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

NCT ID: NCT04531072

Last Updated: 2020-08-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-09-18

Study Completion Date

2019-08-15

Brief Summary

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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

Detailed Description

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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.

Conditions

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Drug Interaction

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Two arm study namely: ATVr arm and AL (Control) arm each consisting of 10 participants in a parallel study design
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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ATVr-arm

10 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.

Group Type EXPERIMENTAL

Artemether-lumefantrine

Intervention Type DRUG

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

Atazanavir-ritonavir 300/100 mg

Intervention Type DRUG

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

AL-arm (Control)

10 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.

Group Type ACTIVE_COMPARATOR

Artemether-lumefantrine

Intervention Type DRUG

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

Interventions

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Artemether-lumefantrine

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

Intervention Type DRUG

Atazanavir-ritonavir 300/100 mg

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

Intervention Type DRUG

Other Intervention Names

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Coartem 80/480, P01BF01 Anzavir-R, J05AR23

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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NIH Office of AIDS Research (OAR)

NIH

Sponsor Role collaborator

National Institute on Minority Health and Health Disparities (NIMHD)

NIH

Sponsor Role collaborator

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

Fogarty International Center of the National Institute of Health

NIH

Sponsor Role lead

Responsible Party

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Sikiru Olatunji Usman

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Sikiru Usman, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Lagos

Ibrahim Oreagba, Ph.D.

Role: STUDY_DIRECTOR

University of Lagos

Locations

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

Surulere, Lagos, Nigeria

Site Status

Countries

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Nigeria

References

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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.

Reference Type DERIVED
PMID: 33755736 (View on PubMed)

Other Identifiers

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D43TW010134

Identifier Type: NIH

Identifier Source: org_study_id

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