Drug Interaction Study of Pyronaridine-artesunate & Metoprolol, & Redosing Study of Pyronaridine-artesunate
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      The primary objective of the drug-drug interaction study is to evaluate any drug interaction
      between the CYP2D6 substrate metoprolol and pyronaridine-artesunate in healthy volunteers.

      The primary objective of the pyronaridine-artesunate redosing study is to determine the
      safety of redosing a 3-day regimen of pyronaridine-artesunate following 60 or 90 days in
      healthy volunteers.
    

Detailed description: 
      This was a phase I, open-label, randomised, 2-arm parallel group study in healthy subjects.
      The study population will include 44 healthy subjects (22 per treatment arm), comprising male
      and female adults (18-55 years) of any ethnic origin.

      Subjects will be randomised to either Arm A or Arm B. Arm A will evaluate
      pyronaridine-artesunate interference on metoprolol pharmacokinetics (PK) and the effect of a
      90-day (±7 days) redosing interval on the safety profile of pyronaridine-artesunate. Arm B
      will evaluate the effect of a 60-day (±7 days) redosing interval on the safety profile of
      pyronaridine-artesunate.

      Screening will be performed in the 14-day period prior to the first dose. In Arm A, each
      subject will partake in 3 inpatients periods between: Days -1 to 2, Days 7 to 11, and Days 97
      to 101, with dosing on Days 1, 8 to 10, and 98 to 100. In Arm B, each subject will partake in
      2 inpatient periods: Days -1 to 4 and Days 60 to 64, with dosing on Days 1 to 3 and 61 to 63.
      Subjects will be considered to have completed the study at Day 140 (Arm A) or at Day 103 (Arm
      B).

      Any adverse event ongoing at the time of study completion will be followed until resolution
      unless no further change is expected according to the investigator.
    

Intervention name(s): Metoprolol and pyronaridine-artesunate; pyronaridine-artesunate
Intervention type(s): Drug; Drug
Intervention description(s): On Day 1, subjects will receive a single oral 100 mg dose of metoprolol tartrate. On Day 8 and Day 9, subjects will receive a once daily oral dose of pyronaridine-artesunate as follows:
55 - < 65 kg: 3 tablets (180:60 mg pyronaridine:artesunate)
≥ 65 kg: 4 tablets (180:60 mg pyronaridine:artesunate)
On Day 10, a 100 mg dose of metoprolol will be coadministered with pyronaridine-artesunate at the above dose.
On Days 98 - 100, subjects will receive pyronaridine-artesunate once daily at the same dose described above. Followed by a 40 day follow-up period.; On Days 1 to 3, subjects will receive 3 days of pyronaridine-artesunate as follows:
55 - < 65 kg: 3 tablets (180:60 mg pyronaridine:artesunate)
≥ 65 kg: 4 tablets (180:60 mg pyronaridine:artesunate)
On Days 61 to 63, subjects will be redosed with a 3 day course of pyronaridine-artesunate at the above dose.
Followed by a 40 day follow-up period.
Other intervention name(s): Pyramax
Intervention MeSH terms: Artesunate; Pyronaridine; Pyronaridine tetraphosphate, artesunate drug combination; Metoprolol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: pyronaridine artesunate (Pyramax); artemisinin based combination therapy (ACT); metoprolol; drug-drug interaction study; redosing study