HIV-1/Hepatitis C co-infected patients MedDRA version: 14.1 Level: PT Classification code 10020161 Term: HIV infection System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Trade Name: Isentress
Product Name: Raltegravir
Pharmaceutical Form: Tablet
INN or Proposed INN: RALTEGRAVIR
CAS Number: 518048-05-0
Concentration unit: mg milligram(s)
Concentration type: equal
Conce
Sponsors
Department of Genito-Urinary Medicine and Infectious Diseases
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Only patients who meet all of the following inclusion criteria will be eligible for enrolment into this study: 1.Male or Female Patients Age = 18 years old. 2.Naïve to antiretroviral treatment. 3.Subject must be willing and able to understand and provide written, informed consent prior to participation in the study. 4.Subjects must be on concurrent methadone maintenance therapy. 5.Documented HIV infection (antibody positive). 6.Documented Hepatitis C co-infection (PCR positive). 7.Indication for starting ART according to guidelines. 8.Documented resistance profile taken at screening 9.Females may be eligible for enrolment in the study if she is of: a.Non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal); or, Child-bearing potential females must have a negative pregnancy test at initial screening and agree to an acceptable barrier and/or hormonal method of contraception (progesterone only hormonal birth control, -oestrogen based contraceptives are not permitted. Any contraception method must be used consistently and correctly, i.e., in accordance with both the approved product label and the instructions of a physician): Sterilization Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients meeting any of the following exclusion criteria are not eligible for enrolment into this study: 1.Subject is in the initial acute phase of a CDC Clinical Category C infection at Baseline (See CDC definitions; Appendix 2). Subjects may be enrolled provided they are receiving treatment for such infections and are clinically improving at the Baseline visit. 2.Concurrent treatment with an investigational drug or participation in another clinical trial. 3.Use of an investigational drug within 4 weeks or 5 half-lives, whichever is longer, preceding the first dose of investigational medicinal product. 4.Subject is, in the opinion of the investigator, unable to complete the study dosing period and protocol evaluations and assessments. 5.Subject has evidence of genotypic (as defined by the current ANRS AC-11 algorithm) resistance to atazanavir and ritonavir at screening. 6.Patients with alcohol and drug use problems that in the view of investigator will compromise participation in the study. 7.Elevated alanine aminotransferase (ALT) > 5 times upper limit of normal (ULN) 8.Subjects with severe hepatic impairment (Child-Pugh score > 9; Appendix 3). 9.Subjects receiving treatment for HCV. 10.Subjects with concurrent HBV infection. 11.Subject is pregnant or breast feeding. 12.Subject suffers from any serious medical condition (such as pancreatitis, diabetes, congestive heart failure, cardiomyopathy or other cardiac dysfunction), which in the opinion of the Investigator, would compromise the safety of the subject. 13.Subject has a pre-existing mental, physical, or substance abuse disorder that, in the opinion of the Investigator, may interfere with the subject’s ability to comply with the dosing schedule and protocol evaluations and assessments. 14.Subject has a history of inflammatory bowel disease or intestinal malignancy, intestinal ischemia, malabsorption, or other gastrointestinal dysfunction, which, in the opinion of the Investigator, may interfere with drug absorption or render the subject unable to take oral medication. 15.Subject has any acute laboratory abnormality at screening, which, in the opinion of the Investigator, would preclude the subject’s participation in the study of an investigational compound. Any verified Grade 4 laboratory abnormality would exclude a subject from study participation. 16.Subject has an estimated creatinine clearance < 50 mL/min via the Cockcroft-Gault method [Cockcroft, 1976]. NOTE: Creatinine clearance should be estimated using the following formula: For serum creatinine concentration in µmol/L: (140-age)(weight in kg)(serum 0.8×0.85 for women only) creatinine 17.Subject is receiving, or has received within 14 days prior to screen, any drug that has been classified as ‘contraindicated’ from use with RAL or ATV/RTV. 18.Subject has received treatment with radiation therapy or cytotoxic chemotherapeutic agents within 28 days prior to Screening, or has an anticipated need for these agents within the study period. 19.Subject has received treatment with an HIV-1 immunotherapeutic vaccine or any agents with documented activity against HIV-1 in vitro within 28 days prior to screening, or an anticipated need during the study. 20.Subjects who require treatment with any contraindicated medications (as outlined in the SmPCs for raltegravir, atazanavir and ritonavir) within 14 days of commencement of investigational medicinal product , or an anticipated need during the study. 21.Subjec
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives of this study are to: 1.To compare the hepatic safety/tolerability of raltegravir to ATV/RTV as initial treatment in HIV/HCV co-infected patients on methadone at 4, 12, 24, 36, 48, 60, 72, 84 and 96 weeks, as determined by incidence of grade 3-4 liver function test (LFT) elevations. 2.To compare the efficacy of raltegravir to ATV/RTV in achieving viral suppression at 24 weeks in this patient group. ;Secondary Objective: The secondary objectives of this study are to: 1.To compare the efficacy of raltegravir to ATV/RTV in achieving viral suppression at 48 weeks. 2.To compare immunologic response of raltegravir to ATV/RTV at 24, 48 and 96 weeks. 3.To compare the overall safety of raltegravir to ATV/RTV in patients with mild-moderate hepatic impairment. 4.To compare the effects on outpatient retention rates between the two treatment arms. 5.To determine and quantify possible effects of raltegravir versus ATV/RTV on QTc interval. ;Primary end point(s): The primary endpoints of this study are: 1.Comparison between raltegravir and ATV/RTV of incidence of grade 3-4 increase of ALT or AST at 4, 12, 24, 36, 48, 60, 72, 84 and 96 weeks. 2.Comparison of efficacy of raltegravir to ATV/RTV in achieving viral suppression (HIV RNA <50 copies/mL) at 24 weeks in this patient group. | — |
Countries
Ireland
Outcome results
None listed