Boceprevir Drug Combination for Hepatitis C Treatment in People With and Without HIV

Exclusion Criteria

• •A participant will be ineligible to participate on this study if any of the following criteria are met:
• •1. Use of other experimental therapies (including expanded access/compassionate use of HIV antiretrovirals) within 30 days or 5 half-lives (whichever is longer), prior to enrollment.
• •2. Current use of an efavirenz-based (or other NNRTI) or protease inhibitor HIV antiretroviral regimen.
• •3. Use of any of the following medications within 6 weeks prior to enrollment.
• •Alfuzosin (Uroxatral )
• •Alprazolam (Xanax )
• •Atorvastatin (Lipitor )
• •AZT or zidovudine (Retrovir )
• •Carbamazepine (Tegretol )
• •Cisapride (Propulsid )
• •Colchicine (Colcrys ) - If patient has renal or hepatic impairment.
• •DDI or didanosine (Videx )
• •d4T or stavudine (Zerit )
• •Delaviridine (Rescriptor )
• •Digoxin (Lanoxin )
• •Dihydroergotamine
• •Drosperinone (Yaz )
• •Efavirenz (Sustiva )
• •Ergonovine (Ergotrate )
• •Ergotamine (Cafergot )
• •Etravirine (Intelence )
• •Ganciclovir (Cytovene )
• •Immunosuppressive therapy (including oral steroids)
• •---Use of any use of any immunosuppressive therapy, including systemic steroids (prednisone equivalent of greater than 10 mg/day) for a duration of 6 weeks or more within 6 months prior to enrollment. Use of inhaled/nasal steroids should be avoided.
• •Isoniazid or INH (Ingredient in Rifater )
• •Ketoconazole (Nizoral )
• •Lovastatin (Mevacor )
• •Methylergonovine (Methergine )
• •Midazolam given orally (Versed )
• •Nevirapine (Viramune )
• •Phenobarbital (Luminal )
• •Phenytoin (Dilantin )
• •Pimozide (Orap )
• •Pyrazinamide (Ingredient in Rifater )
• •Rifabutin (Mycobutin )
• •Rifampin/rifampicin
• •Rilpivirine (Edurant )
• •Sildenafil (Viagra ) - Phosphodiesterase type 5 inhibitors are prohibited when used for pulmonary hypertension
• •Simvistatin (Zocor )
• •St. Johns s Wort
• •Tadalafil (Cialis ) - Phosphodiesterase type 5 inhibitors are prohibited when used for pulmonary hypertension
• •Thalidomide (Thalomid )
• •Theophylline (Slo-Phylllin )
• •Triazolam (Halcion )
• •Vardenafil (Levitra ) - Phosphodiesterase type 5 inhibitors are prohibited when used for pulmonary hypertension
• •Warfarin (Coumadin )
• •Zalcitabine (Hivid )
• •There may be other brand names for these products listed above.
• •4. Has ingested silymarin (milk thistle), s-adenosylmethionine (SAM-e), glycyrrhizin, Sho-saiko-to (SST), or other herbal supplements that may be either liver beneficial or toxic, within 28 days prior to enrollment.
• •5. Mixed HCV genotypes (e.g., 1 \& 2, 1 \& 3, 1 \& 4) (mixed genotype 1a/1b can be included).
• •6. Has any other known, or clinically suspected, cause of liver disease, including active hepatitis B.
• •7. For participants with cirrhosis, a Child Turcotte Pugh score greater than 7, or Child s B or C cirrhosis.
• •8. Certain abnormal hematological and biochemical parameters, including:
• •1. Neutrophil count less than1000 cells/mm3
• •2. Hemoglobin less than10g/dL
• •3. Platelet count less than or equal to 50,000 cells/mm3
• •4. Estimated glomerular filtration rate less than50 mL/min/1.73 m(2), calculated automatically by the NIH lab using the original MDRD (modification of diet in renal disease) study equation
• •5. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) greater than or equal to10 time ULN
• •6. Prothrombin time International Normalized Ratio (PT-INR) less than2 and/or on chronic anticoagulation medications
• •7. If total bilirubin is greater than 1.5 mg/dL, then direct bilirubin can be no more than 70% of the total, up to a direct bilirubin of 2.0 mg/dL.
• •9. Alpha-fetoprotein less than20 ng/mL, unless an ultrasound, computerized tomography scan (CT), or magnetic resonance imaging (MRI) has been performed to rule out hepatoma.
• •10. Hepatic mass suggestive of hepatocellular carcinoma as detected by ultrasound scan, dual-phase CT, or MRI.
• •11. History of esophageal or gastric varices.
• •12. Any neoplastic disease or any nonmetastatic skin, cervical, or anal cancer that has been resected in the past 5 years EXCEPT Kaposi s sarcoma not requiring systemic chemotherapy.
• •13. Prior organ transplantation other than cornea or hair.
• •14. Evidence of severe cardiac disease (greater than or equal to Grade 3 congestive cardiac failure, symptomatic coronary artery disease, significant arrhythmias, or uncontrolled hypertension) despite intervention or medical therapy.
• •15. Evidence of severe chronic pulmonary disease with functional impairment.
• •16. Severe psychiatric disorder that would interfere with adherence to protocol requirements, and that is not stably treated.
• •17. Evidence of autoimmune disorders including inflammatory bowel diseases, psoriasis, and optic neuritis.
• •18. Evidence of an uncontrolled seizure disorder defined as more than 1 episode of generalized seizure within the past year.
• •19. Chronic pancreatitis based on clinical history.
• •20. History of severe retinopathy.
• •21. History of hemophilia.
• •22. Any hemoglobinopathy (e.g., Thalassemia, sickle cell disease).
• •23. Active systemic infections other than HCV and HIV-1.
• •24. Evidence of gastrointestinal malabsorption, chronic nausea, or vomiting.
• •25. Has any systemic illness that will make it unlikely that the participant will be able to return for the required study visits.
• •26. Any condition that, in the opinion of the investigator, contraindicates participation in this protocol.
• •Exclusion of Children:
• •Because there are insufficient data regarding the safety and efficacy of BOC, PEG, or RBV in the pediatric population, children are excluded from this study.
• •Exclusion of Women:
• •Pregnancy: Pregnant women are excluded from this study because the effects of BOC, PEG, and RBV on the developing human fetus are unknown. Preclinical animal data indicate that the use of RBV treatment during pregnancy is potentially teratogenic.
• •Breastfeeding: Because there is an unknown but potential risk for adverse effects in nursing infants secondary to treatment of the mother with BOC, PEG, or RBV, breastfeeding women are excluded from this study.