Atazanavir/Ritonavir and Zinc Pharmacokinetic Study
关键词
抽象
描述
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.
日期
| 最后验证: | 02/29/2012 |
| 首次提交: | 10/30/2011 |
| 提交的预估入学人数: | 11/17/2011 |
| 首次发布: | 11/20/2011 |
| 上次提交的更新: | 03/20/2012 |
| 最近更新发布: | 03/21/2012 |
| 实际学习开始日期: | 11/30/2011 |
| 预计主要完成日期: | 02/29/2012 |
| 预计完成日期: | 02/29/2012 |
状况或疾病
干预/治疗
Drug: Arm A- early Solvazinc group
Drug: Arm B- late Solvazinc group
相
手臂组
| 臂 | 干预/治疗 |
|---|---|
| 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: Arm A- early Solvazinc group Zinc sulphate 125mg, day 2 to day 15 |
| 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: Arm B- late Solvazinc group Zinc sulphate 125mg, day 15 to day 28 |
资格标准
| 有资格学习的年龄 | 18 Years 至 18 Years |
| 有资格学习的性别 | All |
| 接受健康志愿者 | 是 |
| 标准 | Inclusion Criteria: 1. The ability to understand and sign a written informed consent form, prior to participation in any screening procedure and must be willing to comply with all study requirements 2. Male or non-pregnant, non-lactating females. 3. Aged between 18 to 65 years, inclusive. 4. Documented HIV-1 infection 5. Plasma HIV RNA less than 40 copies/mL (note retesting of screening viral load is allowed). 6. CD4 count > 100 at screening (note retesting of screening CD4 count is allowed). 7. Receiving an antiretroviral regimen of Truvada and atazanavir/ritonavir for more than 3 months. 8. Serum total bilirubin concentration greater than 25 micromol/L 9. Agrees not to change regimen, outside the study recommendations, from baseline until end of the treatment period unless this is medically indicated as decided by their treating physician. Exclusion Criteria: 1. Any serious or active medical or psychiatric illness, which, in the opinion of the investigator, would interfere with subject treatment, assessment, or compliance with the protocol. This would include any active clinically significant renal, cardiac, hepatic, pulmonary, vascular, metabolic disorders or malignancy. 2. Body mass index (BMI) >35 kg/m2 3. Presence of any current active AIDS defining illness (Category C conditions according to the CDC Classification System for HIV Infection 1993) with the following exceptions: • Stable cutaneous Kaposi's Sarcoma 4. Clinically relevant alcohol or drug use (positive urine drug screen, with the exception of cannabinoids) or history of alcohol or drug use considered by the Investigator to be sufficient to hinder compliance with treatment, follow-up procedures or evaluation of adverse events. 5. The use of zinc supplements for 1 month before screening and disallowed concomitant therapy (See Concomitant Medication and treatment, section 5.2) or medication that may interfere with the study results (as determined by the principal investigator). 6. Females of childbearing potential who are not using effective non-hormonal birth control methods or not willing to continue using these birth control methods for at least 14 days after the end of the treatment period. 7. Previous allergy to any of the constituents of the zinc sulphate tablets administered in this trial. 8. Subjects with laboratory evidence of significantly decreased hepatic or renal function (as determined by the principal investigator). 9. Exposure to any investigational drug or placebo within 4 weeks of first dose of study drug |
结果
主要结果指标
1. To assess the change in unconjugated hyperbilirubinaemia following acute and chronic administration of zinc sulphate during atazanavir/ritonavir therapy. [baseline and day 29]
次要成果指标
1. safety and tolerability of zinc sulphate supplement when given concomitantly with atazanavir/ritonavir [baseline and day 14]
2. To assess atazanavir plasma exposure in the presence of zinc and relationship between the latter and hyperbilirubin during zinc intake. [baseline and day 14]
