The Effects of Fx-1006A on Transthyretin Stabilization and Clinical Outcome Measures in Patients With Non-V30M Transthyretin Amyloidosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00630864
First received: February 27, 2008
Last updated: January 9, 2013
Last verified: January 2013
Results First Received: November 16, 2012  
Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Transthyretin-associated Amyloidosis With Polyneuropathy
Intervention: Drug: Fx-1006A

  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
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Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Participant Flow for 2 periods

Period 1:   Part 1 (up to Week 6)
    Tafamidis  
STARTED     21  
COMPLETED     20  
NOT COMPLETED     1  
Adverse Event                 1  

Period 2:   Part 2 (After Week 6 up to Month 12)
    Tafamidis  
STARTED     20  
COMPLETED     18  
NOT COMPLETED     2  
Liver transplant                 2  



  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.
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Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Baseline Measures
    Tafamidis  
Number of Participants  
[units: participants]
  21  
Age  
[units: years]
Mean ± Standard Deviation
  63.10  ± 9.86  
Gender  
[units: participants]
 
Female     8  
Male     13  



  Outcome Measures
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1.  Primary:   Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer at Week 6   [ Time Frame: Week 6 ]
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Measure Type Primary
Measure Title Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer at Week 6
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 6  
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.
Intent-to-Treat (ITT) population included all participants who received at least 1 dose of study medication. Here ‘N’ (Number of participants analyzed) signifies those participants who were evaluable for this measure.

Reporting Groups
  Description
Tafamidis Participants with transthyretin (TTR) variants other than valine replaced by methionine at position 30 (V30M) received tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily up to Week 6 in Part 1, participants who achieved TTR stabilization at Week 6 or as per investigator’s discretion continued to receive tafamidis (Fx-1006A) 20 mg capsule orally once daily up to Month 12 in Part 2.

Measured Values
    Tafamidis  
Number of Participants Analyzed  
[units: participants]
  19  
Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer at Week 6  
[units: percentage¬†of¬†participants]
Number ( 95% Confidence Interval )
  94.7  
  ( 74.0 to 99.9 )  

No statistical analysis provided for Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer at Week 6



2.  Secondary:   Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer at Month 6 and 12   [ Time Frame: Month 6, Month 12 ]

3.  Other Pre-specified:   Number of Participants With Treatment-Emergent Adverse Events (AEs)   [ Time Frame: Baseline up to 30 days after the last dose ]

4.  Other Pre-specified:   Number of Participants With Greater Than or Equal to Grade 3 Treatment-Emergent Adverse Events   [ Time Frame: Baseline up to 30 days after the last dose ]

5.  Other Pre-specified:   Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings   [ Time Frame: Day 1 up to Month 12 ]

6.  Other Pre-specified:   Number of Participants With Clinically Significant Treatment-Emergent Electrocardiogram (ECG) Findings   [ Time Frame: Day 1 up to Month 12 ]

7.  Other Pre-specified:   Number of Participants With Clinically Significant Treatment-Emergent Holter Monitoring Findings   [ Time Frame: Day 1 up to Month 12 ]

8.  Other Pre-specified:   Number of Participants Who Discontinued Due to Clinical or Laboratory Adverse Events   [ Time Frame: Baseline up to Month 12 ]

9.  Other Pre-specified:   Change From Baseline in the Neuropathy Impairment Score (NIS) at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

10.  Other Pre-specified:   Change From Baseline in the Neuropathy Impairment Score-Lower Limb (NIS-LL) at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

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

12.  Other Pre-specified:   Change From Baseline in Total Quality of Life (TQOL) Score at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

13.  Other Pre-specified:   Change From Baseline in Norfolk Quality of Life – Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

14.  Other Pre-specified:   Change From Baseline in Nerve Conduction Studies (NCS) at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

15.  Other Pre-specified:   Change From Baseline in Heart Rate Response to Deep Breathing (HRDB) at Month 6 and Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

16.  Other Pre-specified:   Change From Baseline in Modified Body Mass Index (mBMI) at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

17.  Other Pre-specified:   Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

18.  Other Pre-specified:   Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

19.  Other Pre-specified:   Change From Baseline in Left Atrial Volume at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

20.  Other Pre-specified:   Change From Baseline in Left Ventricular (LV) End Systolic Volume, Left Ventricle (LV) Stroke Volume at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

21.  Other Pre-specified:   Change From Baseline in Fractional Shortening at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

22.  Other Pre-specified:   Change From Baseline in Left Ventricular (LV) Ejection Fraction at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

23.  Other Pre-specified:   Change From Baseline in Left Ventricular Mass (LVM) at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

24.  Other Pre-specified:   Change From Baseline in Isovolumetric Relaxation Time (IVRT), Mitral Deceleration Time at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

25.  Other Pre-specified:   Change From Baseline in Aortic Annulus Diameter at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

26.  Other Pre-specified:   Change From Baseline in Tricuspid Peak Velocity at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

27.  Other Pre-specified:   Change From Baseline in Tricuspid Pulmonary Artery Systolic Pressure (PASP) at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

28.  Other Pre-specified:   Change From Baseline in Doppler Data at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

29.  Other Pre-specified:   Change From Baseline in e:e’ Lateral Ratio , Ratio of Peak Mitral Early Diastolic and Atrial Contraction Velocity (E/A Ratio) at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

30.  Other Pre-specified:   Change From Baseline in Left Ventricular (LV) Mass/Voltage Ratio at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

31.  Other Pre-specified:   Change From Baseline in Left Atrial (LA) Volume Index at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

32.  Other Pre-specified:   Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) at Week 2, Week 6, Month 3, Month 6, Month 12   [ Time Frame: Baseline, Week 2, Week 6, Month 3, Month 6, Month 12 ]

33.  Other Pre-specified:   Change From Baseline in Karnofsky Performance Status Scale at Month 6, Month 12   [ Time Frame: Baseline, Month 6, Month 12 ]

34.  Other Pre-specified:   Change From Baseline in Troponin I Levels at Week 2, Week 6 , Month 3, Month 6, Month 12   [ Time Frame: Baseline, Week 2, Week 6 , Month 3, Month 6, Month 12 ]


  Serious Adverse Events


  Other Adverse Events


  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
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