A Phase III Comparative (Double-blind, Double-dummy) Randomised, Multi-centre Study to Assess the Efficacy of Pyronaridine Artesunate (180:60mg) Versus Coartem® (Artemether Lumefantrine) in Children & Adult Patients With Falciparum Malaria
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,272
- 试验地点
- 10
- 主要终点
- PCR-Corrected Adequate Clinical and Parasitological Response (ACPR) Rate on Day 28
研究概览
简要总结
The primary objective of this phase III study is to compare the efficacy and safety of the fixed combination of pyronaridine artesunate (Pyramax®, PA) with that of Coartem® (artemether lumefantrine, AL) in children and adults with uncomplicated P falciparum malaria in Africa and South East Asia.
详细描述
This is a multi-centre, comparative, randomised, (double-blind, double-dummy), parallel-group, non-inferiority study comparing the efficacy and safety of the fixed combination of PA with that of AL in the treatment of acute, uncomplicated P. falciparum malaria. The study population will include 1269 patients, comprising male and female children (≥20 kg body weight) and adults recruited from study sites in Africa and South East Asia.
Patients will be randomised to receive either oral PA (180:60mg tablets) once a day plus AL-placebo (twice a day) for 3 consecutive days (Days 0, 1, and 2) or AL twice a day plus PA-placebo (once a day) for 3 consecutive days (Days 0, 1, and 2) in a 2:1 ratio. The dose range of PA covered by this regimen is 7.2:2.4 mg/kg to 13.8:4.6 mg/kg, respectively, which has been shown to be effective and safe in Phase I and II studies. Posology will be based on body weight ranges for both the PA and AL regimens.
Patients will be confined to the study facility for ≥4 days (Days 0, 1, 2, and 3) and remain near the study site for ≥7 days, or once fever and parasite clearance has been confirmed for ≥24 hours - whichever occurs later.
The primary efficacy end point for the study is the proportion of patients with PCR-corrected adequate clinical and parasitological response (ACPR) on Day 28. Scheduled follow-up visits will continue until completion of the study at Day 42. In the case of adverse events reported and unresolved at Day 42, patients will be followed up for a further 30 days, or until resolution of the event.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 3 Years 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients between the age of 3 and 60 years, inclusive.
- •Body weight between 20 kg and 90 kg with no clinical evidence of severe malnutrition.
- •Presence of acute uncomplicated P. falciparum mono-infection confirmed by:
- •Fever, as defined by axillary/tympanic temperature ≥ 37.5°C or oral/rectal temperature ≥ 38°C, or documented history of fever in the previous 24 hours and,
- •Positive microscopy of P. falciparum with parasite density between 1,000 and 100,000 asexual parasite count/μl of blood.
- •Written informed consent, in accordance with local practice, provided by patient and/or parent/guardian/spouse.
- •Ability to swallow oral medication.
排除标准
- •Patients with signs and symptoms of severe/complicated malaria requiring parenteral treatment according to the World Health Organization Criteria
- •Mixed Plasmodium infection.
- •Severe vomiting or severe diarrhoea.
- •Known history or evidence of clinically significant disorders.
- •Presence of significant anaemia, as defined by Hb <8 g/dL.
- •Presence of febrile conditions caused by diseases other than malaria.
- •Known history of hypersensitivity, allergic or adverse reactions to pyronaridine, lumefantrine or artesunate or other artemisinins.
- •Patients with known disturbances of electrolytes balance, e.g., hypokalaemia or hypomagnesaemia.
- •Use of any other antimalarial agent within 2 weeks prior to start of the study as evidenced by a positive urine test.
- •Female patients of child-bearing potential must be neither pregnant (as demonstrated by a negative pregnancy test) nor lactating, and must be willing to take measures to not become pregnant during the study period.
- •Patients taking any drug which is metabolised by the cytochrome enzyme CYP2D6 (flecainide, metoprol, imipramine, amitriptyline, clomipramine).
- •Received an investigational drug within the past 4 weeks.
- •Known active Hepatitis A IgM (HAV-IgM), Hepatitis B surface antigen. (HBsAg) or Hepatitis C antibody (HCV Ab).
- •Known seropositive HIV antibody.
- •Liver function tests [ASAT/ALAT levels] >2.5 times the upper limit of normal range.
- •Known significant renal impairment as indicated by serum creatinine >1.4 mg/dL.
研究组 & 干预措施
PA group
Pyronaridine artesunate (PA)
干预措施: Pyronaridine artesunate (Drug)
AL group
Arthemether lumefantrine (AL)
干预措施: Coartem® (artemether lumefantrine) (Drug)
结局指标
主要结局
PCR-Corrected Adequate Clinical and Parasitological Response (ACPR) Rate on Day 28
时间窗: Day 28
Percentage of subjects with PCR-corrected adequate clinical and parasitological response (ACPR) on Day 28, defined as absence of parasitaemia on Day 28 without the subject's meeting any of the criteria of early treatment failure, late clinical failure, or late parasitological failure.
次要结局
- PCR-corrected Adequate Clinical and Parasitological Response (ACPR) on Day 14(Day 14)
- Percentage of Patients With Fever Clearance at Day 1, 2 and 3(Days 1, 2, 3)
- Adverse Events and Clinically Significant Laboratory Results(Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study or resolution of the event, whichever was earlier)
- Crude ACPR (Non-PCR Corrected ACPR) on Day 14 and Day 28(Day 14 and 28)
- Fever Clearance Time(Day 0 and every 8 hours over ≥72 hours following first study drug administration or temperature normalization for ≥2 readings between 7 and 25 hours apart, then at each visit and as clinically indicated)
- Parasite Clearance Time(Days 0, 3, 7, 14, 21, 28, 35, and 42 (or on any other day if the subject spontaneously returned))
- Proportion of Patients With Parasite Clearance at Day 1, 2 and 3(Days 1, 2, 3)