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

This study has been completed.
Sponsor:
Collaborator:
London School of Hygiene and Tropical Medicine
Information provided by:
University of Cape Town
ClinicalTrials.gov Identifier:
NCT00869700
First received: March 25, 2009
Last updated: June 25, 2010
Last verified: June 2010
  Purpose

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.


Condition Intervention Phase
HIV Infections
Malaria
Drug: Artemether/Lumefantrine
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacokinetic Interaction Between the Antimalarial Combination Artemether/Lumefantrine and Combination Antiretroviral Therapy Including Lopinavir/Ritonavir in HIV-infected Adults

Resource links provided by NLM:


Further study details as provided by University of Cape Town:

Primary Outcome Measures:
  • Lumefantrine concentration [ Time Frame: day 7 ] [ Designated as safety issue: Yes ]

Enrollment: 18
Study Start Date: June 2009
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Artemether/Lumefantrine

    80mg artemether/480mg lumefantrine

    Trade name: Coartem

    Indication: for management of non-severe malaria

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00869700

Locations
South Africa
Groote Schuur Hospital, Ward J51, Old Main Building
Cape Town, Western Province, South Africa, 7925
Sponsors and Collaborators
University of Cape Town
London School of Hygiene and Tropical Medicine
Investigators
Principal Investigator: Karen I Barnes, MBChB MMed(clin pharm) University of Cape Town
  More Information

No publications provided

Responsible Party: Professor Karen I Barnes, University of Cape Town
ClinicalTrials.gov Identifier: NCT00869700     History of Changes
Other Study ID Numbers: SEACAT 2_4_2, NHREC
Study First Received: March 25, 2009
Last Updated: June 25, 2010
Health Authority: South Africa: Medicines Control Council
South Africa: National Health Research Ethics Council

Keywords provided by University of Cape Town:
HIV
Malaria
Pharmacokinetics
Treatment Experienced

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Malaria
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Protozoan Infections
Parasitic Diseases
Antimalarials
Artemether
Artemisinins
Lumefantrine
Artemether-lumefantrine combination
Ritonavir
Lopinavir
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Coccidiostats
Schistosomicides
Antiplatyhelmintic Agents

ClinicalTrials.gov processed this record on August 25, 2014