Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials
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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
History of Changes
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
No text entered.

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 ]
  Show Outcome Measure 1

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 ]
  Show Outcome Measure 2

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 ]
  Hide Outcome Measure 3

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 ]
  Show Outcome Measure 4

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 ]
  Show Outcome Measure 5

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 ]
  Show Outcome Measure 6

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 ]
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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 ]
  Show Outcome Measure 8

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

10.  Secondary:   Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer   [ Time Frame: Week 8, Month 6, 12, 18 ]
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  Serious Adverse Events
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  Other Adverse Events
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  Limitations and Caveats
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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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