A Phase III Comparative (Double-blind, Double-dummy) Randomised Multicentre Study to Assess the Safety & Efficacy of Oral Pyronaridine Artesunate (180:60 mg) Versus Chloroquine (155 mg) in Children & Adult Patients With Acute Vivax Malaria
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 456
- 试验地点
- 5
- 主要终点
- Crude Cure Rate on Day 14
研究概览
简要总结
The purpose of this study is to compare the efficacy and safety of the fixed combination of pyronaridine artesunate (Pyramax®, PA) (180:60 mg) with that of standard chloroquine therapy in children and adults with acute, uncomplicated Plasmodium vivax malaria.
详细描述
This is a multi-centre, randomised, double-blind, double-dummy, parallel-group, non-inferiority study comparing the efficacy and safety of the fixed combination of pyronaridine/artesunate (ie, PP/AS [PA]) (180:60 mg) with that of standard chloroquine therapy in children and adults with acute uncomplicated P. vivax malaria. The study population will include 456 patients, comprising male and female children (≥20 kg body weight) and adults recruited from study sites in South East Asia and India.
Patients will be randomised in a 1:1 ratio to receive either oral PA (180:60 mg tablets) plus chloroquine-placebo or oral chloroquine (155 mg tablets).plus PA-placebo, once a day for 3 consecutive days (Days 0, 1, and 2). For PA, posology was based on body weight ranges with subjects receiving 1 to 4 tablets depending on their body weight. The dose range covered by this regimen is 7.2:2.4 mg/kg to 13.8:4.6 mg/kg, which has been shown to be effective and safe in Phase I and II studies. The chloroquine daily dose is 10 mg/kg on Days 0 and 1 and 5 mg/kg on Day 2 for children, and 620 mg on Days 0 and 1 and 310 mg on Day 2 for adults.
Patients will be confined to the study facility for ≥4 days (Days 0,1,2 & 3) and ideally 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 crude cure rate on Day 14, which is defined as the absence of P. vivax parasitaemia on Day 14. 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.
For patients who complete the study up to Day 28 and who have normal glucose-6-phosphate dehydrogenase (G-6-PD) activity, a 14-day course of primaquine (15 mg/day for adults and 0.3 mg/kg/day for children) will be administered starting on Day 28 to complete their radical cure. Subjects who are deficient in G-6-PD and who completed the study up to Day 28 will be treated per country policy.
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
- Double (Care Provider, Investigator)
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. vivax mono-infection confirmed by:
- •Fever, as defined by axillary/tympanic temperature ≥37.5°C or oral/rectal temperature ≥38°C, or history of fever in the previous 24 hours (history of fever must be documented) and,
- •Positive microscopy of P. vivax with parasite density ≥250/ mcL of blood (including at least 50% of asexual parasites).
- •Written informed consent, in accordance with local practice, provided by patient and/or parent/guardian/spouse. If the patient is unable to write, witnessed consent is permitted according to local ethical considerations.
- •Ability to swallow oral medication.
- •Ability and willingness to participate based on information given to patient or parent or guardian and access to health facility.
排除标准
- •Presence of a mixed Plasmodium infection.
- •Presence of other clinical condition requiring hospitalization.
- •Presence of significant anaemia, as defined by Hb <8 g/dL.
- •Known history or evidence of clinically significant disorders such as cardiovascular (including arrhythmia, QTc interval ≥450 msec), respiratory (including active tuberculosis), hepatic, renal, gastrointestinal, immunological (including active HIV-AIDS), neurological (including auditory), endocrine, infectious, malignancy, psychiatric or other abnormality (including recent head trauma).
- •Known history of hypersensitivity, allergic or adverse reactions to pyronaridine, chloroquine or artesunate or other artemisinins.
- •Known history of hypersensitivity, allergic or adverse reactions to chloroquine, primaquine and related agents.
- •Known active Hepatitis A IgM (HAV-IgM), Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody (HCV Ab).
- •Known seropositive HIV antibody.
- •Have received any antimalarial treatment in the preceding 2 weeks, as determined by history and, whenever feasible, by screening test.
- •Have received antibacterial with known antimalarial activity in the preceding 2 weeks.
- •Have received any investigational drug within the past 4 weeks.
- •Liver function tests (AST/ALT levels) >2.5 times the upper limit of normal range.
- •Known significant renal impairment as indicated by serum creatinine levels of >1.4 mg/dL.
- •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.
- •Previous participation in the present clinical trial with PA.
研究组 & 干预措施
pyronaridine artesunate
The tablet strength is 180:60 mg oral PA plus chloroquine-placebo. Depending on their body weight, patients receive 1 to 4 tablets once a day, for 3 days. The actual dose-level range covered by this regimen is 7.2: 2.4 mg/kg to 13.8:4.6 mg/kg pyronaridine artesunate.
干预措施: Pyronaridine artesunate (Drug)
chloroquine
The tablet strength is 155 mg oral chloroquine plus PA-placebo.
Patients receive:
For adults: 620 mg (i.e. 4 tablets) on Days 0 and 1 and 310 mg (i.e. 2 tablets) on Day 2. For children: 10 mg/kg on Days 0 and 1 and 5 mg/kg on Day 2.
干预措施: Chloroquine (Drug)
结局指标
主要结局
Crude Cure Rate on Day 14
时间窗: Day 14
Cure rate on Day 14 is defined as the absence of P. vivax parasitaemia on Day 14 irrespective of temperature (axillary, oral, tympanic, rectal) without previously meeting any of the criteria of treatment failure throughout the follow-up period.
次要结局
- Fever Clearance Time(Days 0 to 42)
- Percentage of Subjects With Fever Clearance on Days 1, 2, and 3(Day 1, 2, and 3)
- Crude Cure Rate on Days 21 and 28.(Day 21 and 28)
- Percentage of Subjects With Parasite Clearance on Days 1, 2, and 3(Days 1, 2, and 3)
- Number of Participants With Adverse Events(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 Time(Days 0 to 42)