The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    B3461010
Previous Study | Return to List | Next Study

The Effect Of Tafamidis For The Transthyretin Amyloid Polyneuropathy Patients With V30M Or Non-V30M Transthyretin

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01435655
Recruitment Status : Completed
First Posted : September 16, 2011
Results First Posted : September 9, 2015
Last Update Posted : September 9, 2015
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Transthyretin Familial Amyloid Polyneuropathy
Intervention Drug: tafamidis
Enrollment 10
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Tafamidis 20 mg
Hide Arm/Group Description Participants (V30m and non-V30m transthyretin mutation) received tafamidis 20 mg soft gelatin capsules orally once daily for up to 78 weeks
Period Title: Overall Study
Started 10
Completed 7
Not Completed 3
Reason Not Completed
Death             2
Other             1
Arm/Group Title Tafamidis 20 mg
Hide Arm/Group Description Participants (V30m and non-V30m transthyretin mutation) received tafamidis 20 mg soft gelatin capsules orally once daily for up to 78 weeks
Overall Number of Baseline Participants 10
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 10 participants
60.1  (13.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
Female
3
  30.0%
Male
7
  70.0%
1.Primary Outcome
Title Number of Participants With Transthyretin (TTR) Stabilization at Week 8 Compared With Baseline as Measured by a Validated Immunoturbidimetric Assay
Hide Description 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%.
Time Frame 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) included all participants who received at least one dose of the study drug.
Arm/Group Title Tafamidis 20 mg
Hide Arm/Group Description:
Participants (V30m and non-V30m transthyretin mutation) received tafamidis 20 mg soft gelatin capsules orally once daily for up to 78 weeks
Overall Number of Participants Analyzed 10
Measure Type: Number
Unit of Measure: Participants
10
2.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Baseline, Week 26, Week 52, Week 78
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) included all participants who received at least one dose of the study drug.
Arm/Group Title Tafamidis 20 mg
Hide Arm/Group Description:
Participants (V30m and non-V30m transthyretin mutation) received tafamidis 20 mg soft gelatin capsules orally once daily for up to 78 weeks
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: Units on a scale
NIS-Total: Baseline (n=10) 31.03  (26.260)
NIS-Total: Change at Week 26 (n=10) 4.37  (9.408)
NIS-Total: Change at Week 52 (n=10) 8.30  (8.326)
NIS-Total: Change at Week 78 (n=8) 9.90  (12.584)
NIS-LL: Baseline (n=10) 16.99  (13.143)
NIS-LL: Change at Week 26 (n=10) 2.06  (5.565)
NIS-LL: Change at Week 52 (n=10) 3.62  (4.374)
NIS-LL: Change at Week 78 (n=8) 3.30  (4.739)
NIS-UL: Baseline (n=10) 14.03  (13.716)
NIS-UL: Change at Week 26 (n=10) 2.31  (4.066)
NIS-UL: Change at Week 52 (n=10) 4.68  (5.103)
NIS-UL: Change at Week 78 (n=8) 6.59  (8.724)
3.Secondary Outcome
Title 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.
Hide Description 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.
Time Frame Baseline, Week 26, Week 52, Week 78
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) included all participants who received at least one dose of the study drug.
Arm/Group Title Tafamidis 20 mg
Hide Arm/Group Description:
Participants (V30m and non-V30m transthyretin mutation) received tafamidis 20 mg soft gelatin capsules orally once daily for up to 78 weeks
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: Units on a scale
TQOL: Baseline (n=10) 52.9  (32.76)
TQOL: Change at Week 26 (n=10) 11.8  (20.01)
TQOL: Change at Week 52 (n=10) 9.1  (12.49)
TQOL: Change at Week 78 (n=8) 10.8  (13.69)
Physical Functioning: Baseline (n=10) 25.6  (15.28)
Physical Functioning: Change at Week 26 (n=10) 4.8  (10.02)
Physical Functioning: Change at Week 52 (n=10) 2.2  (8.87)
Physical Functioning: Change at Week 78 (n=8) 4.1  (7.83)
ADL: Baseline (n=10) 8.5  (7.63)
ADL: Change at Week 26 (n=10) 1.2  (3.61)
ADL: Change at Week 52 (n=10) 0.8  (3.52)
ADL: Change at Week 78 (n=8) 0.6  (2.33)
Symptoms: Baseline (n=10) 8.5  (5.34)
Symptoms: Change at Week 26 (n=10) 2.6  (3.47)
Symptoms: Change at Week 52 (n=10) 4.0  (5.73)
Symptoms: Change at Week 78 (n=8) 3.1  (3.94)
Small Fiber: Baseline (n=10) 6.3  (5.31)
Small Fiber: Change at Week 26 (n=10) 1.9  (4.25)
Small Fiber: Change at Week 52 (n=10) 1.6  (2.32)
Small Fiber: Change at Week 78 (n=8) 2.1  (3.76)
Autonomic: Baseline (n=10) 4.0  (3.06)
Autonomic: Change at Week 26 (n=10) 1.3  (1.42)
Autonomic: Change at Week 52 (n=10) 0.5  (1.43)
Autonomic: Change at Week 78 (n=8) 0.8  (1.91)
4.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Baseline, Week 26, Week 52, Week 78
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) included all participants who received at least one dose of the study drug.
Arm/Group Title Tafamidis 20 mg
Hide Arm/Group Description:
Participants (V30m and non-V30m transthyretin mutation) received tafamidis 20 mg soft gelatin capsules orally once daily for up to 78 weeks
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Baseline (n=10) 8.33  (5.574)
Change at Week 26 (n=10) 0.55  (2.657)
Change at Week 52 (n-=10) 1.04  (2.992)
Change at Week 78 (n=8) 1.92  (5.129)
5.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Baseline, Week 26, Week 52, Week 78
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) included all participants who received at least one dose of the study drug.
Arm/Group Title Tafamidis 20 mg
Hide Arm/Group Description:
Participants (V30m and non-V30m transthyretin mutation) received tafamidis 20 mg soft gelatin capsules orally once daily for up to 78 weeks
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Baseline (n=10) 6.39  (3.160)
Change at Week 26 (n=10) 0.16  (1.619)
Change at Week 52 (n=10) -0.13  (1.334)
Change at Week 78 (n=8) 0.40  (1.985)
6.Secondary Outcome
Title Change From Baseline in Modified Body Mass Index (mBMI) at Week 8, Week 26, Week 52 and End of Study
Hide Description 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.
Time Frame Baseline, Week 8, Week 26, Week 52, End of Study
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) included all participants who received at least one dose of the study drug.
Arm/Group Title Tafamidis 20 mg
Hide Arm/Group Description:
Participants (V30m and non-V30m transthyretin mutation) received tafamidis 20 mg soft gelatin capsules orally once daily for up to 78 weeks
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: (kilogram/square meter)*(gram/liter)
Baseline (n=10) 805.70  (193.378)
Change at Week 8 (n=10) 74.86  (88.706)
Change at Week 26 (n=10) 26.61  (61.862)
Change at Week 52 (n=10) 64.86  (80.016)
End of Study (n=7) 53.65  (81.386)
7.Secondary Outcome
Title Change From Baseline in Ambulatory Status at Week 26, Week 52 and Week 78
Hide Description 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.
Time Frame Baseline, Week 26, Week 52, Week 78
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) included all participants who received at least one dose of the study drug.
Arm/Group Title Tafamidis 20 mg
Hide Arm/Group Description:
Participants (V30m and non-V30m transthyretin mutation) received tafamidis 20 mg soft gelatin capsules orally once daily for up to 78 weeks
Overall Number of Participants Analyzed 10
Measure Type: Number
Unit of Measure: Participants
Baseline (n=10): Status 0 0
Baseline (n=10): Status 1 3
Baseline (n=10): Status 2 4
Baseline (n=10): Status 3a 2
Baseline (n=10): Status 3b 1
Baseline (n=10): Status 4 0
Week 26 (n=10): Status 0 1
Week 26 (n=10): Status 1 2
Week 26 (n=10): Status 2 3
Week 26 (n=10): Status 3a 2
Week 26 (n=10): Status 3b 2
Week 26 (n=10): Status 4 0
Week 52 (n=10): Status 0 1
Week 52 (n=10): Status 1 1
Week 52 (n=10): Status 2 4
Week 52 (n=10): Status 3a 2
Week 52 (n=10): Status 3b 2
Week 52 (n=10): Status 4 0
Week 78 (n=8): Status 0 1
Week 78 (n=8): Status 1 1
Week 78 (n=8): Status 2 2
Week 78 (n=8): Status 3a 2
Week 78 (n=8): Status 3b 2
Week 78 (n=8): Status 4 0
8.Secondary Outcome
Title 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
Hide Description 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%.
Time Frame Baseline, Week 26, Week 52, Week 78
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) included all participants who received at least one dose of the study drug.
Arm/Group Title Tafamidis 20 mg
Hide Arm/Group Description:
Participants (V30m and non-V30m transthyretin mutation) received tafamidis 20 mg soft gelatin capsules orally once daily for up to 78 weeks
Overall Number of Participants Analyzed 10
Measure Type: Number
Unit of Measure: Participants
Week 26 10
Week 52 9
Week 78 8
9.Other Pre-specified Outcome
Title Plasma Concentration of Tafamidis at Week 8, Week 26, Week 52 and Week 78
Hide Description Mean plasma concentration of tafamidis at 3 hours after administration
Time Frame Week 8, Week 26, Week 52, Week 78
Hide Outcome Measure Data
Hide Analysis Population Description
The PK Analysis Set included all participants treated who had at least 1 quantifiable plasma tafamidis concentration.
Arm/Group Title Tafamidis 20 mg
Hide Arm/Group Description:
Participants (V30m and non-V30m transthyretin mutation) received tafamidis 20 mg soft gelatin capsules orally once daily for up to 78 weeks
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: ng/mL
Week 8 (n=10) 2773.0  (1777.71)
Week 26 (n=10) 2739.0  (1893.25)
Week 52 (n=10) 2829.0  (2315.58)
Week 78 (n=8) 3655.0  (2268.08)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Tafamidis 20 mg
Hide Arm/Group Description Participants (V30m and non-V30m transthyretin mutation) received tafamidis 20 mg soft gelatin capsules orally once daily for up to 78 weeks
All-Cause Mortality
Tafamidis 20 mg
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
Tafamidis 20 mg
Affected / at Risk (%)
Total   7/10 (70.00%) 
Cardiac disorders   
Atrioventricular block second degree * 1  1/10 (10.00%) 
Sick sinus syndrome * 1  1/10 (10.00%) 
Gastrointestinal disorders   
Ileus * 1  1/10 (10.00%) 
General disorders   
Sudden death * 1  1/10 (10.00%) 
Infections and infestations   
Pneumonia bacterial * 1  3/10 (30.00%) 
Pyelonephritis * 1  1/10 (10.00%) 
Injury, poisoning and procedural complications   
Burns third degree * 1  1/10 (10.00%) 
Metabolism and nutrition disorders   
Decreased appetite * 1  1/10 (10.00%) 
Psychiatric disorders   
Completed suicide * 1  1/10 (10.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 16.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Tafamidis 20 mg
Affected / at Risk (%)
Total   10/10 (100.00%) 
Blood and lymphatic system disorders   
Iron deficiency anaemia * 1  1/10 (10.00%) 
Cardiac disorders   
Atrioventricular block second degree * 1  1/10 (10.00%) 
Palpitations * 1  1/10 (10.00%) 
Ear and labyrinth disorders   
Ear discomfort * 1  1/10 (10.00%) 
Meniere's disease * 1  1/10 (10.00%) 
Eye disorders   
Cataract * 1  2/10 (20.00%) 
Conjunctivitis * 1  1/10 (10.00%) 
Dry eye * 1  1/10 (10.00%) 
Eye discharge * 1  1/10 (10.00%) 
Vitreous opacities * 1  2/10 (20.00%) 
Gastrointestinal disorders   
Diarrhoea * 1  1/10 (10.00%) 
Gingival swelling * 1  1/10 (10.00%) 
Nausea * 1  2/10 (20.00%) 
Paraesthesia oral * 1  1/10 (10.00%) 
Stomatitis * 1  1/10 (10.00%) 
Vomiting * 1  2/10 (20.00%) 
General disorders   
Oedema * 1  1/10 (10.00%) 
Pyrexia * 1  1/10 (10.00%) 
Infections and infestations   
Bronchitis * 1  1/10 (10.00%) 
Hordeolum * 1  1/10 (10.00%) 
Influenza * 1  1/10 (10.00%) 
Nasopharyngitis * 1  5/10 (50.00%) 
Oral herpes * 1  1/10 (10.00%) 
Tinea capitis * 1  1/10 (10.00%) 
Tinea pedis * 1  1/10 (10.00%) 
Injury, poisoning and procedural complications   
Laceration * 1  1/10 (10.00%) 
Limb injury * 1  1/10 (10.00%) 
Muscle strain * 1  1/10 (10.00%) 
Thermal burn * 1  3/10 (30.00%) 
Metabolism and nutrition disorders   
Hyperlipidaemia * 1  1/10 (10.00%) 
Musculoskeletal and connective tissue disorders   
Back pain * 1  1/10 (10.00%) 
Flank pain * 1  1/10 (10.00%) 
Muscle spasms * 1  2/10 (20.00%) 
Muscular weakness * 1  5/10 (50.00%) 
Myalgia * 1  2/10 (20.00%) 
Pain in extremity * 1  1/10 (10.00%) 
Trigger finger * 1  1/10 (10.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Neoplasm skin * 1  1/10 (10.00%) 
Nervous system disorders   
Ataxia * 1  1/10 (10.00%) 
Dementia * 1  1/10 (10.00%) 
Headache * 1  1/10 (10.00%) 
Hypoaesthesia * 1  1/10 (10.00%) 
Loss of consciousness * 1  1/10 (10.00%) 
Psychiatric disorders   
Anxiety * 1  1/10 (10.00%) 
Insomnia * 1  2/10 (20.00%) 
Reproductive system and breast disorders   
Gynaecomastia * 1  1/10 (10.00%) 
Respiratory, thoracic and mediastinal disorders   
Cough * 1  1/10 (10.00%) 
Rhinitis allergic * 1  1/10 (10.00%) 
Sleep apnoea syndrome * 1  1/10 (10.00%) 
Skin and subcutaneous tissue disorders   
Blister * 1  1/10 (10.00%) 
Decubitus ulcer * 1  1/10 (10.00%) 
Dermatitis * 1  1/10 (10.00%) 
Hyperhidrosis * 1  1/10 (10.00%) 
Rash * 1  1/10 (10.00%) 
Skin ulcer * 1  1/10 (10.00%) 
Solar dermatitis * 1  1/10 (10.00%) 
Urticaria * 1  1/10 (10.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 16.1
[Not Specified]
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.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01435655    
Other Study ID Numbers: B3461010
First Submitted: September 13, 2011
First Posted: September 16, 2011
Results First Submitted: February 24, 2015
Results First Posted: September 9, 2015
Last Update Posted: September 9, 2015