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Drug InteractionPhase 4NCT04531072

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

A Phase 4 study testing Artemether-lumefantrine and Atazanavir-ritonavir 300/100 mg in people with Drug Interaction, run by Fogarty International Center of the National Institute of Health at 1 site in Nigeria.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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 Read more about this study

Who is it for?
Ages 18 to 70 yearsHealthy volunteers can take part
Conditions the study is for
Drug Interaction
What is being tested?
Artemether-lumefantrine and Atazanavir-ritonavir 300/100 mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteNigeria
Study dates
18 Sep 2018to 15 Aug 2019
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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
Show all 12Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

Nigeria1 site

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

    Surulere, Lagos, 001

Other trials in Nigeria

About this study

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

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

Read the detailed description

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.

Being tested
Artemether-lumefantrine, Atazanavir-ritonavir 300/100 mg
Keywords
Drug interaction, artemether-lumefantrine, atazanavir-ritonavir, LUTH

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Artemether-lumefantrineDrug

    Also called Coartem 80/480, P01BF01

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

  • Atazanavir-ritonavir 300/100 mgDrug

    Also called Anzavir-R, J05AR23

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

Study groups in NCT04531072
Study groupRoleWhat they receive
ATVr-armExperimental10 participants living with HIV and having uncomplicated Falciparum malaria were administered: Atazanavir-ritonavir (300/100 mg) one tablet once daily continuously + tenofovir-lamivudine (300/300 mg) one tablet once daily continuously and artemether-lumefantrine (80/480 mg) one tablet twice daily for three days at 0, 8, 24, 36, 48 and 60 hour.
Receives: Drug: Artemether-lumefantrine; Drug: Atazanavir-ritonavir 300/100 mg
AL-arm (Control)Active comparator10 participants who were HIV negative but having uncomplicated Falciparum malaria were administered: Artemether-lumefantrine 80/480 mg, one tablet twice daily for three days at 0, 8, 24, 36, 48 and 60 hour.
Receives: Drug: Artemether-lumefantrine

What is being measured

The primary outcome is the main question the study is designed to answer.

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

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

    Measured: 2 weeks

  2. Maximum plasma concentration (Cmax) of lumefantrine

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

    Measured: 2 weeks

  3. Day 7 lumefantrine concentration

    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.

    Measured: 2 weeks

  4. QTc-interval

    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.

    Measured: One week

  5. Haemoglobin level

    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.

    Measured: One week

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

    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.

    Measured: One week

  7. Creatinine level

    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.

    Measured: One week

  8. Adverse events

    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.

    Measured: Two weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Aug 2020
  2. Study start18 Sep 2018
  3. Primary completion15 May 2019
  4. Study completion15 Aug 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Basic science
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Two arm study namely: ATVr arm and AL (Control) arm each consisting of 10 participants in a parallel study design
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04531072
Sponsor's protocol ID
D43TW010134
Status last verified
Aug 2020
First submitted
16 Aug 2020
Last updated
28 Aug 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: IPD would not be made available to other researchers

Publications

  • Usman SO, Oreagba IA, Kadri MR, Adewumi OO, Akinyede A, Agbaje EO, Abideen G, Busari AA, Hassan OO, Akinleye MO, Akanmu AS. Evaluation of the effects of atazanavir-ritonavir on the pharmacokinetics of lumefantrine in patients living with HIV in Lagos University Teaching Hospital, South-Western Nigeria. Eur J Clin Pharmacol. 2021 Sep;77(9):1341-1348. doi: 10.1007/s00228-021-03116-x. Epub 2021 Mar 23.

    PubMed 33755736

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Artemether-lumefantrine and Atazanavir-ritonavir 300/100 mg in people with Drug Interaction, run by Fogarty International Center of the National Institute of Health at 1 site in Nigeria.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Nigeria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Drug exposure (Area under the curve) of lumefantrine (time frame: 2 weeks). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04531072, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2020.

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