E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Transthyretin Amyloidosis (ATTR) |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Body processes [G] - Metabolic Phenomena [G03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057949 |
E.1.2 | Term | Familial amyloid polyneuropathy |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To obtain additional, long-term, open-label safety and efficacy data for Fx-1006A in patients with transthyretin (TTR) amyloidosis (ATTR). |
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E.2.2 | Secondary objectives of the trial |
To continue to provide the investigational product Fx-1006A until market availability or until 31 December 2012 or whichever is earliest, to patients with ATTR who have completed Protocol Fx-006 or Protocol Fx1A-201. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacokinetic sub-study in patients who experience worsening renal function during participation in the open-label phase 3 protocol Fx1A-303, 27th June 2011, Version 1.1(Amendment 1.1).
The primary purpose of this sub-study is to obtain data on the pharmacokinetics (PK) of tafamidis in patients with severe renal dysfunction during their participation in the current study. For the purpose of this sub-study, severe renal dysfunction is defined as creatinine clearance <30 mL/minute and/or need for dialysis. |
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E.3 | Principal inclusion criteria |
1. Patient has successfully completed either Protocol Fx-006 or Fx1A-201. 2. If female, patient is post-menopausal, surgically sterilized, or willing to use two acceptable methods of birth control (i.e., hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide) throughout the study and for 3 months from the end of the study. (A condom alone is not considered an acceptable method of birth control.). 3. Patient is, in the opinion of the investigator, willing and able to comply with the investigational product regimen and all other study requirements. Sub-study: 4.Decrease in creatinine clearance to < 30 mL/minute, or the need for chronic dialysis. 5.Willing to provide written informed consent for this sub-study. |
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E.4 | Principal exclusion criteria |
1. Patient has not successfully completed either Protocol Fx-006 or Fx1A-201. 2. Chronic use of non-protocol approved non-steroidal anti-inflammatory drugs (NSAIDs), defined as greater than 3 to 4 times/month. The following NSAIDs are allowed: acetylsalicylic acid, etodolac, ibuprofen, indomethicin, ketoprofen, nabumetone, naproxen, nimesulide, piroxicam, and sulindac. 3. If female, patient is pregnant or breast feeding. 4. Clinically significant medical condition that, in the opinion of the investigator, would place the patient at an increased risk to participate in the study. 5. An alanine transaminase (ALT) and aspartate transaminase, (AST) value >3X ULN that in the medical judgement of the investigator is due to reduced liver function or active disease. 6. The patient has received a liver or heart transplant. Sub-study: 7. Unwilling to provide written informed consent for this sub-study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety endpoints: - The incidence of treatment-emergent adverse events (TEAEs), physical examinations, clinical laboratory testing, use of concomitant medications and vital signs.
Efficacy endpoints: - The Neuropathy Impairment Score (NIS) - The Total Quality of Life (TQOL) score as measured using the Norfolk Quality of Life for diabetic neuropathy (QOL-DN) questionnaire - The Karnofsky Performance Scale Index -Assessment of Patient Ambulation |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
None described at time of submission |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Brazil |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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This is an open label trial which will continue until Fx-1006A is commercially available in the participating subjects country or until 31 December 2012, whichever is earlier. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |