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

NCT00869700 | Completed Phase 4 DMC

• 2 other identifiers: SEACAT 2_4_2NHREC
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV Infections; Malaria

Keywords

HIV; Malaria; Pharmacokinetics; Treatment Experienced

Outcome Measures

Primary Outcomes (1)

• Lumefantrine concentration

  day 7

Interventions

Artemether/Lumefantrine DRUG

80mg artemether/480mg lumefantrine Trade name: Coartem Indication: for management of non-severe malaria

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Cape Town: lead
• London School of Hygiene and Tropical Medicine: collaborator

Study Sites (1)

Groote Schuur Hospital, Ward J51, Old Main Building

Cape Town, Western Province, 7925, South Africa

Location

Related Publications (1)

• 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.

  PMID: 26818566 DERIVED

MeSH Terms

Conditions

HIV Infections; Malaria

Interventions

Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Protozoan Infections; Parasitic Diseases; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Karen I Barnes, MBChB MMed(clin pharm)

  University of Cape Town

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: March 25, 2009
• First Posted: March 26, 2009
• Study Start: June 1, 2009
• Primary Completion: February 1, 2010
• Study Completion: February 1, 2010
• Last Updated: June 28, 2010

Record last verified: 2010-06

Locations

ZA (1)