Phase IIa Exploratory, Open Label, Single/Multiple Dose Testing Clinical Study to Assess the Preliminary Efficacy, Tolerability and PK of OZ439 in Adult Patients With Acute, Uncomplicated P. Falciparum or Vivax Malaria Mono-infection
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 82
- 主要终点
- Derived Parasite Reduction Rate at 24 Hours (PPR24)
研究概览
简要总结
A Phase IIa Exploratory, Open label, Single Dose Regimen, Multiple Dose Testing Clinical Study to Assess the Preliminary Efficacy, Tolerability and Pharmacokinetics of OZ439 in adult patients with acute, uncomplicated Plasmodium falciparum or vivax malaria mono-infection.
详细描述
This exploratory Phase IIa study aims to investigate the preliminary efficacy in terms of parasite reduction and clearance in malaria patients, and the tolerability of OZ439 administered as single dose regimen at 3 different doses in parallel cohorts of patients with either acute uncomplicated Plasmodium falciparum or Plasmodium vivax malaria mono-infection (10 patients per plasmodium species per dose level).
Treatment with OZ439 will be given as a single dose on Day 0, starting in the first cohort at a dose of 800 mg. Established antimalarial therapy will be given at the latest at 36 hours post dosing.
The primary endpoint will be the derived parasite reduction rate (PRR) at 24 hours after study drug administration.
A review of each individual study cohort (dose/species) will be conducted with the Principal Investigator and the Sponsor and a decision will be reached on whether the dose for the next cohort should increase or decrease (within 200mg-1600mg range). This decision will be based on parasite reduction rate over the first 24 hours following administration of OZ439, tolerability and exposure.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients between the age of 18 and 60 years, inclusive
- •Body weight between 40 kg and 90 kg inclusive
- •Presence of mono-infection of P. falciparum or P. vivax confirmed by:
- •Fever, as defined by axillary temperature ≥ 37.5°C or oral/rectal/tympanic temperature ≥ 38°C, or history of fever in the previous 24 hours (history of fever must be documented) and,
- •Microscopically confirmed parasite infection, 5,000 to 50,000 asexual parasite count/µl of blood
- •Written informed consent, in accordance with local practice, provided by patient. 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 and access the health facility
- •Agree to minimum of 4 days hospitalisation for drug administration and pharmacokinetic sampling
排除标准
- •Patients with signs and symptoms of severe/complicated malaria requiring parenteral treatment according to the World Health Organisation Criteria 2010 (Attachment 2)
- •Mixed Plasmodium infection
- •Severe vomiting, defined as more than three times in the 24 hours prior to inclusion in the study or inability to tolerate oral treatment, or severe diarrhoea defined as 3 or more watery stools per day
- •Presence of other serious or chronic clinical condition requiring hospitalisation.
- •Severe malnutrition (defined as the weight-for-height being below -3 standard deviation or less than 70% of median of the NCHS/WHO normalised reference values).
- •Known history or evidence of clinically significant disorders such as cardiovascular (including arrhythmia, QTc interval greater than or equal to 450 msec), respiratory (including active tuberculosis), history of jaundice, hepatic, renal, gastrointestinal, immunological (including active HIV-AIDS), neurological (including auditory), endocrine, infectious, malignancy, psychiatric, history of convulsions or other abnormality (including head trauma).
- •Known history of hypersensitivity, allergic or adverse reactions to artemisinin containing compounds or mefloquine or drug in the national guidelines for P. vivax.
- •Known active Hepatitis A IgM (HAV-IgM), Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody (HCV Ab).
- •Have received any antimalarial treatment in the preceding 14 days, as determined by history and screening test.
- •Have received antibacterial with known antimalarial activity in the preceding 14 days.
- •Have received an investigational drug within the past 4 weeks.
- •Liver function tests (ASAT/ALAT levels) more than 2 x ULN
- •Hb level below 10 g/dL.
- •Bilirubin levels greater than 40 µmol/L.
- •Serum creatinine levels more than 2 times the upper limit of normal range in absence of dehydration. In case of important dehydration the creatinine should be lower than 2X ULN after oral/parenteral rehydration.
- •Female patients must be neither pregnant (as demonstrated by a negative serum pregnancy test) nor lactating, and must be willing to take measures not to become pregnant during the study period and safety follow-up period
研究组 & 干预措施
800 mg OZ439 po single dose
800 mg OZ439 po single dose
干预措施: OZ439 (Drug)
400 mg OZ439 p.o. single dose
400 mg OZ439 p.o. single dose
干预措施: OZ439 (Drug)
200mg OZ439 p.o. single dose
200mg OZ439 p.o. single dose
干预措施: OZ439 (Drug)
1200 mg OZ439 po single dose
1200 mg OZ439 po single dose
干预措施: OZ439 (Drug)
结局指标
主要结局
Derived Parasite Reduction Rate at 24 Hours (PPR24)
时间窗: 24 hours after study drug administration
PRR24 is the log10 change in parasitemia over 24 hours estimated from a regression model fit separately for each patient. The relationship between parasite counts and time was analyzed by fitting a variable lag phase, then a linear decline to the natural log of parasite count versus time relationship. The slope of this log linear relationship is the primary end-point. The time points chosen for the regression are those that yield the highest degree of significance when assessing the regression when the number of time points are greater than or equal to 3. No extrapolation was performed.
次要结局
未报告次要终点