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

HIV Infections Clinical Trial

— SEACAT 2_4_2  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00869700
• Other study ID #: SEACAT 2_4_2
• Secondary ID: NHREC
• Status: Completed
• Phase: Phase 4
• First received: March 25, 2009
• Last updated: June 25, 2010
• Start date: June 2009
• Est. completion date: February 2010

Study information

• Verified date: June 2010
• Source: University of Cape Town
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Africa: Medicines Control CouncilSouth Africa: National Health Research Ethics Council
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: February 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections
• Malaria

Intervention

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

Locations

Country	Name	City	State
South Africa	Groote Schuur Hospital, Ward J51, Old Main Building	Cape Town	Western Province

Sponsors (2)

Lead Sponsor	Collaborator
University of Cape Town	London School of Hygiene and Tropical Medicine

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Lumefantrine concentration		day 7	Yes