None listed
Conditions
Interventions
Cohort 1 Type of group
Each cohort contains two treatment arms, P. falciparum (a) and P. vivax (b). Cohort progression will be managed independently for each treatment arm. Interim analysis will determine whether the data for a given treatment arm meets the success criteria, is inconclusive, or meets the failure criteria. Crude adequate clinical and parasitological response (ACPR) is defined as the absence of microscopically determined parasitemia (thick smear), irrespective of axillary temperature, in patients who di
10 patients per arm) will be investigated with a maximum of 3 cohorts (60 patients
3 dosing regimens
2 arms
Cohort 3 Type of group
Cohort 3 requires co-dosing with a pharmacoenhancer, if successful, this regimen would reduce the quantity of SJ733 required by 2-fold, reducing cost of goods and potentially improving tolerability
Sponsors
Rodney Kiplin Guy,
Eligibility
Inclusion criteria
Inclusion criteria: 1. Male or female, aged 18 to 70 years of age (inclusive) at screening. 2. Body weight between 45 kg and 90 kg inclusive 3. Presence of mono-infection of P. falciparum or P. vivax confirmed by: a. 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, b. Microscopically confirmed parasite infection: 1,000 to 40,000 asexual parasite count/µL blood 4. Written informed consent provided by participant, in accordance with local practice. If the participant is unable to write, witnessed consent is permitted according to local ethical considerations. 5. Ability to swallow oral medication. 6. Ability and willingness to participate and to comply with the study requirements 7. Agreement to hospitalization for at least 102 hours and/or until malarial parasites are not detected by microscopy on 2 consecutive occasions. 8. Agreement to come back to the hospital on Days 7, 10 or 11, 14, 17 or 18, 21, 24 or 25, 28, 35, and 42. 9. A female is eligible to enter and participate in this study if she is non-pregnant, non-lactating and if she is of: a. non-child bearing potential defined as: post-menopausal (12 months of spontaneous amenorrhea or 40 mIU/mL), pre-menopausal and has had a hysterectomy or a bilateral oophorectomy (removal of the ovaries) or a bilateral tubal ligation with medical report verification, negative pregnancy test or, b. Women of 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 30 days after stopping study drug: i. Use of oral, implantable, or injectable hormonal contraceptive, either combined or progestogen alone used in conjunction with double barrier method as defined below. ii. Use of an intrauterine device with a documented failure rate of <1% per year. iii. Barrier method consisting of either condom or diaphragm. iv. Male partner who is sterile prior to the female subject’s entry into the study and is the sole sexual partner for that female. v. Complete abstinence from intercourse for 2 weeks prior to administration of study drug, throughout the study and for a period of 30 days after stopping study drug.
Exclusion criteria
Exclusion criteria: 1. Signs and symptoms of severe/complicated malaria according to the World Health Organization Criteria 2010 (Attachment 1: Definition of Severe Malaria) 2. Mixed Plasmodium infection. 3. Severe vomiting, defined as more than three times in the 24 hours prior to inclusion in the study, or severe diarrhea defined as 3 or more watery stools per day. 4. Severe malnutrition (defined as the weight-for-height being below -3 standard deviation or less than 70% of median of the NCHS/WHO normalized reference values) 5. Presence of a significant medical or psychiatric condition, or any other serious or chronic clinical condition requiring hospitalization, or any other condition that in the opinion of the investigator precludes participation in the study. 6. Female patients must not be either lactating or pregnant as demonstrated by a negative serum point-of-care pregnancy test pre-dose (the result of the pre-dose assessment must be confirmed negative prior to dosing). 7. Employment under the direct supervision of the investigators or study staff. 8. Clinically significant alterations to hematologic or clinical chemistry parameters that in the opinion of the investigator precludes participation in the study, including: a. AST/ALT > 3 x upper limit of normal range (ULN) and total bilirubin is normal b. AST/ALT > 2 x ULN and total bilirubin is >1 and 35% of the total bilirubin c. Total bilirubin > 1.5 x ULN d. Serum creatinine levels > 2 x ULN e. Hb level < 8 g/dL f. Platelet level < 50,000/mm3 9. Participation in a clinical study of another investigational small molecule within 30 days or investigational biologic within 90 days prior to study enrollment or planning to begin such participation during the study. 10. Have received any antimalarial treatment (alone or in combination) in the past containing: a. Piperaquine, mefloquine, naphthoquine or sulphadoxine /pyrimethamine within the previous 6 weeks b. Amodiaquine or chloroquine within the previous 4 weeks c. Any artemisinin (artesunate, artemether, arteether or dihydroartemisinin) quinine, halofantrine, lumefantrine and any other anti-malarial treatment or antibiotics with antimalarial activity (including cotrimoxazole, tetracyclines, quinolones and fluoroquinolones, and azithromycin) within the past 14 days 11. Any medication from a list of prohibited medications as provided in Section 7.6.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:Crude Adequate clinical and parasitological response (ACPR) is determined microscopically by blood smaer (thick smaer). Crude ACPR is defined as the absence of parasitemia on day 14. This is irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure, late clinical failure, or late parasitological failure. Measure:Crude Adequate Clinical and Parasitological response (ACPR) at day 14 Timepoints:Day 14 ; Outcome name:Medical history, physical examination (including cutaneous adverse reactions), Laboratory assessments (hematology, clinical biochemistry, including hemoglobin level, neutrophil count, liver function test, venous methemoglobin), electrocardiogram (ECG) (including cardiac frequency, PR, QTcB, QTcF, changes in conductions or any abnormalities) Measure:Adverse Events, clinically significant laboratory abnormalities, cutaneous adverse reactions, abnormal clinically signifcant vital signs, ECG Timepoints:Day 42 | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:Physical examination to identify signs related to uncomplicated malaria; fever clearance Measure:Proportion of patients with malaria signs and symptoms Timepoints:each visit up to day 42 ; Outcome name:Absence of microscopically determined parasitemia (P. vivax or P. falciparum; thick smear) Measure:Crude Adequate Clinical and Parasitological Response (ACPR) Timepoints:Days 28, 35, and 42 ; Outcome name:Presence of microscopically determined parasitemia (P. vivax or P. falciparum; thick smear) Measure:Recurrence of parasitemia Timepoints:Up to Day 42 ; Outcome name:Physical examination to identify signs related to uncomplicated malaria Measure:Proportion of patients with malaria signs and symptoms Timepoints:each visit up to day 42 ; Outcome name:The following will be assessed microscopically: • Parasite clearance time (PCT) • PRR (parasite reduction rate) and parasitemia half life • Time to microscopic clearance of asexual parasites Measure:Parasite clearance kinetics by microscopy Timepoints:Blood samples will be taken on the follwing days: Day 1 , Da2, Day3, Day 4, Day 5, Day 7, Day 10 (or 11), Day 14, Day 17 (or 18) , Day 21, Day 24 (or 25), Day 28, Day 35 and Day 42 (or withdrawal) ; Outcome name:The following will be assessed through microscope • Microscopically determined percentage reduction in asexual parasites • Proportion of parasitemia Measure:Parasite clearance kinetics by microscopy at defined times from baseline Timepoints:24, 48 and 72 hours after IP administration ; Outcome name:Assessment of several PK parameters through blood sampling analysis at specific timepoints (AUC0-t, AUC0-inf, Cmax, tmax, t½, Cl, F,etc) Measure:Pharmacokinetic (PK) Parameters up to day 42 Timepoints:Up to Day 42 | — |
Countries
Peru
Contacts
Public ContactFlor de Liz Jacome
Labcorp Peru Services S.A
Outcome results
None listed