Interaction Between Etravirine or Darunavir/Ritonavir and Artemether / Lumefantrine
Condition: HIV
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to investigate the pharmacokinetic interaction between
      etravirine and artemether/lumefantrine and darunavir/ritonavir and artemether/lumefantrine in
      healthy Human Immunodeficiency Virus- (HIV-)negative patients. 'Pharmacokinetic interaction'
      means that one medication can influence the absorption and elimination from the body of the
      other medication.
    

Detailed description: 
      This is a Phase I, partially randomized, open-label, single-center, two-way, two-period
      cross-over study to investigate the pharmacokinetic interaction between etravirine (ETR) or
      darunavir/ritonavir (DRV/rtv) and the antimalarial drugs artemether/lumefantrine at
      steady-state in healthy human immunodeficiency virus (HIV)-negative patients. The study
      population will consist of 32 healthy patients, equally divided over 2 panels. Patients in
      Panel 1 will be treated with ETR and artemether/lumefantrine; patients in Panel 2 will be
      treated with DRV/rtv and artemether/lumefantrine. Treatment A will consist of 3 days of
      treatment with artemether/lumefantrine. Treatment B will consist of 200 mg ETR twice daily
      (b.i.d.) (Panel 1) or 600/100 mg DRV/rtv b.i.d. (Panel 2) from Day 1 to Day 21 with a single
      dose of ETR (Panel 1) or DRV/rtv (Panel 2) in the morning on Day 22. From Day 8, 3 days of
      treatment with artemether/lumefantrine. In a first stage of treatment in Panel 2, only 4
      patients will be allowed to start Treatment B. Based on the ECG results of the first 4
      patients with evaluable ECG data after assessments on Day 11 (66 hours after the combined
      intake of DRV/rtv and artemether/lumefantrine), the Sponsor will decide whether additional
      patients can be allowed to start Treatment B. There will be a washout period of at least 4
      weeks between Treatments A and B. Half of the patients of Panel 1 (8 patients) and Panel 2 (8
      patients) will be randomized to sequence AB and half will be randomized to sequence BA.
      Randomization in Panel 2 will occur in two steps. In Step 1, 4 patients will be allocated to
      sequence BA and evaluated for QTc prolongation. Based on the outcome of their ECG results,
      the Sponsor will decide whether the remainder of patients will be randomized in Step 2, i.e.
      4 patients to BA and 8 patients to AB (1:2 randomization). Serial pharmacokinetic assessments
      will be determined for Panels 1 and 2 in Treatments A and B for artemether and its metabolite
      dihydroartemisinin (DHA) after the first intake of artemether/lumefantrine over 8 hours and
      after the last intake of artemether/lumefantrine over 72 hours (3 days), and for lumefantrine
      after the last intake of artemether/lumefantrine over 264 hours (11 days). Serial
      pharmacokinetic assessments will be determined for ETR (Panel 1) or DRV and rtv (Panel 2)
      over the 12-hour dosing interval on Day 8 (after the morning intake) and Day 11 (after the
      last dose of artemether/lumefantrine) of Treatment B. All ETR, DRV/rtv and
      artemether/lumefantrine treatments will be administered under fed conditions and will be
      taken within 10 minutes after completion of a meal. Safety and tolerability evaluations will
      be recorded on an ongoing basis.
    

Intervention name(s): Etravirine; Darunavir/ritonavir; artemether/lumefantrine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 200 mg ETR b.i.d. from Day 1 to Day 21 with a single 200 mg dose of ETR in the morning on Day 22; DRV/rtv 600/100 mg b.i.d. from Day 1 to Day 21 with a single dose of DRV/rtv in the morning on Day 22; 3 days of treatment with artemether/lumefantrine 80/480 mg (6 doses of 4 tablets [20/120 mg] at 0, 8, 24, 36, 48, and 60 hours)
Intervention MeSH terms: Ritonavir; Darunavir; Lumefantrine; Artemether; Etravirine; Artemether, Lumefantrine Drug Combination
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Health Services Research
Keywords: HIV; pharmacokinetic interaction; healthy HIV-negative person