Please select the eligibility criteria that correspond to the clinical trial below.
Title: The Effect of Diflunisal on Familial Amyloidosis
Brief Summary: The purpose of this study is to determine if diflunisal can prevent progressive lower leg nerve damage in patients with familial amyloidosis polyneuropathy.

Funding Source - FDA Office of Orphan Products Development (OOPD); National Institute of Neurological Disorders and Stroke (NINDS)


Options:
A: Inclusion Criteria:

Male and non-pregnant female patients meeting all of the following criteria are eligible for enrollment in this study:

* Patient has completed the Month 18 visit of Study Fx-005.
* If female, patient is post-menopausal, surgically sterilized, or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide) throughout the study. (A condom alone is not considered an acceptable method of birth control.) If male with a female partner of childbearing potential, willing to use an acceptable method of birth control for the duration of the study. For both females and males, acceptable birth control must be used for at least 3 months after the last dose of study medication.
* Patient is, in the opinion of the investigator, willing and able to comply with the study medication regimen and all other study requirements.
* Patient agrees not to participate in another investigational drug or device study while participating in this open-label extension study.

Exclusion Criteria:

Patients meeting any of the exclusion criteria will not be enrolled in the study:

* Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs), defined as greater than 3-4 times/month (ibuprofen and nimesulide will be permitted).
* If female, patient is pregnant or breast feeding.
* Patient has liver function test abnormalities: alanine transaminases (ALT) and/or aspartate transaminases (AST) \>2 times upper limit of normal (ULN) that in the medical judgment of the investigator are due to reduced liver function or active liver disease.
B: Inclusion Criteria:

* Medical history of Heart Failure (HF) with at least 1 prior hospitalization for HF or clinical evidence of HF (without hospitalization) manifested by signs or symptoms of volume overload or elevated intracardiac pressures (e.g., elevated jugular venous pressure, shortness of breath or signs of pulmonary congestion on x-ray or auscultation, peripheral edema) that required/requires treatment with a diuretic for improvement,
* Evidence of cardiac involvement by echocardiography with an end-diastolic interventricular septal wall thickness \> 12 mm,
* Presence of amyloid deposits in biopsy tissue and presence of a variant TTR genotype and/or TTR precursor protein identification by immunohistochemistry, scintigraphy or mass spectrometry

Exclusion Criteria:

* A New York Heart Association (NYHA) classification of IV.
* Presence of primary (light chain) amyloidosis.
* Prior liver or heart transplantation or implanted cardiac mechanical assist device.
C: Inclusion Criteria:

* Age 18 to 75 years
* Biopsy proven amyloidosis
* Genotyping of variant transthyretin
* Signs of peripheral or autonomic neuropathy

Exclusion Criteria:

* Use of other non-steroidal anti-inflammatory drugs
* Other causes of sensorimotor polyneuropathy
* Anticipated survival \<2 years or liver transplantation in \<1 yr
* Liver transplantation
* Profound nerve, heart or kidney impairment
* Pregnancy or unwillingness to use contraception by women of childbearing age
* Active or recent gastrointestinal bleeding
* Non-steroidal or aspirin drug allergy/hypersensitivity
D: Inclusion Criteria:

1. Amyloid documented by biopsy.
2. Documented V30M TTR mutation.
3. Peripheral and/or autonomic neuropathy with a Karnofsky Performance Status ≥50.
4. Patient is 18-75 years old.
5. If female, patient is post-menopausal, surgically sterilized, or willing to use an acceptable method of birth control. If male with a female partner of childbearing potential, willing to use an acceptable method of birth control for the duration of the study. For both females and males, birth control must be used for at least 3 months after the last dose of study medication.
6. Patient is, in the opinion of the investigator, willing and able to comply with the study medication regimen and all other study requirements.

Exclusion Criteria:

1. Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs).
2. Primary amyloidosis.
3. If female, patient is pregnant or breast feeding.
4. Prior liver transplantation.
5. No recordable sensory threshold for vibration perception in both feet, as measured by CASE IV.
6. Positive results for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV), and/or human immunodeficiency virus (HIV).
7. Renal insufficiency or liver function test abnormalities.
8. New York Heart Association (NYHA) Functional Classification ≥III.
9. Other causes of sensorimotor neuropathy (B12 deficiency, Diabetes Mellitus, HIV treated with retroviral medications, thyroid disorders, alcohol abuse, and chronic inflammatory diseases).
10. Co-morbidity anticipated to limit survival to less than 18 months.
11. Patient received an investigational drug/device and/or participated in another clinical investigational study within 60 days before Baseline.

Answer: C