Atazanavir/Ritonavir and Zinc Pharmacokinetic Study

NCT01475227 | Completed Phase 4

• 1 other identifier: SSAT 043
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV Infection

Keywords

HIV; Bilirubin

Outcome Measures

Primary Outcomes (1)

• To assess the change in unconjugated hyperbilirubinaemia following acute and chronic administration of zinc sulphate during atazanavir/ritonavir therapy.

  Change in serum unconjugated bilirubin concentrations when atazanavir/ritonavir is added to zinc sulphate, adjusted for period effect

  baseline and day 29

Secondary Outcomes (2)

• safety and tolerability of zinc sulphate supplement when given concomitantly with atazanavir/ritonavir

  baseline and day 14

• To assess atazanavir plasma exposure in the presence of zinc and relationship between the latter and hyperbilirubin during zinc intake.

  baseline and day 14

Study Arms (2)

Arm A- early Solvazinc group

EXPERIMENTAL

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

Arm B- late Solvazinc group

EXPERIMENTAL

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

Interventions

1 Solvazinc tablet, day 2 to day 15 DRUG

Zinc sulphate 125mg, day 2 to day 15

Also known as: Zinc sulphate

Arm A- early Solvazinc group

1 Solvazinc tablet, day 15 to day 28 DRUG

Zinc sulphate 125mg, day 15 to day 28

Also known as: Zinc sulphate

Arm B- late Solvazinc group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Male or non-pregnant, non-lactating females.
• Aged between 18 to 65 years, inclusive.
• Documented HIV-1 infection
• Plasma HIV RNA less than 40 copies/mL (note retesting of screening viral load is allowed).
• CD4 count \> 100 at screening (note retesting of screening CD4 count is allowed).
• Receiving an antiretroviral regimen of Truvada and atazanavir/ritonavir for more than 3 months.
• Serum total bilirubin concentration greater than 25 micromol/L
• 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.

You may not qualify if:

• 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.
• Body mass index (BMI) \>35 kg/m2
• 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
• 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.
• 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).
• 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.
• Previous allergy to any of the constituents of the zinc sulphate tablets administered in this trial.
• Subjects with laboratory evidence of significantly decreased hepatic or renal function (as determined by the principal investigator).
• Exposure to any investigational drug or placebo within 4 weeks of first dose of study drug

Sponsors & Collaborators

• St Stephens Aids Trust: lead

Study Sites (1)

St Stephen's AIDS Trust

London, SW10 9NH, United Kingdom

Location

MeSH Terms

Conditions

HIV Infections

Interventions

Zinc Sulfate

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Sulfates; Sulfuric Acids; Sulfur Acids; Sulfur Compounds; Inorganic Chemicals; Zinc Compounds

Study Officials

• Marta Boffito, Dr

  St Stephen's AIDS Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2011
• First Posted: November 21, 2011
• Study Start: December 1, 2011
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: March 22, 2012

Record last verified: 2012-03

Locations

GB (1)