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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00409175
First received: December 6, 2006
Last updated: November 16, 2012
Last verified: November 2012
Results First Received: November 16, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Familial Amyloid Polyneuropathy
Interventions: Drug: Fx-1006A
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
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.

Participant Flow:   Overall Study
    Tafamidis     Placebo  
STARTED     65     63  
COMPLETED     47     44  
NOT COMPLETED     18     19  
Adverse Event                 4                 3  
Withdrawal by Subject                 1                 2  
Negative genotype                 0                 1  
Liver transplantation                 13                 13  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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.
Total Total of all reporting groups

Baseline Measures
    Tafamidis     Placebo     Total  
Number of Participants  
[units: participants]
  64     61     125  
Age, Customized [1]
[units: participants]
     
Less than or equal to 65 years     59     58     117  
Greater than 65 years     5     3     8  
Gender [2]
[units: participants]
     
Female     32     35     67  
Male     32     26     58  
[1] Out of a total of 128 participants, baseline characteristic (Age) was available for only 125 participants who were included in intent-to-treat (ITT) population.
[2] Out of a total of 128 participants, baseline characteristic (Gender) was available for only 125 participants who were included in ITT population.



  Outcome Measures
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1.  Primary:   Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 18   [ Time Frame: Month 18 ]

Measure Type Primary
Measure Title Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 18
Measure Description 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.
Time Frame Month 18  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
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.

Measured Values
    Tafamidis     Placebo  
Number of Participants Analyzed  
[units: participants]
  64     61  
Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 18  
[units: percentage of participants]
Number ( 95% Confidence Interval )
  45.3  
  ( 33.1 to 57.5 )  
  29.5  
  ( 18.1 to 41.0 )  

No statistical analysis provided for Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 18



2.  Primary:   Change From Baseline in Norfolk Quality of Life- Diabetic Neuropathy (QOL-DN) Total Quality of Life (TQOL) Score at Month 18   [ Time Frame: Baseline, Month 18 ]

Measure Type Primary
Measure Title Change From Baseline in Norfolk Quality of Life- Diabetic Neuropathy (QOL-DN) Total Quality of Life (TQOL) Score at Month 18
Measure Description Norfolk QOL-DN: 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on the quality of life of participants with diabetic neuropathy; Item 1 to 7: related to symptoms and presence of 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.
Time Frame Baseline, Month 18  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
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.

Measured Values
    Tafamidis     Placebo  
Number of Participants Analyzed  
[units: participants]
  64     61  
Change From Baseline in Norfolk Quality of Life- Diabetic Neuropathy (QOL-DN) Total Quality of Life (TQOL) Score at Month 18  
[units: units on a scale]
Mean ± Standard Deviation
   
Baseline     27.3  ± 24.2     30.8  ± 26.7  
Change at Month 18     2.4  ± 14.6     6.9  ± 22.9  

No statistical analysis provided for Change From Baseline in Norfolk Quality of Life- Diabetic Neuropathy (QOL-DN) Total Quality of Life (TQOL) Score at Month 18



3.  Secondary:   Change From Baseline in Neuropathy Impairment Score- Lower Limb (NIS-LL) Score at Month 6, 12 and 18   [ Time Frame: Baseline, Month 6, 12, 18 ]

Measure Type Secondary
Measure Title Change From Baseline in Neuropathy Impairment Score- Lower Limb (NIS-LL) Score at Month 6, 12 and 18
Measure Description NIS-LL: assessed muscle weakness, reflexes and sensation; scored separately for left and right limbs. Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) are scored on 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.
Time Frame Baseline, Month 6, 12, 18  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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/LT. ‘n’ = those participants who were evaluable for this measure at given time point for each group respectively.

Reporting Groups
  Description
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.

Measured Values
    Tafamidis     Placebo  
Number of Participants Analyzed  
[units: participants]
  64     61  
Change From Baseline in Neuropathy Impairment Score- Lower Limb (NIS-LL) Score at Month 6, 12 and 18  
[units: units on a scale]
Mean ± Standard Deviation
   
Baseline (n=64, 61)     8.359  ± 11.399     11.445  ± 13.544  
Change at Month 6 (n=60, 57)     1.260  ± 3.007     2.075  ± 6.407  
Change at Month 12 (n=49, 50)     1.005  ± 3.964     4.835  ± 7.697  
Change at Month 18 (n=48, 47)     2.193  ± 4.372     5.402  ± 8.661  

No statistical analysis provided for Change From Baseline in Neuropathy Impairment Score- Lower Limb (NIS-LL) Score at Month 6, 12 and 18



4.  Secondary:   Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 6 and 12   [ Time Frame: Month 6, 12 ]

Measure Type Secondary
Measure Title Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 6 and 12
Measure Description 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.
Time Frame Month 6, 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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/LT. LOCF method was used; participant who discontinued due to death/LT was set non-responder.

Reporting Groups
  Description
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.

Measured Values
    Tafamidis     Placebo  
Number of Participants Analyzed  
[units: participants]
  64     61  
Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 6 and 12  
[units: percentage of participants]
Number ( 95% Confidence Interval )
   
Month 6     60.9  
  ( 49.0 to 72.9 )  
  54.1  
  ( 41.6 to 66.6 )  
Month 12     54.7  
  ( 42.5 to 66.9 )  
  32.8  
  ( 21.0 to 44.6 )  

No statistical analysis provided for Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 6 and 12



5.  Secondary:   Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Total Quality of Life (TQOL) Score at Month 6 and 12   [ Time Frame: Baseline, Month 6, 12 ]

Measure Type Secondary
Measure Title Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Total Quality of Life (TQOL) Score at Month 6 and 12
Measure Description Norfolk QOL-DN: 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on the quality of life of participants with diabetic neuropathy; Item 1 to 7: related to symptoms and presence of 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.
Time Frame Baseline, Month 6, 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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/LT. ‘n’ = those participants who were evaluable for this measure at given time point for each group respectively.

Reporting Groups
  Description
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.

Measured Values
    Tafamidis     Placebo  
Number of Participants Analyzed  
[units: participants]
  64     61  
Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Total Quality of Life (TQOL) Score at Month 6 and 12  
[units: units on a scale]
Mean ± Standard Deviation
   
Baseline (n=64, 61)     27.3  ± 24.2     30.8  ± 26.7  
Change at Month 6 (n=60, 57)     1.2  ± 15.6     0.2  ± 15.1  
Change at Month 12 (n=49, 50)     1.1  ± 14.7     4.6  ± 19.0  

No statistical analysis provided for Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Total Quality of Life (TQOL) Score at Month 6 and 12



6.  Secondary:   Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, 12 and 18   [ Time Frame: Baseline, Month 6, 12, 18 ]

Measure Type Secondary
Measure Title Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, 12 and 18
Measure Description 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).
Time Frame Baseline, Month 6, 12, 18  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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. ‘n’ = those participants who were evaluable for this measure at given time points for each group respectively.

Reporting Groups
  Description
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.

Measured Values
    Tafamidis     Placebo  
Number of Participants Analyzed  
[units: participants]
  64     61  
Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, 12 and 18  
[units: units on a scale]
Mean ± Standard Deviation
   
Baseline: physical functioning(n=64,61)     14.3  ± 13.8     16.6  ± 14.7  
Baseline: ADLs(n=64,61)     1.3  ± 2.9     1.6  ± 3.8  
Baseline: symptoms(n=64,61)     7.2  ± 5.5     7.6  ± 6.1  
Baseline: small fiber neuropathy(n=64,61)     2.7  ± 3.6     3.1  ± 4.0  
Baseline: autonomic neuropathy(n=64,61)     1.9  ± 2.4     2.0  ± 2.6  
Change at Month 6: physical functioning(n=60,57)     -0.6  ± 8.0     -0.9  ± 9.8  
Change at Month 6: ADLs(n=60,57)     0.4  ± 1.9     0.3  ± 1.7  
Change at Month 6: symptoms(n=60,56)     0.8  ± 5.5     0.2  ± 4.4  
Change at Month 6: small fiber neuropathy(n=60,57)     0.4  ± 2.2     0.5  ± 2.5  
Change at Month 6: autonomic neuropathy(n=60,57)     0.2  ± 1.8     0.0  ± 1.7  
Change at Month 12: physical functioning(n=49,50)     -0.9  ± 7.4     0.6  ± 10.7  
Change at Month 12: ADLs(n=49,50)     1.0  ± 2.4     0.7  ± 3.0  
Change at Month 12: symptoms(n=49,49)     0.4  ± 5.0     1.4  ± 4.5  
Change at Month 12:small fiber neuropathy(n=49,50)     0.7  ± 2.8     1.5  ± 3.1  
Change at Month 12: autonomic neuropathy(n=49,50)     -0.1  ± 1.8     0.4  ± 2.8  
Change at Month 18: physical functioning(n=48,47)     -0.1  ± 8.5     3.0  ± 14.0  
Change at Month 18: ADLs(n=48,47)     1.2  ± 2.4     1.2  ± 4.2  
Change at Month 18: symptoms(n=48,47)     -0.1  ± 4.9     1.2  ± 5.4  
Change at Month 18:small fiber neuropathy(n=48,47)     0.8  ± 2.6     1.4  ± 3.6  
Change at Month 18: autonomic neuropathy(n=48,47)     0.2  ± 1.9     0.4  ± 2.8  

No statistical analysis provided for Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, 12 and 18



7.  Secondary:   Change From Baseline in Summated 7 Score for Large Nerve Fiber Function at Month 6, 12 and 18   [ Time Frame: Baseline, Month 6, 12, 18 ]

Measure Type Secondary
Measure Title Change From Baseline in Summated 7 Score for Large Nerve Fiber Function at Month 6, 12 and 18
Measure Description Summated 7 score: composite score included five Nerve Conduction Studies (NCS) attributes (peroneal nerve distal motor latency, peroneal nerve compound muscle action potential, peroneal nerve motor conduction velocity, tibial nerve distal motor latency, and sural nerve sensory nerve action potential amplitude) along with Vibration Detection Threshold (VDT) obtained in great toes, and Heart Rate Response to Deep Breathing (HRDB) value. Score was determined through reference to normal values for age, sex and height. Total score range= -26 to 26, where higher score=worse nerve function.
Time Frame Baseline, Month 6, 12, 18  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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/LT. ‘n’ = those participants who were evaluable for this measure at given time points for each group respectively.

Reporting Groups
  Description
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.

Measured Values
    Tafamidis     Placebo  
Number of Participants Analyzed  
[units: participants]
  64     61  
Change From Baseline in Summated 7 Score for Large Nerve Fiber Function at Month 6, 12 and 18  
[units: units on a scale]
Mean ± Standard Deviation
   
Baseline (n=64, 61)     7.787  ± 9.063     8.718  ± 8.533  
Change at Month 6 (n=60, 57)     0.581  ± 3.542     1.934  ± 3.846  
Change at Month 12 (n=48, 50)     0.833  ± 3.963     2.959  ± 3.879  
Change at Month 18 (n=48, 46)     1.159  ± 3.853     3.333  ± 4.997  

No statistical analysis provided for Change From Baseline in Summated 7 Score for Large Nerve Fiber Function at Month 6, 12 and 18



8.  Secondary:   Change From Baseline in Summated 3 Score for Small Nerve Fiber Function at Month 6, 12 and 18   [ Time Frame: Baseline, Month 6, 12, 18 ]

Measure Type Secondary
Measure Title Change From Baseline in Summated 3 Score for Small Nerve Fiber Function at Month 6, 12 and 18
Measure Description Summated 3 Nerve Tests Small Fiber Normal Deviates Score (NTSFnds) included cooling threshold for the lower limbs, heat pain threshold for the lower limbs and HRDB. Total score range= -11.2 to 11.2, where higher score=worse nerve function.
Time Frame Baseline, Month 6, 12, 18  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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/LT. ‘n’ = those participants who were evaluable for this measure at given time points for each group respectively.

Reporting Groups
  Description
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.

Measured Values
    Tafamidis     Placebo  
Number of Participants Analyzed  
[units: participants]
  64     61  
Change From Baseline in Summated 3 Score for Small Nerve Fiber Function at Month 6, 12 and 18  
[units: units on a scale]
Mean ± Standard Deviation
   
Baseline (n=64, 61)     5.514  ± 4.535     5.624  ± 4.085  
Change at Month 6 (n=60, 57)     0.240  ± 1.679     0.716  ± 2.202  
Change at Month 12 (n=48, 50)     0.375  ± 2.048     1.250  ± 2.010  
Change at Month 18 (n=48, 46)     0.290  ± 2.130     1.489  ± 2.519  

No statistical analysis provided for Change From Baseline in Summated 3 Score for Small Nerve Fiber Function at Month 6, 12 and 18



9.  Secondary:   Change From Baseline in Modified Body Mass Index (mBMI) at Month 6, 12 and 18   [ Time Frame: Baseline, Month 6, 12, 18 ]

Measure Type Secondary
Measure Title Change From Baseline in Modified Body Mass Index (mBMI) at Month 6, 12 and 18
Measure Description BMI was calculated by weight divided by height squared. mBMI was calculated by multiplying BMI by serum albumin levels to compensate for edema formation associated with malnutrition. A progressive decline in mBMI indicated worsening of disease severity.
Time Frame Baseline, Month 6, 12, 18  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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/LT. ‘n’ = those participants who were evaluable for this measure at given time points for each group respectively.

Reporting Groups
  Description
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.

Measured Values
    Tafamidis     Placebo  
Number of Participants Analyzed  
[units: participants]
  64     61  
Change From Baseline in Modified Body Mass Index (mBMI) at Month 6, 12 and 18  
[units: (kilogram/square meter)*(gram/liter)]
Mean ± Standard Deviation
   
Baseline (n=64, 61)     1004.6  ± 165.2     1011.5  ± 212.9  
Change at Month 6 (n=60, 56)     17.1  ± 68.4     -29.8  ± 69.7  
Change at Month 12 (n=49, 50)     19.4  ± 71.8     -30.8  ± 74.9  
Change at Month 18 (n=49, 46)     37.9  ± 73.7     -32.7  ± 88.6  

No statistical analysis provided for Change From Baseline in Modified Body Mass Index (mBMI) at Month 6, 12 and 18



10.  Secondary:   Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer   [ Time Frame: Week 8, Month 6, 12, 18 ]

Measure Type Secondary
Measure Title Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer
Measure Description TTR tetramer was assessed using a validated immunoturbidimetric assay. The Fraction of Initial (FOI) is the ratio of the measured TTR tetramer concentration after denaturation to the measured TTR tetramer concentration before denaturation. TTR tetramer stabilization is based on the difference between the on-treatment FOI and the baseline FOI expressed as a percentage of the baseline FOI.
Time Frame Week 8, Month 6, 12, 18  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
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.

Measured Values
    Tafamidis     Placebo  
Number of Participants Analyzed  
[units: participants]
  63     60  
Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer  
[units: percentage of participants]
Number ( 95% Confidence Interval )
   
Week 8 (n=63, 60)     98.4  
  ( 95.3 to 100.0 )  
  6.7  
  ( 0.4 to 13.0 )  
Month 6 (n= 59, 58)     100.0  
  ( 100.0 to 100.0 )  
  5.2  
  ( 0.0 to 10.9 )  
Month 12 (n=48, 50)     97.9  
  ( 93.9 to 100.0 )  
  2.0  
  ( 0.0 to 5.9 )  
Month 18 (n=48, 44)     97.9  
  ( 93.9 to 100.0 )  
  0.0  
  ( 0.0 to 0.0 )  

No statistical analysis provided for Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Instead of the intended endpoint 'heat pain and cooling threshold', results of 'summated 3 score for small nerve fiber function' were reported.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com


No publications provided


Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00409175     History of Changes
Other Study ID Numbers: FX-005, B3461020
Study First Received: December 6, 2006
Results First Received: November 16, 2012
Last Updated: November 16, 2012
Health Authority: United States: Food and Drug Administration