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Trial record 6 of 14 for:    Atrial Fibrillation, Familial, 12

An Extension of Study Fx-005 Evaluating Long-Term Safety And Clinical Outcomes Of Fx-1006A In Patients With Transthyretin Amyloid Polyneuropathy

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ClinicalTrials.gov Identifier: NCT00791492
Recruitment Status : Completed
First Posted : November 14, 2008
Results First Posted : December 17, 2012
Last Update Posted : December 17, 2012
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Familial Amyloid Polyneuropathy
ATTR-PN
Intervention Drug: Fx-1006A
Enrollment 86
Recruitment Details Participants who completed study FX-005 (NCT00409175), were eligible for the current study FX-006 (NCT00791492).
Pre-assignment Details  
Arm/Group Title Tafamidis-Tafamidis Placebo-Tafamidis
Hide Arm/Group Description Participants who received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months. Participants who received placebo matched to tafamidis (Fx-1006A) 20 mg capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Period Title: Overall Study
Started 45 41
TREATED 44 41
Completed 39 38
Not Completed 6 3
Reason Not Completed
Withdrawal by Subject             1             2
Liver transplantation             5             1
Arm/Group Title Tafamidis-Tafamidis Placebo-Tafamidis Total
Hide Arm/Group Description Participants who received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months. Participants who received placebo matched to tafamidis (Fx-1006A) 20 mg capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months. Total of all reporting groups
Overall Number of Baseline Participants 44 41 85
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 44 participants 41 participants 85 participants
41.3  (13.4) 39.6  (13.2) 40.4  (13.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 41 participants 85 participants
Female
24
  54.5%
23
  56.1%
47
  55.3%
Male
20
  45.5%
18
  43.9%
38
  44.7%
1.Primary Outcome
Title Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 6
Hide Description Response to treatment indicated by either improvement(decrease from baseline) or stabilization(change from baseline of 0 to less than[<] 2) in 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:0(normal)-4(paralysis),higher score=more weakness;reflexes,sensation:0=normal,1=decreased,or 2=absent.Total NIS-LL score range 0-88,higher score=more impairment. For tafamidis-tafamidis group, NIS-LL baseline value of previous study FX-005(NCT00409175) used as reference.
Time Frame Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population included all participants who received at least one dose of study medication and had no more than 2 months interruption between studies FX-005 and FX-006. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
Arm/Group Title Tafamidis-Tafamidis Placebo-Tafamidis
Hide Arm/Group Description:
Participants who received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Participants who received placebo matched to tafamidis (Fx-1006A) 20 mg capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Overall Number of Participants Analyzed 37 32
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
62.2
(44.8 to 77.5)
68.8
(50.0 to 83.9)
2.Primary Outcome
Title Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 12
Hide Description Response to treatment indicated by either improvement(decrease from baseline) or stabilization(change from baseline of 0 to less than[<] 2) in 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:0(normal)-4(paralysis),higher score=more weakness;reflexes,sensation:0=normal,1=decreased,or 2=absent.Total NIS-LL score range 0-88,higher score=more impairment. For tafamidis-tafamidis group, NIS-LL baseline value of previous study FX-005(NCT00409175) used as reference.
Time Frame Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who received at least one dose of study medication and had no more than 2 months interruption between studies FX-005 and FX-006. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
Arm/Group Title Tafamidis-Tafamidis Placebo-Tafamidis
Hide Arm/Group Description:
Participants who received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Participants who received placebo matched to tafamidis (Fx-1006A) 20 mg capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Overall Number of Participants Analyzed 33 30
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
54.5
(36.4 to 71.9)
60.0
(40.6 to 77.3)
3.Primary Outcome
Title Change From Baseline in Norfolk Quality of Life- Diabetic Neuropathy (QOL-DN) Total Quality of Life (TQOL) Score at Month 6
Hide Description Norfolk QOL-DN: 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on the quality of life of participants with diabetic neuropathy; Item 1 to 7: related to symptoms and presence of symptoms 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). TQOL= sum of all the items, total possible score range= -2 to 138, where higher score=worse quality of life.
Time Frame Baseline, Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who received at least one dose of study medication and had no more than 2 months interruption between studies FX-005 and FX-006. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
Arm/Group Title Tafamidis-Tafamidis Placebo-Tafamidis
Hide Arm/Group Description:
Participants who received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Participants who received placebo matched to tafamidis (Fx-1006A) 20 mg capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Overall Number of Participants Analyzed 38 33
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 21.05  (21.88) 38.09  (31.89)
Change at Month 6 0.03  (8.83) -4.88  (15.29)
4.Primary Outcome
Title Change From Baseline in Norfolk Quality of Life- Diabetic Neuropathy (QOL-DN) Total Quality of Life (TQOL) Score at Month 12
Hide Description Norfolk QOL-DN: 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on the quality of life of participants with diabetic neuropathy; Item 1 to 7: related to symptoms and presence of symptoms 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). TQOL= sum of all the items, total possible score range= -2 to 138, where higher score=worse quality of life.
Time Frame Baseline, Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who received at least one dose of study medication and had no more than 2 months interruption between studies FX-005 and FX-006. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
Arm/Group Title Tafamidis-Tafamidis Placebo-Tafamidis
Hide Arm/Group Description:
Participants who received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Participants who received placebo matched to tafamidis (Fx-1006A) 20 mg capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Overall Number of Participants Analyzed 32 30
Mean (Standard Deviation)
Unit of Measure: units on a scale
2.25  (8.91) -2.33  (15.66)
5.Secondary Outcome
Title Change From Baseline in Neuropathy Impairment Score - Lower Limb (NIS-LL) Score at Month 6 and 12
Hide Description NIS-LL: assessed muscle weakness, reflexes and sensation; scored separately for left and right limbs. Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) are scored on scale 0 (normal) to 4 (paralysis), 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, 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who received at least one dose of study medication and had no more than 2 months interruption between studies FX-005 and FX-006. 'N' (number of participants analyzed) signifies participants evaluable for this measure. ‘n’ signifies participants for this measure at specified time point for each arm group.
Arm/Group Title Tafamidis-Tafamidis Placebo-Tafamidis
Hide Arm/Group Description:
Participants who received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Participants who received placebo matched to tafamidis (Fx-1006A) 20 mg capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Overall Number of Participants Analyzed 38 33
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline (n=38,33) 8.38  (13.23) 17.50  (20.82)
Change at Month 6 (n=37,32) 0.93  (3.65) 1.89  (4.55)
Change at Month 12 (n=33,30) 1.36  (4.77) 1.60  (8.20)
6.Secondary Outcome
Title Change From Baseline in Norfolk Quality of Life – Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6 and 12
Hide Description Norfolk QOL-DN: 35-item participant-rated questionnaire to assess impact of DN on QOL; Item 1-7:scored as 1=symptoms present, 0=symptoms 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), symptoms(0 to 32), small fiber neuropathy(0 to 16), autonomic neuropathy(0 to 12); higher score=greater impairment,for each. Total score=-2 to138(higher score=worse QOL).
Time Frame Baseline, Month 6, 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who received at least one dose of study medication and had no more than 2 months interruption between studies FX-005 and FX-006. 'N' (number of participants analyzed) signifies participants evaluable for this measure. ‘n’ signifies participants for this measure at specified time point for each arm group.
Arm/Group Title Tafamidis-Tafamidis Placebo-Tafamidis
Hide Arm/Group Description:
Participants who received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Participants who received placebo matched to tafamidis (Fx-1006A) 20 mg capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Overall Number of Participants Analyzed 38 33
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline: physical functioning (n=38,33) 9.45  (11.43) 19.88  (17.44)
Baseline: ADLs (n=38,33) 2.21  (4.38) 3.48  (5.13)
Baseline: symptoms (n=38,33) 5.34  (4.43) 7.48  (5.48)
Baseline: small fiber neuropathy (n=38,33) 2.50  (3.85) 4.42  (4.23)
Baseline: autonomic neuropathy (n=38,33) 1.55  (2.37) 2.82  (3.12)
Change at Month 6: physical functioning (n=37,32) 0.14  (4.08) -3.00  (8.08)
Change at Month 6: ADLs (n=37,32) -0.30  (1.45) -0.59  (3.02)
Change at Month 6: symptoms (n=34,32) 0.00  (3.18) -0.75  (4.27)
Change at Month 6: small fiber neuropathy(n=37,32) -0.14  (2.64) -0.09  (2.32)
Change at Month 6: autonomic neuropathy (n=37,32) 0.19  (1.33) -0.44  (2.00)
Change at Month 12: physical functioning(n=32,30) 1.84  (6.00) -0.83  (9.62)
Change at Month 12: ADLs (n=32,30) 0.13  (1.01) -0.50  (3.35)
Change at Month 12: symptoms (n=32,30) -0.66  (2.54) -1.10  (3.32)
Change at Month 12:small fiber neuropathy(n=32,30) 0.41  (2.87) 0.40  (2.61)
Change at Month 12: autonomic neuropathy (n=32,30) 0.53  (1.46) -0.30  (1.66)
7.Secondary Outcome
Title Change From Baseline in Summated 7 Score for Large Nerve Fiber Function at Month 6 and 12
Hide Description Summated 7 score: composite score included five Nerve Conduction Studies (NCS) attributes (peroneal nerve distal motor latency, peroneal nerve compound muscle action potential, peroneal nerve motor conduction velocity, tibial nerve distal motor latency, and sural nerve sensory nerve action potential amplitude) along with Vibration Detection Threshold (VDT) obtained in great toes, and Heart Rate Response to Deep Breathing (HRDB) value. Score was determined through reference to normal values for age, sex and height. Total score range= -26 to 26, where higher score=worse nerve function.
Time Frame Baseline, Month 6, 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who received at least one dose of study medication and had no more than 2 months interruption between studies FX-005 and FX-006. 'N' (number of participants analyzed) signifies participants evaluable for this measure. ‘n’ signifies participants for this measure at specified time point for each arm group.
Arm/Group Title Tafamidis-Tafamidis Placebo-Tafamidis
Hide Arm/Group Description:
Participants who received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Participants who received placebo matched to tafamidis (Fx-1006A) 20 mg capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Overall Number of Participants Analyzed 38 33
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline (n=38,33) 6.68  (8.51) 10.06  (10.68)
Change at Month 6 (n=37,32) -0.01  (2.99) 1.38  (3.58)
Change at Month 12 (n=33,30) 0.64  (3.23) 1.48  (4.02)
8.Secondary Outcome
Title Change From Baseline in Summated 3 Score for Small Nerve Fiber Function at Month 6 and 12
Hide Description Summated 3 Nerve Tests Small Fiber Normal Deviates Score (NTSFnds) included cooling threshold for the lower limbs, heat pain threshold for the lower limbs and HRDB. Total score range= -11.2 to 11.2, where higher score=worse nerve function.
Time Frame Baseline, Month 6, 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who received at least one dose of study medication and had no more than 2 months interruption between studies FX-005 and FX-006. 'N' (number of participants analyzed) signifies participants evaluable for this measure. ‘n’ signifies participants for this measure at specified time point for each arm group.
Arm/Group Title Tafamidis-Tafamidis Placebo-Tafamidis
Hide Arm/Group Description:
Participants who received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Participants who received placebo matched to tafamidis (Fx-1006A) 20 mg capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Overall Number of Participants Analyzed 38 33
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline (n=38,33) 4.78  (4.33) 7.08  (4.39)
Change at Month 6 (n=36,32) 0.43  (1.51) 0.38  (1.08)
Change at Month 12 (n=32,30) 0.59  (1.28) 0.50  (1.48)
9.Secondary Outcome
Title Change From Baseline in Modified Body Mass Index (mBMI) at Month 6 and 12
Hide Description BMI was calculated by weight divided by height squared. mBMI was calculated by multiplying BMI by serum albumin levels to compensate for edema formation. A progressive decline in mBMI indicated worsening of disease severity.
Time Frame Baseline, Month 6, 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who received at least one dose of study medication and had no more than 2 months interruption between studies FX-005 and FX-006. 'N' (number of participants analyzed) signifies participants evaluable for this measure. ‘n’ signifies participants for this measure at specified time point for each arm group.
Arm/Group Title Tafamidis-Tafamidis Placebo-Tafamidis
Hide Arm/Group Description:
Participants who received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Participants who received placebo matched to tafamidis (Fx-1006A) 20 mg capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Overall Number of Participants Analyzed 38 33
Mean (Standard Deviation)
Unit of Measure: (kilogram/square meter)*(gram/liter)
Baseline (n=38,33) 23.94  (2.97) 22.71  (5.15)
Change at Month 6 (n=37,32) -0.13  (0.81) 0.42  (1.14)
Change at Month 12 (n=33,30) -0.12  (1.16) 0.73  (1.45)
10.Secondary Outcome
Title Change From Baseline in Troponin I Concentration at Week 6, Month 3, 6 and 12
Hide Description Troponin I was biomarker of cardiac stress (myocardial necrosis and increased filling pressures/ left ventricular [LV] wall stress).
Time Frame Baseline, Week 6, Month 3, 6, 12
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included participants who received at least one dose of study medication. 'N' (number of participants analyzed) signifies participants evaluable for this measure. ‘n’ signifies participants evaluable for this measure at the specified time point for each arm group.
Arm/Group Title Tafamidis-Tafamidis Placebo-Tafamidis
Hide Arm/Group Description:
Participants who received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Participants who received placebo matched to tafamidis (Fx-1006A) 20 mg capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Overall Number of Participants Analyzed 29 30
Median (Full Range)
Unit of Measure: nanogram/milliliter (ng/mL)
Baseline (n=29,30)
0.2
(0.2 to 0.5)
0.2
(0.2 to 0.2)
Change at Week 6 (n=28,29)
0.0
(0.0 to 0.1)
0.0
(0.0 to 0.0)
Change at Month 3 (n=29,30)
0.0
(-0.1 to 0.3)
0.0
(0.0 to 0.7)
Change at Month 6 (n=29,30)
0.0
(0.0 to 0.6)
0.0
(0.0 to 0.1)
Change at Month 12 (n=26,28)
0.0
(-0.3 to 0.4)
0.0
(0.0 to 0.0)
11.Secondary Outcome
Title Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) Concentration at Week 6, Month 3, 6 and 12
Hide Description NT-proBNP was biomarker of cardiac stress (myocardial necrosis and increased filling pressures/ LV wall stress).
Time Frame Baseline, Week 6, Month 3, 6, 12
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included participants who received at least one dose of study medication. 'N' (number of participants analyzed) signifies participants evaluable for this measure. ‘n’ signifies participants evaluable for this measure at the specified time point for each arm group.
Arm/Group Title Tafamidis-Tafamidis Placebo-Tafamidis
Hide Arm/Group Description:
Participants who received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Participants who received placebo matched to tafamidis (Fx-1006A) 20 mg capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Overall Number of Participants Analyzed 33 34
Median (Full Range)
Unit of Measure: picogram/milliliter (pg/mL)
Baseline (n=33,34)
41.0
(19.0 to 2879.0)
75.0
(20.0 to 1127.0)
Change at Week 6 (n=33,33)
6.0
(-650.0 to 525.0)
-1.0
(-292.0 to 97.0)
Change at Month 3 (n=33,34)
11.0
(-52.0 to 1355.0)
1.0
(-514.0 to 229.0)
Change at Month 6 (n=33,33)
9.0
(-210.0 to 3878.0)
0.0
(-473.0 to 170.0)
Change at Month 12 (n=30,29)
15.0
(-104.0 to 3840.0)
-6.0
(-342.0 to 410.0)
12.Secondary Outcome
Title Intraepidermal Nerve Fiber (IENF) Density
Hide Description IENF density was quantified in 3 millimeter (mm) immunostained skin punch biopsies containing epidermis and superficial dermis to evaluate the amount and morphological appearance of small diameter nerve fibers, both somatic and autonomic, in sensory neuropathies. It is used in diagnosing various neuropathic conditions.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who received at least one dose of study medication and had no more than 2 months interruption between studies FX-005 and FX-006. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
Arm/Group Title Tafamidis-Tafamidis Placebo-Tafamidis
Hide Arm/Group Description:
Participants who received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Participants who received placebo matched to tafamidis (Fx-1006A) 20 mg capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Overall Number of Participants Analyzed 11 5
Mean (Standard Deviation)
Unit of Measure: fibers/mm
Left distal leg 8.2  (9.8) 8.0  (9.2)
Left proximal thigh 16.1  (12.6) 15.3  (11.9)
13.Secondary Outcome
Title Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer
Hide Description TTR tetramer was assessed using a validated immunoturbidimetric assay. The Fraction of Initial (FOI) is the ratio of the measured TTR tetramer concentration after denaturation to the measured TTR tetramer concentration before denaturation. TTR tetramer stabilization is based on the difference between the on-treatment FOI and the baseline FOI expressed as a percentage of the baseline FOI.
Time Frame Month 6, 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who received at least one dose of study medication and had no more than 2 months interruption between studies FX-005 and FX-006. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
Arm/Group Title Tafamidis-Tafamidis Placebo-Tafamidis
Hide Arm/Group Description:
Participants who received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Participants who received placebo matched to tafamidis (Fx-1006A) 20 mg capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Overall Number of Participants Analyzed 36 32
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 6
94
(81 to 99)
97
(83 to 99)
Month 12
94
(80 to 99)
93
(77 to 99)
14.Other Pre-specified Outcome
Title Number of Participants With Treatment-emergent Serious Adverse Events (SAEs)
Hide Description An Adverse Event (AE) was any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. SAE: AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent/significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug, 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 last dose of study medication
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included participants who received at least one dose of study medication.
Arm/Group Title Tafamidis-Tafamidis Placebo-Tafamidis
Hide Arm/Group Description:
Participants who received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Participants who received placebo matched to tafamidis (Fx-1006A) 20 mg capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Overall Number of Participants Analyzed 44 41
Measure Type: Number
Unit of Measure: participants
5 4
15.Other Pre-specified Outcome
Title Number of Participants With Treatment-emergent Adverse Events Greater Than or Equal to Grade 3
Hide Description AE=any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Grade 3 (Severe) events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. Grade 5 (Death) events=death related to an AE. Treatment-emergent 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 last dose of study medication
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Hide Analysis Population Description
Safety population included participants who received at least one dose of study medication.
Arm/Group Title Tafamidis-Tafamidis Placebo-Tafamidis
Hide Arm/Group Description:
Participants who received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Participants who received placebo matched to tafamidis (Fx-1006A) 20 mg capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Overall Number of Participants Analyzed 44 41
Measure Type: Number
Unit of Measure: participants
6 4
16.Other Pre-specified Outcome
Title Number of Participants With Clinically Significant Treatment-emergent Echocardiography (ECHO) Findings
Hide Description Clinically significant ECHO findings included: LV posterior wall thickness greater than or equal to (>=)13 mm, LV septal thickness >= 13 mm, right ventricular thickness >= 7 mm, ratio of peak mitral early diastolic and atrial contraction velocity (E/A ratio) >= 2, prime septal (E/E) >15, ejection fraction < 50 percent (%), E deceleration time <= 150 millisecond (ms), isovolumic relaxation time (IVRT) <= 70 ms, any valve thickening (> trace regurgitation in mitral, aortic, pulmonary, or tricuspid valves), abnormal respiratory variation of inferior vena cava, pericardial effusion.
Time Frame Baseline, Day 1 up to Month 12 (anytime on-treatment)
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Hide Analysis Population Description
Safety population included participants who received at least one dose of study medication. 'N' (number of participants analyzed) signifies participants evaluable for this measure. ‘n’ signifies participants evaluable for this measure at the specified time point for each arm group.
Arm/Group Title Tafamidis-Tafamidis Placebo-Tafamidis
Hide Arm/Group Description:
Participants who received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Participants who received placebo matched to tafamidis (Fx-1006A) 20 mg capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Overall Number of Participants Analyzed 38 34
Measure Type: Number
Unit of Measure: participants
Baseline (n=38,34) 23 18
Anytime on-treatment (n=21,23) 16 13
17.Other Pre-specified Outcome
Title Number of Participants With Clinically Significant Treatment-emergent Electrocardiogram (ECG) Findings
Hide Description Clinically significant ECG findings included: corrected QT (QTc) > 450 ms, QTc >500 ms, change in QTc between 30 and 60 ms, change in QTc greater than or equal to 60 ms.
Time Frame Baseline, Day 1 up to Month 12 (anytime on-treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included participants who received at least one dose of study medication. ‘n’ signifies participants for this measure at specified time point for each arm group.
Arm/Group Title Tafamidis-Tafamidis Placebo-Tafamidis
Hide Arm/Group Description:
Participants who received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Participants who received placebo matched to tafamidis (Fx-1006A) 20 mg capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Overall Number of Participants Analyzed 44 41
Measure Type: Number
Unit of Measure: participants
Baseline (n=44,41) 16 17
Anytime on-treatment (n=28,24) 6 6
18.Other Pre-specified Outcome
Title Number of Participants With Clinically Significant Treatment-emergent Holter Monitor Findings
Time Frame Baseline, Day 1 up to Month 12 (anytime on-treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included participants who received at least one dose of study medication. ‘n’ signifies participants for this measure at specified time point for each arm group.
Arm/Group Title Tafamidis-Tafamidis Placebo-Tafamidis
Hide Arm/Group Description:
Participants who received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Participants who received placebo matched to tafamidis (Fx-1006A) 20 mg capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Overall Number of Participants Analyzed 44 41
Measure Type: Number
Unit of Measure: participants
Baseline (n=44,41) 20 21
Anytime on-treatment (n=24,20) 8 7
19.Other Pre-specified Outcome
Title Number of Participants Who Discontinued Due to Clinical or Laboratory Adverse Events
Hide Description An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time Frame Baseline up to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included participants who received at least one dose of study medication.
Arm/Group Title Tafamidis-Tafamidis Placebo-Tafamidis
Hide Arm/Group Description:
Participants who received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Participants who received placebo matched to tafamidis (Fx-1006A) 20 mg capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
Overall Number of Participants Analyzed 44 41
Measure Type: Number
Unit of Measure: participants
0 0
Time Frame [Not Specified]
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
 
Arm/Group Title Tafamidis-Tafamidis Placebo-Tafamidis
Hide Arm/Group Description Participants who received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months. Participants who received placebo matched to tafamidis (Fx-1006A) 20 mg capsule orally once daily for 18 months during previous study FX-005 (NCT00409175), received tafamidis (Fx-1006A) 20 mg capsule orally once daily for 12 months.
All-Cause Mortality
Tafamidis-Tafamidis Placebo-Tafamidis
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Tafamidis-Tafamidis Placebo-Tafamidis
Affected / at Risk (%) Affected / at Risk (%)
Total   5/44 (11.36%)   4/41 (9.76%) 
Blood and lymphatic system disorders     
Anaemia * 1  0/44 (0.00%)  1/41 (2.44%) 
Gastrointestinal disorders     
Vomiting * 1  2/44 (4.55%)  1/41 (2.44%) 
Nausea * 1  1/44 (2.27%)  1/41 (2.44%) 
Immune system disorders     
Hypersensitivity * 1  1/44 (2.27%)  0/41 (0.00%) 
Infections and infestations     
Catheter sepsis * 1  1/44 (2.27%)  0/41 (0.00%) 
Catheter site infection * 1  1/44 (2.27%)  0/41 (0.00%) 
Infection * 1  0/44 (0.00%)  1/41 (2.44%) 
Meningitis * 1  0/44 (0.00%)  1/41 (2.44%) 
Osteomyelitis * 1  0/44 (0.00%)  1/41 (2.44%) 
Urinary tract infection * 1  0/44 (0.00%)  1/41 (2.44%) 
Investigations     
Blood electrolytes decreased * 1  1/44 (2.27%)  0/41 (0.00%) 
Metabolism and nutrition disorders     
Dehydration * 1  0/44 (0.00%)  1/41 (2.44%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Lymphoma * 1  1/44 (2.27%)  0/41 (0.00%) 
Skin and subcutaneous tissue disorders     
Skin lesion * 1  1/44 (2.27%)  0/41 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA v10.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Tafamidis-Tafamidis Placebo-Tafamidis
Affected / at Risk (%) Affected / at Risk (%)
Total   24/44 (54.55%)   24/41 (58.54%) 
Eye disorders     
Punctate keratitis * 1  3/44 (6.82%)  3/41 (7.32%) 
Dry eye * 1  2/44 (4.55%)  3/41 (7.32%) 
Gastrointestinal disorders     
Diarrhoea * 1  4/44 (9.09%)  3/41 (7.32%) 
Vomiting * 1  2/44 (4.55%)  4/41 (9.76%) 
Infections and infestations     
Urinary tract infection * 1  5/44 (11.36%)  6/41 (14.63%) 
Influenza * 1  3/44 (6.82%)  7/41 (17.07%) 
Nasopharyngitis * 1  5/44 (11.36%)  3/41 (7.32%) 
Upper respiratory tract infection * 1  2/44 (4.55%)  3/41 (7.32%) 
Injury, poisoning and procedural complications     
Thermal burn * 1  4/44 (9.09%)  4/41 (9.76%) 
Nervous system disorders     
Headache * 1  2/44 (4.55%)  6/41 (14.63%) 
Psychiatric disorders     
Anxiety * 1  1/44 (2.27%)  5/41 (12.20%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA v10.0
Instead of intended endpoint 'heat pain and cooling threshold', results of 'summated 3 score for small nerve fiber function' were reported. Designation of outcomes as primary and secondary was based on study team input as study did not specify this.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00791492     History of Changes
Other Study ID Numbers: FX-006
B3461021
First Submitted: November 13, 2008
First Posted: November 14, 2008
Results First Submitted: November 16, 2012
Results First Posted: December 17, 2012
Last Update Posted: December 17, 2012