Trial Outcomes & Findings for The Effect Of Tafamidis For The Transthyretin Amyloid Polyneuropathy Patients With V30M Or Non-V30M Transthyretin (NCT NCT01435655)
NCT ID: NCT01435655
Last Updated: 2015-09-09
Results Overview
TTR tetramer level for each plasma sample was assessed using a validated immunoturbidimetric assay before and after urea denaturation. The Fraction of Initial (FOI) tetramer concentration is the ratio of the measured TTR tetramer concentration after denaturation to the measured TTR tetramer average 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. A patient who has the "TTR stabilization" is defined as the patient whose percent stabilization is equal to or more than 32%.
COMPLETED
PHASE3
10 participants
8 weeks
2015-09-09
Participant Flow
Participant milestones
| Measure |
Tafamidis 20 mg
Participants (V30m and non-V30m transthyretin mutation) received tafamidis 20 mg soft gelatin capsules orally once daily for up to 78 weeks
|
|---|---|
|
Overall Study
STARTED
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10
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Overall Study
COMPLETED
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7
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Overall Study
NOT COMPLETED
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3
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Reasons for withdrawal
| Measure |
Tafamidis 20 mg
Participants (V30m and non-V30m transthyretin mutation) received tafamidis 20 mg soft gelatin capsules orally once daily for up to 78 weeks
|
|---|---|
|
Overall Study
Death
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2
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Overall Study
Other
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1
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Baseline Characteristics
The Effect Of Tafamidis For The Transthyretin Amyloid Polyneuropathy Patients With V30M Or Non-V30M Transthyretin
Baseline characteristics by cohort
| Measure |
Tafamidis 20 mg
n=10 Participants
Participants (V30m and non-V30m transthyretin mutation) received tafamidis 20 mg soft gelatin capsules orally once daily for up to 78 weeks
|
|---|---|
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Age, Continuous
|
60.1 years
STANDARD_DEVIATION 13.0 • n=99 Participants
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|
Sex: Female, Male
Female
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3 Participants
n=99 Participants
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Sex: Female, Male
Male
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7 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: 8 weeksPopulation: Full Analysis Set (FAS) included all participants who received at least one dose of the study drug.
TTR tetramer level for each plasma sample was assessed using a validated immunoturbidimetric assay before and after urea denaturation. The Fraction of Initial (FOI) tetramer concentration is the ratio of the measured TTR tetramer concentration after denaturation to the measured TTR tetramer average 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. A patient who has the "TTR stabilization" is defined as the patient whose percent stabilization is equal to or more than 32%.
Outcome measures
| Measure |
Tafamidis 20 mg
n=10 Participants
Participants (V30m and non-V30m transthyretin mutation) received tafamidis 20 mg soft gelatin capsules orally once daily for up to 78 weeks
|
|---|---|
|
Number of Participants With Transthyretin (TTR) Stabilization at Week 8 Compared With Baseline as Measured by a Validated Immunoturbidimetric Assay
|
10 Participants
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SECONDARY outcome
Timeframe: Baseline, Week 26, Week 52, Week 78Population: Full Analysis Set (FAS) included all participants who received at least one dose of the study drug.
The NIS provides a total body single score of neuropathic deficits (score range: 0-122, higher score = more deficit), comprising subset scores for cranial nerves, muscle weakness, reflexes, and sensation (based on mean of 2 scores in 1 week period; each item scored separately for left and right). The NIS-LL is a subscale that provides a score for the lower limbs functions (muscle weakness, reflexes and sensation in great toe) and has a score range of 0-44 (higher score = more deficit). The NIS-UL is a subscale that provides a score for the upper body functions (muscle weakness \[including cranial nerves\], reflexes and sensation in finger) and has a score range of 0-78 (higher score = more deficit). The components for cranial nerves and muscle weakness are scored from 0 (Normal) to 4 (Paralysis), and those for reflexes and sensation from 0 (Normal) to 2 (Absent). For all items, higher scores indicate greater impairment.
Outcome measures
| Measure |
Tafamidis 20 mg
n=10 Participants
Participants (V30m and non-V30m transthyretin mutation) received tafamidis 20 mg soft gelatin capsules orally once daily for up to 78 weeks
|
|---|---|
|
Change From Baseline in Neuropathy Impairment Score (NIS); NIS (Total), NIS-LL (Lower Limb) and NIS-UL (Upper Limb) at Week 26, Week 52 and Week 78
NIS-Total: Baseline (n=10)
|
31.03 Units on a scale
Standard Deviation 26.260
|
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Change From Baseline in Neuropathy Impairment Score (NIS); NIS (Total), NIS-LL (Lower Limb) and NIS-UL (Upper Limb) at Week 26, Week 52 and Week 78
NIS-Total: Change at Week 26 (n=10)
|
4.37 Units on a scale
Standard Deviation 9.408
|
|
Change From Baseline in Neuropathy Impairment Score (NIS); NIS (Total), NIS-LL (Lower Limb) and NIS-UL (Upper Limb) at Week 26, Week 52 and Week 78
NIS-Total: Change at Week 52 (n=10)
|
8.30 Units on a scale
Standard Deviation 8.326
|
|
Change From Baseline in Neuropathy Impairment Score (NIS); NIS (Total), NIS-LL (Lower Limb) and NIS-UL (Upper Limb) at Week 26, Week 52 and Week 78
NIS-Total: Change at Week 78 (n=8)
|
9.90 Units on a scale
Standard Deviation 12.584
|
|
Change From Baseline in Neuropathy Impairment Score (NIS); NIS (Total), NIS-LL (Lower Limb) and NIS-UL (Upper Limb) at Week 26, Week 52 and Week 78
NIS-LL: Baseline (n=10)
|
16.99 Units on a scale
Standard Deviation 13.143
|
|
Change From Baseline in Neuropathy Impairment Score (NIS); NIS (Total), NIS-LL (Lower Limb) and NIS-UL (Upper Limb) at Week 26, Week 52 and Week 78
NIS-LL: Change at Week 26 (n=10)
|
2.06 Units on a scale
Standard Deviation 5.565
|
|
Change From Baseline in Neuropathy Impairment Score (NIS); NIS (Total), NIS-LL (Lower Limb) and NIS-UL (Upper Limb) at Week 26, Week 52 and Week 78
NIS-LL: Change at Week 52 (n=10)
|
3.62 Units on a scale
Standard Deviation 4.374
|
|
Change From Baseline in Neuropathy Impairment Score (NIS); NIS (Total), NIS-LL (Lower Limb) and NIS-UL (Upper Limb) at Week 26, Week 52 and Week 78
NIS-LL: Change at Week 78 (n=8)
|
3.30 Units on a scale
Standard Deviation 4.739
|
|
Change From Baseline in Neuropathy Impairment Score (NIS); NIS (Total), NIS-LL (Lower Limb) and NIS-UL (Upper Limb) at Week 26, Week 52 and Week 78
NIS-UL: Baseline (n=10)
|
14.03 Units on a scale
Standard Deviation 13.716
|
|
Change From Baseline in Neuropathy Impairment Score (NIS); NIS (Total), NIS-LL (Lower Limb) and NIS-UL (Upper Limb) at Week 26, Week 52 and Week 78
NIS-UL: Change at Week 26 (n=10)
|
2.31 Units on a scale
Standard Deviation 4.066
|
|
Change From Baseline in Neuropathy Impairment Score (NIS); NIS (Total), NIS-LL (Lower Limb) and NIS-UL (Upper Limb) at Week 26, Week 52 and Week 78
NIS-UL: Change at Week 52 (n=10)
|
4.68 Units on a scale
Standard Deviation 5.103
|
|
Change From Baseline in Neuropathy Impairment Score (NIS); NIS (Total), NIS-LL (Lower Limb) and NIS-UL (Upper Limb) at Week 26, Week 52 and Week 78
NIS-UL: Change at Week 78 (n=8)
|
6.59 Units on a scale
Standard Deviation 8.724
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SECONDARY outcome
Timeframe: Baseline, Week 26, Week 52, Week 78Population: Full Analysis Set (FAS) included all participants who received at least one dose of the study drug.
Norfolk QOL-DN is a 35-item participant-rated questionnaire. It consists of 5 domains: Physical Functioning/Large Fiber \[score range: -4 - 56\] , Activities of Daily Living (ADL) \[0 - 20\], Symptoms \[0 - 32\], Small Fiber \[0 - 16\] and Autonomic \[0 - 12\]. Total of quality of life (TQOL) score is the sum of all five domains with a range of -4 to 136 (Pfizer Data Standards). Higher scores on each item of the Norfolk QOL-DN TQOL indicate worse quality of life.
Outcome measures
| Measure |
Tafamidis 20 mg
n=10 Participants
Participants (V30m and non-V30m transthyretin mutation) received tafamidis 20 mg soft gelatin capsules orally once daily for up to 78 weeks
|
|---|---|
|
Change From Baseline in Scores of the Total Quality of Life (TQOL) and 5 Domains as Measured by the Norfolk QOL - Diabetic Neuropathy (Norfolk QOL-DN) at Week 26, Week 52 and Week 78.
Autonomic: Baseline (n=10)
|
4.0 Units on a scale
Standard Deviation 3.06
|
|
Change From Baseline in Scores of the Total Quality of Life (TQOL) and 5 Domains as Measured by the Norfolk QOL - Diabetic Neuropathy (Norfolk QOL-DN) at Week 26, Week 52 and Week 78.
TQOL: Baseline (n=10)
|
52.9 Units on a scale
Standard Deviation 32.76
|
|
Change From Baseline in Scores of the Total Quality of Life (TQOL) and 5 Domains as Measured by the Norfolk QOL - Diabetic Neuropathy (Norfolk QOL-DN) at Week 26, Week 52 and Week 78.
TQOL: Change at Week 26 (n=10)
|
11.8 Units on a scale
Standard Deviation 20.01
|
|
Change From Baseline in Scores of the Total Quality of Life (TQOL) and 5 Domains as Measured by the Norfolk QOL - Diabetic Neuropathy (Norfolk QOL-DN) at Week 26, Week 52 and Week 78.
TQOL: Change at Week 52 (n=10)
|
9.1 Units on a scale
Standard Deviation 12.49
|
|
Change From Baseline in Scores of the Total Quality of Life (TQOL) and 5 Domains as Measured by the Norfolk QOL - Diabetic Neuropathy (Norfolk QOL-DN) at Week 26, Week 52 and Week 78.
TQOL: Change at Week 78 (n=8)
|
10.8 Units on a scale
Standard Deviation 13.69
|
|
Change From Baseline in Scores of the Total Quality of Life (TQOL) and 5 Domains as Measured by the Norfolk QOL - Diabetic Neuropathy (Norfolk QOL-DN) at Week 26, Week 52 and Week 78.
Physical Functioning: Baseline (n=10)
|
25.6 Units on a scale
Standard Deviation 15.28
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|
Change From Baseline in Scores of the Total Quality of Life (TQOL) and 5 Domains as Measured by the Norfolk QOL - Diabetic Neuropathy (Norfolk QOL-DN) at Week 26, Week 52 and Week 78.
Physical Functioning: Change at Week 26 (n=10)
|
4.8 Units on a scale
Standard Deviation 10.02
|
|
Change From Baseline in Scores of the Total Quality of Life (TQOL) and 5 Domains as Measured by the Norfolk QOL - Diabetic Neuropathy (Norfolk QOL-DN) at Week 26, Week 52 and Week 78.
Physical Functioning: Change at Week 52 (n=10)
|
2.2 Units on a scale
Standard Deviation 8.87
|
|
Change From Baseline in Scores of the Total Quality of Life (TQOL) and 5 Domains as Measured by the Norfolk QOL - Diabetic Neuropathy (Norfolk QOL-DN) at Week 26, Week 52 and Week 78.
Physical Functioning: Change at Week 78 (n=8)
|
4.1 Units on a scale
Standard Deviation 7.83
|
|
Change From Baseline in Scores of the Total Quality of Life (TQOL) and 5 Domains as Measured by the Norfolk QOL - Diabetic Neuropathy (Norfolk QOL-DN) at Week 26, Week 52 and Week 78.
ADL: Baseline (n=10)
|
8.5 Units on a scale
Standard Deviation 7.63
|
|
Change From Baseline in Scores of the Total Quality of Life (TQOL) and 5 Domains as Measured by the Norfolk QOL - Diabetic Neuropathy (Norfolk QOL-DN) at Week 26, Week 52 and Week 78.
ADL: Change at Week 26 (n=10)
|
1.2 Units on a scale
Standard Deviation 3.61
|
|
Change From Baseline in Scores of the Total Quality of Life (TQOL) and 5 Domains as Measured by the Norfolk QOL - Diabetic Neuropathy (Norfolk QOL-DN) at Week 26, Week 52 and Week 78.
ADL: Change at Week 52 (n=10)
|
0.8 Units on a scale
Standard Deviation 3.52
|
|
Change From Baseline in Scores of the Total Quality of Life (TQOL) and 5 Domains as Measured by the Norfolk QOL - Diabetic Neuropathy (Norfolk QOL-DN) at Week 26, Week 52 and Week 78.
ADL: Change at Week 78 (n=8)
|
0.6 Units on a scale
Standard Deviation 2.33
|
|
Change From Baseline in Scores of the Total Quality of Life (TQOL) and 5 Domains as Measured by the Norfolk QOL - Diabetic Neuropathy (Norfolk QOL-DN) at Week 26, Week 52 and Week 78.
Symptoms: Baseline (n=10)
|
8.5 Units on a scale
Standard Deviation 5.34
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|
Change From Baseline in Scores of the Total Quality of Life (TQOL) and 5 Domains as Measured by the Norfolk QOL - Diabetic Neuropathy (Norfolk QOL-DN) at Week 26, Week 52 and Week 78.
Symptoms: Change at Week 26 (n=10)
|
2.6 Units on a scale
Standard Deviation 3.47
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|
Change From Baseline in Scores of the Total Quality of Life (TQOL) and 5 Domains as Measured by the Norfolk QOL - Diabetic Neuropathy (Norfolk QOL-DN) at Week 26, Week 52 and Week 78.
Symptoms: Change at Week 52 (n=10)
|
4.0 Units on a scale
Standard Deviation 5.73
|
|
Change From Baseline in Scores of the Total Quality of Life (TQOL) and 5 Domains as Measured by the Norfolk QOL - Diabetic Neuropathy (Norfolk QOL-DN) at Week 26, Week 52 and Week 78.
Symptoms: Change at Week 78 (n=8)
|
3.1 Units on a scale
Standard Deviation 3.94
|
|
Change From Baseline in Scores of the Total Quality of Life (TQOL) and 5 Domains as Measured by the Norfolk QOL - Diabetic Neuropathy (Norfolk QOL-DN) at Week 26, Week 52 and Week 78.
Small Fiber: Baseline (n=10)
|
6.3 Units on a scale
Standard Deviation 5.31
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|
Change From Baseline in Scores of the Total Quality of Life (TQOL) and 5 Domains as Measured by the Norfolk QOL - Diabetic Neuropathy (Norfolk QOL-DN) at Week 26, Week 52 and Week 78.
Small Fiber: Change at Week 26 (n=10)
|
1.9 Units on a scale
Standard Deviation 4.25
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Change From Baseline in Scores of the Total Quality of Life (TQOL) and 5 Domains as Measured by the Norfolk QOL - Diabetic Neuropathy (Norfolk QOL-DN) at Week 26, Week 52 and Week 78.
Small Fiber: Change at Week 52 (n=10)
|
1.6 Units on a scale
Standard Deviation 2.32
|
|
Change From Baseline in Scores of the Total Quality of Life (TQOL) and 5 Domains as Measured by the Norfolk QOL - Diabetic Neuropathy (Norfolk QOL-DN) at Week 26, Week 52 and Week 78.
Small Fiber: Change at Week 78 (n=8)
|
2.1 Units on a scale
Standard Deviation 3.76
|
|
Change From Baseline in Scores of the Total Quality of Life (TQOL) and 5 Domains as Measured by the Norfolk QOL - Diabetic Neuropathy (Norfolk QOL-DN) at Week 26, Week 52 and Week 78.
Autonomic: Change at Week 26 (n=10)
|
1.3 Units on a scale
Standard Deviation 1.42
|
|
Change From Baseline in Scores of the Total Quality of Life (TQOL) and 5 Domains as Measured by the Norfolk QOL - Diabetic Neuropathy (Norfolk QOL-DN) at Week 26, Week 52 and Week 78.
Autonomic: Change at Week 52 (n=10)
|
0.5 Units on a scale
Standard Deviation 1.43
|
|
Change From Baseline in Scores of the Total Quality of Life (TQOL) and 5 Domains as Measured by the Norfolk QOL - Diabetic Neuropathy (Norfolk QOL-DN) at Week 26, Week 52 and Week 78.
Autonomic: Change at Week 78 (n=8)
|
0.8 Units on a scale
Standard Deviation 1.91
|
SECONDARY outcome
Timeframe: Baseline, Week 26, Week 52, Week 78Population: Full Analysis Set (FAS) included all participants who received at least one dose of the study drug.
The Σ7 NTs nds measures primarily large-fiber function. It is a composite score derived from five 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 VDT obtained in great toes by Quantitative Sensory Testing (QST), and HRDB value. It is defined as 7 times the mean of non-missing values of, the five normal deviates of NCS, HRDB, and average normal deviate for VDT of toes. Score was determined through reference to normal values for age, sex, height and abnormalities scored. Total score range is approximately -26 to 26, where higher score=worse nerve function.
Outcome measures
| Measure |
Tafamidis 20 mg
n=10 Participants
Participants (V30m and non-V30m transthyretin mutation) received tafamidis 20 mg soft gelatin capsules orally once daily for up to 78 weeks
|
|---|---|
|
Change From Baseline in Summated 7 Nerve Tests Normal Deviate Score (∑ 7 NTs Nds) as Measured by Nerve Conduction Studies (NCS), Vibration Detection Threshold (VDT) and Heart Rate Response to Deep Breathing (HRDB) at Week 26, Week 52, and Week 78
Baseline (n=10)
|
8.33 Units on a scale
Standard Deviation 5.574
|
|
Change From Baseline in Summated 7 Nerve Tests Normal Deviate Score (∑ 7 NTs Nds) as Measured by Nerve Conduction Studies (NCS), Vibration Detection Threshold (VDT) and Heart Rate Response to Deep Breathing (HRDB) at Week 26, Week 52, and Week 78
Change at Week 26 (n=10)
|
0.55 Units on a scale
Standard Deviation 2.657
|
|
Change From Baseline in Summated 7 Nerve Tests Normal Deviate Score (∑ 7 NTs Nds) as Measured by Nerve Conduction Studies (NCS), Vibration Detection Threshold (VDT) and Heart Rate Response to Deep Breathing (HRDB) at Week 26, Week 52, and Week 78
Change at Week 52 (n-=10)
|
1.04 Units on a scale
Standard Deviation 2.992
|
|
Change From Baseline in Summated 7 Nerve Tests Normal Deviate Score (∑ 7 NTs Nds) as Measured by Nerve Conduction Studies (NCS), Vibration Detection Threshold (VDT) and Heart Rate Response to Deep Breathing (HRDB) at Week 26, Week 52, and Week 78
Change at Week 78 (n=8)
|
1.92 Units on a scale
Standard Deviation 5.129
|
SECONDARY outcome
Timeframe: Baseline, Week 26, Week 52, Week 78Population: Full Analysis Set (FAS) included all participants who received at least one dose of the study drug.
The Σ3 NTSF nds measures small-fiber function. It is a composite score defined as 3 times the mean of non-missing values of normal deviates of cooling threshold for lower limbs, heat pain intermediate response for lower limbs, and HRDB. The total score range is approximately -11.2 to 11.2, with a higher score demonstrating worse nerve function.
Outcome measures
| Measure |
Tafamidis 20 mg
n=10 Participants
Participants (V30m and non-V30m transthyretin mutation) received tafamidis 20 mg soft gelatin capsules orally once daily for up to 78 weeks
|
|---|---|
|
Change From Baseline in Summated 3 Nerve Tests Small Fiber Normal Deviate Score (∑ 3 NTSF Nds) as Measured by Cooling and Heat Pain Thresholds by QST and HRDB at Week 26, Week 52 and Week 78
Baseline (n=10)
|
6.39 Units on a scale
Standard Deviation 3.160
|
|
Change From Baseline in Summated 3 Nerve Tests Small Fiber Normal Deviate Score (∑ 3 NTSF Nds) as Measured by Cooling and Heat Pain Thresholds by QST and HRDB at Week 26, Week 52 and Week 78
Change at Week 26 (n=10)
|
0.16 Units on a scale
Standard Deviation 1.619
|
|
Change From Baseline in Summated 3 Nerve Tests Small Fiber Normal Deviate Score (∑ 3 NTSF Nds) as Measured by Cooling and Heat Pain Thresholds by QST and HRDB at Week 26, Week 52 and Week 78
Change at Week 52 (n=10)
|
-0.13 Units on a scale
Standard Deviation 1.334
|
|
Change From Baseline in Summated 3 Nerve Tests Small Fiber Normal Deviate Score (∑ 3 NTSF Nds) as Measured by Cooling and Heat Pain Thresholds by QST and HRDB at Week 26, Week 52 and Week 78
Change at Week 78 (n=8)
|
0.40 Units on a scale
Standard Deviation 1.985
|
SECONDARY outcome
Timeframe: Baseline, Week 8, Week 26, Week 52, End of StudyPopulation: Full Analysis Set (FAS) included all participants who received at least one dose of the study drug.
The mBMI was calculated by multiplying the BMI (the weight in kilograms divided by the square of the height in meters) by serum albumin level (gram/liter). Change in mBMI was calculated as the mBMI at the given week minus the Baseline mBMI.
Outcome measures
| Measure |
Tafamidis 20 mg
n=10 Participants
Participants (V30m and non-V30m transthyretin mutation) received tafamidis 20 mg soft gelatin capsules orally once daily for up to 78 weeks
|
|---|---|
|
Change From Baseline in Modified Body Mass Index (mBMI) at Week 8, Week 26, Week 52 and End of Study
Baseline (n=10)
|
805.70 (kilogram/square meter)*(gram/liter)
Standard Deviation 193.378
|
|
Change From Baseline in Modified Body Mass Index (mBMI) at Week 8, Week 26, Week 52 and End of Study
Change at Week 8 (n=10)
|
74.86 (kilogram/square meter)*(gram/liter)
Standard Deviation 88.706
|
|
Change From Baseline in Modified Body Mass Index (mBMI) at Week 8, Week 26, Week 52 and End of Study
Change at Week 26 (n=10)
|
26.61 (kilogram/square meter)*(gram/liter)
Standard Deviation 61.862
|
|
Change From Baseline in Modified Body Mass Index (mBMI) at Week 8, Week 26, Week 52 and End of Study
Change at Week 52 (n=10)
|
64.86 (kilogram/square meter)*(gram/liter)
Standard Deviation 80.016
|
|
Change From Baseline in Modified Body Mass Index (mBMI) at Week 8, Week 26, Week 52 and End of Study
End of Study (n=7)
|
53.65 (kilogram/square meter)*(gram/liter)
Standard Deviation 81.386
|
SECONDARY outcome
Timeframe: Baseline, Week 26, Week 52, Week 78Population: Full Analysis Set (FAS) included all participants who received at least one dose of the study drug.
Ambulatory status was evaluated using walking ability scale in polyneuropathy disability score. The ambulatory status was evaluated as: 0=Good, 1=Sensory disturbances in the feet but able to walk without difficulty, 2=Some difficulties with walking but can walk without aid, 3a=Able to walk with 1 stick or crutch, 3b=Able to walk with 2 sticks or crutches, 4=Not ambulatory, confined to a wheelchair or bedridden.
Outcome measures
| Measure |
Tafamidis 20 mg
n=10 Participants
Participants (V30m and non-V30m transthyretin mutation) received tafamidis 20 mg soft gelatin capsules orally once daily for up to 78 weeks
|
|---|---|
|
Change From Baseline in Ambulatory Status at Week 26, Week 52 and Week 78
Week 78 (n=8): Status 0
|
1 Participants
|
|
Change From Baseline in Ambulatory Status at Week 26, Week 52 and Week 78
Week 78 (n=8): Status 1
|
1 Participants
|
|
Change From Baseline in Ambulatory Status at Week 26, Week 52 and Week 78
Week 78 (n=8): Status 2
|
2 Participants
|
|
Change From Baseline in Ambulatory Status at Week 26, Week 52 and Week 78
Baseline (n=10): Status 0
|
0 Participants
|
|
Change From Baseline in Ambulatory Status at Week 26, Week 52 and Week 78
Baseline (n=10): Status 1
|
3 Participants
|
|
Change From Baseline in Ambulatory Status at Week 26, Week 52 and Week 78
Baseline (n=10): Status 2
|
4 Participants
|
|
Change From Baseline in Ambulatory Status at Week 26, Week 52 and Week 78
Baseline (n=10): Status 3a
|
2 Participants
|
|
Change From Baseline in Ambulatory Status at Week 26, Week 52 and Week 78
Baseline (n=10): Status 3b
|
1 Participants
|
|
Change From Baseline in Ambulatory Status at Week 26, Week 52 and Week 78
Baseline (n=10): Status 4
|
0 Participants
|
|
Change From Baseline in Ambulatory Status at Week 26, Week 52 and Week 78
Week 26 (n=10): Status 0
|
1 Participants
|
|
Change From Baseline in Ambulatory Status at Week 26, Week 52 and Week 78
Week 26 (n=10): Status 1
|
2 Participants
|
|
Change From Baseline in Ambulatory Status at Week 26, Week 52 and Week 78
Week 26 (n=10): Status 2
|
3 Participants
|
|
Change From Baseline in Ambulatory Status at Week 26, Week 52 and Week 78
Week 26 (n=10): Status 3a
|
2 Participants
|
|
Change From Baseline in Ambulatory Status at Week 26, Week 52 and Week 78
Week 26 (n=10): Status 3b
|
2 Participants
|
|
Change From Baseline in Ambulatory Status at Week 26, Week 52 and Week 78
Week 26 (n=10): Status 4
|
0 Participants
|
|
Change From Baseline in Ambulatory Status at Week 26, Week 52 and Week 78
Week 52 (n=10): Status 0
|
1 Participants
|
|
Change From Baseline in Ambulatory Status at Week 26, Week 52 and Week 78
Week 52 (n=10): Status 1
|
1 Participants
|
|
Change From Baseline in Ambulatory Status at Week 26, Week 52 and Week 78
Week 52 (n=10): Status 2
|
4 Participants
|
|
Change From Baseline in Ambulatory Status at Week 26, Week 52 and Week 78
Week 52 (n=10): Status 3a
|
2 Participants
|
|
Change From Baseline in Ambulatory Status at Week 26, Week 52 and Week 78
Week 52 (n=10): Status 3b
|
2 Participants
|
|
Change From Baseline in Ambulatory Status at Week 26, Week 52 and Week 78
Week 52 (n=10): Status 4
|
0 Participants
|
|
Change From Baseline in Ambulatory Status at Week 26, Week 52 and Week 78
Week 78 (n=8): Status 3a
|
2 Participants
|
|
Change From Baseline in Ambulatory Status at Week 26, Week 52 and Week 78
Week 78 (n=8): Status 3b
|
2 Participants
|
|
Change From Baseline in Ambulatory Status at Week 26, Week 52 and Week 78
Week 78 (n=8): Status 4
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline, Week 26, Week 52, Week 78Population: Full Analysis Set (FAS) included all participants who received at least one dose of the study drug.
TTR tetramer was assessed using a validated immunoturbidimetric assay. The TTR tetramer level for each plasma sample was measured before and after urea denaturation. The Fraction of Initial (FOI) tetramer concentration 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. A patient who has the "TTR stabilization" is defined as the patient whose percent stabilization is equal to or more than 32%.
Outcome measures
| Measure |
Tafamidis 20 mg
n=10 Participants
Participants (V30m and non-V30m transthyretin mutation) received tafamidis 20 mg soft gelatin capsules orally once daily for up to 78 weeks
|
|---|---|
|
Number of Participants With Transthyretin (TTR) Stabilization at Week 26, Week 52, and Week 78 Compared With Baseline as Measured by a Validated Immunoturbidimetric Assay
Week 26
|
10 Participants
|
|
Number of Participants With Transthyretin (TTR) Stabilization at Week 26, Week 52, and Week 78 Compared With Baseline as Measured by a Validated Immunoturbidimetric Assay
Week 52
|
9 Participants
|
|
Number of Participants With Transthyretin (TTR) Stabilization at Week 26, Week 52, and Week 78 Compared With Baseline as Measured by a Validated Immunoturbidimetric Assay
Week 78
|
8 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Week 8, Week 26, Week 52, Week 78Population: The PK Analysis Set included all participants treated who had at least 1 quantifiable plasma tafamidis concentration.
Mean plasma concentration of tafamidis at 3 hours after administration
Outcome measures
| Measure |
Tafamidis 20 mg
n=10 Participants
Participants (V30m and non-V30m transthyretin mutation) received tafamidis 20 mg soft gelatin capsules orally once daily for up to 78 weeks
|
|---|---|
|
Plasma Concentration of Tafamidis at Week 8, Week 26, Week 52 and Week 78
Week 8 (n=10)
|
2773.0 ng/mL
Standard Deviation 1777.71
|
|
Plasma Concentration of Tafamidis at Week 8, Week 26, Week 52 and Week 78
Week 26 (n=10)
|
2739.0 ng/mL
Standard Deviation 1893.25
|
|
Plasma Concentration of Tafamidis at Week 8, Week 26, Week 52 and Week 78
Week 52 (n=10)
|
2829.0 ng/mL
Standard Deviation 2315.58
|
|
Plasma Concentration of Tafamidis at Week 8, Week 26, Week 52 and Week 78
Week 78 (n=8)
|
3655.0 ng/mL
Standard Deviation 2268.08
|
Adverse Events
Tafamidis 20 mg
Serious adverse events
| Measure |
Tafamidis 20 mg
n=10 participants at risk
Participants (V30m and non-V30m transthyretin mutation) received tafamidis 20 mg soft gelatin capsules orally once daily for up to 78 weeks
|
|---|---|
|
Cardiac disorders
Atrioventricular block second degree
|
10.0%
1/10
|
|
Cardiac disorders
Sick sinus syndrome
|
10.0%
1/10
|
|
Gastrointestinal disorders
Ileus
|
10.0%
1/10
|
|
General disorders
Sudden death
|
10.0%
1/10
|
|
Infections and infestations
Pneumonia bacterial
|
30.0%
3/10
|
|
Infections and infestations
Pyelonephritis
|
10.0%
1/10
|
|
Injury, poisoning and procedural complications
Burns third degree
|
10.0%
1/10
|
|
Metabolism and nutrition disorders
Decreased appetite
|
10.0%
1/10
|
|
Psychiatric disorders
Completed suicide
|
10.0%
1/10
|
Other adverse events
| Measure |
Tafamidis 20 mg
n=10 participants at risk
Participants (V30m and non-V30m transthyretin mutation) received tafamidis 20 mg soft gelatin capsules orally once daily for up to 78 weeks
|
|---|---|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
10.0%
1/10
|
|
Cardiac disorders
Atrioventricular block second degree
|
10.0%
1/10
|
|
Cardiac disorders
Palpitations
|
10.0%
1/10
|
|
Ear and labyrinth disorders
Ear discomfort
|
10.0%
1/10
|
|
Ear and labyrinth disorders
Meniere's disease
|
10.0%
1/10
|
|
Eye disorders
Cataract
|
20.0%
2/10
|
|
Eye disorders
Conjunctivitis
|
10.0%
1/10
|
|
Eye disorders
Dry eye
|
10.0%
1/10
|
|
Eye disorders
Eye discharge
|
10.0%
1/10
|
|
Eye disorders
Vitreous opacities
|
20.0%
2/10
|
|
Gastrointestinal disorders
Diarrhoea
|
10.0%
1/10
|
|
Gastrointestinal disorders
Gingival swelling
|
10.0%
1/10
|
|
Gastrointestinal disorders
Nausea
|
20.0%
2/10
|
|
Gastrointestinal disorders
Paraesthesia oral
|
10.0%
1/10
|
|
Gastrointestinal disorders
Stomatitis
|
10.0%
1/10
|
|
Gastrointestinal disorders
Vomiting
|
20.0%
2/10
|
|
General disorders
Oedema
|
10.0%
1/10
|
|
General disorders
Pyrexia
|
10.0%
1/10
|
|
Infections and infestations
Bronchitis
|
10.0%
1/10
|
|
Infections and infestations
Hordeolum
|
10.0%
1/10
|
|
Infections and infestations
Influenza
|
10.0%
1/10
|
|
Infections and infestations
Nasopharyngitis
|
50.0%
5/10
|
|
Infections and infestations
Oral herpes
|
10.0%
1/10
|
|
Infections and infestations
Tinea capitis
|
10.0%
1/10
|
|
Infections and infestations
Tinea pedis
|
10.0%
1/10
|
|
Injury, poisoning and procedural complications
Laceration
|
10.0%
1/10
|
|
Injury, poisoning and procedural complications
Limb injury
|
10.0%
1/10
|
|
Injury, poisoning and procedural complications
Muscle strain
|
10.0%
1/10
|
|
Injury, poisoning and procedural complications
Thermal burn
|
30.0%
3/10
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
10.0%
1/10
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
10.0%
1/10
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
10.0%
1/10
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
20.0%
2/10
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
50.0%
5/10
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
20.0%
2/10
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
10.0%
1/10
|
|
Musculoskeletal and connective tissue disorders
Trigger finger
|
10.0%
1/10
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm skin
|
10.0%
1/10
|
|
Nervous system disorders
Ataxia
|
10.0%
1/10
|
|
Nervous system disorders
Dementia
|
10.0%
1/10
|
|
Nervous system disorders
Headache
|
10.0%
1/10
|
|
Nervous system disorders
Hypoaesthesia
|
10.0%
1/10
|
|
Nervous system disorders
Loss of consciousness
|
10.0%
1/10
|
|
Psychiatric disorders
Anxiety
|
10.0%
1/10
|
|
Psychiatric disorders
Insomnia
|
20.0%
2/10
|
|
Reproductive system and breast disorders
Gynaecomastia
|
10.0%
1/10
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.0%
1/10
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
10.0%
1/10
|
|
Respiratory, thoracic and mediastinal disorders
Sleep apnoea syndrome
|
10.0%
1/10
|
|
Skin and subcutaneous tissue disorders
Blister
|
10.0%
1/10
|
|
Skin and subcutaneous tissue disorders
Decubitus ulcer
|
10.0%
1/10
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
10.0%
1/10
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
10.0%
1/10
|
|
Skin and subcutaneous tissue disorders
Rash
|
10.0%
1/10
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
10.0%
1/10
|
|
Skin and subcutaneous tissue disorders
Solar dermatitis
|
10.0%
1/10
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
10.0%
1/10
|
Additional Information
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