Skip to main content
OpenTrials
Completed

NCT Number: NCT04531072

Effect of Atazanavir-ritonavir on the Pharmacokinetics and Toxicity of Lumefantrine

A case control pharmacokinetic study evaluating the effects of atazanavir-ritonavir on the pharmacokinetics and toxicity of lumefantrine in people living with HIV attending APIN clinic of the Lagos University Teaching Hospital

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Drug Interaction

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Apin (Aids Prevention Initiatives in Nigeria) clinic, Lagos University Teaching Hospital

Surulere, Lagos, 001, Nigeria

About this study

Atazanavir-ritonavir (ATVr) based antiretroviral therapy and artemether-lumefantrine (AL) are commonly used drugs for the treatment of Human Immune Deficiency Virus (HIV) infection and malaria respectively in Nigeria. However, both drugs interact with Cytochrome P 3A4 (CYP 3A4) isoenzymes which may spawn clinically significant pharmacokinetic interactions.

The study was aimed at evaluating the effects of atazanavir-ritonavir on the pharmacokinetics and toxicity of lumefantrine.

In a case control pharmacokinetic study, twenty participants who tested positive for Plasmodium falciparum malaria were recruited and divided into two groups (ATVr-arm, n=10; and Control-arm, n= 10). All the participants were administered with 6 doses of AL 80-480 mg (Coartem). Thereafter, blood samples were collected from them at different time intervals over seven days. The lumefantrine concentration in each sample was determined with high-performance liquid chromatography (HPLC) and entered into WinNonlin® software to determine the pharmacokinetic parameters of lumefantrine which were compared between the test and control groups. Toxicity was evaluated with adverse events monitoring, electrocardiography, haematological and blood chemistry tests at pre and post doses of artemether-lumefantrine.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Adult male or non-gravid female ≥18 years of age,
  • Informed written consent,
  • Malaria parasitaemia
  • Axillary temperature ≥37.5°C or history of fever within 24 hours before visiting the clinic and with, at least, any of the following signs and symptoms of uncomplicated malaria: chills, sweats, headaches, muscle aches, nausea, vomiting, diarrhoea, body weakness, poor appetite and pallor.
  • Hemoglobin (Hb) ≥8 g/dl
  • Body weight ≥35 kg
  • HIV positive (ATVr arm), HIV negative (AL/control arm)

Exclusion criteria

  • Severe anaemia' (Haemoglobin levels < 8g/dl)
  • Smokers/alcoholics and users of substances which inhibit or induce CYP3A4 iso enzymes
  • Withdrawal of consent
  • Known allergy to any of the study drugs
  • Development of complications or severe adverse effects
  • Smokers/alcoholics and users of caffeine, drugs which induce or inhibit CYP3A4 and CYP2B6
  • Evidence of chronic illnesses such as diabetes, hypertension, psychiatric illnesses
  • Subject taking any drugs or having any condition known to prolong QT-intervals
  • Signs of severe malaria
  • Use of anti-tubercular drugs for at least three months prior to enrolment
  • Being on anti-malarial drugs within four weeks prior to enrolment
  • Pregnant or nursing mother.

Treatment and study plan

Artemether-lumefantrine

Drug

Safety and efficacy evaluation during concurrent use of artemether-lumefantrine and atazanavir-ritonavir based antiretroviral therapy

Other names: Coartem 80/480, P01BF01

Atazanavir-ritonavir 300/100 mg

Drug

Safety and efficacy evaluation during concurrent use of artemether-lumefantrine and atazanavir-ritonavir based antiretroviral therapy

Other names: Anzavir-R, J05AR23

Primary outcomes

  1. Drug exposure (Area under the curve) of lumefantrine

    Time frame: 2 weeks

    Change in drug exposure (AUC) of lumefantrine may indicate interaction between atazanavir-ritonavir and lumefantrine via Cytochrome P3A4 induction

  2. Maximum plasma concentration (Cmax) of lumefantrine

    Time frame: 2 weeks

    Change in maximum plasma concentration (Cmax) of lumefantrine may indicate interaction between atazanavir-ritonavir and lumefantrine via Cytochrome P3A4 induction

  3. Day 7 lumefantrine concentration

    Time frame: 2 weeks

    This the plasma concentration of lumefantrine at the seventh day of commencement of the first dose. Efficacy is indicated when it is 280 ng/mL and above.

  4. QTc-interval

    Time frame: One week

    Change in mean or median QTc-interval above therapeutic range at post-dose of artemether-lumefantrine indicates cardio-toxicity caused by interaction between atazanavir-ritonavir and lumefantrine via Cytochrome P3A4 induction.

  5. Haemoglobin level

    Time frame: One week

    Change in mean or median hemoglobin level above therapeutic range at post-dose of artemether-lumefantrine indicates haemotoxicity caused by interaction between atazanavir-ritonavir and lumefantrine via Cytochrome P3A4 induction.

  6. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels

    Time frame: One week

    Change in mean or median ALT and AST levels above therapeutic range at post-dose of artemether-lumefantrine indicates liver toxicity caused by interaction between atazanavir-ritonavir and lumefantrine via Cytochrome P3A4 induction.

  7. Creatinine level

    Time frame: One week

    Change in mean or median creatinine level above therapeutic range at post-dose of artemether-lumefantrine indicates renal toxicity caused by interaction between atazanavir-ritonavir and lumefantrine via Cytochrome P3A4 induction.

  8. Adverse events

    Time frame: Two weeks

    Change in frequency of adverse events post-dose of artemether-lumefantrine indicates toxicity caused by interaction between atazanavir-ritonavir and lumefantrine via Cytochrome P3A4 induction.

Sponsors and collaborators

Lead sponsor

Fogarty International Center of the National Institute of Health

Nih

Collaborators

  • NIH Office of AIDS Research (OAR)
  • National Institute of Neurological Disorders and Stroke (NINDS)
  • National Institute on Minority Health and Health Disparities (NIMHD)

Registry information

Official study title

Effect of Atazanavir-ritonavir on the Pharmacokinetics and Toxicity of Lumefantrine in People Living With HIV Attending Lagos University Teaching Hospital

Important dates

Study start
2018
Primary completion
2019
Study completion
2019
First posted
Aug 28, 2020
Registry last updated
Aug 28, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.