Cardiomyopathy
Conditions
Keywords
Transthyretin, TTR, ATTR, TTR amyloidosis, cardiomyopathy, V122I, wild-type TTR, SSA, Patients with V122I or wild-type TTR amyloid cardiomyopathy
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.
Interventions
DRUGFx-1006A
Fx-1006A 20mg soft gelatin capsules once daily (at the same time each day) for 12 months
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
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). 3. 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. 4. 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. 5. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Number of Participants Discontinuing From The Study Due to Clinically Significant Clinical or Laboratory Adverse Events (AEs) | Baseline up to Month 12 | — |
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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). |
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tafamidis Participants with variant transthyretin (TTR) genotype (valine replaced at position 122 by isoleucine or V122I) and wild-type TTR genotype received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1 and participants who achieved TTR stabilization at Week 6 continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2. | 35 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Part 2 (After Week 6 up to Month 12) | Adverse Event | 1 |
| Part 2 (After Week 6 up to Month 12) | Death | 1 |
| Part 2 (After Week 6 up to Month 12) | Physician Decision | 1 |
Baseline characteristics
| Characteristic | Tafamidis |
|---|---|
| Age Continuous | 76.4 Years STANDARD_DEVIATION 4.7 |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 34 / 35 |
| serious Total, serious adverse events | 15 / 35 |
Outcome results
Primary
Percentage of Participants With Stabilized Transthyretin (TTR Tetramer) at 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.
Time frame: Week 6
Population: Intent-to-Treat (ITT) population included all participants who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tafamidis | Percentage of Participants With Stabilized Transthyretin (TTR Tetramer) at Week 6 | 97.1 Percentage of participants |
Secondary
Percentage of Participants With Stabilized Transthyretin (TTR Tetramer) at Month 6 and 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.
Time frame: Month 6, Month 12
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tafamidis | Percentage of Participants With Stabilized Transthyretin (TTR Tetramer) at Month 6 and 12 | Month 6 | 88.2 Percentage of participants |
| Tafamidis | Percentage of Participants With Stabilized Transthyretin (TTR Tetramer) at Month 6 and 12 | Month 12 | 87.5 Percentage of participants |
Other Pre-specified
24-Hour Average Heart Rate and Maximium/Minimum Heart Rate
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | 24-Hour Average Heart Rate and Maximium/Minimum Heart Rate | 24-hour average heart rate: Baseline (n=34) | 74.7 beats per minute (bpm) | Standard Deviation 7.8 |
| Tafamidis | 24-Hour Average Heart Rate and Maximium/Minimum Heart Rate | 24-hour average heart rate: Month 6 (n=33) | 73.0 beats per minute (bpm) | Standard Deviation 7.2 |
| Tafamidis | 24-Hour Average Heart Rate and Maximium/Minimum Heart Rate | 24-hour average heart rate: Month 12 (n=30) | 76.6 beats per minute (bpm) | Standard Deviation 9 |
| Tafamidis | 24-Hour Average Heart Rate and Maximium/Minimum Heart Rate | Maximum Heart Rate: Baseline (n=34) | 111.7 beats per minute (bpm) | Standard Deviation 22.3 |
| Tafamidis | 24-Hour Average Heart Rate and Maximium/Minimum Heart Rate | Maximum Heart Rate: Month 6 (n=33) | 112.3 beats per minute (bpm) | Standard Deviation 17 |
| Tafamidis | 24-Hour Average Heart Rate and Maximium/Minimum Heart Rate | Maximum Heart Rate: Month 12 (n=30) | 121.9 beats per minute (bpm) | Standard Deviation 20.4 |
| Tafamidis | 24-Hour Average Heart Rate and Maximium/Minimum Heart Rate | Minimum Heart Rate: Baseline (n=34) | 56.6 beats per minute (bpm) | Standard Deviation 8 |
| Tafamidis | 24-Hour Average Heart Rate and Maximium/Minimum Heart Rate | Minimum Heart Rate: Month 6: (n=33) | 53.1 beats per minute (bpm) | Standard Deviation 11.5 |
| Tafamidis | 24-Hour Average Heart Rate and Maximium/Minimum Heart Rate | Minimum Heart Rate Month 12: (n=30) | 55.3 beats per minute (bpm) | Standard Deviation 10.1 |
Other Pre-specified
Cardiothoracic (CT) Ratio
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
Population: ITT population included all participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Cardiothoracic (CT) Ratio | Baseline | 55.130 Ratio | Standard Deviation 6.075 |
| Tafamidis | Cardiothoracic (CT) Ratio | Month 6 | 56.620 Ratio | Standard Deviation 5.904 |
| Tafamidis | Cardiothoracic (CT) Ratio | Month 12 | 57.830 Ratio | Standard Deviation 5.366 |
Other Pre-specified
Change From Baseline in 4 Chamber Interatrial Septal Thickness at Month 6 and 12
Cardiac MRI was done to measure interatrial septal thickness in the 4 chamber view.
Time frame: Baseline, Month 6, Month 12
Population: Data for this measure was not collected due to a change in the planned analysis.
Other Pre-specified
Change From Baseline in 4 Chamber Left Atrial Dimension and 4 Chamber Right Atrial Dimension at Month 6 and 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.
Time frame: Baseline, Month 6, Month 12
Population: Data for this measure was not collected due to a change in the planned analysis.
Other Pre-specified
Change From Baseline in 6-Minute Walk Test (6MWT) at Month 3, 6 and 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.
Time frame: Baseline, Month 3, Month 6, Month 12
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in 6-Minute Walk Test (6MWT) at Month 3, 6 and 12 | Distance walked: Baseline (n=34) | 354.5 meters | Standard Deviation 126 |
| Tafamidis | Change From Baseline in 6-Minute Walk Test (6MWT) at Month 3, 6 and 12 | Distance walked: Change at Month 3 (n=31) | -4.6 meters | Standard Deviation 63.1 |
| Tafamidis | Change From Baseline in 6-Minute Walk Test (6MWT) at Month 3, 6 and 12 | Distance walked: Change at Month 6 (n=33) | 3.9 meters | Standard Deviation 58.2 |
| Tafamidis | Change From Baseline in 6-Minute Walk Test (6MWT) at Month 3, 6 and 12 | Distance walked: Change at Month 12 (n=28) | -11.2 meters | Standard Deviation 76.4 |
Other Pre-specified
Change From Baseline in Doppler Data: E/A and E/e' Ratio at Month 6 and 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.
Time frame: Baseline, Month 6, Month 12
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in Doppler Data: E/A and E/e' Ratio at Month 6 and 12 | E/A ratio: Baseline (n=19) | 2.516 Ratio | Standard Deviation 1.084 |
| Tafamidis | Change From Baseline in Doppler Data: E/A and E/e' Ratio at Month 6 and 12 | E/A ratio: Change at Month 6 (n=12) | 0.425 Ratio | Standard Deviation 1.117 |
| Tafamidis | Change From Baseline in Doppler Data: E/A and E/e' Ratio at Month 6 and 12 | E/A ratio: Change at Month 12 (n=9) | 0.544 Ratio | Standard Deviation 0.575 |
| Tafamidis | Change From Baseline in Doppler Data: E/A and E/e' Ratio at Month 6 and 12 | E/e' ratio: Baseline (n=26) | 16.240 Ratio | Standard Deviation 9.089 |
| Tafamidis | Change From Baseline in Doppler Data: E/A and E/e' Ratio at Month 6 and 12 | E/e' ratio: Change at Month 6 (n=15) | 2.217 Ratio | Standard Deviation 3.166 |
| Tafamidis | Change From Baseline in Doppler Data: E/A and E/e' Ratio at Month 6 and 12 | E/e' ratio: Change at Month 12 (n=14) | -0.717 Ratio | Standard Deviation 5.681 |
Other Pre-specified
Change From Baseline in Doppler Data: Mitral Deceleration Time at Month 6 and 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.
Time frame: Baseline, Month 6, Month 12
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in Doppler Data: Mitral Deceleration Time at Month 6 and 12 | Baseline (n=33) | 152.9 msec | Standard Deviation 35.3 |
| Tafamidis | Change From Baseline in Doppler Data: Mitral Deceleration Time at Month 6 and 12 | Change at Month 6 (n=27) | 1.0 msec | Standard Deviation 37.5 |
| Tafamidis | Change From Baseline in Doppler Data: Mitral Deceleration Time at Month 6 and 12 | Change at Month 12 (n=27) | -7.1 msec | Standard Deviation 32.6 |
Other Pre-specified
Change From Baseline in Echocardiographic (ECHO) Parameters at Month 6 and 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).
Time frame: Baseline, Month 6, Month 12
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in Echocardiographic (ECHO) Parameters at Month 6 and 12 | IVST: Baseline (n=34) | 20.71 millimeter (mm) | Standard Deviation 3.58 |
| Tafamidis | Change From Baseline in Echocardiographic (ECHO) Parameters at Month 6 and 12 | IVST: Change at Month 6 (n=33) | -0.64 millimeter (mm) | Standard Deviation 2.41 |
| Tafamidis | Change From Baseline in Echocardiographic (ECHO) Parameters at Month 6 and 12 | IVST: Change at Month 12 (n=30) | 0.87 millimeter (mm) | Standard Deviation 2.52 |
| Tafamidis | Change From Baseline in Echocardiographic (ECHO) Parameters at Month 6 and 12 | PLVWT: Baseline (n=34) | 20.20 millimeter (mm) | Standard Deviation 3.37 |
| Tafamidis | Change From Baseline in Echocardiographic (ECHO) Parameters at Month 6 and 12 | PLVWT: Change at Month 6 (n=33) | -0.50 millimeter (mm) | Standard Deviation 3.83 |
| Tafamidis | Change From Baseline in Echocardiographic (ECHO) Parameters at Month 6 and 12 | PLVWT: Change at Month 12 (n=30) | -0.00 millimeter (mm) | Standard Deviation 2.11 |
| Tafamidis | Change From Baseline in Echocardiographic (ECHO) Parameters at Month 6 and 12 | RVWT: Baseline (n=27) | 9.21 millimeter (mm) | Standard Deviation 2.34 |
| Tafamidis | Change From Baseline in Echocardiographic (ECHO) Parameters at Month 6 and 12 | RVWT: Change at Month 6 (n=21) | -0.47 millimeter (mm) | Standard Deviation 2.47 |
| Tafamidis | Change From Baseline in Echocardiographic (ECHO) Parameters at Month 6 and 12 | RVWT: Change at Month 12 (n=20) | 0.26 millimeter (mm) | Standard Deviation 2.25 |
| Tafamidis | Change From Baseline in Echocardiographic (ECHO) Parameters at Month 6 and 12 | LAD (ant-post): Baseline (n=34) | 45.00 millimeter (mm) | Standard Deviation 6.14 |
| Tafamidis | Change From Baseline in Echocardiographic (ECHO) Parameters at Month 6 and 12 | LAD (ant-post): Change at Month 6 (n=33) | -0.40 millimeter (mm) | Standard Deviation 4.33 |
| Tafamidis | Change From Baseline in Echocardiographic (ECHO) Parameters at Month 6 and 12 | LAD (ant-post): Change at Month 12 (n=30) | -0.30 millimeter (mm) | Standard Deviation 4.19 |
| Tafamidis | Change From Baseline in Echocardiographic (ECHO) Parameters at Month 6 and 12 | LAD (medio-lateral): Baseline (n=34) | 44.10 millimeter (mm) | Standard Deviation 5.56 |
| Tafamidis | Change From Baseline in Echocardiographic (ECHO) Parameters at Month 6 and 12 | LAD (medio-lateral): Change at Month 6 (n=32) | 0.70 millimeter (mm) | Standard Deviation 5.17 |
| Tafamidis | Change From Baseline in Echocardiographic (ECHO) Parameters at Month 6 and 12 | LAD (medio-lateral): Change at Month 12 (n=30) | -0.90 millimeter (mm) | Standard Deviation 6.41 |
| Tafamidis | Change From Baseline in Echocardiographic (ECHO) Parameters at Month 6 and 12 | LAD (sup-inf): Baseline (n=34) | 61.50 millimeter (mm) | Standard Deviation 8.43 |
| Tafamidis | Change From Baseline in Echocardiographic (ECHO) Parameters at Month 6 and 12 | LAD (sup-inf): Change at Month 6 (n=32) | 3.00 millimeter (mm) | Standard Deviation 5.9 |
| Tafamidis | Change From Baseline in Echocardiographic (ECHO) Parameters at Month 6 and 12 | LAD (sup-inf): Change at Month 12 (n=30) | 0.80 millimeter (mm) | Standard Deviation 6.29 |
| Tafamidis | Change From Baseline in Echocardiographic (ECHO) Parameters at Month 6 and 12 | LVEDD: Baseline (n=34) | 37.94 millimeter (mm) | Standard Deviation 5.19 |
| Tafamidis | Change From Baseline in Echocardiographic (ECHO) Parameters at Month 6 and 12 | LVEDD: Change at Month 6 (n=33) | 0.45 millimeter (mm) | Standard Deviation 3.49 |
| Tafamidis | Change From Baseline in Echocardiographic (ECHO) Parameters at Month 6 and 12 | LVEDD: Change at Month 12 (n=30) | 0.10 millimeter (mm) | Standard Deviation 3.41 |
Other Pre-specified
Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 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.
Time frame: Baseline, Month 3, Month 6, Month 12
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Clinical summary: Change at Month 6 (n=34) | -2.0 Units on a scale | Standard Deviation 11.9 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Physical limitations: Baseline (n=35) | 72.9 Units on a scale | Standard Deviation 20.8 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Physical limitations: Change at Month 3 (n=33) | -2.7 Units on a scale | Standard Deviation 15 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Physical limitations: Change at Month 6 (n=34) | -0.4 Units on a scale | Standard Deviation 13.6 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Physical limitations: Change at Month 12 (n=31) | -8.1 Units on a scale | Standard Deviation 18.8 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Symptom stability: Baseline (n=35) | 55.7 Units on a scale | Standard Deviation 13.7 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Symptom stability: Change at Month 3 (n=34) | 3.7 Units on a scale | Standard Deviation 27.6 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Symptom stability: Change at Month 6 (n=34) | -5.9 Units on a scale | Standard Deviation 25.4 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Symptom stability: Change at Month 12 (n=31) | 0.0 Units on a scale | Standard Deviation 22.4 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Symptom frequency: Baseline (n=35) | 73.8 Units on a scale | Standard Deviation 22.2 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Symptom frequency: Change at Month 3 (n=34) | -1.8 Units on a scale | Standard Deviation 18.5 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Symptom frequency: Change at Month 6 (n=34) | -2.5 Units on a scale | Standard Deviation 15.9 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Symptom frequency: Change at Month 12 (n=31) | -6.0 Units on a scale | Standard Deviation 18.2 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Symptom burden: Baseline (n=35) | 76.9 Units on a scale | Standard Deviation 18.1 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Symptom burden: Change at Month 3 (n=34) | -4.0 Units on a scale | Standard Deviation 18.3 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Symptom burden: Change at Month 6 (n=34) | -4.7 Units on a scale | Standard Deviation 15.2 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Symptom burden: Change at Month 12 (n=31) | -8.6 Units on a scale | Standard Deviation 19.2 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Total symptom: Baseline (n=35) | 75.4 Units on a scale | Standard Deviation 19.2 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Total symptom: Change at Month 3 (n=34) | -2.9 Units on a scale | Standard Deviation 16.9 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Total symptom: Change at Month 6 (n=34) | -3.6 Units on a scale | Standard Deviation 14.3 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Total symptom: Change at Month 12 (n=31) | -7.3 Units on a scale | Standard Deviation 18.2 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Self-efficacy: Baseline (n=35) | 85.7 Units on a scale | Standard Deviation 19 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Self-efficacy: Change at Month 3 (n=33) | 1.9 Units on a scale | Standard Deviation 14.7 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Self-efficacy: Change at Month 6 (n=34) | 1.1 Units on a scale | Standard Deviation 13.5 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Self-efficacy: Change at Month 12 (n=31) | 1.6 Units on a scale | Standard Deviation 16.7 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Quality of life: Baseline (n=35) | 66.9 Units on a scale | Standard Deviation 19.2 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Quality of life: Change at Month 3 (n=34) | 1.0 Units on a scale | Standard Deviation 18.2 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Quality of life: Change at Month 6 (n=34) | -0.2 Units on a scale | Standard Deviation 14.4 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Quality of life: Change at Month 12 (n=31) | -4.0 Units on a scale | Standard Deviation 20.4 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Social limitation: Baseline (n=33) | 69.3 Units on a scale | Standard Deviation 25.4 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Social limitation: Change at Month 3 (n=30) | -0.6 Units on a scale | Standard Deviation 19.6 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Social limitation: Change at Month 6 (n=31) | -2.4 Units on a scale | Standard Deviation 22.6 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Social limitation: Change at Month 12 (n=27) | -9.2 Units on a scale | Standard Deviation 25.2 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Overall summary: Baseline (n=35) | 71.4 Units on a scale | Standard Deviation 18.8 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Overall summary: Change at Month 3 (n=34) | -0.8 Units on a scale | Standard Deviation 14.9 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Overall summary: Change at Month 6 (n=34) | -1.5 Units on a scale | Standard Deviation 12.4 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Overall summary: Change at Month 12 (n=31) | -6.9 Units on a scale | Standard Deviation 18 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Clinical summary: Baseline (n=35) | 74.1 Units on a scale | Standard Deviation 18.9 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Clinical summary: Change at Month 3 (n=34) | -2.0 Units on a scale | Standard Deviation 15.9 |
| Tafamidis | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 | Clinical summary: Change at Month 12 (n=31) | -7.7 Units on a scale | Standard Deviation 17.9 |
Other Pre-specified
Change From Baseline in Left Ventricle End Diastolic Volume, Left Ventricle End Systolic Volume, Left Ventricle Stroke Volume, Right Ventricle End Diastolic Volume, Right Ventricle End Systolic Volume, Right Ventricle Stroke Volume at Month 6 and 12.
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | 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. | LVEDV: Baseline (n=18) | 166.673 mL | Standard Deviation 40.417 |
| Tafamidis | 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. | LVEDV: Change at Month 6 (n=18) | -0.922 mL | Standard Deviation 21.164 |
| Tafamidis | 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. | LVEDV: Change at Month 12 (n=15) | -1.606 mL | Standard Deviation 20.323 |
| Tafamidis | 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. | LVESV: Baseline (n=18) | 84.651 mL | Standard Deviation 29.271 |
| Tafamidis | 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. | LVESV: Change at Month 6 (n=18) | 3.727 mL | Standard Deviation 20.963 |
| Tafamidis | 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. | LVESV: Change at Month 12 (n=15) | 6.479 mL | Standard Deviation 16.81 |
| Tafamidis | 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. | LVSV: Baseline (n=18) | 82.022 mL | Standard Deviation 19.866 |
| Tafamidis | 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. | LVSV: Change at Month 6 (n=18) | -4.651 mL | Standard Deviation 21.391 |
| Tafamidis | 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. | LVSV: Change at Month 12 (n=15) | -8.083 mL | Standard Deviation 15.614 |
| Tafamidis | 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. | RVEDV: Baseline (n=18) | 175.124 mL | Standard Deviation 67.977 |
| Tafamidis | 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. | RVEDV: Change at Month 6 (n=18) | -4.836 mL | Standard Deviation 37.879 |
| Tafamidis | 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. | RVEDV: Change at Month 12 (n=15) | 19.540 mL | Standard Deviation 39.413 |
| Tafamidis | 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. | RVESV: Baseline (n=18) | 104.662 mL | Standard Deviation 48.775 |
| Tafamidis | 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. | RVESV: Change at Month 6 (n=18) | -1.727 mL | Standard Deviation 21.438 |
| Tafamidis | 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. | RVESV: Change at Month 12 (n=15) | 26.250 mL | Standard Deviation 30.858 |
| Tafamidis | 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. | RVSV: Baseline (n=18) | 70.478 mL | Standard Deviation 26.364 |
| Tafamidis | 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. | RVSV: Change at Month 6 (n=18) | -3.125 mL | Standard Deviation 26.125 |
| Tafamidis | 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. | RVSV: Change at Month 12 (n=15) | -6.730 mL | Standard Deviation 33.975 |
Other Pre-specified
Change From Baseline in Left Ventricular Anteroseptal, Left Ventricular Inferolateral Wall Thickness and Right Ventricular End Diastolic Free Wall Thickness at Month 6 and 12
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | 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 | LVAS wall thickness: Baseline (n=18) | 15.808 mm | Standard Deviation 3.603 |
| Tafamidis | 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 | LVAS wall thickness: Change at Month 6 (n=18) | 0.810 mm | Standard Deviation 3.447 |
| Tafamidis | 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 | LVAS wall thickness: Change at Month 12 (n=15) | 0.813 mm | Standard Deviation 3.099 |
| Tafamidis | 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 | LVIL wall thickness: Baseline (n=18) | 15.405 mm | Standard Deviation 4.616 |
| Tafamidis | 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 | LVIL wall thickness: Change at Month 6 (n=18) | -1.472 mm | Standard Deviation 4.333 |
| Tafamidis | 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 | LVIL wall thickness: Change at Month 12 (n=15) | 1.182 mm | Standard Deviation 4.782 |
| Tafamidis | 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 | RVEDF wall thickness: Baseline (n=17) | 10.871 mm | Standard Deviation 14.001 |
| Tafamidis | 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 | RVEDF wall thickness: Change at Month 6 (n=17) | -4.501 mm | Standard Deviation 14.734 |
| Tafamidis | 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 | RVEDF wall thickness: Change at Month 12 (n=15) | -1.577 mm | Standard Deviation 4.722 |
Other Pre-specified
Change From Baseline in Left Ventricular Cardiac Output and Right Ventricular Cardiac Output at Month 6 and 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.
Time frame: Baseline, Month 6, Month 12
Population: MRI data was collected and reported for cardiac output through the measure of stroke volume as given in outcome measure 17.
Other Pre-specified
Change From Baseline in Left Ventricular Ejection Fraction and Right Ventricular Ejection Fraction at Month 6 and 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.
Time frame: Baseline, Month 6, Month 12
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in Left Ventricular Ejection Fraction and Right Ventricular Ejection Fraction at Month 6 and 12 | LVEF: Baseline (n=18) | 50.176 Percentage of EDV | Standard Deviation 9.183 |
| Tafamidis | Change From Baseline in Left Ventricular Ejection Fraction and Right Ventricular Ejection Fraction at Month 6 and 12 | LVEF: Change at Month 6 (n=18) | -2.713 Percentage of EDV | Standard Deviation 13.362 |
| Tafamidis | Change From Baseline in Left Ventricular Ejection Fraction and Right Ventricular Ejection Fraction at Month 6 and 12 | LVEF: Change at Month 12 (n=14) | -3.511 Percentage of EDV | Standard Deviation 9.063 |
| Tafamidis | Change From Baseline in Left Ventricular Ejection Fraction and Right Ventricular Ejection Fraction at Month 6 and 12 | RVEF: Baseline (n=18) | 42.323 Percentage of EDV | Standard Deviation 11.949 |
| Tafamidis | Change From Baseline in Left Ventricular Ejection Fraction and Right Ventricular Ejection Fraction at Month 6 and 12 | RVEF: Change at Month 6 (n=18) | -1.756 Percentage of EDV | Standard Deviation 10.381 |
| Tafamidis | Change From Baseline in Left Ventricular Ejection Fraction and Right Ventricular Ejection Fraction at Month 6 and 12 | RVEF: Change at Month 12 (n=15) | -7.381 Percentage of EDV | Standard Deviation 12.04 |
Other Pre-specified
Change From Baseline in Left Ventricular Ejection Fraction at Month 6 and 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.
Time frame: Baseline, Month 6, Month 12
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in Left Ventricular Ejection Fraction at Month 6 and 12 | Baseline (n=34) | 46.8 Percentage of EDV | Standard Deviation 14.1 |
| Tafamidis | Change From Baseline in Left Ventricular Ejection Fraction at Month 6 and 12 | Change at Month 6 (n=33) | -0.4 Percentage of EDV | Standard Deviation 10.3 |
| Tafamidis | Change From Baseline in Left Ventricular Ejection Fraction at Month 6 and 12 | Change at Month 12 (n=30) | -3.7 Percentage of EDV | Standard Deviation 10.4 |
Other Pre-specified
Change From Baseline in Left Ventricular Mass (LVM) at Month 6 and 12
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in Left Ventricular Mass (LVM) at Month 6 and 12 | Change at Month 12 (n=30) | 13.73 Gram | Standard Deviation 77.12 |
| Tafamidis | Change From Baseline in Left Ventricular Mass (LVM) at Month 6 and 12 | Baseline (n=34) | 372.50 Gram | Standard Deviation 123.96 |
| Tafamidis | Change From Baseline in Left Ventricular Mass (LVM) at Month 6 and 12 | Change at Month 6 (n=33) | -19.76 Gram | Standard Deviation 54.38 |
Other Pre-specified
Change From Baseline in Left Ventricular Mass, Mass of Left Ventricular Myocardium With Amyloidosis, Mass of Left Ventricular Myocardium With Fibrosis/Scar and Right Ventricular End Diastolic Mass at Month 6 and 12
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | 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 | RVEDM: Change at Month 6 (n=18) | -4.377 Gram | Standard Deviation 20.648 |
| Tafamidis | 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 | LVM: Baseline (n=18) | 221.599 Gram | Standard Deviation 63.68 |
| Tafamidis | 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 | LVM: Change at Month 6 (n=18) | 0.557 Gram | Standard Deviation 24.901 |
| Tafamidis | 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 | LVM: Change at Month 12 (n=15) | 0.119 Gram | Standard Deviation 20.027 |
| Tafamidis | 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 | LV Amyloidosis: Baseline (n=15) | 63.963 Gram | Standard Deviation 25.614 |
| Tafamidis | 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 | LV Amyloidosis : Change at Month 6 (n=14) | -13.854 Gram | Standard Deviation 23.921 |
| Tafamidis | 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 | LV Amyloidosis: Change at Month 12 (n=9) | -4.346 Gram | Standard Deviation 38.364 |
| Tafamidis | 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 | LV Fibrosis/Scar: Baseline (n=15) | 87.746 Gram | Standard Deviation 60.297 |
| Tafamidis | 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 | LV Fibrosis/Scar: Change at Month 6 (n=14) | -30.496 Gram | Standard Deviation 52.176 |
| Tafamidis | 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 | LV Fibrosis/Scar: Change at Month 12 (n=9) | -20.238 Gram | Standard Deviation 64.487 |
| Tafamidis | 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 | RVEDM: Baseline (n=18) | 65.999 Gram | Standard Deviation 20.296 |
| Tafamidis | 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 | RVEDM: Change at Month 12 (n=15) | 0.215 Gram | Standard Deviation 18.038 |
Other Pre-specified
Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide(NT-proBNP) Levels at Week 2, 6, Month 3, 6 and 12
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide(NT-proBNP) Levels at Week 2, 6, Month 3, 6 and 12 | Baseline (n=33) | 4934.2 picogram/mL (pg/mL) | Standard Deviation 4324.9 |
| Tafamidis | Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide(NT-proBNP) Levels at Week 2, 6, Month 3, 6 and 12 | Change at Week 2 (n=35) | -1.6 picogram/mL (pg/mL) | Standard Deviation 1349.1 |
| Tafamidis | Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide(NT-proBNP) Levels at Week 2, 6, Month 3, 6 and 12 | Change at Week 6 (n=35) | 295.0 picogram/mL (pg/mL) | Standard Deviation 1632 |
| Tafamidis | Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide(NT-proBNP) Levels at Week 2, 6, Month 3, 6 and 12 | Change at Month 3 (n=34) | 102.8 picogram/mL (pg/mL) | Standard Deviation 1998 |
| Tafamidis | Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide(NT-proBNP) Levels at Week 2, 6, Month 3, 6 and 12 | Change at Month 6 (n=33) | 111.6 picogram/mL (pg/mL) | Standard Deviation 2032.4 |
| Tafamidis | Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide(NT-proBNP) Levels at Week 2, 6, Month 3, 6 and 12 | Change at Month 12 (n=31) | 958.2 picogram/mL (pg/mL) | Standard Deviation 3178 |
Other Pre-specified
Change From Baseline in Percentage of Left Ventricular Myocardial Mass With Amyloidosis and Left Ventricular Myocardial Mass With Fibrosis/Scar at Month 6 and 12
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | 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 | LV Amyloidosis: Baseline (n=15) | 29.069 Percentage of LVM | Standard Deviation 11.111 |
| Tafamidis | 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 | LV Amyloidosis: Change at Month 6 (n=14) | -8.200 Percentage of LVM | Standard Deviation 14.115 |
| Tafamidis | 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 | LV Amyloidosis: Change at Month 12 (n=9) | -7.017 Percentage of LVM | Standard Deviation 13.66 |
| Tafamidis | 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 | LV Fibrosis/Scar: Baseline (n=15) | 36.513 Percentage of LVM | Standard Deviation 17.789 |
| Tafamidis | 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 | LV Fibrosis/Scar: Change at Month 6 (n=14) | -10.126 Percentage of LVM | Standard Deviation 26.397 |
| Tafamidis | 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 | LV Fibrosis/Scar: Change at Month 12 (n=9) | -8.268 Percentage of LVM | Standard Deviation 24.884 |
Other Pre-specified
Change From Baseline in Pericardial Effusion at Month 6 and 12
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
Population: Data for this pre-specified outcome measure was collected and reported in individual participant listings but not statistically summarized for analysis.
Other Pre-specified
Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 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.
Time frame: Baseline, Month 3, Month 6, Month 12
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 | PCS: Baseline (n=33) | 41.0 Units on a scale | Standard Deviation 9.69 |
| Tafamidis | Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 | PCS: Change at Month 6 (n=32) | -1.4 Units on a scale | Standard Deviation 5.87 |
| Tafamidis | Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 | PCS: Change at Month 12 (n=29) | -2.4 Units on a scale | Standard Deviation 7.58 |
| Tafamidis | Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 | MCS: Baseline (n=33) | 52.7 Units on a scale | Standard Deviation 9.51 |
| Tafamidis | Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 | MCS: Change at Month 6 (n=32) | 0.3 Units on a scale | Standard Deviation 8.4 |
| Tafamidis | Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 | MCS: Change at Month 12 (n=29) | -2.0 Units on a scale | Standard Deviation 9.56 |
| Tafamidis | Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 | Physical functioning: Baseline (n=34) | 37.7 Units on a scale | Standard Deviation 11.28 |
| Tafamidis | Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 | Physical functioning: Change at Month 6 (n=33) | -0.7 Units on a scale | Standard Deviation 6.89 |
| Tafamidis | Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 | Physical functioning: Change at Month 12 (n=29) | -2.0 Units on a scale | Standard Deviation 7.34 |
| Tafamidis | Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 | Role-physical: Baseline (n=35) | 42.3 Units on a scale | Standard Deviation 10.84 |
| Tafamidis | Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 | Role-physical: Change at Month 6 (n=34) | -1.4 Units on a scale | Standard Deviation 7.12 |
| Tafamidis | Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 | Role-physical: Change at Month 12 (n=30) | -3.5 Units on a scale | Standard Deviation 9.29 |
| Tafamidis | Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 | Bodily pain: Baseline (n=35) | 53.2 Units on a scale | Standard Deviation 9.57 |
| Tafamidis | Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 | Bodily pain: Change at Month 6 (n=34) | -4.0 Units on a scale | Standard Deviation 8.74 |
| Tafamidis | Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 | Bodily pain: Change at Month 12 (n=30) | -3.2 Units on a scale | Standard Deviation 11.81 |
| Tafamidis | Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 | General health: Baseline (n=35) | 41.5 Units on a scale | Standard Deviation 9.33 |
| Tafamidis | Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 | General health: Change at Month 6 (n=34) | 0.7 Units on a scale | Standard Deviation 9.23 |
| Tafamidis | Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 | General health: Change at Month 12 (n=30) | -1.6 Units on a scale | Standard Deviation 8.44 |
| Tafamidis | Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 | Vitality: Baseline (n=34) | 50.6 Units on a scale | Standard Deviation 8.11 |
| Tafamidis | Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 | Vitality: Change at Month 6 (n=33) | -0.1 Units on a scale | Standard Deviation 6.83 |
| Tafamidis | Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 | Vitality: Change at Month 12 (n=30) | -2.2 Units on a scale | Standard Deviation 7.83 |
| Tafamidis | Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 | Social functioning: Baseline (n=35) | 48.4 Units on a scale | Standard Deviation 9.84 |
| Tafamidis | Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 | Social functioning: Change at Month 6 (n=34) | -2.9 Units on a scale | Standard Deviation 9.23 |
| Tafamidis | Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 | Social functioning: Change at Month 12 (n=30) | -3.6 Units on a scale | Standard Deviation 11.4 |
| Tafamidis | Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 | Role-emotional: Baseline (n=35) | 45.2 Units on a scale | Standard Deviation 11.71 |
| Tafamidis | Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 | Role-emotional: Change at Month 6 (n=34) | 0.6 Units on a scale | Standard Deviation 12.26 |
| Tafamidis | Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 | Role-emotional: Change at Month 12 (n=30) | -3.0 Units on a scale | Standard Deviation 12.53 |
| Tafamidis | Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 | Mental health: Baseline (n=34) | 53.3 Units on a scale | Standard Deviation 8.5 |
| Tafamidis | Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 | Mental health: Change at Month 6 (n=33) | 0.3 Units on a scale | Standard Deviation 5.01 |
| Tafamidis | Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 | Mental health: Change at Month 12 (n=30) | -1.1 Units on a scale | Standard Deviation 7.5 |
Other Pre-specified
Change From Baseline in Tissue Doppler- Septal and Lateral Velocity at Month 6 and 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.
Time frame: Baseline, Month 6, Month 12
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in Tissue Doppler- Septal and Lateral Velocity at Month 6 and 12 | Septal s': Baseline (n=23) | 3.70 centimeter/second (cm/sec) | Standard Deviation 1.31 |
| Tafamidis | Change From Baseline in Tissue Doppler- Septal and Lateral Velocity at Month 6 and 12 | Septal s': Change at Month 6 (n=16) | -0.57 centimeter/second (cm/sec) | Standard Deviation 0.73 |
| Tafamidis | Change From Baseline in Tissue Doppler- Septal and Lateral Velocity at Month 6 and 12 | Septal s': Change at Month 12 (n=14) | -0.69 centimeter/second (cm/sec) | Standard Deviation 0.77 |
| Tafamidis | Change From Baseline in Tissue Doppler- Septal and Lateral Velocity at Month 6 and 12 | Septal e': Baseline (n=23) | 3.67 centimeter/second (cm/sec) | Standard Deviation 1.6 |
| Tafamidis | Change From Baseline in Tissue Doppler- Septal and Lateral Velocity at Month 6 and 12 | Septal e': Change at Month 6 (n=17) | -0.09 centimeter/second (cm/sec) | Standard Deviation 1.12 |
| Tafamidis | Change From Baseline in Tissue Doppler- Septal and Lateral Velocity at Month 6 and 12 | Septal e': Change at Month 12 (n=14) | -0.33 centimeter/second (cm/sec) | Standard Deviation 1.32 |
| Tafamidis | Change From Baseline in Tissue Doppler- Septal and Lateral Velocity at Month 6 and 12 | Septal a': Baseline (n=16) | 2.51 centimeter/second (cm/sec) | Standard Deviation 1.6 |
| Tafamidis | Change From Baseline in Tissue Doppler- Septal and Lateral Velocity at Month 6 and 12 | Septal a': Change at Month 6 (n=6) | -0.40 centimeter/second (cm/sec) | Standard Deviation 0.43 |
| Tafamidis | Change From Baseline in Tissue Doppler- Septal and Lateral Velocity at Month 6 and 12 | Septal a': Change at Month 12 (n=6) | -0.42 centimeter/second (cm/sec) | Standard Deviation 0.72 |
| Tafamidis | Change From Baseline in Tissue Doppler- Septal and Lateral Velocity at Month 6 and 12 | Lateral s': Baseline (n=24) | 4.53 centimeter/second (cm/sec) | Standard Deviation 1.59 |
| Tafamidis | Change From Baseline in Tissue Doppler- Septal and Lateral Velocity at Month 6 and 12 | Lateral s': Change at Month 6 (n=14) | -0.50 centimeter/second (cm/sec) | Standard Deviation 1.16 |
| Tafamidis | Change From Baseline in Tissue Doppler- Septal and Lateral Velocity at Month 6 and 12 | Lateral s': Change at Month 12 (n=13) | -0.73 centimeter/second (cm/sec) | Standard Deviation 1.22 |
| Tafamidis | Change From Baseline in Tissue Doppler- Septal and Lateral Velocity at Month 6 and 12 | Lateral e': Baseline (n=26) | 5.09 centimeter/second (cm/sec) | Standard Deviation 2 |
| Tafamidis | Change From Baseline in Tissue Doppler- Septal and Lateral Velocity at Month 6 and 12 | Lateral e': Change at Month 6 (n=16) | -0.76 centimeter/second (cm/sec) | Standard Deviation 0.8 |
| Tafamidis | Change From Baseline in Tissue Doppler- Septal and Lateral Velocity at Month 6 and 12 | Lateral e': Change at Month 12 (n=14) | 0.05 centimeter/second (cm/sec) | Standard Deviation 0.88 |
| Tafamidis | Change From Baseline in Tissue Doppler- Septal and Lateral Velocity at Month 6 and 12 | Lateral a': Baseline (n=17) | 3.16 centimeter/second (cm/sec) | Standard Deviation 1.94 |
| Tafamidis | Change From Baseline in Tissue Doppler- Septal and Lateral Velocity at Month 6 and 12 | Lateral a': Change at Month 6 (n=7) | -0.41 centimeter/second (cm/sec) | Standard Deviation 0.6 |
| Tafamidis | Change From Baseline in Tissue Doppler- Septal and Lateral Velocity at Month 6 and 12 | Lateral a': Change at Month 12 (n=9) | 0.06 centimeter/second (cm/sec) | Standard Deviation 1.03 |
Other Pre-specified
Change From Baseline in Troponin I and Troponin T at Week 2, 6, Month 3, 6 and 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.
Time frame: Baseline, Week 2, Week 6, Month 3, Month 6, Month 12
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in Troponin I and Troponin T at Week 2, 6, Month 3, 6 and 12 | Troponin I: Baseline (n=33) | 0.135 nanogram/milliliter (ng/mL) | Standard Deviation 0.08 |
| Tafamidis | Change From Baseline in Troponin I and Troponin T at Week 2, 6, Month 3, 6 and 12 | Troponin I: Change at Week 2 (n=35) | 0.003 nanogram/milliliter (ng/mL) | Standard Deviation 0.06 |
| Tafamidis | Change From Baseline in Troponin I and Troponin T at Week 2, 6, Month 3, 6 and 12 | Troponin I: Change at Week 6 (n=35) | -0.000 nanogram/milliliter (ng/mL) | Standard Deviation 0.055 |
| Tafamidis | Change From Baseline in Troponin I and Troponin T at Week 2, 6, Month 3, 6 and 12 | Troponin I: Change at Month 3 (n=34) | 0.008 nanogram/milliliter (ng/mL) | Standard Deviation 0.057 |
| Tafamidis | Change From Baseline in Troponin I and Troponin T at Week 2, 6, Month 3, 6 and 12 | Troponin I: Change at Month 6 (n=34) | -0.016 nanogram/milliliter (ng/mL) | Standard Deviation 0.051 |
| Tafamidis | Change From Baseline in Troponin I and Troponin T at Week 2, 6, Month 3, 6 and 12 | Troponin I: Change at Month 12 (n=32) | 0.016 nanogram/milliliter (ng/mL) | Standard Deviation 0.064 |
| Tafamidis | Change From Baseline in Troponin I and Troponin T at Week 2, 6, Month 3, 6 and 12 | Troponin T: Baseline (n=33) | 0.044 nanogram/milliliter (ng/mL) | Standard Deviation 0.037 |
| Tafamidis | Change From Baseline in Troponin I and Troponin T at Week 2, 6, Month 3, 6 and 12 | Troponin T: Change at Week 2 (n=35) | 0.001 nanogram/milliliter (ng/mL) | Standard Deviation 0.025 |
| Tafamidis | Change From Baseline in Troponin I and Troponin T at Week 2, 6, Month 3, 6 and 12 | Troponin T: Change at Week 6 (n=35) | 0.006 nanogram/milliliter (ng/mL) | Standard Deviation 0.02 |
| Tafamidis | Change From Baseline in Troponin I and Troponin T at Week 2, 6, Month 3, 6 and 12 | Troponin T: Change at Month 3 (n=34) | 0.008 nanogram/milliliter (ng/mL) | Standard Deviation 0.021 |
| Tafamidis | Change From Baseline in Troponin I and Troponin T at Week 2, 6, Month 3, 6 and 12 | Troponin T: Change at Month 6 (n=33) | 0.002 nanogram/milliliter (ng/mL) | Standard Deviation 0.02 |
| Tafamidis | Change From Baseline in Troponin I and Troponin T at Week 2, 6, Month 3, 6 and 12 | Troponin T: Change at Month 12 (n=32) | 0.012 nanogram/milliliter (ng/mL) | Standard Deviation 0.023 |
Other Pre-specified
Heart Rate Variability (HRV)- Standard Deviation (SD) Parameters
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Heart Rate Variability (HRV)- Standard Deviation (SD) Parameters | HRV- Magid SD: Month 12 (n=30) | 78.6 msec | Standard Deviation 50.1 |
| Tafamidis | Heart Rate Variability (HRV)- Standard Deviation (SD) Parameters | HRV- RMS SD: Baseline (n=30) | 75.9 msec | Standard Deviation 71 |
| Tafamidis | Heart Rate Variability (HRV)- Standard Deviation (SD) Parameters | HRV- RMS SD: Month 6 (n=26) | 88.1 msec | Standard Deviation 71 |
| Tafamidis | Heart Rate Variability (HRV)- Standard Deviation (SD) Parameters | HRV- RMS SD: Month 12 (n=21) | 91.7 msec | Standard Deviation 72.1 |
| Tafamidis | Heart Rate Variability (HRV)- Standard Deviation (SD) Parameters | HRV- Magid SD: Baseline (n=31) | 58.3 msec | Standard Deviation 42.1 |
| Tafamidis | Heart Rate Variability (HRV)- Standard Deviation (SD) Parameters | HRV- Magid SD: Month 6 (n=33) | 82.6 msec | Standard Deviation 55.5 |
| Tafamidis | Heart Rate Variability (HRV)- Standard Deviation (SD) Parameters | HRV- Kleiger SD: Baseline (n=31) | 100.3 msec | Standard Deviation 49.1 |
| Tafamidis | Heart Rate Variability (HRV)- Standard Deviation (SD) Parameters | HRV- Kleiger SD: Month 6 (n=33) | 123.9 msec | Standard Deviation 52.8 |
| Tafamidis | Heart Rate Variability (HRV)- Standard Deviation (SD) Parameters | HRV- Kleiger SD: Month 12 (n=30) | 120.3 msec | Standard Deviation 48.7 |
Other Pre-specified
Heart Rate Variability- Percentage of Successive R-R Intervals With Greater Than 50 Msec Difference Between Normal Beats (pNN50)
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Heart Rate Variability- Percentage of Successive R-R Intervals With Greater Than 50 Msec Difference Between Normal Beats (pNN50) | Baseline (n=30) | 19.7 Percentage of intervals | Standard Deviation 25.5 |
| Tafamidis | Heart Rate Variability- Percentage of Successive R-R Intervals With Greater Than 50 Msec Difference Between Normal Beats (pNN50) | Month 6 (n=26) | 29.3 Percentage of intervals | Standard Deviation 32.7 |
| Tafamidis | Heart Rate Variability- Percentage of Successive R-R Intervals With Greater Than 50 Msec Difference Between Normal Beats (pNN50) | Month 12 (n=21) | 23.6 Percentage of intervals | Standard Deviation 27.3 |
Other Pre-specified
Number of Participants Discontinuing From The Study Due to Clinically Significant Clinical or Laboratory Adverse Events (AEs)
Time frame: Baseline up to Month 12
Population: ITT population included all participants who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tafamidis | Number of Participants Discontinuing From The Study Due to Clinically Significant Clinical or Laboratory Adverse Events (AEs) | 1 Participants |
Other Pre-specified
Number of Participants With Atrial Fibrillation/Flutter, Atrial Tachycardia, Non-Sustained Ventricular Tachycardia (NSVT) Beats), Sustained Ventricular Tachycardia (SVT), Sinus Pause at Month 6 and 12
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tafamidis | 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 | Atrial fibrillation/flutter: Baseline (n=33) | 6 Participants |
| Tafamidis | 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 | Atrial fibrillation/flutter: Month 6 (n=27) | 9 Participants |
| Tafamidis | 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 | Atrial fibrillation/flutter: Month 12 (n=22) | 9 Participants |
| Tafamidis | 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 | Atrial tachycardia: Baseline (n=34) | 14 Participants |
| Tafamidis | 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 | Atrial tachycardia: Month 6 (n=20) | 0 Participants |
| Tafamidis | 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 | Atrial tachycardia: Month 12 (n=17) | 0 Participants |
| Tafamidis | 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 | NSVT (<30 beats): Baseline (n=34) | 20 Participants |
| Tafamidis | 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 | NSVT (<30 beats): Month 6 (n=13) | 3 Participants |
| Tafamidis | 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 | NSVT (<30 beats): Month 12 (n=12) | 5 Participants |
| Tafamidis | 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 | SVT (>= 30 beats): Baseline (n=34) | 0 Participants |
| Tafamidis | 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 | SVT (>= 30 beats): Month 6 (n=33) | 0 Participants |
| Tafamidis | 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 | SVT (>= 30 beats): Month 12 (n=30) | 1 Participants |
| Tafamidis | 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 | Sinus pause: Baseline (n=34) | 2 Participants |
| Tafamidis | 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 | Sinus pause: Month 6 (n=31) | 4 Participants |
| Tafamidis | 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 | Sinus pause: Month 12 (n=28) | 5 Participants |
Other Pre-specified
Number of Participants With Change From Baseline in New York Heart Association (NYHA) Classification at Week 6, Month 3, 6 and 12
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tafamidis | Number of Participants With Change From Baseline in New York Heart Association (NYHA) Classification at Week 6, Month 3, 6 and 12 | Baseline: Class I (n=35) | 5 Participants |
| Tafamidis | Number of Participants With Change From Baseline in New York Heart Association (NYHA) Classification at Week 6, Month 3, 6 and 12 | Baseline: Class II (n=35) | 28 Participants |
| Tafamidis | Number of Participants With Change From Baseline in New York Heart Association (NYHA) Classification at Week 6, Month 3, 6 and 12 | Baseline: Class III (n=35) | 2 Participants |
| Tafamidis | Number of Participants With Change From Baseline in New York Heart Association (NYHA) Classification at Week 6, Month 3, 6 and 12 | Baseline: Class IV (n=35) | 0 Participants |
| Tafamidis | Number of Participants With Change From Baseline in New York Heart Association (NYHA) Classification at Week 6, Month 3, 6 and 12 | Change at Month 3: improved (n=34) | 5 Participants |
| Tafamidis | Number of Participants With Change From Baseline in New York Heart Association (NYHA) Classification at Week 6, Month 3, 6 and 12 | Change at Month 3: no change (n=34) | 23 Participants |
| Tafamidis | Number of Participants With Change From Baseline in New York Heart Association (NYHA) Classification at Week 6, Month 3, 6 and 12 | Change at Month 3: worsened (n=34) | 6 Participants |
| Tafamidis | Number of Participants With Change From Baseline in New York Heart Association (NYHA) Classification at Week 6, Month 3, 6 and 12 | Change at Month 6: improved (n=34) | 1 Participants |
| Tafamidis | Number of Participants With Change From Baseline in New York Heart Association (NYHA) Classification at Week 6, Month 3, 6 and 12 | Change at Month 6: no change (n=34) | 27 Participants |
| Tafamidis | Number of Participants With Change From Baseline in New York Heart Association (NYHA) Classification at Week 6, Month 3, 6 and 12 | Change at Month 6: worsened (n=34) | 6 Participants |
| Tafamidis | Number of Participants With Change From Baseline in New York Heart Association (NYHA) Classification at Week 6, Month 3, 6 and 12 | Change at Month 12: improved (n=32) | 4 Participants |
| Tafamidis | Number of Participants With Change From Baseline in New York Heart Association (NYHA) Classification at Week 6, Month 3, 6 and 12 | Change at Month 12: no change (n=32) | 20 Participants |
| Tafamidis | Number of Participants With Change From Baseline in New York Heart Association (NYHA) Classification at Week 6, Month 3, 6 and 12 | Change at Month 12: worsened (n=32) | 8 Participants |
Other Pre-specified
Number of Participants With Change From Baseline in Valvular Abnormalities at Month 6 and 12
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
Population: Data for this pre-specified outcome measure was collected and reported in individual participant listings but not statistically summarized for analysis.
Other Pre-specified
Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 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.
Time frame: Baseline, Month 3, Month 6, Month 12
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tafamidis | Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12 | Excellent: Baseline (n=33) | 5 Participants |
| Tafamidis | Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12 | Very good: Baseline (n=33) | 14 Participants |
| Tafamidis | Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12 | Good: Baseline (n=33) | 12 Participants |
| Tafamidis | Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12 | Fair: Baseline (n=33) | 2 Participants |
| Tafamidis | Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12 | Poor: Baseline (n=33) | 0 Participants |
| Tafamidis | Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12 | Markedly improved: Month 3 (n=34) | 2 Participants |
| Tafamidis | Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12 | Moderately improved: Month 3 (n=34) | 7 Participants |
| Tafamidis | Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12 | Mildly improved: Month 3 (n=34) | 6 Participants |
| Tafamidis | Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12 | Unchanged: Month 3 (n=34) | 15 Participants |
| Tafamidis | Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12 | Mildly worsened: Month 3 (n=34) | 2 Participants |
| Tafamidis | Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12 | Moderately worsened: Month 3 (n=34) | 2 Participants |
| Tafamidis | Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12 | Markedly worsened: Month 3 (n=34) | 0 Participants |
| Tafamidis | Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12 | Markedly improved: Month 6 (n=34) | 3 Participants |
| Tafamidis | Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12 | Moderately improved: Month 6 (n=34) | 4 Participants |
| Tafamidis | Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12 | Mildly improved: Month 6 (n=34) | 3 Participants |
| Tafamidis | Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12 | Unchanged: Month 6 (n=34) | 16 Participants |
| Tafamidis | Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12 | Mildly worsened: Month 6 (n=34) | 8 Participants |
| Tafamidis | Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12 | Moderately worsened: Month 6 (n=34) | 0 Participants |
| Tafamidis | Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12 | Markedly worsened: Month 6 (n=34) | 0 Participants |
| Tafamidis | Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12 | Markedly improved: Month 12 (n=32) | 0 Participants |
| Tafamidis | Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12 | Moderately improved: Month 12 (n=32) | 5 Participants |
| Tafamidis | Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12 | Mildly improved: Month 12 (n=32) | 3 Participants |
| Tafamidis | Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12 | Unchanged: Month 12 (n=32) | 16 Participants |
| Tafamidis | Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12 | Mildly worsened: Month 12 (n=32) | 4 Participants |
| Tafamidis | Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12 | Moderately worsened: Month 12 (n=32) | 3 Participants |
| Tafamidis | Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12 | Markedly worsened: Month 12 (n=32) | 1 Participants |
Other Pre-specified
Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings | Any ECHO abnormalities (n=34) | 31 Participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings | Pericardial effusion (n=28) | 6 Participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings | Valvular abnormalities- thickening (n=4) | 4 Participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings | Valvular abnormalities- regurgitation (n=7) | 6 Participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings | Abnormal regional wall motion (n=19) | 10 Participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings | Inferior vena cava respiratory variation (n=14) | 7 Participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings | Left ventricular posterior wall thickness (n=0) | NA Participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings | Left ventricular septal thickness (n=0) | NA Participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings | Right ventricular thickness (n=7) | 6 Participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings | E/A ratio (n=8) | 4 Participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings | E/e' prime lateral (n=13) | 5 Participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings | E/e' prime septal (n=6) | 5 Participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings | Ejection fraction (n=18) | 11 Participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings | E deceleration time (n=16) | 8 Participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings | Isovolumic relaxation time (n=16) | 4 Participants |
Other Pre-specified
Number of Participants With Complete Heart Block
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
Population: No summary was prepared for this data as there were no reports of complete heart block.
Other Pre-specified
Number of Participants With Greater Than or Equal to (>=) Grade 3 Treatment-Emergent AEs
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
Population: ITT population included all participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tafamidis | Number of Participants With Greater Than or Equal to (>=) Grade 3 Treatment-Emergent AEs | Grade 3 (severe) | 18 Participants |
| Tafamidis | Number of Participants With Greater Than or Equal to (>=) Grade 3 Treatment-Emergent AEs | Grade 4 (life-threatening) | 1 Participants |
| Tafamidis | Number of Participants With Greater Than or Equal to (>=) Grade 3 Treatment-Emergent AEs | Grade 5 (death) | 2 Participants |
Other Pre-specified
Number of Participants With Increased Interstitial Markings and Pleural Effusions
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
Population: Intent to Treat (ITT) population included all participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tafamidis | Number of Participants With Increased Interstitial Markings and Pleural Effusions | Pleural effusion- right: Month 6 | 8 Participants |
| Tafamidis | Number of Participants With Increased Interstitial Markings and Pleural Effusions | Increased interstitial markings: Baseline | 11 Participants |
| Tafamidis | Number of Participants With Increased Interstitial Markings and Pleural Effusions | Increased interstitial markings: Month 6 | 4 Participants |
| Tafamidis | Number of Participants With Increased Interstitial Markings and Pleural Effusions | Increased interstitial markings: Month 12 | 4 Participants |
| Tafamidis | Number of Participants With Increased Interstitial Markings and Pleural Effusions | Pleural effusion- right: Baseline | 9 Participants |
| Tafamidis | Number of Participants With Increased Interstitial Markings and Pleural Effusions | Pleural effusion- right: Month 12 | 6 Participants |
| Tafamidis | Number of Participants With Increased Interstitial Markings and Pleural Effusions | Pleural effusion- left: Baseline | 6 Participants |
| Tafamidis | Number of Participants With Increased Interstitial Markings and Pleural Effusions | Pleural effusion- left: Month 6 | 5 Participants |
| Tafamidis | Number of Participants With Increased Interstitial Markings and Pleural Effusions | Pleural effusion- left: Month 12 | 4 Participants |
| Tafamidis | Number of Participants With Increased Interstitial Markings and Pleural Effusions | Pleural effusion- bilateral: Baseline | 6 Participants |
| Tafamidis | Number of Participants With Increased Interstitial Markings and Pleural Effusions | Pleural effusion- bilateral: Month 6 | 4 Participants |
| Tafamidis | Number of Participants With Increased Interstitial Markings and Pleural Effusions | Pleural effusion- bilateral: Month 12 | 3 Participants |
Other Pre-specified
Number of Participants With Treatment-Emergent Adverse Events (AEs)
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
Population: ITT population included all participants who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tafamidis | Number of Participants With Treatment-Emergent Adverse Events (AEs) | 35 Participants |