Trial Outcomes & Findings for Safety and Efficacy Study of Fx-1006A in Patients With Familial Amyloidosis (NCT NCT00409175)

Last Updated: 2012-12-17

Results Overview

Response to treatment was 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 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.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

128 participants

Primary outcome timeframe

Month 18

Results posted on

2012-12-17

Participant Flow

Participant milestones

Participant milestones
Measure	Tafamidis Tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months.	Placebo Placebo, matched to tafamidis (Fx-1006A) 20 mg capsule, orally once daily for 18 months.
Overall Study STARTED	65	63
Overall Study COMPLETED	47	44
Overall Study NOT COMPLETED	18	19

Reasons for withdrawal

Reasons for withdrawal
Measure	Tafamidis Tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months.	Placebo Placebo, matched to tafamidis (Fx-1006A) 20 mg capsule, orally once daily for 18 months.
Overall Study Adverse Event	4	3
Overall Study Withdrawal by Subject	1	2
Overall Study Negative genotype	0	1
Overall Study Liver transplantation	13	13

Baseline Characteristics

Safety and Efficacy Study of Fx-1006A in Patients With Familial Amyloidosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tafamidis n=64 Participants Tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months.	Placebo n=61 Participants Placebo, matched to tafamidis (Fx-1006A) 20 mg capsule, orally once daily for 18 months.	Total n=125 Participants Total of all reporting groups
Age, Customized Less than or equal to 65 years	59 participants n=5 Participants	58 participants n=7 Participants	117 participants n=5 Participants
Age, Customized Greater than 65 years	5 participants n=5 Participants	3 participants n=7 Participants	8 participants n=5 Participants
Sex: Female, Male Female	32 Participants n=5 Participants	35 Participants n=7 Participants	67 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants	26 Participants n=7 Participants	58 Participants n=5 Participants

PRIMARY outcome

Timeframe: Month 18

Population: ITTset:randomized participants received atleast(\>=)1 dose of study drug, had \>=1 post-baseline efficacy assessment for NIS-LL,Norfolk Quality of Life-Diabetic Neuropathy(QOL-DN) or discontinued study due to death/liver transplant(LT).Last-observation-carried-forward(LOCF) used;participant who discontinued due to death/LT was set non-responder.

Outcome measures

Outcome measures
Measure	Tafamidis n=64 Participants Tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months.	Placebo n=61 Participants Placebo, matched to tafamidis (Fx-1006A) 20 mg capsule, orally once daily for 18 months.
Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 18	45.3 percentage of participants Interval 33.1 to 57.5	29.5 percentage of participants Interval 18.1 to 41.0

PRIMARY outcome

Timeframe: Baseline, Month 18

Population: ITT population included all randomized participants who received at least 1 dose of study medication and had at least 1 post-baseline efficacy assessment for NIS-LL and Norfolk QOL-DN or discontinued study due to death or LT. LOCF method was used.

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 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). TQOL= sum of all the items, total possible score range= -2 to 138, where higher score=worse quality of life.

Outcome measures

Outcome measures
Measure	Tafamidis n=64 Participants Tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months.	Placebo n=61 Participants Placebo, matched to tafamidis (Fx-1006A) 20 mg capsule, orally once daily for 18 months.
Change From Baseline in Norfolk Quality of Life- Diabetic Neuropathy (QOL-DN) Total Quality of Life (TQOL) Score at Month 18 Baseline	27.3 units on a scale Standard Deviation 24.2	30.8 units on a scale Standard Deviation 26.7
Change From Baseline in Norfolk Quality of Life- Diabetic Neuropathy (QOL-DN) Total Quality of Life (TQOL) Score at Month 18 Change at Month 18	2.4 units on a scale Standard Deviation 14.6	6.9 units on a scale Standard Deviation 22.9

SECONDARY outcome

Timeframe: Baseline, Month 6, 12, 18

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(normal) to 4(paralysis) 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.

Outcome measures

Outcome measures
Measure	Tafamidis n=64 Participants Tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months.	Placebo n=61 Participants Placebo, matched to tafamidis (Fx-1006A) 20 mg capsule, orally once daily for 18 months.
Change From Baseline in Neuropathy Impairment Score- Lower Limb (NIS-LL) Score at Month 6, 12 and 18 Baseline (n=64, 61)	8.359 units on a scale Standard Deviation 11.399	11.445 units on a scale Standard Deviation 13.544
Change From Baseline in Neuropathy Impairment Score- Lower Limb (NIS-LL) Score at Month 6, 12 and 18 Change at Month 6 (n=60, 57)	1.260 units on a scale Standard Deviation 3.007	2.075 units on a scale Standard Deviation 6.407
Change From Baseline in Neuropathy Impairment Score- Lower Limb (NIS-LL) Score at Month 6, 12 and 18 Change at Month 12 (n=49, 50)	1.005 units on a scale Standard Deviation 3.964	4.835 units on a scale Standard Deviation 7.697
Change From Baseline in Neuropathy Impairment Score- Lower Limb (NIS-LL) Score at Month 6, 12 and 18 Change at Month 18 (n=48, 47)	2.193 units on a scale Standard Deviation 4.372	5.402 units on a scale Standard Deviation 8.661

SECONDARY outcome

Timeframe: Month 6, 12

Response to treatment was indicated by either improvement (decrease from baseline) or stabilization (change from baseline of 0 to \<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 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.

Outcome measures

Outcome measures
Measure	Tafamidis n=64 Participants Tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months.	Placebo n=61 Participants Placebo, matched to tafamidis (Fx-1006A) 20 mg capsule, orally once daily for 18 months.
Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 6 and 12 Month 6	60.9 percentage of participants Interval 49.0 to 72.9	54.1 percentage of participants Interval 41.6 to 66.6
Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 6 and 12 Month 12	54.7 percentage of participants Interval 42.5 to 66.9	32.8 percentage of participants Interval 21.0 to 44.6

SECONDARY outcome

Timeframe: Baseline, Month 6, 12

Outcome measures

Outcome measures
Measure	Tafamidis n=64 Participants Tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months.	Placebo n=61 Participants Placebo, matched to tafamidis (Fx-1006A) 20 mg capsule, orally once daily for 18 months.
Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Total Quality of Life (TQOL) Score at Month 6 and 12 Baseline (n=64, 61)	27.3 units on a scale Standard Deviation 24.2	30.8 units on a scale Standard Deviation 26.7
Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Total Quality of Life (TQOL) Score at Month 6 and 12 Change at Month 6 (n=60, 57)	1.2 units on a scale Standard Deviation 15.6	0.2 units on a scale Standard Deviation 15.1
Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Total Quality of Life (TQOL) Score at Month 6 and 12 Change at Month 12 (n=49, 50)	1.1 units on a scale Standard Deviation 14.7	4.6 units on a scale Standard Deviation 19.0

SECONDARY outcome

Timeframe: Baseline, Month 6, 12, 18

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), 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).

Outcome measures

Outcome measures
Measure	Tafamidis n=64 Participants Tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months.	Placebo n=61 Participants Placebo, matched to tafamidis (Fx-1006A) 20 mg capsule, orally once daily for 18 months.
Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, 12 and 18 Baseline: physical functioning(n=64,61)	14.3 units on a scale Standard Deviation 13.8	16.6 units on a scale Standard Deviation 14.7
Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, 12 and 18 Baseline: ADLs(n=64,61)	1.3 units on a scale Standard Deviation 2.9	1.6 units on a scale Standard Deviation 3.8
Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, 12 and 18 Baseline: symptoms(n=64,61)	7.2 units on a scale Standard Deviation 5.5	7.6 units on a scale Standard Deviation 6.1
Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, 12 and 18 Baseline: small fiber neuropathy(n=64,61)	2.7 units on a scale Standard Deviation 3.6	3.1 units on a scale Standard Deviation 4.0
Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, 12 and 18 Baseline: autonomic neuropathy(n=64,61)	1.9 units on a scale Standard Deviation 2.4	2.0 units on a scale Standard Deviation 2.6
Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, 12 and 18 Change at Month 6: physical functioning(n=60,57)	-0.6 units on a scale Standard Deviation 8.0	-0.9 units on a scale Standard Deviation 9.8
Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, 12 and 18 Change at Month 6: ADLs(n=60,57)	0.4 units on a scale Standard Deviation 1.9	0.3 units on a scale Standard Deviation 1.7
Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, 12 and 18 Change at Month 6: symptoms(n=60,56)	0.8 units on a scale Standard Deviation 5.5	0.2 units on a scale Standard Deviation 4.4
Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, 12 and 18 Change at Month 6: small fiber neuropathy(n=60,57)	0.4 units on a scale Standard Deviation 2.2	0.5 units on a scale Standard Deviation 2.5
Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, 12 and 18 Change at Month 6: autonomic neuropathy(n=60,57)	0.2 units on a scale Standard Deviation 1.8	0.0 units on a scale Standard Deviation 1.7
Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, 12 and 18 Change at Month 12: physical functioning(n=49,50)	-0.9 units on a scale Standard Deviation 7.4	0.6 units on a scale Standard Deviation 10.7
Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, 12 and 18 Change at Month 12: ADLs(n=49,50)	1.0 units on a scale Standard Deviation 2.4	0.7 units on a scale Standard Deviation 3.0
Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, 12 and 18 Change at Month 12: symptoms(n=49,49)	0.4 units on a scale Standard Deviation 5.0	1.4 units on a scale Standard Deviation 4.5
Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, 12 and 18 Change at Month 12:small fiber neuropathy(n=49,50)	0.7 units on a scale Standard Deviation 2.8	1.5 units on a scale Standard Deviation 3.1
Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, 12 and 18 Change at Month 12: autonomic neuropathy(n=49,50)	-0.1 units on a scale Standard Deviation 1.8	0.4 units on a scale Standard Deviation 2.8
Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, 12 and 18 Change at Month 18: physical functioning(n=48,47)	-0.1 units on a scale Standard Deviation 8.5	3.0 units on a scale Standard Deviation 14.0
Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, 12 and 18 Change at Month 18: ADLs(n=48,47)	1.2 units on a scale Standard Deviation 2.4	1.2 units on a scale Standard Deviation 4.2
Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, 12 and 18 Change at Month 18: symptoms(n=48,47)	-0.1 units on a scale Standard Deviation 4.9	1.2 units on a scale Standard Deviation 5.4
Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, 12 and 18 Change at Month 18:small fiber neuropathy(n=48,47)	0.8 units on a scale Standard Deviation 2.6	1.4 units on a scale Standard Deviation 3.6
Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, 12 and 18 Change at Month 18: autonomic neuropathy(n=48,47)	0.2 units on a scale Standard Deviation 1.9	0.4 units on a scale Standard Deviation 2.8

SECONDARY outcome

Timeframe: Baseline, Month 6, 12, 18

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.

Outcome measures

Outcome measures
Measure	Tafamidis n=64 Participants Tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months.	Placebo n=61 Participants Placebo, matched to tafamidis (Fx-1006A) 20 mg capsule, orally once daily for 18 months.
Change From Baseline in Summated 7 Score for Large Nerve Fiber Function at Month 6, 12 and 18 Baseline (n=64, 61)	7.787 units on a scale Standard Deviation 9.063	8.718 units on a scale Standard Deviation 8.533
Change From Baseline in Summated 7 Score for Large Nerve Fiber Function at Month 6, 12 and 18 Change at Month 6 (n=60, 57)	0.581 units on a scale Standard Deviation 3.542	1.934 units on a scale Standard Deviation 3.846
Change From Baseline in Summated 7 Score for Large Nerve Fiber Function at Month 6, 12 and 18 Change at Month 12 (n=48, 50)	0.833 units on a scale Standard Deviation 3.963	2.959 units on a scale Standard Deviation 3.879
Change From Baseline in Summated 7 Score for Large Nerve Fiber Function at Month 6, 12 and 18 Change at Month 18 (n=48, 46)	1.159 units on a scale Standard Deviation 3.853	3.333 units on a scale Standard Deviation 4.997

SECONDARY outcome

Timeframe: Baseline, Month 6, 12, 18

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.

Outcome measures

Outcome measures
Measure	Tafamidis n=64 Participants Tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months.	Placebo n=61 Participants Placebo, matched to tafamidis (Fx-1006A) 20 mg capsule, orally once daily for 18 months.
Change From Baseline in Summated 3 Score for Small Nerve Fiber Function at Month 6, 12 and 18 Baseline (n=64, 61)	5.514 units on a scale Standard Deviation 4.535	5.624 units on a scale Standard Deviation 4.085
Change From Baseline in Summated 3 Score for Small Nerve Fiber Function at Month 6, 12 and 18 Change at Month 6 (n=60, 57)	0.240 units on a scale Standard Deviation 1.679	0.716 units on a scale Standard Deviation 2.202
Change From Baseline in Summated 3 Score for Small Nerve Fiber Function at Month 6, 12 and 18 Change at Month 12 (n=48, 50)	0.375 units on a scale Standard Deviation 2.048	1.250 units on a scale Standard Deviation 2.010
Change From Baseline in Summated 3 Score for Small Nerve Fiber Function at Month 6, 12 and 18 Change at Month 18 (n=48, 46)	0.290 units on a scale Standard Deviation 2.130	1.489 units on a scale Standard Deviation 2.519

SECONDARY outcome

Timeframe: Baseline, Month 6, 12, 18

BMI was calculated by weight divided by height squared. mBMI was calculated by multiplying BMI by serum albumin levels to compensate for edema formation associated with malnutrition. A progressive decline in mBMI indicated worsening of disease severity.

Outcome measures

Outcome measures
Measure	Tafamidis n=64 Participants Tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months.	Placebo n=61 Participants Placebo, matched to tafamidis (Fx-1006A) 20 mg capsule, orally once daily for 18 months.
Change From Baseline in Modified Body Mass Index (mBMI) at Month 6, 12 and 18 Baseline (n=64, 61)	1004.6 (kilogram/square meter)*(gram/liter) Standard Deviation 165.2	1011.5 (kilogram/square meter)*(gram/liter) Standard Deviation 212.9
Change From Baseline in Modified Body Mass Index (mBMI) at Month 6, 12 and 18 Change at Month 6 (n=60, 56)	17.1 (kilogram/square meter)*(gram/liter) Standard Deviation 68.4	-29.8 (kilogram/square meter)*(gram/liter) Standard Deviation 69.7
Change From Baseline in Modified Body Mass Index (mBMI) at Month 6, 12 and 18 Change at Month 12 (n=49, 50)	19.4 (kilogram/square meter)*(gram/liter) Standard Deviation 71.8	-30.8 (kilogram/square meter)*(gram/liter) Standard Deviation 74.9
Change From Baseline in Modified Body Mass Index (mBMI) at Month 6, 12 and 18 Change at Month 18 (n=49, 46)	37.9 (kilogram/square meter)*(gram/liter) Standard Deviation 73.7	-32.7 (kilogram/square meter)*(gram/liter) Standard Deviation 88.6

SECONDARY outcome

Timeframe: Week 8, Month 6, 12, 18

Population: ITT population. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. 'n' = those participants who were evaluable for this measure at given time points for each group respectively.

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.

Outcome measures

Outcome measures
Measure	Tafamidis n=63 Participants Tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months.	Placebo n=60 Participants Placebo, matched to tafamidis (Fx-1006A) 20 mg capsule, orally once daily for 18 months.
Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer Week 8 (n=63, 60)	98.4 percentage of participants Interval 95.3 to 100.0	6.7 percentage of participants Interval 0.4 to 13.0
Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer Month 6 (n= 59, 58)	100.0 percentage of participants Interval 100.0 to 100.0	5.2 percentage of participants Interval 0.0 to 10.9
Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer Month 12 (n=48, 50)	97.9 percentage of participants Interval 93.9 to 100.0	2.0 percentage of participants Interval 0.0 to 5.9
Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer Month 18 (n=48, 44)	97.9 percentage of participants Interval 93.9 to 100.0	0.0 percentage of participants Interval 0.0 to 0.0

Adverse Events

Tafamidis

Serious events: 6 serious events

Other events: 57 other events

Deaths: 0 deaths

Placebo

Serious events: 5 serious events

Other events: 56 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Tafamidis n=65 participants at risk Tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months.	Placebo n=63 participants at risk Placebo, matched to tafamidis (Fx-1006A) 20 mg capsule, orally once daily for 18 months.
Blood and lymphatic system disorders Anaemia	0.00% 0/65 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.	1.6% 1/63 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.
Cardiac disorders Conduction disorder	1.5% 1/65 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.	0.00% 0/63 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.
Cardiac disorders Cardiac amyloidosis	0.00% 0/65 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.	1.6% 1/63 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.
Gastrointestinal disorders Nausea	0.00% 0/65 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.	1.6% 1/63 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.
Gastrointestinal disorders Vomiting	0.00% 0/65 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.	1.6% 1/63 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.
General disorders Catheter site phlebitis	0.00% 0/65 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.	1.6% 1/63 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.
General disorders Oedema peripheral	0.00% 0/65 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.	1.6% 1/63 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.
Infections and infestations Urinary tract infection	3.1% 2/65 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.	0.00% 0/63 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.
Infections and infestations Localised infection	1.5% 1/65 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.	0.00% 0/63 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.
Infections and infestations Pneumonia	1.5% 1/65 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.	0.00% 0/63 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.
Infections and infestations Viral infection	1.5% 1/65 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.	0.00% 0/63 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.
Infections and infestations Cellulitis	0.00% 0/65 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.	1.6% 1/63 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.
Infections and infestations Lymphangitis	0.00% 0/65 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.	1.6% 1/63 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.
Infections and infestations Staphylococcal infection	0.00% 0/65 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.	1.6% 1/63 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.
Injury, poisoning and procedural complications Burns third degree	0.00% 0/65 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.	1.6% 1/63 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.
Nervous system disorders Syncope	0.00% 0/65 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.	1.6% 1/63 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.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/65 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.	1.6% 1/63 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.
Skin and subcutaneous tissue disorders Urticaria	1.5% 1/65 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.	0.00% 0/63 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.
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/65 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.	1.6% 1/63 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.
Vascular disorders Hypertensive emergency	0.00% 0/65 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.	1.6% 1/63 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.