A Phase III Comparative, Open-label, Randomised, Multi-centre Study to Assess the Efficacy of Pyronaridine Artesunate (180:60mg) Versus Mefloquine (250mg) Plus Artesunate (100mg) in Children & Adult Patients With Acute Falciparum Malaria
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,271
- 试验地点
- 9
- 主要终点
- Percentage of Subjects With PCR-corrected Adequate Clinical and Parasitological Response (ACPR) on Day 28
研究概览
简要总结
The primary objective of this phase III clinical study is to compare the efficacy and safety of the fixed combination of pyronaridine artesunate (Pyramax®, PA) with that of the combination of mefloquine plus artesunate (MQ + AS) in children and adults with uncomplicated P falciparum malaria in South East Asia, India and Africa.
详细描述
This is a multi-centre, comparative, randomised, open-label, parallel-group, non-inferiority study comparing the efficacy and safety of a fixed combination of PA to a loose combination of MQ + AS for patients with acute, symptomatic, uncomplicated P. falciparum malaria. The study population will include 1271 patients, comprising male and female children (≥20 kg body weight) and adults, recruited from study sites in South East Asia, India and Africa. Patients will be randomised in a 2:1 ratio to receive either oral PA (180:60mg tablets) or MQ (250mg tablets) plus AS (100mg tablets) once a day for 3 consecutive days (Days 0, 1, and 2). The study drug will be administered by a Third-Party Investigator unblinded to the study treatment, while the Investigator remains blinded.
Patients will be confined to the 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.
The primary efficacy end point for the study is the proportion of subjects with PCR-corrected adequate clinical and parasitological response (ACPR) on Day 28 (defined as the absence of parasitaemia without the subject's meeting any of the criteria of early treatment failure, late clinical failure, or late parasitological failure). 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
- None
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 ages 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 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, mefloquine or artesunate or other artemisinins.
- •Use of any other antimalarial agent within 2 weeks prior to start of the study as evidenced by 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.
- •Presence of significant renal or hepatic impairment.
- •Receipt of an investigational drug within the past 4 weeks.
- •Known active Hepatitis A IgM, Hepatitis B surface antigen or Hepatitis C antibody.
- •Known seropositive HIV antibody.
- •Previous participation in any clinical study with PA.
研究组 & 干预措施
Pyronaridine - artesunate
Oral pyronaridine artesunate (180:60mg tablets) once a day for 3 consecutive days (Day 0, 1, and 2). Posology based on body weight ranges.
干预措施: Pyronaridine - artesunate (Drug)
Mefloquine plus artesunate
Mefloquine (250mg tablets) plus artesunate (100mg tablets) once a day for 3 consecutive days (Day 0, 1, and 2). Posology based on body weight ranges.
干预措施: Mefloquine plus artesunate (Drug)
结局指标
主要结局
Percentage of Subjects With PCR-corrected Adequate Clinical and Parasitological Response (ACPR) 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 ACPR on Day 14(Day 14)
- Fever Clearance at Day 1, 2 and 3(Days 1, 2 and 3)
- Crude ACPR on Days 14 and 28(Days 14 and 28)
- Parasite Clearance Time(Thick blood films were examined every 8 hours until ≥72 hours or until 2 consecutive negative readings occurred 7 to 25 hours apart, and on Days 3, 7, 14, 21, 28, 35, and 42 (or any other day if the subject returned).)
- Fever Clearance Time(Every 8 hours over ≥72 hours following first study drug administration or temperature normalisation for ≥2 readings between 7 and 25 hours apart, then at each visit.)
- 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)
- Parasite Clearance at Day 1, 2 and 3(Days 1, 2 and 3)