Drug-drug Interaction Study of Ganaplacide and Lumefantrine With Efavirenz
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      This study assessed the effect of multiple doses of a moderate inducer of cytochrome P450
      (CYP) 3A4 (efavirenz) on the pharmacokinetics (PK) of ganaplacide and lumefantrine
      combination. Results from this study will provide guidance on prescribing ganaplacide and
      lumefantrine combination when co-administered with moderate inducers of CYP3A4.
    

Detailed description: 
      This is an open-label, fixed-sequence, 2-period, crossover, Drug-drug interaction (DDI)
      study, to evaluate the effect of multiple doses of efavirenz on the single-dose PK of
      ganaplacide and lumefantrine in healthy participants. The study consisted of a screening
      period of up to 28 days, 2 Baseline evaluations (on Day 1 of each treatment period), and 2
      treatment periods which were separated by a washout period.

      Participants who meet the eligibility criteria at Screening were admitted to the study site
      for First Baseline evaluations on Day -1 of Period 1. Baseline safety assessments were
      performed prior to first dosing of study treatment in each period. The participants were
      domiciled from the First Baseline visit until the end of the PK sampling in Period 1 and were
      released from the site. Participants returned to the site for the Second Baseline visit and
      were domiciled until the Study Completion visit in Period 2.

      Participants enrolled received a single oral dose of ganaplacide and lumefantrine combination
      under fasting conditions on Day 1 of Period 1. In Period 2, participants received an oral
      dose of efavirenz q.d. under fasting conditions in the evening on Days 1 through 24 and a
      single dose of ganaplacide and lumefantrine combination under fasting conditions on the
      morning of Day 11. Between the two treatment periods, there was a washout period of at least
      14 days, beginning from the last PK sample collection in Period 1 and continuing until the
      first dose of study treatment in Period 2.

      Safety assessments (including physical examinations, ECGs, vital signs, clinical laboratory
      evaluations, C-SSRS, and AE and SAE monitoring) were performed during the study. The Study
      Completion evaluations occurred on Day 25 of Period 2, followed by a post-study safety
      contact (e.g. follow-up telephone call, email) approximately 30 days after the last dose of
      study treatment. Total duration of study was approximately 55 days from the First Baseline
      visit to the Study Completion visit.
    

Intervention name(s): Ganaplacide; Lumefantrine; Efavirenz
Intervention type(s): Drug; Combination Product; Drug
Intervention description(s): Period 1: 400 mg (4 x 100 mg tablets) for oral administration Period 2: 400 mg (4 x 100 mg tablets) for oral administration; Period 1: 480 mg (2 x 240 mg sachets) for oral administration Period 2: 480 mg (2 x 240 mg sachets) for oral administration; Period 2: 600 mg (1 x 600 mg tablet) for oral administration once daily (q.d.)
Other intervention name(s): KAF156; LUM566
Intervention MeSH terms: Efavirenz; Lumefantrine
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Drug-drug interaction; DDI; ganaplacide; lumefantrine; efavirenz; Pharmacokinetic; PK; safety and tolerability; healthy participants