Atazanavir/Ritonavir and Zinc Pharmacokinetic Study (SSAT043)
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|ClinicalTrials.gov Identifier: NCT01475227|
Recruitment Status : Completed
First Posted : November 21, 2011
Last Update Posted : March 22, 2012
The study is being conducted as the most common side effect of the HIV drug atazanavir (taken with ritonavir) is hyperbilirubinaemia. Bilirubin is a normal waste product from the body and gets broken down in the liver so it can leave the body through the gut. Atazanavir slows the breakdown of this chemical, which can cause jaundice (yellowing of the skin) and/or scleral icterus (yellowing of the eyes). This is completely harmless; in fact up to 1 in 10 of the UK population have an inherited condition that causes the same yellowing. However, some patients don't like this side effect and it is the commonest reason for switching off the drug.
A study in people with Gilberts syndrome (the inherited condition that causes the same changes in the chemical bilirubin) showed that a mineral supplement (zinc sulphate) reduced the levels of bilirubin in the blood. The aim of this study is to see if using zinc supplements can achieve the same effect in patients with high bilirubin due to atazanavir use.
|Condition or disease||Intervention/treatment||Phase|
|HIV Infection||Drug: 1 Solvazinc tablet, day 2 to day 15 Drug: 1 Solvazinc tablet, day 15 to day 28||Phase 4|
Atazanavir is a protease inhibitor (PI) and, like other agents in this class, requires pharmacological 'boosting' with the cytochrome p450 inhibitor ritonavir. Ritonavir slows the hepatic clearance of PIs, increasing plasma concentration and allowing the us eof lower, and less frequent doses. Atazanavir, boosted with ritonavir, is approved for once-daily use, is an internationally preferred first-line agent (in combination with a backbone of two nucleosides [NRTI]) and the most commonly prescribed PI in the UK. Once-daily atazanavir/ritonavir with two NRTI is an effective and well-tolerated therapeutic option for people living with HIV infection. The most common adverse event associated with atazanavir use is unconjugated hyperbilirubinaemia. This is observed in over 40% of patients and up to 5% of patients discontinue the drug due jaundice and/or scleral icterus.
Truvada is a fixed dose combination of two NRTI, tenofovir (245mg) and emtricitabine (200mg), administered as one tablet once daily. Truvada is a preferred NRTI backbone in national and international guidelines and the first line, therefore most commonly used, NRTI backbone in our unit.
Benefits of atazanavir/ritonavir compared with alternative agents include once daily dosing, low pill burden, low rates of gastro-intestinal toxicity and, importantly in a patient population already at an elevated risk of cardiovascular disease, a favourable lipid profile. If a simple intervention could reduce the incidence of hyperbilirubinaemia this could reduce the risk of treatment discontinuation/switch. The aim of this study is to explore the benefit, and safety, of adding zinc sulphate in patients on a stable regimen of Truvada, atazanavir and ritonavir.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||16 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Randomized Crossover Study of the Effects of Zinc Sulphate Supplementation on Atazanavir/Ritonavir-associated Hyperbilirubinemia|
|Study Start Date :||December 2011|
|Actual Primary Completion Date :||March 2012|
|Actual Study Completion Date :||March 2012|
Experimental: Arm A- early Solvazinc group
Zinc sulphate 125mg (1 Solvazinc tablet) once daily orally after dissolution in water, day 2 to day 15
Drug: 1 Solvazinc tablet, day 2 to day 15
Zinc sulphate 125mg, day 2 to day 15
Other Name: Zinc sulphate
Experimental: Arm B- late Solvazinc group
Zinc sulphate 125mg (1 Solvazinc tablet) once daily orally after dissolution in water, day 15 to day 28
Drug: 1 Solvazinc tablet, day 15 to day 28
Zinc sulphate 125mg, day 15 to day 28
Other Name: Zinc sulphate
- To assess the change in unconjugated hyperbilirubinaemia following acute and chronic administration of zinc sulphate during atazanavir/ritonavir therapy. [ Time Frame: baseline and day 29 ]Change in serum unconjugated bilirubin concentrations when atazanavir/ritonavir is added to zinc sulphate, adjusted for period effect
- safety and tolerability of zinc sulphate supplement when given concomitantly with atazanavir/ritonavir [ Time Frame: baseline and day 14 ]Assessment of the impact of adding zinc sulphate to atazanavir/ritonavir-based HAART on grade 2-4 laboratory abnormalities and adverse events.
- To assess atazanavir plasma exposure in the presence of zinc and relationship between the latter and hyperbilirubin during zinc intake. [ Time Frame: baseline and day 14 ]Atazanavir plasma exposure in the presence of zinc and relationship between the latter and hyperbilirubin during zinc intake.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01475227
|St Stephen's AIDS Trust|
|London, United Kingdom, SW10 9NH|
|Principal Investigator:||Marta Boffito, Dr||St Stephen's AIDS Trust|