Pharmacokinetic Interaction Between the Antimalarial Combination Artemether/Lumefantrine and Combination Antiretroviral Therapy Including Lopinavir/Ritonavir in HIV-infected Adults (SEACAT 2_4_2)

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.

The aim of the study is to investigate the pharmacokinetics (PK) of antimalarial combination artemether/lumefantrine (AL) and combination antiretroviral therapy (cART) including lopinavir/ritonavir (LPV/r) in HIV-infected adults.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Malaria
• Intervention / Treatment: Drug: Artemether/Lumefantrine

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 4

Contacts and Locations

Study Locations

• South Africa
  • Western Province
    • Cape Town, Western Province, South Africa, 7925
      • Groote Schuur Hospital, Ward J51, Old Main Building

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• 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 of 18 years of age or older.
• 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 15.2).
• Karnofsky score above 70 (See Appendix 15.5).
• CD4 count ≥ 200 cells/mm3
• Patients on LPV/r-based cART at stable doses without significant toxicity for at least 6 weeks at screening.

Exclusion Criteria:

• Patients diagnosed with malaria
• Contraindications to artemether/lumefantrine:
• Hypersensitivity to the artemether, lumefantrine or to any of the excipients of Coartem®.
• 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) or CYP3A4.
• 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.
• Haemoglobin below 8.5g/dL for female and 9.5g/dL for male subjects.
• 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 alcohol abuse.
• The subject has consumed any alcohol, grapefruit or caffeine-containing products (ie tea, coffee, cola, chocolate) within 24 hours before any dose of AL during each PK profile.
• The subject has participated in strenuous exercise within 24 hours before any AL dose.
• 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

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Lumefantrine concentration	day 7

Collaborators and Investigators

• Sponsor: University of Cape Town
• Collaborators: London School of Hygiene and Tropical Medicine
• Investigators: Principal Investigator: Karen I Barnes, MBChB MMed(clin pharm), University of Cape Town

Publications and helpful links

General Publications

• Kredo T, Mauff K, Workman L, Van der Walt JS, Wiesner L, Smith PJ, Maartens G, Cohen K, Barnes KI. The interaction between artemether-lumefantrine and lopinavir/ritonavir-based antiretroviral therapy in HIV-1 infected patients. BMC Infect Dis. 2016 Jan 27;16:30. doi: 10.1186/s12879-016-1345-1.

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): February 1, 2010

Study Registration Dates

• First Submitted: March 25, 2009
• First Submitted That Met QC Criteria: March 25, 2009
• First Posted (Estimate): March 26, 2009

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: HIV; Malaria; Pharmacokinetics; Treatment Experienced
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Lumefantrine; Artemether; Artemether, Lumefantrine Drug Combination
• Other Study ID Numbers: SEACAT 2_4_2; NHREC