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CompletedNCT00630864Updated Jan 18, 2013Results posted

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

A Phase 2 interventional study of Fx-1006A in Transthyretin-associated Amyloidosis With Polyneuropathy, sponsored by Pfizer. Completed at 4 sites in 4 countries. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2013-01-18.

Sponsored by Pfizer · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
21
Allocation
Not applicable
Ages
18 Years to 75 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Transthyretin-associated Amyloidosis With Polyneuropathy

Keywords

  • Transthyretin, TTR, amyloidosis, TTR amyloidosis, polyneuropathy
03

In context

Polyneuropathies

256 studies on the registry are indexed under Polyneuropathies; 50 are open to participants now.

This study's enrollment of 21 is below the median of 75 across 162 interventional studies indexed under Polyneuropathies.

Browse Polyneuropathies studies →

Lead sponsor

Pfizer is the lead sponsor of 3,244 studies on the registry; 139 are open to participants now.

Of its 582 completed or terminated interventional studies of FDA-regulated products, 381 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts 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

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).
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
21 participants (actual)

Study arms

  • Experimental
    1

    Fx-1006A 20mg soft gelatin capsules once daily for 12 months

    Drug: Fx-1006A

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

06

What researchers measure

Primary outcomes

  1. 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

Secondary outcomes

  1. 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

Other outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. Number of Participants Who Discontinued Due to Clinical or Laboratory Adverse Events

    Time frame: Baseline up to Month 12

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  21. 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

  22. 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

  23. 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

  24. 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

  25. 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

  26. 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

  27. 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

  28. 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

  29. 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

  30. 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

  31. 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

  32. 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

07

Results

Posted Dec 17, 2012

Participant flow

Part 1 (up to Week 6)
Participant flow — Part 1 (up to Week 6)
MilestoneTafamidis
Started21
Completed20
Not completed1
Withdrew: Adverse event1
Part 2 (After Week 6 up to Month 12)
Participant flow — Part 2 (After Week 6 up to Month 12)
MilestoneTafamidis
Started20
Completed18
Not completed2
Withdrew: Liver transplant2

Outcome measures

PrimaryPercentage 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
Reported as:
Number · percentage of participants
Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer at Week 6
percentage of participantsTafamidis
Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer at Week 694.7 (74.0 to 99.9)
SecondaryPercentage 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
Reported as:
Number · percentage of participants
Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer at Month 6 and 12
percentage of participantsTafamidis
Month 6 (n= 18)100.0 (81.5 to 100.0)
Month 12 (n= 17)100.0 (80.5 to 100.0)
Other pre-specifiedNumber 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
Reported as:
Number · participants
Number of Participants With Treatment-Emergent Adverse Events (AEs)
participantsTafamidis
Number of Participants With Treatment-Emergent Adverse Events (AEs)17
Other pre-specifiedNumber 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
Reported as:
Number · participants
Number of Participants With Greater Than or Equal to Grade 3 Treatment-Emergent Adverse Events
participantsTafamidis
Number of Participants With Greater Than or Equal to Grade 3 Treatment-Emergent Adverse Events3
Other pre-specifiedNumber 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
Reported as:
Number · participants
Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings
participantsTafamidis
Any ECHO abnormalities (n= 19)12
Pericardial effusion (n= 19)2
Valvular abnormalities- thickening (n= 5)3
Valvular abnormalities - regurgitation (n= 9)2
Abnormal regional wall motion (n= 11)2
Inferior vena cava respiratory variation (n= 13)0
LV P wall thickness >=13 millimeter (mm) (n= 3)2
LV S thickness >=13 mm (n= 3)1
Right ventricular thickness >=7 mm (n= 13)6
E/A ratio >=2 (n= 16)3
E/e'prime Lateral >15 (n= 15)3
E/e'prime Septal >15 (n= 10)2
Ejection fraction < 50 percent (%) (n= 17)2
EDT <= 150 milliseconds (msec) (n= 14)1
IVRT <=70 msec (n= 13)2
Other pre-specifiedNumber 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
Reported as:
Number · participants
Number of Participants With Clinically Significant Treatment-Emergent Electrocardiogram (ECG) Findings
participantsTafamidis
Any ECG abnormalities (n= 21)9
Arrhythmia (n= 18)8
Rhythm (n= 18)1
Conduction (n= 8)2
Morphology (n= 20)0
Myocardial infarction (n= 18)0
ST segment (n= 20)1
T waves (n=18)1
Abnormal U waves (n= 21)0
Other pre-specifiedNumber 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
Reported as:
Number · participants
Number of Participants With Clinically Significant Treatment-Emergent Holter Monitoring Findings
participantsTafamidis
Any Holter monitoring abnormalities (n= 19)9
Atrial fibrillation/flutter (n= 18)1
Atrial tachycardia (n= 9)4
Non-sustained VT <30 beats (n= 11)4
Sustained VT >=30 beats (n= 19)0
Sinus pause (n= 18)1
Other pre-specifiedNumber of Participants Who Discontinued Due to Clinical or Laboratory Adverse Events
Time frame:
Baseline up to Month 12
Reported as:
Number · participants
Number of Participants Who Discontinued Due to Clinical or Laboratory Adverse Events
participantsTafamidis
Number of Participants Who Discontinued Due to Clinical or Laboratory Adverse Events1
Other pre-specifiedChange 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
Reported as:
Mean · units on a scale
Change From Baseline in the Neuropathy Impairment Score (NIS) at Month 6, Month 12
units on a scaleTafamidis
Baseline (n= 21)48.70 ± 44.31
Change at Month 6 (n= 17)2.00 ± 9.52
Change at Month 12 (n= 18)5.30 ± 12.62
Other pre-specifiedChange 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
Reported as:
Mean · units on a scale
Change From Baseline in the Neuropathy Impairment Score-Lower Limb (NIS-LL) at Month 6, Month 12
units on a scaleTafamidis
Baseline (n= 21)27.60 ± 24.67
Change at Month 6 (n= 19)-0.50 ± 5.73
Change at Month 12 (n= 18)2.70 ± 6.21
Other pre-specifiedPercentage 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

No measurements were reported for this outcome.

Other pre-specifiedChange 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
Reported as:
Mean · units on a scale
Change From Baseline in Total Quality of Life (TQOL) Score at Month 6, Month 12
units on a scaleTafamidis
Baseline (n= 21)47.80 ± 35.14
Change at Month 6 (n= 19)-4.30 ± 13.25
Change at Month 12 (n= 18)0.10 ± 18.01
Other pre-specifiedChange 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
Reported as:
Mean · units on a scale
Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, Month 12
units on a scaleTafamidis
Physical (P)functioning/large fiber:Baseline(n=21)25.60 ± 18.50
P functioning/large fiber: Change at Month 6(n=19)-2.60 ± 8.66
P functioning/large fiber:Change at Month 12(n=18)-1.40 ± 11.71
ADLs: Baseline (n=21)7.30 ± 7.01
ADLs: Change at Month 6 (n=19)0.10 ± 3.07
ADLs: Change at Month 12 (n=18)0.90 ± 2.58
Symptoms: Baseline (n=21)9.00 ± 7.50
Symptoms: Change at Month 6 (n=19)-0.90 ± 3.05
Symptoms: Change at Month 12 (n=18)-0.10 ± 4.28
Small fiber neuropathy (SFN): Baseline (n=21)3.90 ± 4.92
SFN: Change at Month 6 (n=19)-0.30 ± 2.54
SFN: Change at Month 12 (n=18)0.70 ± 3.22
Autonomic neuropathy (AN): Baseline (n=21))2.00 ± 1.96
AN: Change at Month 6 (n=19)-0.50 ± 1.61
AN: Change at Month 12 (n=18)-0.10 ± 1.13
Other pre-specifiedChange 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
Reported as:
Mean · Z-score
Change From Baseline in Nerve Conduction Studies (NCS) at Month 6, Month 12
Z-scoreTafamidis
Baseline (n= 21)6.10 ± 5.90
Change at Month 6 (n= 19)0.60 ± 2.69
Change at Month 12 (n= 18)0.20 ± 3.30
Other pre-specifiedChange 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
Reported as:
Mean · Z-score
Change From Baseline in Heart Rate Response to Deep Breathing (HRDB) at Month 6 and Month 12
Z-scoreTafamidis
Baseline (n= 12)-0.70 ± 2.17
Change at Month 6 (n= 6)0.00 ± 2.26
Change at Month 12 (n= 7)-0.1 ± 1.36
Other pre-specifiedChange 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
Reported as:
Mean · kg/m^2*g/L
Change From Baseline in Modified Body Mass Index (mBMI) at Month 6, Month 12
kg/m^2*g/LTafamidis
Baseline (n= 20)1052.50 ± 206.66
Change at Month 6 (n= 17)-22.40 ± 77.01
Change at Month 12 (n= 16)16.60 ± 89.33
Other pre-specifiedChange 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
Reported as:
Mean · units on a scale
Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12
units on a scaleTafamidis
PCS: Baseline (n= 21)36.20 ± 11.90
PCS: Change at Month 6 (n= 18)1.60 ± 7.25
PCS: Change at Month 12 (n= 18)-0.40 ± 8.47
MCS: Baseline (n= 21)47.00 ± 10.96
MCS: Change at Month 6 (n= 18)-1.70 ± 10.02
MCS: Change at Month 12 (n= 18)3.00 ± 11.11
Physical functioning: Baseline (n= 21)33.20 ± 14.68
Physical functioning: Change at Month 6 (n= 19)0.90 ± 7.50
Physical functioning: Change at Month 12 (n= 18)-0.10 ± 10.84
Role-physical: Baseline (n= 21)38.90 ± 13.80
Role-physical: Change at Month 6 (n= 19)-1.80 ± 10.42
Role-physical: Change at Month 12 (n= 18)-3.80 ± 12.91
Bodily pain: Baseline (n= 21)45.50 ± 11.27
Bodily pain: Change at Month 6 (n= 19)0.80 ± 9.42
Bodily pain: Change at Month 12 (n= 18)1.50 ± 10.11
General health: Baseline (n= 21)36.00 ± 9.47
General health: Change at Month 6 (n= 19)2.70 ± 9.97
General health: Change at Month 12 (n= 18)4.00 ± 10.33
Vitality: Baseline (n= 21)43.30 ± 11.83
Vitality: Change at Month 6 (n= 18)1.20 ± 7.95
Vitality: Change at Month 12 (n= 18)3.10 ± 9.93
Social functioning: Baseline (n= 21)41.80 ± 11.16
Social functioning: Change at Month 6 (n= 19)2.00 ± 11.09
Social functioning: Change at Month 12 (n= 18)3.00 ± 11.72
Role-emotional: Baseline (n= 21)41.60 ± 14.82
Role-emotional: Change at Month 6 (n= 19)-1.20 ± 7.45
Role-emotional: Change at Month 12 (n= 18)0.40 ± 12.43
Mental health: Baseline (n= 21)46.90 ± 10.11
Mental health: Change at Month 6 (n= 18)-3.80 ± 11.47
Mental health: Change at Month 12 (n= 18)2.00 ± 12.44
Other pre-specifiedChange 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
Reported as:
Mean · millimeter (mm)
Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 12
millimeter (mm)Tafamidis
IVST: Baseline (n=19)15.24 ± 2.77
IVST: Change at Month 6 (n=15)0.57 ± 2.10
IVST: Change at Month 12 (n=14)1.04 ± 2.04
PLVWT: Baseline (n=19)14.60 ± 2.59
PLVWT: Change at Month 6 (n=15)0.30 ± 1.98
PLVWT: Change at Month 12 (n=14)0.70 ± 1.73
RVWT: Baseline (n=17)6.09 ± 2.01
RVWT: Change at Month 6 (n=8)1.12 ± 1.72
RVWT: Change at Month 12 (n=12)1.08 ± 1.29
LAD (ant-post): Baseline (n=21)36.30 ± 6.20
LAD (ant-post): Change at Month 6 (n=17)1.50 ± 4.57
LAD (ant-post): Change at Month 12 (n=16)1.60 ± 3.52
LAD (medio-lateral): Baseline (n=16)37.40 ± 4.80
LAD (medio-lateral): Change at Month 6 (n=7)4.30 ± 6.90
LAD (medio-lateral): Change at Month 12 (n=9)1.90 ± 4.20
LAD (sup-inf): Baseline (n=16)48.30 ± 9.88
LAD (sup-inf): Change at Month 6 (n= 8)3.10 ± 5.03
LAD (sup-inf): Change at Month 6 (n= 9)4.20 ± 6.46
LVED: Baseline (n= 19)39.66 ± 4.84
LVED: Change at Month 6 (n= 15)-1.03 ± 3.88
LVED: Change at Month 12 (n= 14)0.11 ± 3.42
RLVWT: Baseline (n=19)0.75 ± 0.19
RLVWT: Change at Month 6 (n= 15)0.05 ± 0.16
RLVWT: Change at Month 12 (n= 14)0.03 ± 0.12
Other pre-specifiedChange 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
Reported as:
Mean · cubic centimeter (cc)
Change From Baseline in Left Atrial Volume at Month 6, Month 12
cubic centimeter (cc)Tafamidis
Baseline (n= 15)51.50 ± 23.81
Change at Month 6 (n= 6)12.30 ± 17.20
Change at Month 12 (n= 9)1.90 ± 18.90
Other pre-specifiedChange 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
Reported as:
Mean · milliliter (mL)
Change From Baseline in Left Ventricular (LV) End Systolic Volume, Left Ventricle (LV) Stroke Volume at Month 6, Month 12
milliliter (mL)Tafamidis
LV end systolic volume: Baseline (n= 11)30.4 ± 13.93
LV end systolic volume: Change at Month 6 (n= 6)3.50 ± 7.79
LV end systolic volume: Change at Month 12 (n= 6)4.70 ± 3.01
LV stroke volume: Baseline (n= 11)43.10 ± 13.26
LV stroke volume: Change at Month 6 (n= 6)-2.50 ± 15.23
LV stroke volume: Change at Month 12 (n= 6)3.70 ± 10.69
Other pre-specifiedChange 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
Reported as:
Mean · percentage of EDD
Change From Baseline in Fractional Shortening at Month 6, Month 12
percentage of EDDTafamidis
Baseline (n= 18)31.20 ± 5.68
Change at Month 6 (n= 14)-1.10 ± 5.91
Change at Month 12 (n= 14)-0.90 ± 6.24
Other pre-specifiedChange 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
Reported as:
Mean · percentage of EDV
Change From Baseline in Left Ventricular (LV) Ejection Fraction at Month 6, Month 12
percentage of EDVTafamidis
Baseline (n= 21)60.30 ± 9.96
Change at Month 6 (n= 18)-3.80 ± 7.73
Change at Month 12 (n=18)-2.20 ± 5.37
Other pre-specifiedChange 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
Reported as:
Mean · gram
Change From Baseline in Left Ventricular Mass (LVM) at Month 6, Month 12
gramTafamidis
Baseline: (n= 19)230.84 ± 62.54
Change at Month 6 (n= 15)1.11 ± 46.53
Change at Month 12 (n= 14)20.91 ± 35.07
Other pre-specifiedChange 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
Reported as:
Mean · msec
Change From Baseline in Isovolumetric Relaxation Time (IVRT), Mitral Deceleration Time at Month 6, Month 12
msecTafamidis
IVRT: Baseline (n= 10)84.10 ± 17.51
IVRT: Change at Month 6 (n= 3)2.70 ± 20.03
IVRT: Change at Month 12 (n= 8)-4.00 ± 25.63
MDT: Baseline (n= 18)164.00 ± 35.59
MDT: Change at Month 6 (n= 14)1.90 ± 28.17
MDT: Change at Month 12 (n= 15)11.90 ± 29.45
Other pre-specifiedChange 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
Reported as:
Mean · centimeter (cm)
Change From Baseline in Aortic Annulus Diameter at Month 6, Month 12
centimeter (cm)Tafamidis
Baseline (n= 21)2.045 ± 0.184
Change at Month 6 (n= 17)-0.009 ± 0.160
Change at Month 12 (n= 16)-0.041 ± 0.108
Other pre-specifiedChange 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
Reported as:
Mean · meter per second (m/sec)
Change From Baseline in Tricuspid Peak Velocity at Month 6, Month 12
meter per second (m/sec)Tafamidis
Baseline (n= 11)26.80 ± 8.62
Change at Month 6 (n= 9)0.90 ± 4.86
Change at Month 12 (n= 8)2.10 ± 9.25
Other pre-specifiedChange 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
Reported as:
Mean · millimeter of mercury (mmHg)
Change From Baseline in Tricuspid Pulmonary Artery Systolic Pressure (PASP) at Month 6, Month 12
millimeter of mercury (mmHg)Tafamidis
Baseline (n= 11)35.50 ± 11.55
Change at Month 6 (n= 6)3.80 ± 7.81
Change at Month 12 (n= 7)2.10 ± 13.08
Other pre-specifiedChange 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
Reported as:
Mean · centimeter per second (cm/sec)
Change From Baseline in Doppler Data at Month 6, Month 12
centimeter per second (cm/sec)Tafamidis
Mitral Peak A: Baseline (n= 18)59.00 ± 23.77
Mitral Peak A: Change at Month 6 (n= 13)-0.50 ± 16.01
Mitral Peak A: Change at Month 12 (n= 15)-3.70 ± 15.43
Mitral Peak E: Baseline (n= 19)74.10 ± 15.58
Mitral Peak E: Change at Month 6 (n= 15)4.70 ± 10.28
Mitral Peak E: Change at Month 12 (n= 16)5.10 ± 13.75
Septal s': Baseline (n= 16)4.72 ± 1.64
Septal s': Change at Month 6 (n= 12)0.43 ± 0.51
Septal s': Change at Month 12 (n= 8)-0.33 ± 0.90
Septal e': Baseline (n= 16)4.54 ± 1.88
Septal e': Change at Month 6 (n= 12)1.25 ± 2.29
Septal e': Change at Month 12 (n= 8)0.04 ± 0.61
Septal a': Baseline (n= 15)4.66 ± 2.67
Septal a': Change at Month 6 (n= 11)0.53 ± 1.39
Septal a': Change at Month 12 (n= 8)-0.10 ± 1.74
Lateral s': Baseline (n= 16)6.71 ± 2.97
Lateral s': Change at Month 6 (n= 10)0.55 ± 1.41
Lateral s': Change at Month 12 (n= 7)0.19 ± 1.20
Lateral e': Baseline (n= 16)6.91 ± 2.90
Lateral e': Change at Month 6 (n= 11)0.65 ± 1.27
Lateral e': Change at Month 12 (n= 7)0.16 ± 1.42
Lateral a': Baseline (n= 15)5.93 ± 3.38
Lateral a': Change at Month 6 (n= 10)0.31 ± 2.69
Lateral a': Change at Month 12 (n= 6)-0.45 ± 2.94
Other pre-specifiedChange 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
Reported as:
Mean · ratio
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
ratioTafamidis
e:e' Lateral: Baseline (n= 16)13.148 ± 7.781
e:e' Lateral: Change at Month 6 (n= 10)-0.145 ± 3.227
e:e' Lateral: Change at Month 12 (n= 7)-0.243 ± 5.245
E/A: Baseline (n= 18)1.463 ± 0.667
E/A: Change at Month 6 (n= 13)0.175 ± 0.565
E/A: Change at Month 12 (n= 15)0.185 ± 0.658
Other pre-specifiedChange 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
Reported as:
Mean · gram/millivolt
Change From Baseline in Left Ventricular (LV) Mass/Voltage Ratio at Month 6, Month 12
gram/millivoltTafamidis
Baseline (n= 19)5.495 ± 2.149
Change at Month 6 (n= 14)0.028 ± 1.479
Change at Month 12 (n= 14)0.878 ± 1.437
Other pre-specifiedChange 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
Reported as:
Mean · milliliter/square meter (mL/m^2)
Change From Baseline in Left Atrial (LA) Volume Index at Month 6, Month 12
milliliter/square meter (mL/m^2)Tafamidis
Baseline (n= 15)27.33 ± 10.21
Change at Month 6 (n= 5)7.23 ± 8.78
Change at Month 12 (n= 9)1.06 ± 9.66
Other pre-specifiedChange 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
Reported as:
Mean · picogram/mL (pg/mL)
Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) at Week 2, Week 6, Month 3, Month 6, Month 12
picogram/mL (pg/mL)Tafamidis
Baseline (n= 19)1248.89 ± 1529.37
Change at Month 6 (n= 18)228.39 ± 834.91
Change at Month 12 (n= 16)306.61 ± 1447.67
Other pre-specifiedChange 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
Reported as:
Mean · units on a scale
Change From Baseline in Karnofsky Performance Status Scale at Month 6, Month 12
units on a scaleTafamidis
Baseline (n= 21)74.80 ± 14.01
Change at Month 6 (n= 19)-1.10 ± 5.67
Change at Month 12 (n= 18)-3.30 ± 5.94
Other pre-specifiedChange 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
Reported as:
Mean · nanogram/mL
Change From Baseline in Troponin I Levels at Week 2, Week 6 , Month 3, Month 6, Month 12
nanogram/mLTafamidis
Baseline (n= 20)0.0234 ± 0.0409
Change at Month 6 (n= 18)0.0015 ± 0.0501
Change at Month 12 (n= 18)0.0025 ± 0.0487

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Tafamidis—8/21 (38.1%)13/21 (61.9%)
Most frequent serious events
Showing 10 of 12
Most frequent serious events
EventTafamidis
FallInjury, poisoning and procedural complications2/21
Atrioventricular blockCardiac disorders1/21
Coronary artery stenosisCardiac disorders1/21
FaecalomaGastrointestinal disorders1/21
SubileusGastrointestinal disorders1/21
MalaiseGeneral disorders1/21
Ankle fractureInjury, poisoning and procedural complications1/21
Avulsion fractureInjury, poisoning and procedural complications1/21
ArthritisMusculoskeletal and connective tissue disorders1/21
Transient ischaemic attackNervous system disorders1/21
Most frequent other events
Showing 10 of 20
Most frequent other events
EventTafamidis
DiarrhoeaGastrointestinal disorders5/21
FallInjury, poisoning and procedural complications4/21
Pain in extremityMusculoskeletal and connective tissue disorders4/21
VomitingGastrointestinal disorders3/21
ConstipationGastrointestinal disorders3/21
DizzinessNervous system disorders3/21
DyspnoeaRespiratory, thoracic and mediastinal disorders3/21
NauseaGastrointestinal disorders2/21
FatigueGeneral disorders2/21
Oedema peripheralGeneral disorders2/21

Baseline characteristics

Age Continuous
Age Continuous(years)Tafamidis
Mean63.10 ± 9.86
Sex: Female, Male
Sex: Female, Male(Participants)Tafamidis
Female8
Male13
08

Study locations

4 sites
  • Johns Hopkins Hospital
    Baltimore, Maryland 21205, United States
  • CHU de Bicetre
    Paris, France
  • Universitatsklinikum Munster, Transplant Hepatology
    Munster, Germany
  • Centro per lo Studio e la Cura delle Amiloidosi Sistemiche
    IRCCS - Policlinico San Matteo, Pavia 19 - 27100, Italy
09

References and documents

Publications

  • Merlini G, Coelho T, Waddington Cruz M, Li H, Stewart M, Ebede B. Evaluation of Mortality During Long-Term Treatment with Tafamidis for Transthyretin Amyloidosis with Polyneuropathy: Clinical Trial Results up to 8.5 Years. Neurol Ther. 2020 Jun;9(1):105-115. doi: 10.1007/s40120-020-00180-w. Epub 2020 Feb 27. PubMed 32107748 ↗
  • Huber P, Flynn A, Sultan MB, Li H, Rill D, Ebede B, Gundapaneni B, Schwartz JH. A comprehensive safety profile of tafamidis in patients with transthyretin amyloid polyneuropathy. Amyloid. 2019 Dec;26(4):203-209. doi: 10.1080/13506129.2019.1643714. Epub 2019 Jul 27. PubMed 31353964 ↗
  • Gundapaneni BK, Sultan MB, Keohane DJ, Schwartz JH. Tafamidis delays neurological progression comparably across Val30Met and non-Val30Met genotypes in transthyretin familial amyloid polyneuropathy. Eur J Neurol. 2018 Mar;25(3):464-468. doi: 10.1111/ene.13510. Epub 2017 Dec 26. PubMed 29115008 ↗
  • Merlini G, Plante-Bordeneuve V, Judge DP, Schmidt H, Obici L, Perlini S, Packman J, Tripp T, Grogan DR. Effects of tafamidis on transthyretin stabilization and clinical outcomes in patients with non-Val30Met transthyretin amyloidosis. J Cardiovasc Transl Res. 2013 Dec;6(6):1011-20. doi: 10.1007/s12265-013-9512-x. Epub 2013 Oct 8. PubMed 24101373 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 18, 2013, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT00630864
Lead sponsor
Pfizer
Responsible party
Sponsor
First posted
Mar 7, 2008
Start date
Jun 2008
Primary completion
Jan 2010
Completion
Jan 2010
Results posted
Dec 17, 2012
Last update
Jan 18, 2013

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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