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

Summary: 
      The study will assess the effect of multiple doses of itraconazole, a strong CYP3A4/5
      inhibitor, on the PK of ganaplacide and lumefantrine in healthy participants. This study will
      provide data that is relevant for advice regarding possible concomitant medications that are
      inhibitors of CYP3A4/5 in future clinical studies with ganaplacide and lumefantrine and for
      potential future labeling considerations
    

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 itraconazole on the single dose PK of
      ganaplacide and lumefantrine in healthy participants.

      The study will consist of a screening period of up to 28 days, 2 Baseline evaluations (on Day
      -1 of each treatment period), and 2 treatment periods which are separated by a washout
      period. Participants who meet the eligibility criteria at Screening will be admitted to the
      study site for First Baseline evaluations on Day -1 of Period 1. Baseline safety assessments
      will be performed prior to first dosing of study treatment in each period.

      Participants enrolled will receive a single oral dose of ganaplacide and lumefantrine
      combination on Day 1 of Period 1. In Period 2, participants will receive itraconazole once
      daily (q.d.) on Days 1 to 18 and a single dose of ganaplacide and lumefantrine combination on
      Day 5, approximately 2 hours after the itraconazole dose. There will be 336 hours of
      sequential blood sampling for PK assessment starting after ganaplacide and lumefantrine
      dosing in each treatment period. Between the 2 treatment periods, there will be an additional
      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.

      Each dose of ganaplacide and lumefantrine combination will be administered after at least 10
      hours of overnight fasting and will be followed by at least 4 hours of fasting post dose. In
      Period 2, itraconazole will be administered after at least 10 hours of overnight fasting and
      followed by at least 1 hour of fasting post dose (except on Day 5 when ganaplacide and
      lumefantrine will be administered approximately 2 hours after itraconazole dosing and
      participants will continue fasting for at least 4 hours post ganaplacide and lumefantrine
      dosing).

      Safety assessments (including physical examinations, electrocardiograms (ECGs), vital signs,
      clinical laboratory evaluations [hematology, chemistry, coagulation, and urinalysis], and
      adverse event [AE] and serious adverse event [SAE] monitoring) will be performed during the
      study.

      The Study Completion evaluations will occur on Day 19 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. In the case of early termination, Study Completion evaluations will
      be conducted prior to discharge from the study.
    

Intervention name(s): Ganaplacide; Lumefantrine; Itraconazole
Intervention type(s): Drug; Combination Product; Drug
Intervention description(s): Treatment A/Period 1: 400 mg (4 x 100 mg tablets) at Hour 0 on Day 1 Treatment B/Period 2: 400 mg (4 x 100 mg tablets) at Hour 0, approximately 2 hours after itraconazole dosing, on Day 5.; Treatment A/Period 1: 480 mg (2 x 240 mg sachets) at Hour 0 on Day 1 Treatment B/Period 2: 480 mg (2 x 240 mg sachets) at Hour 0, approximately 2 hours after itraconazole dosing, on Day 5.; 200 mg (20 mL of 10 mg/mL oral solution) q.d. on Days 1 to 18
Other intervention name(s): KAF156; LUM566
Intervention MeSH terms: Itraconazole; Lumefantrine
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Drug-drug interaction; DDI; ganaplacide; lumefantrine; itraconazole; Cytochrome P450; CYP; Pharmacokinetic; PK; safety and tolerability; healthy participants