysis provided for Change From Baseline in Left Ventricular (LV) Mass/Voltage Ratio at Month 6, Month 12



31.  Other Pre-specified:   Change From Baseline in Left Atrial (LA) Volume Index at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in Left Atrial (LA) Volume Index at Month 6, Month 12
Measure Description LA volume index (LAVI), was the value of LA volume divided by body surface area, to measure LA size.
Time Frame Baseline, Month 6, Month 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who received at least 1 dose of study medication. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants who were analyzed for the specific category.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  15  
Change From Baseline in Left Atrial (LA) Volume Index at Month 6, Month 12  
[units: milliliter/square meter (mL/m^2)]
Mean ± Standard Deviation
 
Baseline (n= 15)     27.33  ± 10.21  
Change at Month 6 (n= 5)     7.23  ± 8.78  
Change at Month 12 (n= 9)     1.06  ± 9.66  

No statistical analysis provided for Change From Baseline in Left Atrial (LA) Volume Index at Month 6, Month 12



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

Measure Type Other Pre-specified
Measure Title Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) at Week 2, Week 6, Month 3, Month 6, Month 12
Measure Description NT-proBNP was a cardiac marker which had the prognostic value for participants with heart failure or left ventricular dysfunction. Higher level of the marker was indicative of heart damage.
Time Frame Baseline, Week 2, Week 6, Month 3, Month 6, Month 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants who were analyzed for the specific category. Data prior Month 6 were not anticipated to be informative hence were not analyzed.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  19  
Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) at Week 2, Week 6, Month 3, Month 6, Month 12  
[units: picogram/mL (pg/mL)]
Mean ± Standard Deviation
 
Baseline (n= 19)     1248.89  ± 1529.37  
Change at Month 6 (n= 18)     228.39  ± 834.91  
Change at Month 12 (n= 16)     306.61  ± 1447.67  

No statistical analysis provided for Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) at Week 2, Week 6, Month 3, Month 6, Month 12



33.  Other Pre-specified:   Change From Baseline in Karnofsky Performance Status Scale at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in Karnofsky Performance Status Scale at Month 6, Month 12
Measure Description Karnofsky performance score is used to quantify participant’s general well-being and activities of daily life and participants are classified based on their functional impairment. Karnofsky performance score is 11 level score which ranges between 0 (death) to 100 (no evidence of disease). Higher score means higher ability to perform daily tasks.
Time Frame Baseline, Month 6, Month 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were analyzed for the specific category.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  21  
Change From Baseline in Karnofsky Performance Status Scale at Month 6, Month 12  
[units: units on a scale]
Mean ± Standard Deviation
 
Baseline (n= 21)     74.80  ± 14.01  
Change at Month 6 (n= 19)     -1.10  ± 5.67  
Change at Month 12 (n= 18)     -3.30  ± 5.94  

No statistical analysis provided for Change From Baseline in Karnofsky Performance Status Scale at Month 6, Month 12



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

Measure Type Other Pre-specified
Measure Title Change From Baseline in Troponin I Levels at Week 2, Week 6 , Month 3, Month 6, Month 12
Measure Description Troponin I is a cardiac injury biomarker. Higher concentrations of this marker in blood are associated with heart injury.
Time Frame Baseline, Week 2, Week 6 , Month 3, Month 6, Month 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants who were analyzed for the specific category. Data prior Month 6 were not anticipated to be informative hence were not analyzed.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  20  
Change From Baseline in Troponin I Levels at Week 2, Week 6 , Month 3, Month 6, Month 12  
[units: nanogram/mL]
Mean ± Standard Deviation
 
Baseline (n= 20)     0.0234  ± 0.0409  
Change at Month 6 (n= 18)     0.0015  ± 0.0501  
Change at Month 12 (n= 18)     0.0025  ± 0.0487  

No statistical analysis provided for Change From Baseline in Troponin I Levels at Week 2, Week 6 , Month 3, Month 6, Month 12




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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