Safety Study on the Effect of Eurartesim™ on QT/QTc Interval Compared to Riamet in Healthy Volunteers
Condition: Malaria, Falciparum
MeSH terms: Malaria; Malaria, Falciparum
Study type: Interventional
Phase: Phase 1

Summary: 
      The aim of such a study is to evaluate the impact of a therapeutic dose of Eurartesim™
      compared to Riamet®, after multiple dose administration for 3 days in healthy male and female
      subjects on electrocardiographic parameters.
    

Detailed description: 
      The fight against malaria, which the WHO reactivated in 1999 with its Roll Back Malaria
      programme, emphasizes early curative treatment of malaria, particularly in children, in order
      to decrease mortality and morbidity. Recent estimates confirm a disturbing persistence of
      endemic malaria with around 515 million cases and 1.0 million deaths per year.The available
      range of standard antimalarial drugs is narrow. There are only four classes of compounds,
      probably with different mechanisms of action: 4-aminoquinolines, amino-alcohols, artemisinin
      derivatives (isolated from a plant, Artemisia annua), and antifolates and drugs related to
      them.

      From a public health perspective, drug resistance is a critical factor that undermines
      malaria control.Plasmodium falciparum and resistance to chloroquine and
      sulfadoxine/pyrimethamine is widespread. At present, natural quinine is still effective
      against P. falciparum everywhere in the world except partially in South-east Asia and South
      America, where decreased susceptibility is reported. Only the artemisinin derivatives, used
      for 15 years in Asia and, more recently in Africa, have not generated clinical resistance.
      Overcoming or reducing resistance requires the adoption of several strategies; central to
      these is the use of effective chemotherapy for those who need it. In addition, to new
      molecules, we need to develop and implement strategies to protect drugs against resistance.
      Resistance to single-drug therapies will inevitably occur. Drug combinations, which have been
      standard practice for viral and bacterial diseases, are now being adopted for malaria as
      well. The artemisinin derivatives in combination with standard antimalarials are now being
      promoted as the best therapeutic option for treating drug-resistant malaria and retarding the
      development of resistance.

      The aim of the present study is to investigate the effect of this new Artemisinin Combination
      Therapy (ACT) formulation on electrocardiographic parameters. In the literature no relevant
      QT prolongation associated with Piperaquine treatment has been reported in not-company
      sponsored trials but no specific TQT trials have been published. On the contrary it has been
      reported that quinine, quinidine and halofantrine induced a QT prolongation (from slight to
      severe).
    

Intervention name(s): Eurartesim™; Riamet®; Placebo and finally Moxifloxacin; Eurartesim™; Eurartesim™; Placebo and finally Moxifloxacin
Intervention type(s): Drug; Drug; Other; Drug; Drug; Other
Intervention description(s): 3 or 4 tablets of Eurartesim™ (40mg Dihydroartemisinin and 320 mg Piperaquine phosphate), depending of body weight (3 tablets for subjects weighting less than 75 kg, 4 tablets for subjects weighting 75 kg or more), once daily from Day 1 to Day 3; 4 tablets of Riamet® (20mg artemether/120mg lumefantrine) on Day -1 evening, 4 tablets of Riamet® bid (with an interval of 12 ± 0.5 h), in the morning and in the evening of Day 1 and Day 2, 4 tablets of Riamet® in the morning of Day 3.; 3 or 4 tablets of Eurartesim™ placebo, depending of body weight, (3 tablets for subjects weighting less than 75 kg, 4 tablets for subjects weighting 75 kg or more), once daily from Day1 to Day 3.
1 tablet of Izilox® (400 mg moxifloxacin) on Day 4 morning.; 3 or 4 tablets of Eurartesim™ (40mg Dihydroartemisinin and 320 mg Piperaquine phosphate), depending of body weight (3 tablets for subjects weighting less than 75 kg, 4 tablets for subjects weighting 75 kg or more), once daily from Day 1 to Day 3.; 3 or 4 tablets of Eurartesim™ (40mg Dihydroartemisinin and 320 mg Piperaquine phosphate), depending of body weight (3 tablets for subjects weighting less than 75 kg, 4 tablets for subjects weighting 75 kg or more), once daily from Day 1 to Day 3.; 3 or 4 tablets of Eurartesim™ placebo, depending of body weight, (3 tablets for subjects weighting less than 75 kg, 4 tablets for subjects weighting 75 kg or more), once daily from Day1 to Day 3.
1 tablet of Izilox® (400 mg moxifloxacin)on Day 4 morning.
Other intervention name(s): Dihydroartemisinin and Piperaquine combination therapy; artemether and lumefantrine combination therapy; moxifloxacin; Dihydroartemisinin and Piperaquine combination therapy; Dihydroartemisinin and Piperaquine combination therapy; moxifloxacin
Intervention MeSH terms: Moxifloxacin; Lumefantrine; Artemether; Piperaquine; Artenimol; Artemisinins; Artemether, Lumefantrine Drug Combination; Norgestimate, ethinyl estradiol drug combination
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: P. falciparum Malaria, Eurartesim, ACT