Transthyretin-associated Amyloidosis With Polyneuropathy
Conditions
Keywords
Transthyretin, TTR, amyloidosis, TTR amyloidosis, polyneuropathy
Brief summary
This is an open-label, multicenter, international study designed to determine TTR stabilization as well as Fx-1006A safety and tolerability, and its effects on clinical outcomes in patients with non-V30M TTR amyloidosis. Strong pre-clinical and clinical evidence support a daily dose of 20 mg of Fx-1006A to be the optimum dose to achieve stabilization of tetrameric TTR in ATTR-PN patients. Since disease presentation is similar between V30M and non-V30M TTR mutations associated with ATTR-PN and Fx-1006A has been shown to stabilize wild-type and V30M TTR in vitro and ex vivo, the present study is being conducted to determine the effects of Fx-1006A on TTR stabilization in ATTR-PN patients with TTR mutations other than V30M. Safety and exploratory efficacy of Fx-1006A administered once daily for 12 months will also be evaluated in this patient population. This is an open-label, multicenter, international study designed to determine TTR stabilization as well as Fx-1006A safety and tolerability, and its effects on clinical outcomes in patients with non-V30M TTR amyloidosis. The study will be conducted in two parts. Part 1 will include a six-week dosing period during which all enrolled patients will receive 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 receiving 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, the patient will be discontinued from the study. During Part 2, clinical outcomes will be measured at Months 6 and 12, based on NIS, Norfolk QOL-DN, mBMI, NCS, HRDB, SF-36, Karnofsky score, and echocardiography; NT-pro-BNP and troponin I levels will be measured at Baseline, Weeks 2 and 6, and Months 3, 6, and 12. Pharmacokinetic measurements will be made using samples collected at Baseline, Week 6, and Months 6 and 12. Safety and tolerability will be assessed throughout the study based on vital signs, physical examinations, ECG, echocardiography, 24-hour Holter monitoring, clinical laboratory tests (hematology, serum chemistry, and urinalysis), and monitoring adverse events and concomitant medication use. Day 1 will be defined as administration of the first dose of study drug. Clinic Visits will be conducted during Screening (Days -30 to -1) and at Baseline (Day 0), and Week 2, and Week 6, and Months 3, 6, and 12 (± 2 weeks of the scheduled date for post-Baseline visits). Monthly telephone contacts (+ 1 week of the scheduled date) will be made during months in which no investigative site visits are scheduled (Months 4, 5, 7, 8, 9, 10, and 11) for assessment of adverse events and concomitant medications. A final telephone contact to assess adverse events and concomitant medication usage will be made 30 days after the last dose of study drug. Patients who discontinue from the study at any time following enrollment 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
During Part 1, patients will receive Fx-1006A 20mg soft gelatin capsules once daily (at the same time each day) for two weeks. During Part 2, patients will receive Fx-1006A 20mg soft gelatin capsules once daily to complete a total of 12 months of dosing
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patient has amyloid documented by biopsy (in accordance with institutional site standard of care). * Patient has documentation of one of the following targeted TTR mutations: Ser77Tyr, Thr60Ala, Tyr114Cys, Leu58His, Glu89Gln, Ser77Phe, Thr49Ala, Ile107Val, Val30Ala, Gly47Ala, Gly47Glu, Leu55Arg, Lys70Asn, Ile84Thr, Ile107Met. Patients with mutations other than those listed may be enrolled only after approval by the Sponsor. * Patient has peripheral and/or autonomic neuropathy and/or cardiomyopathy with a Karnofsky Performance Status ≥ 50. * Patient is aged ≥18 to 75 years, inclusive. * If female, patient is post-menopausal, surgically sterilized, or willing to use two acceptable methods of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide) throughout the study and for 3 months from the end of the study. (A condom alone is not considered an acceptable method of birth control.) If male with a female partner of childbearing potential, willing to use two acceptable methods of birth control for the duration of the study. For both females and males, acceptable birth control must be used for at least 3 months after the last dose of study medication. * 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
* Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs), defined as greater than 3-4 times/month (ibuprofen and nimesulide will be permitted). * Patient has primary or secondary amyloidosis. * Patient has TTR-associated amyloidosis with V30M mutation. * If female, patient is pregnant or breast feeding. * Patient has received prior liver transplantation. * Patient is expected to undergo liver transplantation within 12 months after enrollment. * Patient with positive results for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV), and/or human immunodeficiency virus (HIV). * Patient has renal insufficiency (creatinine clearance \< 30 ml/min). * 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. * Patient has a New York Heart Association (NYHA) Functional Classification ≥ III. * Patient has other causes of sensorimotor neuropathy (B12 deficiency, Diabetes Mellitus, HIV treated with retroviral medications, thyroid disorders, alcohol abuse, and chronic inflammatory diseases). * Patient has prior non-amyloid cardiac disease such as: myocardial infarction due to obstructive coronary artery disease, active non-amyloid cardiomyopathy (e.g., symptomatic left ventricular dysfunction from any cause other than amyloid, patients with a primary diagnosis of symptomatic valvular heart disease) * Patient has a co-morbidity anticipated to limit survival to less than 12 months. * Patient has received an investigational drug/device and/or participated in another clinical investigational study within 60 days before Baseline (Day 0).
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 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 | Day 1 up to Month 12 | ECHO: investigator assessed test to assess cardiac function. ECHO abnormality criteria: any abnormality, valvular abnormality, pericardial effusion, abnormal regional wall motion, inferior vena cava respiratory variation, posterior (P) left ventricular (LV) wall/septal (S) thickness, right ventricular thickness, ejection fraction, ratio of early (E) diastolic transmitral flow and atrial(A) contraction velocity (E/A), ratio of 'E'to lateral/septal mitral annular velocity (e') (E/e'prime lateral, E/e'prime septal), E deceleration time (DT), isovolumic relaxation time (IVRT). |
| Number of Participants With Clinically Significant Treatment-Emergent Electrocardiogram (ECG) Findings | Day 1 up to Month 12 | ECG: investigator assessed test to assess cardiac function. ECG abnormality criteria: any abnormality, arrhythmia, rhythm, conduction, morphology, myocardial infarction, ST segment, T waves and abnormal U waves. |
| Number of Participants With Clinically Significant Treatment-Emergent Holter Monitoring Findings | Day 1 up to Month 12 | Holter monitoring recorded heart rhythm. Holter monitoring abnormality criteria: any abnormality, atrial fibrillation/flutter, atrial tachycardia, non-sustained ventricular tachycardia (VT), sustained VT and sinus pause. |
| Number of Participants Who Discontinued Due to Clinical or Laboratory Adverse Events | Baseline up to Month 12 | — |
| Change From Baseline in the Neuropathy Impairment Score (NIS) at Month 6, Month 12 | Baseline, Month 6, Month 12 | NIS assessed cranial nerves(nerve 3,6; facial, palate and tongue weakness),muscle weakness (respiratory; neck, elbow(E), wrist(W), finger(F), hip, knee(K) flexion; shoulder, thumb abduction; brachioradialis; E, W, hip, K extension; F spread; toe, dorsal and plantar ankle flexors; toe extensors); score: 0-4, higher score=more weakness, reflexes(biceps and triceps brachii; brachioradialis; quadriceps femoris; triceps surae), index F and great toe sensation(touch pressure, pin-prick, vibration, joint position)score:0=normal,1=decreased or 2=absent. Total score=0-244, higher score=more impairment. |
| Change From Baseline in the Neuropathy Impairment Score-Lower Limb (NIS-LL) at Month 6, Month 12 | Baseline, Month 6, Month 12 | NIS-LL: assessed muscle weakness, reflexes and sensation; scored separately for left and right limbs. Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) are scored on 0 to 4 scale, higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae) and sensation (touch pressure, pin-prick, vibration, joint position) were scored 0 = normal, 1= decreased, or 2 = absent. Total possible NIS-LL score range 0-88, higher score=greater impairment. |
| Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 6, Month 12 | Month 6, Month 12 | Response to treatment was indicated by either improvement (decrease from baseline) or stabilization (change from baseline of 0 to less than \[\<\] 2) in Neuropathy Impairment Score- Lower Limb (NIS-LL) score, based on mean of 2 scores in 1 week period. NIS-LL: assessed muscle weakness, reflexes, sensation. Each item scored separately for left, right limbs. Components of muscle weakness scored on 0(normal) to 4(paralysis) scale, higher score=greater weakness. Components of reflexes, sensation scored 0=normal, 1=decreased, or 2=absent. Total NIS-LL score range 0-88, higher score=greater impairment. |
| Change From Baseline in Total Quality of Life (TQOL) Score at Month 6, Month 12 | Baseline, Month 6, Month 12 | TQOL= sum of all Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) items,a 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on QOL of participants with DN; Item 1 to 7: related to symptoms and presence of symptom was assessed as 1 and absence was assessed as 0. Item 8-35: related to activities of daily living and scored on a 5-point Likert scale, where 0= no problem and 4= severe problem (except item 32, where -2= much better, 0=about the same, 2=much worse). Total TQOL score=-2 to 138;higher score=worse quality of life. |
| Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, Month 12 | Baseline, Month 6, Month 12 | Norfolk QOL-DN:35-item participant-rated questionnaire to assess impact of DN on QOL; Item 1-7: scored as 1=symptom present, 0=symptom absent. Item 8-35: scored on 5-point Likert scale:0=no problem, 4=severe problem(except item 32: -2=much better, 0=about same, 2=much worse).Norfolk QOL-DN summarized in 5 domains (score range): physical functioning/large fiber neuropathy(-2 to 58), activities of daily living(ADLs) (0 to 20), symptom(0 to 32), small fiber neuropathy(0 to 16), autonomic neuropathy(0 to 12);higher score=greater impairment, for each. Total score=-2 to 138 (higher score=worse QOL). |
| Change From Baseline in Nerve Conduction Studies (NCS) at Month 6, Month 12 | Baseline, Month 6, Month 12 | NCS: quantitative measures of peripheral nerve dysfunction consists of 5 attributes: peroneal nerve (PN) motor distal latency, PN compound muscle action potential, PN motor conduction velocity, tibial nerve distal motor latency, sural nerve sensory nerve action potential. Normal deviates (Z-score) summated into composite score (higher score=worsened nerve fiber function). Z-score is the defined position of the result in normal probability distribution with a mean of 0 and standard deviation (std) of 1 and describes how far a score is (in std) from the mean. |
| Change From Baseline in Heart Rate Response to Deep Breathing (HRDB) at Month 6 and Month 12 | Baseline, Month 6, Month 12 | HRDB test was used to evaluate the cardio-vagal response. Participant took a series of 8 deep breaths and average heart rate difference was measured and compared to normative data. The main factor affecting HRDB is age, with older patients showing less heart rate variability. R-R (time between two consecutive R waves in the electrocardiogram) response to deep breathing was reported as the normal deviates (Z-score), the defined position of the result in normal probability distribution with a mean of 0 and standard deviation (std) of 1 and describes how far a score is (in std) from the mean. |
| Change From Baseline in Modified Body Mass Index (mBMI) at Month 6, Month 12 | Baseline, Month 6, Month 12 | BMI was calculated by weight divided by height squared and measured as kilogram per square meter (kg/m\^2). mBMI was calculated by multiplying BMI by serum albumin levels \[gram/liter (g/L)\]. mBMI was measured as kg/m\^2\*g/L. A progressive decline in mBMI indicated worsening of disease severity. |
| Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12 | Baseline, Month 6, Month 12 | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health and two total scores (physical component summary \[PCS\] and mental component summary \[MCS\]. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). |
| Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 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 (LVED), relative LV wall thickness (RLVWT). |
| Change From Baseline in Left Atrial Volume at Month 6, Month 12 | Baseline, Month 6, Month 12 | Left atrial volume was measured by echocardiography. |
| 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 Fractional Shortening at Month 6, Month 12 | Baseline, Month 6, Month 12 | Fractional shortening (FS) is the fraction of any diastolic dimension that is lost in systole. Percent of FS was calculated as difference between end-diastolic dimension (EDD) and end-systolic dimension (EDS) divided by EDD. |
| Change From Baseline in Left Ventricular (LV) Ejection Fraction at Month 6, Month 12 | Baseline, Month 6, Month 12 | Cardiac MRI was done to measure left ventricular ejection fraction (LVEF) which was the fraction of the end-diastolic volume (EDV) that was ejected out of left ventricle with each contraction. |
| Change From Baseline in Left Ventricular Mass (LVM) at Month 6, Month 12 | Baseline, Month 6, Month 12 | LV mass was calculated from the product of the myocardial volume and specific gravity of heart muscle, estimated by echocardiography. Increased LVM was associated with cardiovascular morbidity and mortality. |
| Change From Baseline in Isovolumetric Relaxation Time (IVRT), Mitral Deceleration Time at Month 6, Month 12 | Baseline, Month 6, Month 12 | Doppler echocardiography was a procedure which used ultrasound technology to examine the heart. IVRT is the time between the closure of the aortic valve and the opening of the mitral valve. Mitral deceleration time (MDT) was the time taken from the maximum E point wave to baseline. E wave arises due to early diastolic filling. |
| Change From Baseline in Aortic Annulus Diameter at Month 6, Month 12 | Baseline, Month 6, Month 12 | The diameter at the base of the aortic root, the basal ring, is also called the aortic annulus diameter. |
| Change From Baseline in Tricuspid Peak Velocity at Month 6, Month 12 | Baseline, Month 6, Month 12 | Tricuspid peak velocity was measured by echocardiography. |
| Change From Baseline in Tricuspid Pulmonary Artery Systolic Pressure (PASP) at Month 6, Month 12 | Baseline, Month 6, Month 12 | Systolic right ventricular pressure can be estimated on echocardiography by adding right atrial pressure (RAP) to the trans-tricuspid gradient derived from the tricuspid regurgitation velocity. |
| Change From Baseline in Doppler Data at Month 6, Month 12 | Baseline, Month 6, Month 12 | Doppler echocardiography was a procedure which used ultrasound technology to examine the heart. Doppler principle was used to measure the mitral peak early (E) diastolic transmitral flow, mitral peak atrial (A) contraction velocity and annular velocities at the lateral and septal areas of the mitral annulus. s': systolic velocity during ejection, e': early diastolic mitral annular velocity, a': late diastolic mitral annular velocity. |
| Change From Baseline in e:e' Lateral Ratio , Ratio of Peak Mitral Early Diastolic and Atrial Contraction Velocity (E/A Ratio) at Month 6, Month 12 | 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 Left Ventricular (LV) Mass/Voltage Ratio at Month 6, Month 12 | Baseline, Month 6, Month 12 | LV mass was calculated from the product of the myocardial volume and specific gravity of heart muscle, estimated by echocardiography. QRS score (the sum of QRS voltages in the peripheral leads) was used as an index of electrical LV mass. |
| Change From Baseline in Left Atrial (LA) Volume Index at Month 6, Month 12 | Baseline, Month 6, Month 12 | LA volume index (LAVI), was the value of LA volume divided by body surface area, to measure LA size. |
| Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) at Week 2, Week 6, Month 3, Month 6, Month 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 Karnofsky Performance Status Scale at Month 6, Month 12 | Baseline, Month 6, Month 12 | Karnofsky performance score is used to quantify participant's general well-being and activities of daily life and participants are classified based on their functional impairment. Karnofsky performance score is 11 level score which ranges between 0 (death) to 100 (no evidence of disease). Higher score means higher ability to perform daily tasks. |
| Change From Baseline in Troponin I Levels at Week 2, Week 6 , Month 3, Month 6, Month 12 | Baseline, Week 2, Week 6 , Month 3, Month 6, Month 12 | Troponin I is a cardiac injury biomarker. Higher concentrations of this marker in blood are associated with heart injury. |
| Change From Baseline in Left Ventricular (LV) End Systolic Volume, Left Ventricle (LV) Stroke Volume at Month 6, Month 12 | Baseline, Month 6, Month 12 | Cardiac MRI was done to measure left ventricular (LV) end systolic volume, left ventricle (LV) stroke volume. |
| Number of Participants With Greater Than or Equal to Grade 3 Treatment-Emergent Adverse Events | 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
France, Germany, Italy, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator's discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2. | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Part 1 (up to Week 6) | Adverse Event | 1 |
| Part 2 (After Week 6 up to Month 12) | Liver transplant | 2 |
Baseline characteristics
| Characteristic | Tafamidis |
|---|---|
| Age Continuous | 63.10 years STANDARD_DEVIATION 9.86 |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 13 / 21 |
| serious Total, serious adverse events | 8 / 21 |
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 1 dose of study medication. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tafamidis | Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer at Week 6 | 94.7 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 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 1 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 (n= 18) | 100.0 percentage of participants |
| Tafamidis | Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer at Month 6 and 12 | Month 12 (n= 17) | 100.0 percentage of participants |
Other Pre-specified
Change From Baseline in Aortic Annulus Diameter at Month 6, Month 12
The diameter at the base of the aortic root, the basal ring, is also called the aortic annulus diameter.
Time frame: Baseline, Month 6, Month 12
Population: ITT population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were analyzed for the specific category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in Aortic Annulus Diameter at Month 6, Month 12 | Baseline (n= 21) | 2.045 centimeter (cm) | Standard Deviation 0.184 |
| Tafamidis | Change From Baseline in Aortic Annulus Diameter at Month 6, Month 12 | Change at Month 6 (n= 17) | -0.009 centimeter (cm) | Standard Deviation 0.16 |
| Tafamidis | Change From Baseline in Aortic Annulus Diameter at Month 6, Month 12 | Change at Month 12 (n= 16) | -0.041 centimeter (cm) | Standard Deviation 0.108 |
Other Pre-specified
Change From Baseline in Doppler Data at Month 6, Month 12
Doppler echocardiography was a procedure which used ultrasound technology to examine the heart. Doppler principle was used to measure the mitral peak early (E) diastolic transmitral flow, mitral peak atrial (A) contraction velocity and annular velocities at the lateral and septal areas of the mitral annulus. s': systolic velocity during ejection, e': early diastolic mitral annular velocity, a': late diastolic mitral annular velocity.
Time frame: Baseline, Month 6, Month 12
Population: ITT population included all participants who received at least 1 dose of study medication. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants who were analyzed for the specific category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in Doppler Data at Month 6, Month 12 | Mitral Peak A: Change at Month 12 (n= 15) | -3.70 centimeter per second (cm/sec) | Standard Deviation 15.43 |
| Tafamidis | Change From Baseline in Doppler Data at Month 6, Month 12 | Septal s': Baseline (n= 16) | 4.72 centimeter per second (cm/sec) | Standard Deviation 1.64 |
| Tafamidis | Change From Baseline in Doppler Data at Month 6, Month 12 | Septal s': Change at Month 6 (n= 12) | 0.43 centimeter per second (cm/sec) | Standard Deviation 0.51 |
| Tafamidis | Change From Baseline in Doppler Data at Month 6, Month 12 | Septal e': Change at Month 6 (n= 12) | 1.25 centimeter per second (cm/sec) | Standard Deviation 2.29 |
| Tafamidis | Change From Baseline in Doppler Data at Month 6, Month 12 | Septal e': Change at Month 12 (n= 8) | 0.04 centimeter per second (cm/sec) | Standard Deviation 0.61 |
| Tafamidis | Change From Baseline in Doppler Data at Month 6, Month 12 | Septal a': Change at Month 12 (n= 8) | -0.10 centimeter per second (cm/sec) | Standard Deviation 1.74 |
| Tafamidis | Change From Baseline in Doppler Data at Month 6, Month 12 | Lateral s': Baseline (n= 16) | 6.71 centimeter per second (cm/sec) | Standard Deviation 2.97 |
| Tafamidis | Change From Baseline in Doppler Data at Month 6, Month 12 | Lateral s': Change at Month 6 (n= 10) | 0.55 centimeter per second (cm/sec) | Standard Deviation 1.41 |
| Tafamidis | Change From Baseline in Doppler Data at Month 6, Month 12 | Lateral s': Change at Month 12 (n= 7) | 0.19 centimeter per second (cm/sec) | Standard Deviation 1.2 |
| Tafamidis | Change From Baseline in Doppler Data at Month 6, Month 12 | Mitral Peak A: Baseline (n= 18) | 59.00 centimeter per second (cm/sec) | Standard Deviation 23.77 |
| Tafamidis | Change From Baseline in Doppler Data at Month 6, Month 12 | Mitral Peak A: Change at Month 6 (n= 13) | -0.50 centimeter per second (cm/sec) | Standard Deviation 16.01 |
| Tafamidis | Change From Baseline in Doppler Data at Month 6, Month 12 | Mitral Peak E: Baseline (n= 19) | 74.10 centimeter per second (cm/sec) | Standard Deviation 15.58 |
| Tafamidis | Change From Baseline in Doppler Data at Month 6, Month 12 | Mitral Peak E: Change at Month 6 (n= 15) | 4.70 centimeter per second (cm/sec) | Standard Deviation 10.28 |
| Tafamidis | Change From Baseline in Doppler Data at Month 6, Month 12 | Mitral Peak E: Change at Month 12 (n= 16) | 5.10 centimeter per second (cm/sec) | Standard Deviation 13.75 |
| Tafamidis | Change From Baseline in Doppler Data at Month 6, Month 12 | Septal s': Change at Month 12 (n= 8) | -0.33 centimeter per second (cm/sec) | Standard Deviation 0.9 |
| Tafamidis | Change From Baseline in Doppler Data at Month 6, Month 12 | Septal e': Baseline (n= 16) | 4.54 centimeter per second (cm/sec) | Standard Deviation 1.88 |
| Tafamidis | Change From Baseline in Doppler Data at Month 6, Month 12 | Septal a': Baseline (n= 15) | 4.66 centimeter per second (cm/sec) | Standard Deviation 2.67 |
| Tafamidis | Change From Baseline in Doppler Data at Month 6, Month 12 | Septal a': Change at Month 6 (n= 11) | 0.53 centimeter per second (cm/sec) | Standard Deviation 1.39 |
| Tafamidis | Change From Baseline in Doppler Data at Month 6, Month 12 | Lateral e': Baseline (n= 16) | 6.91 centimeter per second (cm/sec) | Standard Deviation 2.9 |
| Tafamidis | Change From Baseline in Doppler Data at Month 6, Month 12 | Lateral e': Change at Month 6 (n= 11) | 0.65 centimeter per second (cm/sec) | Standard Deviation 1.27 |
| Tafamidis | Change From Baseline in Doppler Data at Month 6, Month 12 | Lateral e': Change at Month 12 (n= 7) | 0.16 centimeter per second (cm/sec) | Standard Deviation 1.42 |
| Tafamidis | Change From Baseline in Doppler Data at Month 6, Month 12 | Lateral a': Baseline (n= 15) | 5.93 centimeter per second (cm/sec) | Standard Deviation 3.38 |
| Tafamidis | Change From Baseline in Doppler Data at Month 6, Month 12 | Lateral a': Change at Month 6 (n= 10) | 0.31 centimeter per second (cm/sec) | Standard Deviation 2.69 |
| Tafamidis | Change From Baseline in Doppler Data at Month 6, Month 12 | Lateral a': Change at Month 12 (n= 6) | -0.45 centimeter per second (cm/sec) | Standard Deviation 2.94 |
Other Pre-specified
Change From Baseline in Echocardiography (ECHO) Parameters at 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 (LVED), relative LV wall thickness (RLVWT).
Time frame: Baseline, Month 6, Month 12
Population: ITT population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were analyzed for the specific category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 12 | LAD (medio-lateral): Baseline (n=16) | 37.40 millimeter (mm) | Standard Deviation 4.8 |
| Tafamidis | Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 12 | LAD (medio-lateral): Change at Month 12 (n=9) | 1.90 millimeter (mm) | Standard Deviation 4.2 |
| Tafamidis | Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 12 | LAD (sup-inf): Baseline (n=16) | 48.30 millimeter (mm) | Standard Deviation 9.88 |
| Tafamidis | Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 12 | RLVWT: Baseline (n=19) | 0.75 millimeter (mm) | Standard Deviation 0.19 |
| Tafamidis | Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 12 | IVST: Baseline (n=19) | 15.24 millimeter (mm) | Standard Deviation 2.77 |
| Tafamidis | Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 12 | IVST: Change at Month 6 (n=15) | 0.57 millimeter (mm) | Standard Deviation 2.1 |
| Tafamidis | Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 12 | IVST: Change at Month 12 (n=14) | 1.04 millimeter (mm) | Standard Deviation 2.04 |
| Tafamidis | Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 12 | PLVWT: Baseline (n=19) | 14.60 millimeter (mm) | Standard Deviation 2.59 |
| Tafamidis | Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 12 | PLVWT: Change at Month 6 (n=15) | 0.30 millimeter (mm) | Standard Deviation 1.98 |
| Tafamidis | Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 12 | PLVWT: Change at Month 12 (n=14) | 0.70 millimeter (mm) | Standard Deviation 1.73 |
| Tafamidis | Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 12 | RVWT: Baseline (n=17) | 6.09 millimeter (mm) | Standard Deviation 2.01 |
| Tafamidis | Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 12 | RVWT: Change at Month 6 (n=8) | 1.12 millimeter (mm) | Standard Deviation 1.72 |
| Tafamidis | Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 12 | RVWT: Change at Month 12 (n=12) | 1.08 millimeter (mm) | Standard Deviation 1.29 |
| Tafamidis | Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 12 | LAD (ant-post): Baseline (n=21) | 36.30 millimeter (mm) | Standard Deviation 6.2 |
| Tafamidis | Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 12 | LAD (ant-post): Change at Month 6 (n=17) | 1.50 millimeter (mm) | Standard Deviation 4.57 |
| Tafamidis | Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 12 | LAD (ant-post): Change at Month 12 (n=16) | 1.60 millimeter (mm) | Standard Deviation 3.52 |
| Tafamidis | Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 12 | LAD (medio-lateral): Change at Month 6 (n=7) | 4.30 millimeter (mm) | Standard Deviation 6.9 |
| Tafamidis | Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 12 | LAD (sup-inf): Change at Month 6 (n= 8) | 3.10 millimeter (mm) | Standard Deviation 5.03 |
| Tafamidis | Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 12 | LAD (sup-inf): Change at Month 6 (n= 9) | 4.20 millimeter (mm) | Standard Deviation 6.46 |
| Tafamidis | Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 12 | LVED: Baseline (n= 19) | 39.66 millimeter (mm) | Standard Deviation 4.84 |
| Tafamidis | Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 12 | LVED: Change at Month 6 (n= 15) | -1.03 millimeter (mm) | Standard Deviation 3.88 |
| Tafamidis | Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 12 | LVED: Change at Month 12 (n= 14) | 0.11 millimeter (mm) | Standard Deviation 3.42 |
| Tafamidis | Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 12 | RLVWT: Change at Month 6 (n= 15) | 0.05 millimeter (mm) | Standard Deviation 0.16 |
| Tafamidis | Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 12 | RLVWT: Change at Month 12 (n= 14) | 0.03 millimeter (mm) | Standard Deviation 0.12 |
Other Pre-specified
Change From Baseline in e:e' Lateral Ratio , Ratio of Peak Mitral Early Diastolic and Atrial Contraction Velocity (E/A Ratio) at Month 6, Month 12
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 1 dose of study medication. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants who were analyzed for the specific category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in e:e' Lateral Ratio , Ratio of Peak Mitral Early Diastolic and Atrial Contraction Velocity (E/A Ratio) at Month 6, Month 12 | e:e' Lateral: Change at Month 12 (n= 7) | -0.243 ratio | Standard Deviation 5.245 |
| Tafamidis | Change From Baseline in e:e' Lateral Ratio , Ratio of Peak Mitral Early Diastolic and Atrial Contraction Velocity (E/A Ratio) at Month 6, Month 12 | E/A: Change at Month 6 (n= 13) | 0.175 ratio | Standard Deviation 0.565 |
| Tafamidis | Change From Baseline in e:e' Lateral Ratio , Ratio of Peak Mitral Early Diastolic and Atrial Contraction Velocity (E/A Ratio) at Month 6, Month 12 | E/A: Change at Month 12 (n= 15) | 0.185 ratio | Standard Deviation 0.658 |
| Tafamidis | Change From Baseline in e:e' Lateral Ratio , Ratio of Peak Mitral Early Diastolic and Atrial Contraction Velocity (E/A Ratio) at Month 6, Month 12 | e:e' Lateral: Baseline (n= 16) | 13.148 ratio | Standard Deviation 7.781 |
| Tafamidis | Change From Baseline in e:e' Lateral Ratio , Ratio of Peak Mitral Early Diastolic and Atrial Contraction Velocity (E/A Ratio) at Month 6, Month 12 | e:e' Lateral: Change at Month 6 (n= 10) | -0.145 ratio | Standard Deviation 3.227 |
| Tafamidis | Change From Baseline in e:e' Lateral Ratio , Ratio of Peak Mitral Early Diastolic and Atrial Contraction Velocity (E/A Ratio) at Month 6, Month 12 | E/A: Baseline (n= 18) | 1.463 ratio | Standard Deviation 0.667 |
Other Pre-specified
Change From Baseline in Fractional Shortening at Month 6, Month 12
Fractional shortening (FS) is the fraction of any diastolic dimension that is lost in systole. Percent of FS was calculated as difference between end-diastolic dimension (EDD) and end-systolic dimension (EDS) divided by EDD.
Time frame: Baseline, Month 6, Month 12
Population: ITT population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were analyzed for the specific category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in Fractional Shortening at Month 6, Month 12 | Baseline (n= 18) | 31.20 percentage of EDD | Standard Deviation 5.68 |
| Tafamidis | Change From Baseline in Fractional Shortening at Month 6, Month 12 | Change at Month 6 (n= 14) | -1.10 percentage of EDD | Standard Deviation 5.91 |
| Tafamidis | Change From Baseline in Fractional Shortening at Month 6, Month 12 | Change at Month 12 (n= 14) | -0.90 percentage of EDD | Standard Deviation 6.24 |
Other Pre-specified
Change From Baseline in Heart Rate Response to Deep Breathing (HRDB) at Month 6 and Month 12
HRDB test was used to evaluate the cardio-vagal response. Participant took a series of 8 deep breaths and average heart rate difference was measured and compared to normative data. The main factor affecting HRDB is age, with older patients showing less heart rate variability. R-R (time between two consecutive R waves in the electrocardiogram) response to deep breathing was reported as the normal deviates (Z-score), the defined position of the result in normal probability distribution with a mean of 0 and standard deviation (std) of 1 and describes how far a score is (in std) from the mean.
Time frame: Baseline, Month 6, Month 12
Population: ITT population included all participants who received at least 1 dose of study medication. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants who were analyzed for the specific category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in Heart Rate Response to Deep Breathing (HRDB) at Month 6 and Month 12 | Change at Month 6 (n= 6) | 0.00 Z-score | Standard Deviation 2.26 |
| Tafamidis | Change From Baseline in Heart Rate Response to Deep Breathing (HRDB) at Month 6 and Month 12 | Baseline (n= 12) | -0.70 Z-score | Standard Deviation 2.17 |
| Tafamidis | Change From Baseline in Heart Rate Response to Deep Breathing (HRDB) at Month 6 and Month 12 | Change at Month 12 (n= 7) | -0.1 Z-score | Standard Deviation 1.36 |
Other Pre-specified
Change From Baseline in Isovolumetric Relaxation Time (IVRT), Mitral Deceleration Time at Month 6, Month 12
Doppler echocardiography was a procedure which used ultrasound technology to examine the heart. IVRT is the time between the closure of the aortic valve and the opening of the mitral valve. Mitral deceleration time (MDT) was the time taken from the maximum E point wave to baseline. E wave arises due to early diastolic filling.
Time frame: Baseline, Month 6, Month 12
Population: ITT population included all participants who received at least 1 dose of study medication. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants who were analyzed for the specific category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in Isovolumetric Relaxation Time (IVRT), Mitral Deceleration Time at Month 6, Month 12 | IVRT: Change at Month 12 (n= 8) | -4.00 msec | Standard Deviation 25.63 |
| Tafamidis | Change From Baseline in Isovolumetric Relaxation Time (IVRT), Mitral Deceleration Time at Month 6, Month 12 | MDT: Baseline (n= 18) | 164.00 msec | Standard Deviation 35.59 |
| Tafamidis | Change From Baseline in Isovolumetric Relaxation Time (IVRT), Mitral Deceleration Time at Month 6, Month 12 | IVRT: Baseline (n= 10) | 84.10 msec | Standard Deviation 17.51 |
| Tafamidis | Change From Baseline in Isovolumetric Relaxation Time (IVRT), Mitral Deceleration Time at Month 6, Month 12 | IVRT: Change at Month 6 (n= 3) | 2.70 msec | Standard Deviation 20.03 |
| Tafamidis | Change From Baseline in Isovolumetric Relaxation Time (IVRT), Mitral Deceleration Time at Month 6, Month 12 | MDT: Change at Month 6 (n= 14) | 1.90 msec | Standard Deviation 28.17 |
| Tafamidis | Change From Baseline in Isovolumetric Relaxation Time (IVRT), Mitral Deceleration Time at Month 6, Month 12 | MDT: Change at Month 12 (n= 15) | 11.90 msec | Standard Deviation 29.45 |
Other Pre-specified
Change From Baseline in Karnofsky Performance Status Scale at Month 6, Month 12
Karnofsky performance score is used to quantify participant's general well-being and activities of daily life and participants are classified based on their functional impairment. Karnofsky performance score is 11 level score which ranges between 0 (death) to 100 (no evidence of disease). Higher score means higher ability to perform daily tasks.
Time frame: Baseline, Month 6, Month 12
Population: ITT population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were analyzed for the specific category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in Karnofsky Performance Status Scale at Month 6, Month 12 | Baseline (n= 21) | 74.80 units on a scale | Standard Deviation 14.01 |
| Tafamidis | Change From Baseline in Karnofsky Performance Status Scale at Month 6, Month 12 | Change at Month 6 (n= 19) | -1.10 units on a scale | Standard Deviation 5.67 |
| Tafamidis | Change From Baseline in Karnofsky Performance Status Scale at Month 6, Month 12 | Change at Month 12 (n= 18) | -3.30 units on a scale | Standard Deviation 5.94 |
Other Pre-specified
Change From Baseline in Left Atrial (LA) Volume Index at Month 6, Month 12
LA volume index (LAVI), was the value of LA volume divided by body surface area, to measure LA size.
Time frame: Baseline, Month 6, Month 12
Population: ITT population included all participants who received at least 1 dose of study medication. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants who were analyzed for the specific category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in Left Atrial (LA) Volume Index at Month 6, Month 12 | Baseline (n= 15) | 27.33 milliliter/square meter (mL/m^2) | Standard Deviation 10.21 |
| Tafamidis | Change From Baseline in Left Atrial (LA) Volume Index at Month 6, Month 12 | Change at Month 6 (n= 5) | 7.23 milliliter/square meter (mL/m^2) | Standard Deviation 8.78 |
| Tafamidis | Change From Baseline in Left Atrial (LA) Volume Index at Month 6, Month 12 | Change at Month 12 (n= 9) | 1.06 milliliter/square meter (mL/m^2) | Standard Deviation 9.66 |
Other Pre-specified
Change From Baseline in Left Atrial Volume at Month 6, Month 12
Left atrial volume was measured by echocardiography.
Time frame: Baseline, Month 6, Month 12
Population: ITT population included all participants who received at least 1 dose of study medication. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants who were analyzed for the specific category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in Left Atrial Volume at Month 6, Month 12 | Baseline (n= 15) | 51.50 cubic centimeter (cc) | Standard Deviation 23.81 |
| Tafamidis | Change From Baseline in Left Atrial Volume at Month 6, Month 12 | Change at Month 6 (n= 6) | 12.30 cubic centimeter (cc) | Standard Deviation 17.2 |
| Tafamidis | Change From Baseline in Left Atrial Volume at Month 6, Month 12 | Change at Month 12 (n= 9) | 1.90 cubic centimeter (cc) | Standard Deviation 18.9 |
Other Pre-specified
Change From Baseline in Left Ventricular (LV) Ejection Fraction at Month 6, Month 12
Cardiac MRI was done to measure left ventricular ejection fraction (LVEF) which was the fraction of the end-diastolic volume (EDV) that was ejected out of left ventricle with each contraction.
Time frame: Baseline, Month 6, Month 12
Population: ITT population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were analyzed for the specific category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in Left Ventricular (LV) Ejection Fraction at Month 6, Month 12 | Baseline (n= 21) | 60.30 percentage of EDV | Standard Deviation 9.96 |
| Tafamidis | Change From Baseline in Left Ventricular (LV) Ejection Fraction at Month 6, Month 12 | Change at Month 6 (n= 18) | -3.80 percentage of EDV | Standard Deviation 7.73 |
| Tafamidis | Change From Baseline in Left Ventricular (LV) Ejection Fraction at Month 6, Month 12 | Change at Month 12 (n=18) | -2.20 percentage of EDV | Standard Deviation 5.37 |
Other Pre-specified
Change From Baseline in Left Ventricular (LV) End Systolic Volume, Left Ventricle (LV) Stroke Volume at Month 6, Month 12
Cardiac MRI was done to measure left ventricular (LV) end systolic volume, left ventricle (LV) stroke volume.
Time frame: Baseline, Month 6, Month 12
Population: ITT population included all participants who received at least 1 dose of study medication. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants who were analyzed for the specific category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in Left Ventricular (LV) End Systolic Volume, Left Ventricle (LV) Stroke Volume at Month 6, Month 12 | LV end systolic volume: Baseline (n= 11) | 30.4 milliliter (mL) | Standard Deviation 13.93 |
| Tafamidis | Change From Baseline in Left Ventricular (LV) End Systolic Volume, Left Ventricle (LV) Stroke Volume at Month 6, Month 12 | LV end systolic volume: Change at Month 6 (n= 6) | 3.50 milliliter (mL) | Standard Deviation 7.79 |
| Tafamidis | Change From Baseline in Left Ventricular (LV) End Systolic Volume, Left Ventricle (LV) Stroke Volume at Month 6, Month 12 | LV end systolic volume: Change at Month 12 (n= 6) | 4.70 milliliter (mL) | Standard Deviation 3.01 |
| Tafamidis | Change From Baseline in Left Ventricular (LV) End Systolic Volume, Left Ventricle (LV) Stroke Volume at Month 6, Month 12 | LV stroke volume: Baseline (n= 11) | 43.10 milliliter (mL) | Standard Deviation 13.26 |
| Tafamidis | Change From Baseline in Left Ventricular (LV) End Systolic Volume, Left Ventricle (LV) Stroke Volume at Month 6, Month 12 | LV stroke volume: Change at Month 6 (n= 6) | -2.50 milliliter (mL) | Standard Deviation 15.23 |
| Tafamidis | Change From Baseline in Left Ventricular (LV) End Systolic Volume, Left Ventricle (LV) Stroke Volume at Month 6, Month 12 | LV stroke volume: Change at Month 12 (n= 6) | 3.70 milliliter (mL) | Standard Deviation 10.69 |
Other Pre-specified
Change From Baseline in Left Ventricular (LV) Mass/Voltage Ratio at Month 6, Month 12
LV mass was calculated from the product of the myocardial volume and specific gravity of heart muscle, estimated by echocardiography. QRS score (the sum of QRS voltages in the peripheral leads) was used as an index of electrical LV mass.
Time frame: Baseline, Month 6, Month 12
Population: ITT population included all participants who received at least 1 dose of study medication. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants who were analyzed for the specific category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in Left Ventricular (LV) Mass/Voltage Ratio at Month 6, Month 12 | Baseline (n= 19) | 5.495 gram/millivolt | Standard Deviation 2.149 |
| Tafamidis | Change From Baseline in Left Ventricular (LV) Mass/Voltage Ratio at Month 6, Month 12 | Change at Month 6 (n= 14) | 0.028 gram/millivolt | Standard Deviation 1.479 |
| Tafamidis | Change From Baseline in Left Ventricular (LV) Mass/Voltage Ratio at Month 6, Month 12 | Change at Month 12 (n= 14) | 0.878 gram/millivolt | Standard Deviation 1.437 |
Other Pre-specified
Change From Baseline in Left Ventricular Mass (LVM) at Month 6, Month 12
LV mass was calculated from the product of the myocardial volume and specific gravity of heart muscle, estimated by echocardiography. Increased LVM was associated with cardiovascular morbidity and mortality.
Time frame: Baseline, Month 6, Month 12
Population: ITT population included all participants who received at least 1 dose of study medication. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants who were analyzed for the specific category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in Left Ventricular Mass (LVM) at Month 6, Month 12 | Change at Month 12 (n= 14) | 20.91 gram | Standard Deviation 35.07 |
| Tafamidis | Change From Baseline in Left Ventricular Mass (LVM) at Month 6, Month 12 | Baseline: (n= 19) | 230.84 gram | Standard Deviation 62.54 |
| Tafamidis | Change From Baseline in Left Ventricular Mass (LVM) at Month 6, Month 12 | Change at Month 6 (n= 15) | 1.11 gram | Standard Deviation 46.53 |
Other Pre-specified
Change From Baseline in Modified Body Mass Index (mBMI) at Month 6, Month 12
BMI was calculated by weight divided by height squared and measured as kilogram per square meter (kg/m\^2). mBMI was calculated by multiplying BMI by serum albumin levels \[gram/liter (g/L)\]. mBMI was measured as kg/m\^2\*g/L. A progressive decline in mBMI indicated worsening of disease severity.
Time frame: Baseline, Month 6, Month 12
Population: ITT population included all participants who received at least 1 dose of study medication. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants who were analyzed for the specific category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in Modified Body Mass Index (mBMI) at Month 6, Month 12 | Change at Month 12 (n= 16) | 16.60 kg/m^2*g/L | Standard Deviation 89.33 |
| Tafamidis | Change From Baseline in Modified Body Mass Index (mBMI) at Month 6, Month 12 | Baseline (n= 20) | 1052.50 kg/m^2*g/L | Standard Deviation 206.66 |
| Tafamidis | Change From Baseline in Modified Body Mass Index (mBMI) at Month 6, Month 12 | Change at Month 6 (n= 17) | -22.40 kg/m^2*g/L | Standard Deviation 77.01 |
Other Pre-specified
Change From Baseline in Nerve Conduction Studies (NCS) at Month 6, Month 12
NCS: quantitative measures of peripheral nerve dysfunction consists of 5 attributes: peroneal nerve (PN) motor distal latency, PN compound muscle action potential, PN motor conduction velocity, tibial nerve distal motor latency, sural nerve sensory nerve action potential. Normal deviates (Z-score) summated into composite score (higher score=worsened nerve fiber function). Z-score is the defined position of the result in normal probability distribution with a mean of 0 and standard deviation (std) of 1 and describes how far a score is (in std) from the mean.
Time frame: Baseline, Month 6, Month 12
Population: ITT population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were analyzed for the specific category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in Nerve Conduction Studies (NCS) at Month 6, Month 12 | Baseline (n= 21) | 6.10 Z-score | Standard Deviation 5.9 |
| Tafamidis | Change From Baseline in Nerve Conduction Studies (NCS) at Month 6, Month 12 | Change at Month 6 (n= 19) | 0.60 Z-score | Standard Deviation 2.69 |
| Tafamidis | Change From Baseline in Nerve Conduction Studies (NCS) at Month 6, Month 12 | Change at Month 12 (n= 18) | 0.20 Z-score | Standard Deviation 3.3 |
Other Pre-specified
Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, Month 12
Norfolk QOL-DN:35-item participant-rated questionnaire to assess impact of DN on QOL; Item 1-7: scored as 1=symptom present, 0=symptom absent. Item 8-35: scored on 5-point Likert scale:0=no problem, 4=severe problem(except item 32: -2=much better, 0=about same, 2=much worse).Norfolk QOL-DN summarized in 5 domains (score range): physical functioning/large fiber neuropathy(-2 to 58), activities of daily living(ADLs) (0 to 20), symptom(0 to 32), small fiber neuropathy(0 to 16), autonomic neuropathy(0 to 12);higher score=greater impairment, for each. Total score=-2 to 138 (higher score=worse QOL).
Time frame: Baseline, Month 6, Month 12
Population: ITT population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were analyzed for the specific category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, Month 12 | Physical (P)functioning/large fiber:Baseline(n=21) | 25.60 units on a scale | Standard Deviation 18.5 |
| Tafamidis | Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, Month 12 | Small fiber neuropathy (SFN): Baseline (n=21) | 3.90 units on a scale | Standard Deviation 4.92 |
| Tafamidis | Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, Month 12 | P functioning/large fiber: Change at Month 6(n=19) | -2.60 units on a scale | Standard Deviation 8.66 |
| Tafamidis | Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, Month 12 | P functioning/large fiber:Change at Month 12(n=18) | -1.40 units on a scale | Standard Deviation 11.71 |
| Tafamidis | Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, Month 12 | ADLs: Baseline (n=21) | 7.30 units on a scale | Standard Deviation 7.01 |
| Tafamidis | Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, Month 12 | ADLs: Change at Month 6 (n=19) | 0.10 units on a scale | Standard Deviation 3.07 |
| Tafamidis | Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, Month 12 | ADLs: Change at Month 12 (n=18) | 0.90 units on a scale | Standard Deviation 2.58 |
| Tafamidis | Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, Month 12 | Symptoms: Baseline (n=21) | 9.00 units on a scale | Standard Deviation 7.5 |
| Tafamidis | Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, Month 12 | Symptoms: Change at Month 6 (n=19) | -0.90 units on a scale | Standard Deviation 3.05 |
| Tafamidis | Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, Month 12 | Symptoms: Change at Month 12 (n=18) | -0.10 units on a scale | Standard Deviation 4.28 |
| Tafamidis | Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, Month 12 | SFN: Change at Month 6 (n=19) | -0.30 units on a scale | Standard Deviation 2.54 |
| Tafamidis | Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, Month 12 | SFN: Change at Month 12 (n=18) | 0.70 units on a scale | Standard Deviation 3.22 |
| Tafamidis | Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, Month 12 | Autonomic neuropathy (AN): Baseline (n=21)) | 2.00 units on a scale | Standard Deviation 1.96 |
| Tafamidis | Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, Month 12 | AN: Change at Month 6 (n=19) | -0.50 units on a scale | Standard Deviation 1.61 |
| Tafamidis | Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, Month 12 | AN: Change at Month 12 (n=18) | -0.10 units on a scale | Standard Deviation 1.13 |
Other Pre-specified
Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) at Week 2, Week 6, Month 3, Month 6, Month 12
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. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants who were analyzed for the specific category. Data prior Month 6 were not anticipated to be informative hence were not analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) at Week 2, Week 6, Month 3, Month 6, Month 12 | Change at Month 12 (n= 16) | 306.61 picogram/mL (pg/mL) | Standard Deviation 1447.67 |
| Tafamidis | Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) at Week 2, Week 6, Month 3, Month 6, Month 12 | Baseline (n= 19) | 1248.89 picogram/mL (pg/mL) | Standard Deviation 1529.37 |
| Tafamidis | Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) at Week 2, Week 6, Month 3, Month 6, Month 12 | Change at Month 6 (n= 18) | 228.39 picogram/mL (pg/mL) | Standard Deviation 834.91 |
Other Pre-specified
Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12
SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health and two total scores (physical component summary \[PCS\] and mental component summary \[MCS\]. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).
Time frame: Baseline, Month 6, Month 12
Population: ITT population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were analyzed for the specific category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12 | PCS: Change at Month 6 (n= 18) | 1.60 units on a scale | Standard Deviation 7.25 |
| Tafamidis | Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12 | PCS: Change at Month 12 (n= 18) | -0.40 units on a scale | Standard Deviation 8.47 |
| Tafamidis | Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12 | Physical functioning: Baseline (n= 21) | 33.20 units on a scale | Standard Deviation 14.68 |
| Tafamidis | Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12 | Bodily pain: Change at Month 6 (n= 19) | 0.80 units on a scale | Standard Deviation 9.42 |
| Tafamidis | Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12 | General health: Change at Month 12 (n= 18) | 4.00 units on a scale | Standard Deviation 10.33 |
| Tafamidis | Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12 | Social functioning: Baseline (n= 21) | 41.80 units on a scale | Standard Deviation 11.16 |
| Tafamidis | Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12 | Social functioning: Change at Month 6 (n= 19) | 2.00 units on a scale | Standard Deviation 11.09 |
| Tafamidis | Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12 | Social functioning: Change at Month 12 (n= 18) | 3.00 units on a scale | Standard Deviation 11.72 |
| Tafamidis | Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12 | PCS: Baseline (n= 21) | 36.20 units on a scale | Standard Deviation 11.9 |
| Tafamidis | Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12 | MCS: Baseline (n= 21) | 47.00 units on a scale | Standard Deviation 10.96 |
| Tafamidis | Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12 | MCS: Change at Month 6 (n= 18) | -1.70 units on a scale | Standard Deviation 10.02 |
| Tafamidis | Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12 | MCS: Change at Month 12 (n= 18) | 3.00 units on a scale | Standard Deviation 11.11 |
| Tafamidis | Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12 | Physical functioning: Change at Month 6 (n= 19) | 0.90 units on a scale | Standard Deviation 7.5 |
| Tafamidis | Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12 | Physical functioning: Change at Month 12 (n= 18) | -0.10 units on a scale | Standard Deviation 10.84 |
| Tafamidis | Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12 | Role-physical: Baseline (n= 21) | 38.90 units on a scale | Standard Deviation 13.8 |
| Tafamidis | Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12 | Role-physical: Change at Month 6 (n= 19) | -1.80 units on a scale | Standard Deviation 10.42 |
| Tafamidis | Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12 | Role-physical: Change at Month 12 (n= 18) | -3.80 units on a scale | Standard Deviation 12.91 |
| Tafamidis | Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12 | Bodily pain: Baseline (n= 21) | 45.50 units on a scale | Standard Deviation 11.27 |
| Tafamidis | Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12 | Bodily pain: Change at Month 12 (n= 18) | 1.50 units on a scale | Standard Deviation 10.11 |
| Tafamidis | Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12 | General health: Baseline (n= 21) | 36.00 units on a scale | Standard Deviation 9.47 |
| Tafamidis | Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12 | General health: Change at Month 6 (n= 19) | 2.70 units on a scale | Standard Deviation 9.97 |
| Tafamidis | Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12 | Vitality: Baseline (n= 21) | 43.30 units on a scale | Standard Deviation 11.83 |
| Tafamidis | Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12 | Vitality: Change at Month 6 (n= 18) | 1.20 units on a scale | Standard Deviation 7.95 |
| Tafamidis | Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12 | Vitality: Change at Month 12 (n= 18) | 3.10 units on a scale | Standard Deviation 9.93 |
| Tafamidis | Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12 | Role-emotional: Baseline (n= 21) | 41.60 units on a scale | Standard Deviation 14.82 |
| Tafamidis | Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12 | Role-emotional: Change at Month 6 (n= 19) | -1.20 units on a scale | Standard Deviation 7.45 |
| Tafamidis | Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12 | Role-emotional: Change at Month 12 (n= 18) | 0.40 units on a scale | Standard Deviation 12.43 |
| Tafamidis | Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12 | Mental health: Baseline (n= 21) | 46.90 units on a scale | Standard Deviation 10.11 |
| Tafamidis | Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12 | Mental health: Change at Month 6 (n= 18) | -3.80 units on a scale | Standard Deviation 11.47 |
| Tafamidis | Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12 | Mental health: Change at Month 12 (n= 18) | 2.00 units on a scale | Standard Deviation 12.44 |
Other Pre-specified
Change From Baseline in the Neuropathy Impairment Score-Lower Limb (NIS-LL) at Month 6, Month 12
NIS-LL: assessed muscle weakness, reflexes and sensation; scored separately for left and right limbs. Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) are scored on 0 to 4 scale, higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae) and sensation (touch pressure, pin-prick, vibration, joint position) were scored 0 = normal, 1= decreased, or 2 = absent. Total possible NIS-LL score range 0-88, higher score=greater impairment.
Time frame: Baseline, Month 6, Month 12
Population: ITT population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were analyzed for the specific category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in the Neuropathy Impairment Score-Lower Limb (NIS-LL) at Month 6, Month 12 | Baseline (n= 21) | 27.60 units on a scale | Standard Deviation 24.67 |
| Tafamidis | Change From Baseline in the Neuropathy Impairment Score-Lower Limb (NIS-LL) at Month 6, Month 12 | Change at Month 6 (n= 19) | -0.50 units on a scale | Standard Deviation 5.73 |
| Tafamidis | Change From Baseline in the Neuropathy Impairment Score-Lower Limb (NIS-LL) at Month 6, Month 12 | Change at Month 12 (n= 18) | 2.70 units on a scale | Standard Deviation 6.21 |
Other Pre-specified
Change From Baseline in the Neuropathy Impairment Score (NIS) at Month 6, Month 12
NIS assessed cranial nerves(nerve 3,6; facial, palate and tongue weakness),muscle weakness (respiratory; neck, elbow(E), wrist(W), finger(F), hip, knee(K) flexion; shoulder, thumb abduction; brachioradialis; E, W, hip, K extension; F spread; toe, dorsal and plantar ankle flexors; toe extensors); score: 0-4, higher score=more weakness, reflexes(biceps and triceps brachii; brachioradialis; quadriceps femoris; triceps surae), index F and great toe sensation(touch pressure, pin-prick, vibration, joint position)score:0=normal,1=decreased or 2=absent. Total score=0-244, higher score=more impairment.
Time frame: Baseline, Month 6, Month 12
Population: ITT population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were analyzed for the specific category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in the Neuropathy Impairment Score (NIS) at Month 6, Month 12 | Baseline (n= 21) | 48.70 units on a scale | Standard Deviation 44.31 |
| Tafamidis | Change From Baseline in the Neuropathy Impairment Score (NIS) at Month 6, Month 12 | Change at Month 6 (n= 17) | 2.00 units on a scale | Standard Deviation 9.52 |
| Tafamidis | Change From Baseline in the Neuropathy Impairment Score (NIS) at Month 6, Month 12 | Change at Month 12 (n= 18) | 5.30 units on a scale | Standard Deviation 12.62 |
Other Pre-specified
Change From Baseline in Total Quality of Life (TQOL) Score at Month 6, Month 12
TQOL= sum of all Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) items,a 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on QOL of participants with DN; Item 1 to 7: related to symptoms and presence of symptom was assessed as 1 and absence was assessed as 0. Item 8-35: related to activities of daily living and scored on a 5-point Likert scale, where 0= no problem and 4= severe problem (except item 32, where -2= much better, 0=about the same, 2=much worse). Total TQOL score=-2 to 138;higher score=worse quality of life.
Time frame: Baseline, Month 6, Month 12
Population: ITT population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were analyzed for the specific category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in Total Quality of Life (TQOL) Score at Month 6, Month 12 | Baseline (n= 21) | 47.80 units on a scale | Standard Deviation 35.14 |
| Tafamidis | Change From Baseline in Total Quality of Life (TQOL) Score at Month 6, Month 12 | Change at Month 6 (n= 19) | -4.30 units on a scale | Standard Deviation 13.25 |
| Tafamidis | Change From Baseline in Total Quality of Life (TQOL) Score at Month 6, Month 12 | Change at Month 12 (n= 18) | 0.10 units on a scale | Standard Deviation 18.01 |
Other Pre-specified
Change From Baseline in Tricuspid Peak Velocity at Month 6, Month 12
Tricuspid peak velocity was measured by echocardiography.
Time frame: Baseline, Month 6, Month 12
Population: ITT population included all participants who received at least 1 dose of study medication. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants who were analyzed for the specific category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in Tricuspid Peak Velocity at Month 6, Month 12 | Baseline (n= 11) | 26.80 meter per second (m/sec) | Standard Deviation 8.62 |
| Tafamidis | Change From Baseline in Tricuspid Peak Velocity at Month 6, Month 12 | Change at Month 6 (n= 9) | 0.90 meter per second (m/sec) | Standard Deviation 4.86 |
| Tafamidis | Change From Baseline in Tricuspid Peak Velocity at Month 6, Month 12 | Change at Month 12 (n= 8) | 2.10 meter per second (m/sec) | Standard Deviation 9.25 |
Other Pre-specified
Change From Baseline in Tricuspid Pulmonary Artery Systolic Pressure (PASP) at Month 6, Month 12
Systolic right ventricular pressure can be estimated on echocardiography by adding right atrial pressure (RAP) to the trans-tricuspid gradient derived from the tricuspid regurgitation velocity.
Time frame: Baseline, Month 6, Month 12
Population: ITT population included all participants who received at least 1 dose of study medication. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants who were analyzed for the specific category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in Tricuspid Pulmonary Artery Systolic Pressure (PASP) at Month 6, Month 12 | Baseline (n= 11) | 35.50 millimeter of mercury (mmHg) | Standard Deviation 11.55 |
| Tafamidis | Change From Baseline in Tricuspid Pulmonary Artery Systolic Pressure (PASP) at Month 6, Month 12 | Change at Month 6 (n= 6) | 3.80 millimeter of mercury (mmHg) | Standard Deviation 7.81 |
| Tafamidis | Change From Baseline in Tricuspid Pulmonary Artery Systolic Pressure (PASP) at Month 6, Month 12 | Change at Month 12 (n= 7) | 2.10 millimeter of mercury (mmHg) | Standard Deviation 13.08 |
Other Pre-specified
Change From Baseline in Troponin I Levels at Week 2, Week 6 , Month 3, Month 6, Month 12
Troponin I is a cardiac injury biomarker. Higher concentrations of this marker in blood are associated with heart injury.
Time frame: Baseline, Week 2, Week 6 , Month 3, Month 6, Month 12
Population: ITT population. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants who were analyzed for the specific category. Data prior Month 6 were not anticipated to be informative hence were not analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Change From Baseline in Troponin I Levels at Week 2, Week 6 , Month 3, Month 6, Month 12 | Baseline (n= 20) | 0.0234 nanogram/mL | Standard Deviation 0.0409 |
| Tafamidis | Change From Baseline in Troponin I Levels at Week 2, Week 6 , Month 3, Month 6, Month 12 | Change at Month 6 (n= 18) | 0.0015 nanogram/mL | Standard Deviation 0.0501 |
| Tafamidis | Change From Baseline in Troponin I Levels at Week 2, Week 6 , Month 3, Month 6, Month 12 | Change at Month 12 (n= 18) | 0.0025 nanogram/mL | Standard Deviation 0.0487 |
Other Pre-specified
Number of Participants Who Discontinued Due to Clinical or Laboratory Adverse Events
Time frame: Baseline up to Month 12
Population: ITT population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tafamidis | Number of Participants Who Discontinued Due to Clinical or Laboratory Adverse Events | 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 abnormality, valvular abnormality, pericardial effusion, abnormal regional wall motion, inferior vena cava respiratory variation, posterior (P) left ventricular (LV) wall/septal (S) thickness, right ventricular thickness, ejection fraction, ratio of early (E) diastolic transmitral flow and atrial(A) contraction velocity (E/A), ratio of 'E'to lateral/septal mitral annular velocity (e') (E/e'prime lateral, E/e'prime septal), E deceleration time (DT), isovolumic relaxation time (IVRT).
Time frame: Day 1 up to Month 12
Population: ITT population. The 'n' for any post-dose incidence included participants with baseline values that were not abnormal (that is treatment-emergent abnormalities). Abnormalities at early termination were excluded from the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings | Any ECHO abnormalities (n= 19) | 12 participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings | IVRT <=70 msec (n= 13) | 2 participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings | Pericardial effusion (n= 19) | 2 participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings | Valvular abnormalities- thickening (n= 5) | 3 participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings | Valvular abnormalities - regurgitation (n= 9) | 2 participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings | Abnormal regional wall motion (n= 11) | 2 participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings | Inferior vena cava respiratory variation (n= 13) | 0 participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings | LV P wall thickness >=13 millimeter (mm) (n= 3) | 2 participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings | LV S thickness >=13 mm (n= 3) | 1 participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings | Right ventricular thickness >=7 mm (n= 13) | 6 participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings | E/A ratio >=2 (n= 16) | 3 participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings | E/e'prime Lateral >15 (n= 15) | 3 participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings | E/e'prime Septal >15 (n= 10) | 2 participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings | Ejection fraction < 50 percent (%) (n= 17) | 2 participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings | EDT <= 150 milliseconds (msec) (n= 14) | 1 participants |
Other Pre-specified
Number of Participants With Clinically Significant Treatment-Emergent Electrocardiogram (ECG) Findings
ECG: investigator assessed test to assess cardiac function. ECG abnormality criteria: any abnormality, arrhythmia, rhythm, conduction, morphology, myocardial infarction, ST segment, T waves and abnormal U waves.
Time frame: Day 1 up to Month 12
Population: ITT population. The 'n' for any post-dose incidence included participants with baseline values that were not abnormal (that is treatment-emergent abnormalities). Abnormalities at early termination were excluded from the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Electrocardiogram (ECG) Findings | Any ECG abnormalities (n= 21) | 9 participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Electrocardiogram (ECG) Findings | Arrhythmia (n= 18) | 8 participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Electrocardiogram (ECG) Findings | Rhythm (n= 18) | 1 participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Electrocardiogram (ECG) Findings | Conduction (n= 8) | 2 participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Electrocardiogram (ECG) Findings | Morphology (n= 20) | 0 participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Electrocardiogram (ECG) Findings | Myocardial infarction (n= 18) | 0 participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Electrocardiogram (ECG) Findings | ST segment (n= 20) | 1 participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Electrocardiogram (ECG) Findings | T waves (n=18) | 1 participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Electrocardiogram (ECG) Findings | Abnormal U waves (n= 21) | 0 participants |
Other Pre-specified
Number of Participants With Clinically Significant Treatment-Emergent Holter Monitoring Findings
Holter monitoring recorded heart rhythm. Holter monitoring abnormality criteria: any abnormality, atrial fibrillation/flutter, atrial tachycardia, non-sustained ventricular tachycardia (VT), sustained VT and sinus pause.
Time frame: Day 1 up to Month 12
Population: ITT population. The 'n' for any post-dose incidence included participants with baseline values that were not abnormal (that is treatment-emergent abnormalities). Abnormalities at early termination were excluded from the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Holter Monitoring Findings | Any Holter monitoring abnormalities (n= 19) | 9 participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Holter Monitoring Findings | Atrial fibrillation/flutter (n= 18) | 1 participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Holter Monitoring Findings | Atrial tachycardia (n= 9) | 4 participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Holter Monitoring Findings | Non-sustained VT <30 beats (n= 11) | 4 participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Holter Monitoring Findings | Sustained VT >=30 beats (n= 19) | 0 participants |
| Tafamidis | Number of Participants With Clinically Significant Treatment-Emergent Holter Monitoring Findings | Sinus pause (n= 18) | 1 participants |
Other Pre-specified
Number of Participants With Greater Than or Equal to Grade 3 Treatment-Emergent Adverse Events
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 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tafamidis | Number of Participants With Greater Than or Equal to Grade 3 Treatment-Emergent Adverse Events | 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 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tafamidis | Number of Participants With Treatment-Emergent Adverse Events (AEs) | 17 participants |
Other Pre-specified
Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 6, Month 12
Response to treatment was indicated by either improvement (decrease from baseline) or stabilization (change from baseline of 0 to less than \[\<\] 2) in Neuropathy Impairment Score- Lower Limb (NIS-LL) score, based on mean of 2 scores in 1 week period. NIS-LL: assessed muscle weakness, reflexes, sensation. Each item scored separately for left, right limbs. Components of muscle weakness scored on 0(normal) to 4(paralysis) scale, higher score=greater weakness. Components of reflexes, sensation scored 0=normal, 1=decreased, or 2=absent. Total NIS-LL score range 0-88, higher score=greater impairment.
Time frame: Month 6, Month 12
Population: Data on NIS-LL was reported in individual participant listings but responder status was not statistically summarized.