Pharmacokinetic Study of Primaquine and Pyronaridine-Artesunate in Healthy Subjects
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      The observed changes of P. falciparum sensitivity to artemisinin lead to the intensification
      of early detection as well as treatment monitoring in malaria infection. It is widely
      accepted that the development of resistance can be delayed by the use of combination therapy,
      especially combinations that include artemisinin derivatives (acts). As the resistance
      problem is considered extremely serious; as a consequence, who has recommended that all
      monotherapy for malaria should be stopped.

      Current WHO guidelines recommend that the drug combination regimens using ACT with effective
      partner medicines should be used to decrease the risk of development or spreading of
      artemisinin resistance.
    

Detailed description: 
      Current WHO guidelines recommend that the drug combination regimens using ACT with effective
      partner medicines should be used to decrease the risk of development or spreading of
      artemisinin resistance.

      Pyronaridine (PP) and artesunate (AS) are antimalarial agents with a history of clinical use
      both separately and in combination with other drugs. Each drug has powerful
      anti-schizonticidal actions. The action of artesunate is a rapid knock-down of the parasites,
      after which the drug is rapidly cleared as it has a short systemic half-life. Pyronaridine is
      also effective in the short-term but has an intermediate blood half-life thus providing a
      sustained schizonticidal effect. The aim of the fixed dose combination of pyronaridine and
      artesunate (PA or PYRAMAX®) in the treatment of uncomplicated acute malaria is to provide a
      rapid reduction in parasitemia with a short-term regimen, thereby improving compliance and
      reducing the risk of recrudescence through the slower elimination of pyronaridine. Doses have
      been selected to be in line with current prescribing practice for these agents when used as
      mono-therapy.

      Primaquine (PQ) is an effective gametocytocide for P. falciparum transmission prevention and
      as tissue killing for the radical cure in P. vivax and P. ovale infection. It will be given
      only in the presence of other antimalarials, so it is necessary to study the drug
      interactions between primaquine, pyronaridine and artesunate. It is inevitable that in the
      near future, pyronaridine-artesunate (PA) and primaquine (PQ) combination treatment will
      become necessary. These drugs are metabolized by cytochrome P450 enzymes which potentially
      causes pharmacokinetic alteration and clinically significant drug-drug interactions that can
      lead to unanticipated adverse reactions or therapeutic failures because of the suboptimal
      exposure of the parasite.

      This study is planned to evaluate potential pharmacokinetic interaction of orally
      administered primaquine and pyronaridine-artesunate (PYRAMAX®) in healthy adult subjects. The
      results of these interaction studies are important in order to provide clinical guidance for
      the optimum combination primaquine and pyronaridine-artesunate (PYRAMAX®) treatment regimens
      in malaria infections.
    

Intervention name(s): Primaquine and Pyronaridine-artesunate; Primaquine and Pyronaridine-Artesunate
Intervention type(s): Drug; Drug
Intervention description(s): Subject will receive primaquine (PQ) then receive pyronaridine-artesunate (PA)after 1 week washout period and receive PQ together with PA for the third regimen after 8 weeks washout period
Primaquine:
- Dosage: 2 tablets
and
Pyronaridine-Artesunate:
- Dosage: 3 tablets; Subject will receive primaquine (PQ) then receive PQ together dihydroartemisinin-piperaquine (DHA-PQP) after 1 week washout period and receive DHA-PQP for the third regimen after 8 weeks washout period.
Primaquine:
- Dosage: 2 tablets
and
Pyronaridine-Artesunate:
- Dosage: 3 tablets
Other intervention name(s): Pyramax; Pyramax
Intervention MeSH terms: Artesunate; Primaquine; Pyronaridine; Pyronaridine tetraphosphate, artesunate drug combination
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Primaquine; Pyronaridine-artesunate