Trial Outcomes & Findings for The Effect Of Tafamidis Meglumine In Transthyretin Amyloid Polyneuropathy Patients (NCT NCT04828993)
NCT ID: NCT04828993
Last Updated: 2024-03-12
Results Overview
NIS-LL: assess muscle weakness, reflexes, 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) scored on scale 0 (normal) to 4 (paralysis), higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae); sensation (touch pressure, pin-prick, vibration, joint position) scored 0 = normal, 1 = decreased, or 2 = absent. Total possible NIS-LL score range 0-88, high score = more impairment. Components of muscle weakness are scored to eight levels: 0 = Normal, 1 = 25% Weak, 2 = 50% Weak, 3 = 75% Weak, 3.25 = Move against gravity, 3.5 = Movement, gravity eliminated, 3.75 = Muscle flicker, no movement, 4 = Paralysis.
COMPLETED
PHASE4
15 participants
Baseline, Week 72
2024-03-12
Participant Flow
A total of 15 participants were screened and assigned to treatment.
Participant milestones
| Measure |
Tafamidis Meglumine 20 mg Once Daily (QD)
All enrolled participants received a once-daily (QD) oral dose of tafamidis meglumine 20 mg in a soft capsule formulation.
|
|---|---|
|
Disposition Phase: TREATMENT
STARTED
|
15
|
|
Disposition Phase: TREATMENT
COMPLETED
|
15
|
|
Disposition Phase: TREATMENT
NOT COMPLETED
|
0
|
|
Disposition Phase: FOLLOW-UP
STARTED
|
15
|
|
Disposition Phase: FOLLOW-UP
COMPLETED
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15
|
|
Disposition Phase: FOLLOW-UP
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
The Effect Of Tafamidis Meglumine In Transthyretin Amyloid Polyneuropathy Patients
Baseline characteristics by cohort
| Measure |
Tafamidis Meglumine 20 mg Once Daily (QD)
n=15 Participants
All enrolled participants received a once-daily (QD) oral dose of tafamidis meglumine 20 mg in a soft capsule formulation.
|
|---|---|
|
Age, Continuous
|
51.1 Years
STANDARD_DEVIATION 15.75 • n=5 Participants
|
|
Age, Customized
18-44 years
|
6 Participants
n=5 Participants
|
|
Age, Customized
45-64 years
|
5 Participants
n=5 Participants
|
|
Age, Customized
>=65 years
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
15 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
15 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 72Population: All participants who took at least 1 dose of tafamidis meglumine soft gelatin capsule 20 mg.
NIS-LL: assess muscle weakness, reflexes, 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) scored on scale 0 (normal) to 4 (paralysis), higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae); sensation (touch pressure, pin-prick, vibration, joint position) scored 0 = normal, 1 = decreased, or 2 = absent. Total possible NIS-LL score range 0-88, high score = more impairment. Components of muscle weakness are scored to eight levels: 0 = Normal, 1 = 25% Weak, 2 = 50% Weak, 3 = 75% Weak, 3.25 = Move against gravity, 3.5 = Movement, gravity eliminated, 3.75 = Muscle flicker, no movement, 4 = Paralysis.
Outcome measures
| Measure |
Tafamidis Meglumine 20 mg Once Daily (QD)
n=15 Participants
All enrolled participants received a once-daily (QD) oral dose of tafamidis meglumine 20 mg in a soft capsule formulation.
|
|---|---|
|
Change From Baseline in Neuropathy Impairment Score-lower Limb (NIS-LL) Total Score at Week 72
|
2.3 Units on a scale
Interval -3.0 to 46.0
|
SECONDARY outcome
Timeframe: Baseline, Week 24, Week 48Population: All participants who took at least 1 dose of tafamidis meglumine soft gelatin capsule 20 mg.
NIS-LL: assess muscle weakness, reflexes, 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) scored on scale 0 (normal) to 4 (paralysis), higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae); sensation (touch pressure, pin-prick, vibration, joint position) scored 0 = normal, 1 = decreased, or 2 = absent. Total possible NIS-LL score range 0-88, high score = more impairment. Components of muscle weakness are scored to eight levels: 0 = Normal, 1 = 25% Weak, 2 = 50% Weak, 3 = 75% Weak, 3.25 = Move against gravity, 3.5 = Movement, gravity eliminated, 3.75 = Muscle flicker, no movement, 4 = Paralysis.
Outcome measures
| Measure |
Tafamidis Meglumine 20 mg Once Daily (QD)
n=15 Participants
All enrolled participants received a once-daily (QD) oral dose of tafamidis meglumine 20 mg in a soft capsule formulation.
|
|---|---|
|
Change From Baseline in Neuropathy Impairment Score-lower Limb (NIS-LL) Total Score at Weeks 24, and 48
Change From Baseline in Neuropathy Impairment Score-lower limb (NIS-LL) Total Score at Week 24
|
3.0 Units on a scale
Interval -20.0 to 20.0
|
|
Change From Baseline in Neuropathy Impairment Score-lower Limb (NIS-LL) Total Score at Weeks 24, and 48
Change From Baseline in Neuropathy Impairment Score-lower limb (NIS-LL) Total Score at Week 48
|
8.0 Units on a scale
Interval -13.5 to 18.0
|
SECONDARY outcome
Timeframe: Baseline, Week 24, Week 48, Week 72Population: All participants who took at least 1 dose of tafamidis meglumine soft gelatin capsule 20 mg.
Norfolk QOL-DN: 35-item participant-rated questionnaire assess the impact of neuropathy on the quality of life of participants diagnosed with transthyretin amyloid (ATTR). Scoring is based on 35 questions that yield a TQOL as well as 5 subscale scores: activities of daily living, large fiber neuropathy/physical functioning, small fiber neuropathy, autonomic neuropathy, and symptoms. TQOL= sum of all the items, total possible score range= -2 to 138, where higher score=worse quality of life.
Outcome measures
| Measure |
Tafamidis Meglumine 20 mg Once Daily (QD)
n=15 Participants
All enrolled participants received a once-daily (QD) oral dose of tafamidis meglumine 20 mg in a soft capsule formulation.
|
|---|---|
|
Change From Baseline in Total Quality of Life (TQOL) of Norfolk Quality of Life - Diabetic Neuropathy (Norfolk QOL-DN) at Weeks 24, 48, and 72
Change From Baseline in TQOL of Norfolk QOL-DN at Week 24
|
-1.00 Units on a scale
Interval -26.0 to 54.0
|
|
Change From Baseline in Total Quality of Life (TQOL) of Norfolk Quality of Life - Diabetic Neuropathy (Norfolk QOL-DN) at Weeks 24, 48, and 72
Change From Baseline in TQOL of Norfolk QOL-DN at Week 48
|
2.00 Units on a scale
Interval -26.0 to 63.0
|
|
Change From Baseline in Total Quality of Life (TQOL) of Norfolk Quality of Life - Diabetic Neuropathy (Norfolk QOL-DN) at Weeks 24, 48, and 72
Change From Baseline in TQOL of Norfolk QOL-DN at Week 72
|
8.00 Units on a scale
Interval -11.0 to 74.0
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SECONDARY outcome
Timeframe: Baseline, Week 24, Week 48, Week 72Population: All participants who took at least 1 dose of tafamidis meglumine soft gelatin capsule 20 mg.
Norfolk QOL-DN: 35-item participant-rated questionnaire assess the impact of neuropathy on the quality of life of participants diagnosed with transthyretin amyloid (ATTR). It is summarized in 5 domains: (1) Activities of daily living (score ranges from 0 to 20, where higher score=worse quality of life); (2) Large fiber neuropathy/physical functioning (score ranges from -2 to 58, where higher score=worse condition); (3) Small fiber neuropathy (score ranges from 0 to 16, where higher score=worse condition); (4) Autonomic neuropathy (score ranges from 0 to 12, where higher score=worse condition) and (5) Symptoms (score ranges from 0 to 32, where higher score=less symptoms of disease). Total possible score range= -2 to 138, where higher score=worse quality of life.
Outcome measures
| Measure |
Tafamidis Meglumine 20 mg Once Daily (QD)
n=15 Participants
All enrolled participants received a once-daily (QD) oral dose of tafamidis meglumine 20 mg in a soft capsule formulation.
|
|---|---|
|
Change From Baseline in 5 Domains of Norfolk QOL-DN at Weeks 24, 48, and 72
Change From Baseline in Physical Functioning/Large Fiber Domain of Norfolk QOL-DN at Week 24
|
-3.00 Units on a scale
Interval -22.0 to 28.0
|
|
Change From Baseline in 5 Domains of Norfolk QOL-DN at Weeks 24, 48, and 72
Change From Baseline in Physical Functioning/Large Fiber Domain of Norfolk QOL-DN at Week 48
|
2.00 Units on a scale
Interval -13.0 to 38.0
|
|
Change From Baseline in 5 Domains of Norfolk QOL-DN at Weeks 24, 48, and 72
Change From Baseline in Physical Functioning/Large Fiber Domain of Norfolk QOL-DN at Week 72
|
4.00 Units on a scale
Interval -10.0 to 39.0
|
|
Change From Baseline in 5 Domains of Norfolk QOL-DN at Weeks 24, 48, and 72
Change From Baseline in Activities of Daily Living Domain of Norfolk QOL-DN at Week 24
|
0.00 Units on a scale
Interval -4.0 to 12.0
|
|
Change From Baseline in 5 Domains of Norfolk QOL-DN at Weeks 24, 48, and 72
Change From Baseline in Activities of Daily Living Domain of Norfolk QOL-DN at Week 48
|
1.00 Units on a scale
Interval -4.0 to 15.0
|
|
Change From Baseline in 5 Domains of Norfolk QOL-DN at Weeks 24, 48, and 72
Change From Baseline in Activities of Daily Living Domain of Norfolk QOL-DN at Week 72
|
3.00 Units on a scale
Interval -2.0 to 15.0
|
|
Change From Baseline in 5 Domains of Norfolk QOL-DN at Weeks 24, 48, and 72
Change From Baseline in Symptoms Domain of Norfolk QOL-DN at Week 24
|
1.00 Units on a scale
Interval -13.0 to 9.0
|
|
Change From Baseline in 5 Domains of Norfolk QOL-DN at Weeks 24, 48, and 72
Change From Baseline in Symptoms Domain of Norfolk QOL-DN at Week 48
|
2.00 Units on a scale
Interval -6.0 to 9.0
|
|
Change From Baseline in 5 Domains of Norfolk QOL-DN at Weeks 24, 48, and 72
Change From Baseline in Symptoms Domain of Norfolk QOL-DN at Week 72
|
2.00 Units on a scale
Interval -2.0 to 23.0
|
|
Change From Baseline in 5 Domains of Norfolk QOL-DN at Weeks 24, 48, and 72
Change From Baseline in Small Fiber Domain of Norfolk QOL-DN at Week 24
|
0.00 Units on a scale
Interval -3.0 to 6.0
|
|
Change From Baseline in 5 Domains of Norfolk QOL-DN at Weeks 24, 48, and 72
Change From Baseline in Small Fiber Domain of Norfolk QOL-DN at Week 48
|
1.00 Units on a scale
Interval -2.0 to 9.0
|
|
Change From Baseline in 5 Domains of Norfolk QOL-DN at Weeks 24, 48, and 72
Change From Baseline in Small Fiber Domain of Norfolk QOL-DN at Week 72
|
3.00 Units on a scale
Interval -3.0 to 10.0
|
|
Change From Baseline in 5 Domains of Norfolk QOL-DN at Weeks 24, 48, and 72
Change From Baseline in Autonomic Domain of Norfolk QOL-DN at Week 24
|
0.00 Units on a scale
Interval -4.0 to 3.0
|
|
Change From Baseline in 5 Domains of Norfolk QOL-DN at Weeks 24, 48, and 72
Change From Baseline in Autonomic Domain of Norfolk QOL-DN at Week 48
|
0.00 Units on a scale
Interval -5.0 to 4.0
|
|
Change From Baseline in 5 Domains of Norfolk QOL-DN at Weeks 24, 48, and 72
Change From Baseline in Autonomic Domain of Norfolk QOL-DN at Week 72
|
2.00 Units on a scale
Interval -5.0 to 6.0
|
SECONDARY outcome
Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, 48, and 72Population: All participants who took at least 1 dose of tafamidis meglumine soft gelatin capsule 20 mg.
BMI is calculated by weight divided by height squared and measured as kilogram per square meter (kg/m\^2). mBMI is calculated by multiplying BMI by serum albumin levels \[gram/liter (g/L)\]. mBMI is measured as kg/m\^2\*g/L. A progressive decline in mBMI indicates worsening of disease severity.
Outcome measures
| Measure |
Tafamidis Meglumine 20 mg Once Daily (QD)
n=15 Participants
All enrolled participants received a once-daily (QD) oral dose of tafamidis meglumine 20 mg in a soft capsule formulation.
|
|---|---|
|
Change From Baseline in Modified Body Mass Index (mBMI) at Weeks 4, 8, 12, 24, 36, 48, and 72
Change From Baseline in mBMI at Week 4
|
-5.9 kg/m^2*g/L
Interval -87.2 to 95.5
|
|
Change From Baseline in Modified Body Mass Index (mBMI) at Weeks 4, 8, 12, 24, 36, 48, and 72
Change From Baseline in Modified Body Mass Index (mBMI) at Week 8
|
22.3 kg/m^2*g/L
Interval -101.2 to 219.7
|
|
Change From Baseline in Modified Body Mass Index (mBMI) at Weeks 4, 8, 12, 24, 36, 48, and 72
Change From Baseline in Modified Body Mass Index (mBMI) at Week 12
|
9.2 kg/m^2*g/L
Interval -39.0 to 199.3
|
|
Change From Baseline in Modified Body Mass Index (mBMI) at Weeks 4, 8, 12, 24, 36, 48, and 72
Change From Baseline in Modified Body Mass Index (mBMI) at Week 24
|
21.8 kg/m^2*g/L
Interval -132.8 to 179.1
|
|
Change From Baseline in Modified Body Mass Index (mBMI) at Weeks 4, 8, 12, 24, 36, 48, and 72
Change From Baseline in Modified Body Mass Index (mBMI) at Week 36
|
37.0 kg/m^2*g/L
Interval -79.3 to 207.7
|
|
Change From Baseline in Modified Body Mass Index (mBMI) at Weeks 4, 8, 12, 24, 36, 48, and 72
Change From Baseline in Modified Body Mass Index (mBMI) at Week 48
|
41.4 kg/m^2*g/L
Interval -130.2 to 152.6
|
|
Change From Baseline in Modified Body Mass Index (mBMI) at Weeks 4, 8, 12, 24, 36, 48, and 72
Change From Baseline in Modified Body Mass Index (mBMI) at Week 72
|
9.4 kg/m^2*g/L
Interval -161.8 to 179.5
|
SECONDARY outcome
Timeframe: Baseline, Weeks 24, 48, and 72Population: All participants who took at least 1 dose of tafamidis meglumine soft gelatin capsule 20 mg.
The SF-36 is a participant administered scale assessing general quality of life. It consists of self-administered 36-item questionnaire that measured 8 health domains: physical function, role-physical, bodily pain, general health, vitality, social function, role-emotional, and mental health. These 8 domains are also summarized as physical and mental component scores. The score for each domain and component score is the mean of the individual question scores, which are scaled from 0 (minimum) to 100 (maximum), where high scores in each dimension and high overall scores indicate a better quality of life.
Outcome measures
| Measure |
Tafamidis Meglumine 20 mg Once Daily (QD)
n=15 Participants
All enrolled participants received a once-daily (QD) oral dose of tafamidis meglumine 20 mg in a soft capsule formulation.
|
|---|---|
|
Change From Baseline in Physical Component Summary and Mental Component Summary of 36-Item Short Form Survey (SF-36) at Weeks 24, 48, and 72
Change from Baseline in Physical Component Summary at Week 24
|
-2.15 Units on a scale
Interval -9.29 to 11.84
|
|
Change From Baseline in Physical Component Summary and Mental Component Summary of 36-Item Short Form Survey (SF-36) at Weeks 24, 48, and 72
Change from Baseline in Physical Component Summary at Week 48
|
-0.12 Units on a scale
Interval -12.13 to 12.08
|
|
Change From Baseline in Physical Component Summary and Mental Component Summary of 36-Item Short Form Survey (SF-36) at Weeks 24, 48, and 72
Change from Baseline in Physical Component Summary at Week 72
|
-1.60 Units on a scale
Interval -17.61 to 8.89
|
|
Change From Baseline in Physical Component Summary and Mental Component Summary of 36-Item Short Form Survey (SF-36) at Weeks 24, 48, and 72
Change from Baseline in Mental Component Summary at Week 24
|
1.21 Units on a scale
Interval -9.56 to 19.3
|
|
Change From Baseline in Physical Component Summary and Mental Component Summary of 36-Item Short Form Survey (SF-36) at Weeks 24, 48, and 72
Change from Baseline in Mental Component Summary at Week 48
|
-2.56 Units on a scale
Interval -31.69 to 9.36
|
|
Change From Baseline in Physical Component Summary and Mental Component Summary of 36-Item Short Form Survey (SF-36) at Weeks 24, 48, and 72
Change from Baseline in Mental Component Summary at Week 72
|
-6.10 Units on a scale
Interval -31.85 to 8.17
|
SECONDARY outcome
Timeframe: Baseline, Weeks 24, 48, and 72Population: All participants who took at least 1 dose of tafamidis meglumine soft gelatin capsule 20 mg.
EQ-5D-5L: standardized participant (aged \>17 years) completed questionnaire consists of 2 components: a health state profile and an optional VAS. EQ-5D health state profile has 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems. Responses to 5 dimensions comprise a health state/a single utility index value. E.g. if a participant responds "no problems" for each 5 dimensions, then health state was coded as "11111" with a predefined index value to it. Every health state (coded as combination of responses on each of 5 dimensions) has a unique predefined utility index value assigned to it, by EuroQol. Chinese value sets (with all possible health states) is used for adults in the study, range from -0.391 to 1. Higher (positive) scores = better health state.
Outcome measures
| Measure |
Tafamidis Meglumine 20 mg Once Daily (QD)
n=15 Participants
All enrolled participants received a once-daily (QD) oral dose of tafamidis meglumine 20 mg in a soft capsule formulation.
|
|---|---|
|
Change From Baseline in EuroQoL 5 Dimensions 5 Levels (EQ-5D-5L) Index Score at Weeks 24, 48, and 72
Change from Baseline in EQ-5D-5L Index Score at Week 24
|
0.00 Units on a scale
Interval -0.5 to 0.22
|
|
Change From Baseline in EuroQoL 5 Dimensions 5 Levels (EQ-5D-5L) Index Score at Weeks 24, 48, and 72
Change from Baseline in EQ-5D-5L Index Score at Week 48
|
-0.05 Units on a scale
Interval -0.51 to 0.11
|
|
Change From Baseline in EuroQoL 5 Dimensions 5 Levels (EQ-5D-5L) Index Score at Weeks 24, 48, and 72
Change from Baseline in EQ-5D-5L Index Score at Week 72
|
-0.16 Units on a scale
Interval -0.75 to 0.11
|
SECONDARY outcome
Timeframe: Baseline up to Week 77Population: All participants who took at least 1 dose of tafamidis meglumine soft gelatin capsule 20 mg.
An adverse event is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Treatment emergent adverse event is defined as any adverse event started after the first dose. The TEAEs were collected until Week 77.
Outcome measures
| Measure |
Tafamidis Meglumine 20 mg Once Daily (QD)
n=15 Participants
All enrolled participants received a once-daily (QD) oral dose of tafamidis meglumine 20 mg in a soft capsule formulation.
|
|---|---|
|
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs)
|
13 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Week 72Population: All participants who took at least 1 dose of tafamidis meglumine soft gelatin capsule 20 mg.
Vital signs categorical criteria: 1) pulse rate \<40 beats per minute (bpm), or \>120 bpm; 2) standing diastolic blood pressure (BP) \<50 mmHg, or increase ≥20 mmHg, or decrease ≥20 mmHg; 3) standing systolic BP \<90 mmHg, or increase ≥30 mmHg, or decrease ≥30 mmHg; 4) supine diastolic BP \<50 mmHg, or increase ≥20 mmHg, or decrease ≥20 mmHg; 5) supine systolic BP \<90 mmHg, or increase ≥30 mmHg, or decrease ≥30 mmHg.
Outcome measures
| Measure |
Tafamidis Meglumine 20 mg Once Daily (QD)
n=15 Participants
All enrolled participants received a once-daily (QD) oral dose of tafamidis meglumine 20 mg in a soft capsule formulation.
|
|---|---|
|
Number of Participants With Categorical Vital Signs Data
Pulse rate <40 bpm
|
0 Participants
|
|
Number of Participants With Categorical Vital Signs Data
Pulse rate >120 bpm
|
0 Participants
|
|
Number of Participants With Categorical Vital Signs Data
Standing diastolic BP <50 mmHg
|
4 Participants
|
|
Number of Participants With Categorical Vital Signs Data
Standing diastolic BP increase ≥20 mmHg
|
3 Participants
|
|
Number of Participants With Categorical Vital Signs Data
Standing diastolic BP decrease ≥20 mmHg
|
0 Participants
|
|
Number of Participants With Categorical Vital Signs Data
Standing systolic BP <90 mmHg
|
6 Participants
|
|
Number of Participants With Categorical Vital Signs Data
Standing systolic BP increase ≥30 mmHg
|
5 Participants
|
|
Number of Participants With Categorical Vital Signs Data
Standing systolic BP decrease ≥30 mmHg
|
3 Participants
|
|
Number of Participants With Categorical Vital Signs Data
Supine diastolic BP <50 mmHg
|
0 Participants
|
|
Number of Participants With Categorical Vital Signs Data
Supine diastolic BP increase ≥20 mmHg
|
2 Participants
|
|
Number of Participants With Categorical Vital Signs Data
Supine diastolic BP decrease ≥20 mmHg
|
2 Participants
|
|
Number of Participants With Categorical Vital Signs Data
Supine systolic BP <90 mmHg
|
0 Participants
|
|
Number of Participants With Categorical Vital Signs Data
Supine systolic BP increase ≥30 mmHg
|
1 Participants
|
|
Number of Participants With Categorical Vital Signs Data
Supine systolic BP decrease ≥30 mmHg
|
1 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Week 72Population: All participants who took at least 1 dose of tafamidis meglumine soft gelatin capsule 20 mg.
ECG categorical criteria: 1) ECG mean heart rate \<40 beats/minute, or \>120 beats/minute; 2) PR interval not otherwise specified ≥300 milliseconds (msec), or baseline \>200 msec and %increase ≥25%/ baseline ≤200 msec and %increase ≥50% (% change ≥25/50%); 3) QRS interval not otherwise specified ≥140 msec, or %change ≥50%; 4) QT interval not otherwise specified ≥500 msec; 5) corrected QT (QTc) interval not otherwise specified ≥450 and \<480 msec, or ≥480 and \<500 msec, or ≥500 msec; or change ≥30 and \<60 msec, or change ≥60 msec.
Outcome measures
| Measure |
Tafamidis Meglumine 20 mg Once Daily (QD)
n=15 Participants
All enrolled participants received a once-daily (QD) oral dose of tafamidis meglumine 20 mg in a soft capsule formulation.
|
|---|---|
|
Number of Participants With Categorical Electrocardiogram (ECG) Data
ECG mean heart rate <40 beats/minute
|
0 Participants
|
|
Number of Participants With Categorical Electrocardiogram (ECG) Data
ECG mean heart rate >120 beats/minute
|
0 Participants
|
|
Number of Participants With Categorical Electrocardiogram (ECG) Data
PR interval not otherwise specified ≥300 milliseconds (msec)
|
0 Participants
|
|
Number of Participants With Categorical Electrocardiogram (ECG) Data
PR interval not otherwise specified % change ≥25/50%
|
0 Participants
|
|
Number of Participants With Categorical Electrocardiogram (ECG) Data
QRS interval not otherwise specified ≥140 msec
|
1 Participants
|
|
Number of Participants With Categorical Electrocardiogram (ECG) Data
QRS interval not otherwise specified %change ≥50%
|
1 Participants
|
|
Number of Participants With Categorical Electrocardiogram (ECG) Data
QT interval not otherwise specified ≥500 msec
|
0 Participants
|
|
Number of Participants With Categorical Electrocardiogram (ECG) Data
corrected QT (QTc) interval not otherwise specified ≥450 and <480 msec
|
9 Participants
|
|
Number of Participants With Categorical Electrocardiogram (ECG) Data
corrected QT (QTc) interval not otherwise specified ≥480 and <500 msec
|
7 Participants
|
|
Number of Participants With Categorical Electrocardiogram (ECG) Data
corrected QT (QTc) interval not otherwise specified ≥500 msec
|
3 Participants
|
|
Number of Participants With Categorical Electrocardiogram (ECG) Data
corrected QT (QTc) interval not otherwise specified change ≥30 and <60 msec
|
5 Participants
|
|
Number of Participants With Categorical Electrocardiogram (ECG) Data
corrected QT (QTc) interval not otherwise specified change ≥60 msec
|
1 Participants
|
SECONDARY outcome
Timeframe: Baseline, Weeks 24, 48, and 72Population: All participants who took at least 1 dose of tafamidis meglumine soft gelatin capsule 20 mg.
Clinically significant ECHO findings include: left ventricular (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.
Outcome measures
| Measure |
Tafamidis Meglumine 20 mg Once Daily (QD)
n=15 Participants
All enrolled participants received a once-daily (QD) oral dose of tafamidis meglumine 20 mg in a soft capsule formulation.
|
|---|---|
|
Number of Participants With Clinically Significant Echocardiography (ECHO) Value Related to Primary Diagnosis (Transthyretin Amyloidosis [ATTR]) at Baseline, Weeks 24, 48, and 72
Number of Participants at Baseline
|
9 Participants
|
|
Number of Participants With Clinically Significant Echocardiography (ECHO) Value Related to Primary Diagnosis (Transthyretin Amyloidosis [ATTR]) at Baseline, Weeks 24, 48, and 72
Number of Participants at Week 24
|
11 Participants
|
|
Number of Participants With Clinically Significant Echocardiography (ECHO) Value Related to Primary Diagnosis (Transthyretin Amyloidosis [ATTR]) at Baseline, Weeks 24, 48, and 72
Number of Participants at Week 48
|
9 Participants
|
|
Number of Participants With Clinically Significant Echocardiography (ECHO) Value Related to Primary Diagnosis (Transthyretin Amyloidosis [ATTR]) at Baseline, Weeks 24, 48, and 72
Number of Participants at Week 72
|
10 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Week 72Population: All participants who took at least 1 dose of tafamidis meglumine soft gelatin capsule 20 mg
Protocol-required safety laboratory assessments include: Lymphocytes \<0.8 × LLN; Neutrophils \<0.8 × LLN, or \>1.2 × ULN; Basophils \>1.2 × ULN; Activated Partial Thromboplastin Time \>1.1 × ULN; Prothrombin Time \>1.1 × ULN; Prothrombin International Normalized Ratio \>1.1 × ULN; Bilirubin \>1.5 × ULN; Urate \> 1.2 × ULN; Cholesterol \>1.3 × ULN; Potassium \<0.9 × LLN; Phosphate \>1.2 × ULN; Bicarbonate \>1.1 × ULN; Thyroid Stimulating Hormone \>1.2 × ULN; URINE Protein ≥1; URINE Hemoglobin ≥1; Nitrite ≥1; URINE Erythrocytes ≥20; Epithelial Cells ≥6; and Casts \>1.
Outcome measures
| Measure |
Tafamidis Meglumine 20 mg Once Daily (QD)
n=15 Participants
All enrolled participants received a once-daily (QD) oral dose of tafamidis meglumine 20 mg in a soft capsule formulation.
|
|---|---|
|
Number of Participants With Clinical Laboratory Abnormalities
|
12 Participants
|
SECONDARY outcome
Timeframe: Baseline, Weeks 8, 12, 24, 48, and 72Population: All participants who took at least 1 dose of tafamidis meglumine soft gelatin capsule 20 mg and who had at least 1 TTR concentration value.
The TTR (also referred to as pre-albumin) concentrations were determined as pharmacodynamic (PD) biomarkers.
Outcome measures
| Measure |
Tafamidis Meglumine 20 mg Once Daily (QD)
n=15 Participants
All enrolled participants received a once-daily (QD) oral dose of tafamidis meglumine 20 mg in a soft capsule formulation.
|
|---|---|
|
Transthyretin (TTR) Concentrations on Day 1 (Baseline), and at Weeks 8, 12, 24, 48, and 72
Median and Range of TTR Concentration on Day 1 (baseline)
|
18.70 Milligrams per deciliter (mg/dL)
Interval 9.03 to 28.0
|
|
Transthyretin (TTR) Concentrations on Day 1 (Baseline), and at Weeks 8, 12, 24, 48, and 72
Median and Range of TTR Concentration at Week 8
|
23.20 Milligrams per deciliter (mg/dL)
Interval 13.5 to 36.2
|
|
Transthyretin (TTR) Concentrations on Day 1 (Baseline), and at Weeks 8, 12, 24, 48, and 72
Median and Range of TTR Concentration at Week 12
|
28.00 Milligrams per deciliter (mg/dL)
Interval 13.5 to 33.3
|
|
Transthyretin (TTR) Concentrations on Day 1 (Baseline), and at Weeks 8, 12, 24, 48, and 72
Median and Range of TTR Concentration at Week 24
|
25.70 Milligrams per deciliter (mg/dL)
Interval 13.3 to 30.9
|
|
Transthyretin (TTR) Concentrations on Day 1 (Baseline), and at Weeks 8, 12, 24, 48, and 72
Median and Range of TTR Concentration at Week 48
|
27.90 Milligrams per deciliter (mg/dL)
Interval 19.0 to 33.4
|
|
Transthyretin (TTR) Concentrations on Day 1 (Baseline), and at Weeks 8, 12, 24, 48, and 72
Median and Range of TTR Concentration at Week 72
|
26.60 Milligrams per deciliter (mg/dL)
Interval 14.4 to 32.2
|
SECONDARY outcome
Timeframe: Weeks 8, 12, 24, 48, and 72Population: All participants who took at least 1 dose of tafamidis meglumine soft gelatin capsule 20 mg and who had at least 1 TTR stabilization value.
The Fraction of Initial (FOI) is the ratio of the measured TTR tetramer concentration (post-denaturation) to the measured TTR concentration (pre-denaturation). Percent Stabilization (%) is the difference between the dosed FOI and the baseline FOI expressed as a percentage of the baseline FOI. Responder was the participant who achieved TTR stabilization (ie, who had been TTR stabilized). Percentage of responders was number of responders / number of evaluable (i.e., analyzed) participants.
Outcome measures
| Measure |
Tafamidis Meglumine 20 mg Once Daily (QD)
n=15 Participants
All enrolled participants received a once-daily (QD) oral dose of tafamidis meglumine 20 mg in a soft capsule formulation.
|
|---|---|
|
TTR Stabilization and Percentage and 95% CI of Responders in TTR Stabilization at Post Baseline Visit
Percentage and 95% CI of Responders in TTR Stabilization at Week 8
|
100.0 Percentage of participants
Interval 66.4 to 100.0
|
|
TTR Stabilization and Percentage and 95% CI of Responders in TTR Stabilization at Post Baseline Visit
Percentage and 95% CI of Responders in TTR Stabilization at Week 12
|
100.0 Percentage of participants
Interval 69.2 to 100.0
|
|
TTR Stabilization and Percentage and 95% CI of Responders in TTR Stabilization at Post Baseline Visit
Percentage and 95% CI of Responders in transthyretin (TTR) Stabilization at Week 24
|
100.0 Percentage of participants
Interval 69.2 to 100.0
|
|
TTR Stabilization and Percentage and 95% CI of Responders in TTR Stabilization at Post Baseline Visit
Percentage and 95% CI of Responders in transthyretin (TTR) Stabilization at Week 48
|
100.0 Percentage of participants
Interval 54.1 to 100.0
|
|
TTR Stabilization and Percentage and 95% CI of Responders in TTR Stabilization at Post Baseline Visit
Percentage and 95% CI of Responders in transthyretin (TTR) Stabilization at Week 72
|
87.5 Percentage of participants
Interval 47.3 to 99.7
|
Adverse Events
Tafamidis Meglumine 20 mg Once Daily (QD)
Serious adverse events
| Measure |
Tafamidis Meglumine 20 mg Once Daily (QD)
n=15 participants at risk
All enrolled participants received a once-daily (QD) oral dose of tafamidis meglumine 20 mg in a soft capsule formulation.
|
|---|---|
|
Immune system disorders
Amyloidosis
|
6.7%
1/15 • Baseline up to Week 77
|
|
Injury, poisoning and procedural complications
Femur fracture
|
6.7%
1/15 • Baseline up to Week 77
|
|
Vascular disorders
Orthostatic hypotension
|
6.7%
1/15 • Baseline up to Week 77
|
Other adverse events
| Measure |
Tafamidis Meglumine 20 mg Once Daily (QD)
n=15 participants at risk
All enrolled participants received a once-daily (QD) oral dose of tafamidis meglumine 20 mg in a soft capsule formulation.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
13.3%
2/15 • Baseline up to Week 77
|
|
Blood and lymphatic system disorders
Coagulopathy
|
6.7%
1/15 • Baseline up to Week 77
|
|
Blood and lymphatic system disorders
Leukopenia
|
6.7%
1/15 • Baseline up to Week 77
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
6.7%
1/15 • Baseline up to Week 77
|
|
Cardiac disorders
Palpitations
|
6.7%
1/15 • Baseline up to Week 77
|
|
Cardiac disorders
Supraventricular extrasystoles
|
6.7%
1/15 • Baseline up to Week 77
|
|
Cardiac disorders
Supraventricular tachycardia
|
6.7%
1/15 • Baseline up to Week 77
|
|
Eye disorders
Cataract
|
6.7%
1/15 • Baseline up to Week 77
|
|
Gastrointestinal disorders
Abdominal discomfort
|
6.7%
1/15 • Baseline up to Week 77
|
|
Gastrointestinal disorders
Abdominal pain
|
6.7%
1/15 • Baseline up to Week 77
|
|
Gastrointestinal disorders
Constipation
|
6.7%
1/15 • Baseline up to Week 77
|
|
Gastrointestinal disorders
Diarrhoea
|
13.3%
2/15 • Baseline up to Week 77
|
|
Gastrointestinal disorders
Nausea
|
6.7%
1/15 • Baseline up to Week 77
|
|
Gastrointestinal disorders
Vomiting
|
6.7%
1/15 • Baseline up to Week 77
|
|
General disorders
Oedema peripheral
|
6.7%
1/15 • Baseline up to Week 77
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
6.7%
1/15 • Baseline up to Week 77
|
|
Immune system disorders
Hypersensitivity
|
6.7%
1/15 • Baseline up to Week 77
|
|
Immune system disorders
Seasonal allergy
|
6.7%
1/15 • Baseline up to Week 77
|
|
Infections and infestations
COVID-19
|
6.7%
1/15 • Baseline up to Week 77
|
|
Infections and infestations
Upper respiratory tract infection
|
20.0%
3/15 • Baseline up to Week 77
|
|
Infections and infestations
Urinary tract infection
|
20.0%
3/15 • Baseline up to Week 77
|
|
Injury, poisoning and procedural complications
Compression fracture
|
6.7%
1/15 • Baseline up to Week 77
|
|
Injury, poisoning and procedural complications
Fall
|
20.0%
3/15 • Baseline up to Week 77
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
6.7%
1/15 • Baseline up to Week 77
|
|
Injury, poisoning and procedural complications
Limb injury
|
6.7%
1/15 • Baseline up to Week 77
|
|
Investigations
Blood creatine phosphokinase increased
|
6.7%
1/15 • Baseline up to Week 77
|
|
Investigations
Blood lactate dehydrogenase increased
|
6.7%
1/15 • Baseline up to Week 77
|
|
Investigations
Blood pressure increased
|
6.7%
1/15 • Baseline up to Week 77
|
|
Investigations
Blood thyroid stimulating hormone decreased
|
13.3%
2/15 • Baseline up to Week 77
|
|
Investigations
Electrocardiogram ST segment elevation
|
6.7%
1/15 • Baseline up to Week 77
|
|
Investigations
Electrocardiogram abnormal
|
6.7%
1/15 • Baseline up to Week 77
|
|
Investigations
Myoglobin blood increased
|
6.7%
1/15 • Baseline up to Week 77
|
|
Investigations
N-terminal prohormone brain natriuretic peptide increased
|
6.7%
1/15 • Baseline up to Week 77
|
|
Investigations
Protein urine present
|
6.7%
1/15 • Baseline up to Week 77
|
|
Investigations
QRS axis abnormal
|
6.7%
1/15 • Baseline up to Week 77
|
|
Investigations
Total bile acids increased
|
6.7%
1/15 • Baseline up to Week 77
|
|
Investigations
Urinary casts present
|
6.7%
1/15 • Baseline up to Week 77
|
|
Investigations
Urinary occult blood positive
|
6.7%
1/15 • Baseline up to Week 77
|
|
Investigations
Urinary sediment present
|
13.3%
2/15 • Baseline up to Week 77
|
|
Investigations
White blood cell count decreased
|
6.7%
1/15 • Baseline up to Week 77
|
|
Investigations
White blood cells urine positive
|
13.3%
2/15 • Baseline up to Week 77
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
6.7%
1/15 • Baseline up to Week 77
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
13.3%
2/15 • Baseline up to Week 77
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
13.3%
2/15 • Baseline up to Week 77
|
|
Metabolism and nutrition disorders
Hypozincaemia
|
6.7%
1/15 • Baseline up to Week 77
|
|
Musculoskeletal and connective tissue disorders
Osteoporosis
|
6.7%
1/15 • Baseline up to Week 77
|
|
Nervous system disorders
Dizziness
|
6.7%
1/15 • Baseline up to Week 77
|
|
Psychiatric disorders
Insomnia
|
6.7%
1/15 • Baseline up to Week 77
|
|
Renal and urinary disorders
Urethral haemorrhage
|
6.7%
1/15 • Baseline up to Week 77
|
|
Vascular disorders
Aortic arteriosclerosis
|
6.7%
1/15 • Baseline up to Week 77
|
|
Vascular disorders
Hypertension
|
6.7%
1/15 • Baseline up to Week 77
|
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