Artemether/Lumefantrine and Nevirapine Interaction Study in HIV-infected Adults

June 25, 2010 updated by: University of Cape Town

Pharmacokinetic Interaction Between the Antimalarial Combination Artemether/Lumefantrine and Combination Antiretroviral Therapy Including Nevirapine in HIV-infected Adults

Despite the clinical significance of potential interactions between antimalarials and antiretrovirals, no drug interaction studies have been published and there is an urgent need to address this gap in current knowledge.

This study aims to assess the drug interaction between the antimalarial Artemether/Lumefantrine used for management of uncomplicated malaria and Nevirapine-based antiretroviral therapy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

36

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • South Africa
      • Cape Town, South Africa
        • Groote Schuur Hospital, Research ward

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Informed and given ample time and opportunity to think about participation and willing and able to comprehend and comply with all trial requirements. The participant has given written informed consent to participate in the study and to abide by study restrictions.
  • Male or female subjects older than 18 years of age.
  • HIV-infected as documented by positive HIV-antibody test and confirmed by Western blot.
  • Body weight more than 35kg with a body mass index (BMI) ranging between 18.5 to 30kg/m2 inclusive (See Appendix 16.2).
  • Karnofsky score above 70 (See Appendix 16.5).
  • CD4 count ≥ 200 cells/mm3
  • Patients on NVP-based cART at stable doses without significant toxicity for at least 6 weeks at screening (Group 2 only).

Exclusion Criteria:

  • Patients diagnosed with Plasmodium falciparum malaria

  • Contraindications to artemether/lumefantrine:

    • Hypersensitivity to the artemether, lumefantrine or to any of the excipients of Coartem®.
    • Patients with severe malaria according to WHO definition.
    • Pregnant (as confirmed by an HCG test performed at screening) or breast-feeding female.
    • Patients with a family history of congenital prolongation of the QTc interval or sudden death or with any other clinical condition known to prolong the QTc interval such as patients with a history of symptomatic cardiac arrhythmias, with clinically relevant bradycardia or with severe cardiac disease.
    • Patients with known disturbances of electrolyte balance e.g. hypokalaemia or hypomagnesaemia.
    • Patients taking any drug which is metabolised by the cytochrome enzyme CYP2D6 (e.g. flecainide, metoprolol, imipramine, amitriptyline, clomipramine).
    • Patients taking drugs that are known to prolong the QTc interval such as antiarrhythmics of classes IA and III, neuroleptics, antidepressive agents, certain antibiotics including some agents of the following classes: macrolides, fluoroquinolones, imidazole, and triazole antifungal agents, certain non-sedating antihistaminics (terfenadine, astemizole), cisapride.

  • Contraindication to nevirapine:

    • Hypersensitivity to nevirapine or any of the excipients of Aspen Nevirapine®.
    • Severe hepatic dysfunction: Child-Pugh class B or C and in endstage renal failure in patients not on haemodialysis.
    • Aspartate transaminase (AST) or alanine aminotransferase (ALT) > 5 x upper limit of normal (ULN).
    • History of severe rash, rash accompanied by constitutional symptoms; hypersensitivity syndrome, or clinical hepatitis due to nevirapine.
  • Haemoglobin below 8.5g/dL for female and 9.5g/dL for male subjects.

  • Pharmacokinetic exclusion criteria:

    • Relevant history or current condition(s) that might interfere with drug absorption, distribution, metabolism or excretion.
    • Current smokers, or subjects who have stopped smoking less than 3 months prior to the date of screening.
    • History of or current substance abuse problem or a positive urine screen for drugs of abuse.
    • History of or current compulsive alcohol abuse problem.
    • The subject has consumed any alcohol, grapefruit or caffeine-containing products (ie tea, coffee, cola, chocolate) within 24 hours before the first dose of AL during each PK profile.
    • The subject has participated in strenuous exercise within 24 hours before the first IP administration.

  • General exclusion criteria:

    • Severely ill or suffering from any serious underlying disease (particularly cardiac, hepatic or renal disease) that in the opinion of the Investigator would make the participant unsuitable for the study in terms of their safety or study analysis.
    • The volunteer has participated in another study with any investigational product within 8 weeks before the first administration of the current investigational products, or until at least 5 x t½ elimination has lapsed, whichever is the greater.
    • Subjects who, in the opinion of the Investigator, should not participate in the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Antiretroviral-naive
Antiretroviral-naive included as control group
Drug: Artemether/Lumefantrine
Coartem (fixed dose Artemether20mg /Lumefantrine 120mg) Dose: 4 tablets(80mg/480mg) twice daily for 3 days at 0,8,24,36,48 and 60 hours
Other Names:
  • Coartem
Active Comparator: Nevirapine-based antiretroviral therapy
Drug: Artemether/ lumefantrine
Coartem (fixed dose Artemether20mg /Lumefantrine 120mg) Dose: 4 tablets(80mg/480mg) twice daily for 3 days at 0,8,24,36,48 and 60 hours
Other Names:
  • Coartem

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Lumefantrine plasma concentration
Time Frame: day 7
day 7

Secondary Outcome Measures

Outcome Measure
Time Frame
Point estimates and 90% confidence intervals for the mean ratios of the lumefantrine, artemether and DHA log-transformed Cmax, AUC0-t, AUC0 ∞ , t½,z, tmax and MRT with/without NVP
Time Frame: 21 days
21 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Cape Town

Collaborators

London School of Hygiene and Tropical Medicine

Investigators

  • Principal Investigator: Karen Barnes, MD, University of Cape Town
  • Study Director: Tamara Kredo, MD, University of Cape Town

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2008

Primary Completion (Actual)

August 1, 2009

Study Completion (Actual)

December 1, 2009

Study Registration Dates

First Submitted

November 13, 2008

First Submitted That Met QC Criteria

November 13, 2008

First Posted (Estimate)

November 14, 2008

Study Record Updates

Last Update Posted (Estimate)

June 28, 2010

Last Update Submitted That Met QC Criteria

June 25, 2010

Last Verified

June 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SEACAT 2.4.1
  • DOH-27-0807-2012

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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