Efficacy, Safety and Tolerability of ISIS 304801 in People With Partial Lipodystrophy With an Open-Label Extension

• INCLUSION CRITERIA:
• Age greater than or equal to 18 years at enrollment (the time of informed consent, week -1)
• Fasting triglyceride (TG) levels greater than or equal to 500 mg/dL (greater than or equal to 5.7 mmol/L) at enrollment. If the fasting TG value is 55 years of age or, in females less than or equal to 55 years, 12 months of spontaneous amenorrhea without an alternative medical cause and follicle-stimulating hormone (FSH) levels in the postmenopausal range for the laboratory involved), abstinent, or if engaged in sexual relations of child-bearing potential, patient is using an acceptable contraceptive method from time of signing the informed consent form until at least 13 weeks after the last dose of Study Drug administration.
• Males: Surgically sterile, abstinent, or if engaged in sexual relations with a female of child bearing potential, patient is utilizing an acceptable contraceptive method from the time of signing the informed consent form until at least 13 weeks after the last dose of study drug administration.

Note: Abstinence is only an effective method of birth control when this is the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial and withdrawal are not acceptable methods of contraception.

EXCLUSION CRITERIA

• A diagnosis of generalized lipodystrophy
• Current or history of autoimmune diseases (even with a diagnosis of PL) unless approved by the Investigator and Sponsor Medical Monitor
• Acute pancreatitis within 4 weeks of enrollment
• History within 6 months of enrollment of acute or unstable cardiac ischemia (myocardial infarction, acute coronary syndrome, new onset angina), stroke, transient ischemic attack, or unstable congestive heart failure requiring a change in medication
• Major surgery within 3 months of enrollment
• History of heart failure with New York Heart Association functional classification (NYHA) greater than Class II
• Uncontrolled hypertension (blood pressure [BP] >160/100 mm Hg)
• Any of the following laboratory values at enrollment:
• Cardiac troponin T > upper limit of normal (ULN)
• Measured or estimated (in case of triglycerides > 400 mg/dL) LDL-C >130 mg/dL on maximal tolerated statin therapy
• Hemoglobin HbA1c greater than or equal to 9.5%
• Hepatic:
• Total bilirubin >ULN
• Alanine transaminase (ALT) >3.0 x ULN. Higher levels will be permitted after a safety review by a hepatologist, that includes no evidence of cirrhosis.
• Aspartate aminotransferase ( (AST) >3.0 x ULN. Higher levels will be permitted after a safety review by a hepatologist, that includes no evidence of cirrhosis.
• Renal:
• Persistently positive (2 out of 3 tests greater than or equal to trace positive) for blood on urine dipstick. In the event of a positive test eligibility may be confirmed with urine microscopy showing less than or equal to 5 red blood cells per high power field (urine will be screened at admission and repeated if abnormal). If red blood cell counts (RBC) are high every effort will be made to determine if the source is renal or benign, such as from menstrual bleeding. If the presence of RBC is determined to be from a non-renal source, the PI will make the decision to proceed with protocol testing and/or randomization.
• Two out of three consecutive tests greater than or equal to 1+ for protein on urine dipstick. In the event of a positive test eligibility may be confirmed by either a spot urine albumin to creatinine ratio 499 mL within 60 days
• Have any other conditions, which, in the opinion of the Investigator or the Sponsor would make the patient unsuitable for inclusion, or could interfere with the patient participating in or completing the study