Defining the effectiveness of Piperaquine in early Plasmodium falciparum malaria infection in healthy volunteers.
- Conditions
- MalariaInfection - Studies of infection and infectious agents
- Registration Number
- ACTRN12613000565741
- Lead Sponsor
- Queensland Institute of Medical Research
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 24
1. Adults (males or non pregnant females), with no history of malaria, aged between 18 and 45 years who do not live alone (from Day 1 until at least the end of the antimalarial drug treatment).
2. A BMI within the range 18–30 kg/m2 and must weigh more than 50kg in adults in which the proposed dose has already been used.
3. Be contactable and available for the duration of the trial and be available up to 2 weeks following end of study visit. (maximum of 8 weeks).
4. Be non-smokers for at least three months prior to screening. Note: Tobacco use” includes smoking and the use of snuff and chewing tobacco, and other nicotine or nicotine containing products and in good health, as assessed during pre-study medical examination and by review of screening results.
5. Female volunteers of childbearing potential, should be surgically sterile or using an insertable, injectable, transdermal, or combination oral contraceptive approved by the US FDA or TGA combined with a barrier contraceptive through completion of the study and have negative results on a serum or urine pregnancy test done before administration of study medication.
6. Good peripheral venous access.
1. History of malaria or travelled to or lived (2 weeks or more ) in a malaria-endemic country during the past 12 months or planned travel to a malaria-endemic country during the course of the study.
2. Evidence of increased cardiovascular disease risk
3. History of splenectomy.
4. Pregnant or breast feeding
5. History of a severe allergic reaction, anaphylaxis or convulsions following any vaccination or infusion.
6. Presence of current or suspected serious chronic diseases such as cardiac or autoimmune disease, HIV or other immunodeficiencies, insulin dependent diabetes, progressive neurological disease, severe arthritis, asthma, epilepsy or obsessive compulsive disorder, skin carcinoma excluding non spreadable skin cancers such as basal cell and squamous cell carcinoma, significant psychiatric diagnosis.
7. Volunteers unwilling to defer blood donations to the ARCBS for 6 months.
8. Abnormal ECG findings
9. Recent or current therapy with an antibiotic or drug with potential antimalarial activity (tetracycline, azthromycin, clindamycin, hydroxychloroquine etc.).
10. Known hypersensitivity to Piperaquine, artemether or lumefantrine.
11. Concomitant use of any of the following drugs: those metabolised by the cytochrome enzyme CYP2D6 (e.g. flecainide, metoprolol, imipramine, amitriptyline, clomipramine); drugs that are known to prolong the QTc interval (e.g. antiarrhythmics of classes IA and III, neuroleptics, certain antidepressant agents, certain antibiotics, certain nonsedating antihistamines; corticosteroids, anti-inflammatory drugs, any immunomodulators or anticoagulants.
12. Presence of acute infectious disease or fever (e.g., sub-lingual temperature greater than 38.5 degree Celsius) within the five days prior to study product administration).
13. Evidence of acute illness within the four weeks before trial prior to screening.
14. Significant intercurrent disease of any type, in particular liver, renal, cardiac, pulmonary, neurologic, rheumatologic, or autoimmune disease by history, physical examination, and/or laboratory studies including urinalysis.
15. Participant has a clinically significant disease or any condition or disease that might affect drug absorption, distribution or excretion, e.g. gastrectomy, diarrhoea.
16. Alcohol consumption greater than community norms (i.e. more than 21 standard drinks per week for males and 14 standard drinks per week for females).
17. A history of drug habituation, or any prior intravenous usage of an illicit substance.
18. Medical requirement for intravenous immunoglobulin or blood transfusions.
19. Participation in any investigational product study within the 8 weeks preceding the study.
20. Participation in any research study involving significant blood sampling, or blood donation to Red Cross (or other) blood bank during the 8 weeks preceding the reference drug dose in the study.
21. Have ever received a blood transfusion.
22. Positive test for HIV, Hepatitis B, hepatitis C.
23. Any clinically significant biochemical or haematologic abnormality (Hb must be greater than or equal to 11.5g/dL for females; 13.5g/dL for males)
24. Ingestion of any poppy seeds within the 24 hours prior to the screening blood test (volunteers will be advised by phone not to consume any poppy seed in this time period).
25. Detection of any drug listed in this protocol in the urine drug screen unless there is an explanation acceptable to the medical investigator (e.g. the participant has stat
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The pharmacokinetic-pharmacodynamic relationship between blood piperaquine levels on the clearance of Plasmodium falciparum parasites from the blood in healthy volunteers following infection with blood stage parasites. This outcome will be measured by monitoring blood levels of parasites by PCR and of drug levels by LCMS.[28 days]
- Secondary Outcome Measures
Name Time Method To characterize the pharmacokinetics of piperaquine in healthy volunteers following infection with blood stage Plasmodium falciparum. This outcome will be measured by monitoring drug levels in the blood[28 days];To assess the tolerability of piperaquine in the experimental malaria challenge system. This outcome will be assessed by reviewing the signs and symptoms of adverse effects of drug (eg gastrointestinal intolerance); changes in ECG; changes in haematology or biochemistry results.[28 days]