Phase I/II Trial of Everolimus in Combination With Lonafarnib in Progeria

Exclusion Criteria

• •Subjects must not be taking medications that significantly affect the metabolism of lonafarnib
• •Subjects receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Subjects with endocrine deficiencies are allowed to receive physiologic or stress doses of steroids if necessary. Topical or inhaled steroids are allowed.
• •Subjects who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug; have not recovered from the side effects of any major surgery (defined as requiring general anesthesia but excluding a procedure for insertion of central venous access); or who may require major surgery during the course of the study.
• •13.2.5 Subjects with an active bleeding diathesis or on oral anti-vitamin K medication (except low dose coumadin).
• •Subjects who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
• •* known severely impaired lung function
• •* active (acute or chronic) or uncontrolled severe infections.
• •* liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis.
• •* History of hepatitis B or hepatitis C
• •Other concurrent severe and/or uncontrolled medical disease that could compromise participation in the study (i.e., uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, chronic liver or renal disease, active upper GI tract ulceration).
• •A known history of Human Immunodeficiency Virus (HIV) seropositivity or known immunodeficiency.
• •Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection). A nasogastric tube (NG tube) or gastric tube (G tube) is allowed.
• •Subjects who have known or suspected hypersensitivity to any of the excipients included in the formulation should not be treated.
• •Subjects must not be pregnant or breast-feeding. Female subjects of childbearing potential must have negative serum or urine pregnancy test. Sexually active male and female subjects of reproductive potential must agree to use a medically accepted form of birth control while on study and up to 10 weeks after treatment. It is permissible for female subjects to take oral contraceptives or other hormonal methods while receiving treatment with everolimus.