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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
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Raltegravir is the first integrase inhibitor used in humans. It has been shown to be highly efficacious and well tolerated in phase III clinical trials in multidrug experienced human immunodeficiency virus(HIV)-infected patients, as well as initial therapy in untreated patients. Pharmacokinetic studies in healthy adult subjects indicate that the major mechanism of clearance of the drug is glucuronidation mediated by UGT1A1, with a minor contribution of renal excretion of unchanged parent compound. Unlike CYP-based metabolism, glucuronidation is generally found to be relatively unaffected by hepatic disease. A single dose pharmacokinetic study of raltegravir in patients with mild to moderate hepatic insufficiency (Steigbigel et al. 2008) found no clinically important effect on the drug pharmacokinetic profile, with no dosage adjustment being necessary. The liver safety and tolerability of boosted atazanavir (ATV/r) has been evaluated in human immunodeficiency virus and hepatitis C virus (HIV/HCV) coinfected patients with advanced liver disease (decompensated cirrhosis) (Hermida JM et al. 4th IAS: Sidney, 2007). Similar to Raltegravir, ATV is also mainly metabolized by conjugation through UGT1A1. There is an urgent need for potent and efficacious ARV drugs with a clean safety liver profile even in patients with severe liver disease. The investigators hypothesized that pharmacokinetics will not be altered in HIV/HCV patients with advanced (Child-Pugh grade C) cirrhosis or in those with no histologic liver damage.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients with Child-Pugh C hepatic-cirrhosis. | Experimental | VIH/VHC coinfected patients with advanced (Child-Pugh C) hepatic cirrhosis. |
|
| VIH/VHC coinfected patients without liver damage. | Active Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Raltegravir 400 mg/12hours | Drug |
| ||
| Raltegravir 400 mg/12hours |
| Measure | Description | Time Frame |
|---|---|---|
| The area under the curve (AUC0-12) calculated from plasma concentrations, the maximum concentration (Cmax) and the the minimum concentration (Cmin) of Raltegravir 400 mg/12 hours in the steady state for both arms. | On the fifth day of treatment, patient will be hospitalized in the clinical trial unit in order to obtaine plasma concentrations previous to the administration of the corresponding dose (basal) and at the following times post-administration: 30min, 1h, 1h30min, 2h, 3h, 4h, 6h, 8h, and 12h. With these measures, (AUC0-12), Cmax and Cmin will be calculated in order to describe the pharmacokinetic of Raltegravir 400 mgBID in the steady state in both arms | On the fifth day of treatment with raltegravir |
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline in hematology and biochemistry parameters at day 5 and 15, number of adverse events (serious and non serious) notified and number of patients who discontinue the study (drop-out rate). | Hematology and biochemistry parameters, adverse events notified during the study and drop-out rate will be recorded in order to evaluate the safety and tolerability of multiple doses of raltegravir in HIV/HCV coinfected patients, with no liver damage and with advanced cirrhosis. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Santiago Moreno Guillen, MD | Hospital Universitario Ramón y Cajal. Madrid | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Universitario Ramón y Cajal. | Madrid | Madrid | 28034 | Spain |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24097843 | Derived | Hernandez-Novoa B, Moreno A, Perez-Elias MJ, Quereda C, Dronda F, Casado JL, Madrid-Elena N, Aguilar M, Fumero E, Molto J, Moreno S. Raltegravir pharmacokinetics in HIV/HCV-coinfected patients with advanced liver cirrhosis (Child-Pugh C). J Antimicrob Chemother. 2014 Feb;69(2):471-5. doi: 10.1093/jac/dkt386. Epub 2013 Oct 4. |
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| Drug |
|
| On day 1, 5 and 15 |
| ID | Term |
|---|---|
| D000163 | Acquired Immunodeficiency Syndrome |
| D006526 | Hepatitis C |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012897 | Slow Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D006525 | Hepatitis, Viral, Human |
| D018178 | Flaviviridae Infections |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D000068898 | Raltegravir Potassium |
| ID | Term |
|---|---|
| D011760 | Pyrrolidinones |
| D011759 | Pyrrolidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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