Plasmodium vivax, malaria
Conditions
Interventions
Tafenoquine plus chloroquine arm: 200 subjects will be followed-up till 180 days, receiving chloroquine from days 1 to 3 and Tafenoquine as a single dose on day 1 or day 2, the Primaquine matching pl
Drug
Sponsors
GlaxoSmithKline
Medicines for Malaria Venture
Eligibility
Age
16 Years to No maximum
Inclusion criteria
Inclusion criteria: A female is eligible to enter and participate in the study if she is non pregnant, nonlactating and if she is of a: non-childbearing potential defined as post-menopausal (12 months of spontaneous amenorrhea or less than 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone greater than 40 milli-international units per milliliter, or pre-menopausal and has had a hysterectomy or a bilateral oophorectomy (removal of the ovaries) or a bilateral tubal ligation, negative pregnancy test or, b. child-bearing potential, has a negative pregnancy test at screening, and agrees to comply with one of the following during the treatment stage of the study and for a period of 90 days after stopping study medication: use of oral contraceptive, either combined or progestogen alone used in conjunction with double barrier method as defined below. Use of an intrauterine device with a documented failure rate of less than 1% per year; use of depo provera injection; double barrier method consisting of spermicide with either condom or diaphragm; male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female. Complete abstinence from intercourse for 2 weeks prior to administration of study medication, throughout the study and for a period of 90 days after stopping study medication. The subject has a glucose 6-phosphate dehydrogenase (G6PD) value (measured by a quantitative spectrophotometric phenotype assay) as follows: female subjects must have an enzyme level greater or equal than 40 percent of the site median value for G6PD normal males. Male subjects must have an enzyme level greater or equal than 70 percent of the site median value for G6PD normal males. The subject has a screening hemoglobin (Hb) value as follows: any subject with a G6PD value greater or equal than 70 percent of the site median value must have a screening Hb value greater or equal than 7 g/dL; female subjects with a G6PD value is greater or equal than 40 - less than 70 percent of the site median value must have a screening Hb value greater or equal than 8 g/dL. The subject has a qt duration corrected for heart rate by fridericia's formula (QTcF) less than 450 milisecond (msec). Reading based on an average of triplicate electrocardiograms (ECGs) obtained over a brief recording period by machine or manual over-read. The subject has a positive malarial smear for P. vivax.The subject has a parasite density of greater than 100 and less than 100,000 per microliter (?L). Male or female subject aged 16 years or older at the time of signing the informed consent. The subject agrees to G6PD genotyping. The subject is willing and able to comply with the study protocol. The subject or parent/legal guardian, as applicable, has given written informed, dated consent; and the subject has given written assent, if applicable, to participate in the study.
Exclusion criteria
Exclusion criteria: Mixed malaria infectio; severe P. vivax malaria as defined by world health organization criteria, history of allergy to chloroquine, mefloquine, tafenoquine, primaquine, or to any other 4- or 8-aminoquinoline; liver alanine aminotransferase (ALT) greater than 2 time the upper limit of normal; severe vomiting , condition that may affect absorption of study medication (e.g., vomiting, severe diarrhea), or clinical signs and symptoms of severe cardiovascular disease; history of porphyria, psoriasis, or epilepsy; history of significant ocular disease or evidence of corneal or retinal abnormalities identified in the clinical ophthalmologic examination,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| •Proportion of all subjects with plasmodium vivax (P. vivax) experiencing clinically relevant hemolysis (Time Frame: Up to Day 180 ), clinically relevant hemolysis in all subjects is defined as, a decrease in haemoglobin (Hb) of greater or equal than 30% or greater than 3 gram per decilitre (g/dL) from baseline; or, an overall drop in haemoglobin below 6.0 g/dL, proportion of female subjects with p. vivax who are moderately (40-70 percent) G6PD deficient experiencing clinically relevant hemolysis (Time Frame: Up to Day 180); clinically relevant hemolysis in all subjects is defined as, a decrease in haemoglobin (Hb) of greater or equal than 30% or greater than 3 g/dL from baseline; or, an overall drop in haemoglobin below 6.0 g/dL. | — |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of subjects with relapse-free efficacy six months post-dosing (after day 32 of the study up to day 180 ). Relapse is defined by a positive blood smear with or without p. vivax symptoms. The term "relapse" will be used to describe any recurrence of malaria that occurs after day 32 of the study. Proportion of subjects with relapse-free efficacy four months post-dosing (after day 32 of the study up to day 120 ), time to relapse (after day 32 of the study Up to day 180 ), parasite clearance time (up to day 180). Time needed to clear asexual parasite from the blood defined as parasite numbers falling below the limit of detection in the thick blood smear and remaining undetectable 6-12 hours later. Fever clearance time (up to day 180), time from first dose of treatment to the time when body temperature falls to normal and remains normal for at least 48 hours. Gametocyte clearance time (up to day 180): time from first dose until the first slide that was gametocyte negative and remained so at the next slide reading. Subjects with no gametocytes at baseline will be censored, with a time to clearance of zero. Proportion of subjects with recrudescence (up to Day 29). Recrudescence is defined as any p. vivax parasitemia occurring on or before day 29 (i.e., blood stage treatment failure), incidence of genetically homologous and genetically heterologous p. vivax infections ( up to Day 180). Polymerase chain reaction analysis of plasmodium species such as PvMSP-1, PvCSP and PvAMA-1 will be used to distinguish between genetically homologous and genetically heterologous infection on all subjects at screening (day 1; pre-dose), and at all times of potential recrudescence/relapse or re-infection. Healthcare resource use for p. vivax relapses (up to day 180). Healthcare resource use (excluding clinic visits scheduled as part of the study) data will be collected to characterize p. vivax relapse at study enrolment (for the primary p. vivax infection), the day 15 visit, and a | — |
Countries
Brazil, Cambodia, Colombia, Ethiopia, Peru, Philippines, Thailand, Viet Nam
Contacts
Public ContactPesquisador Responsável - Contato Público
GlaxoSmithKline Brasil
Outcome results
None listed