Malaria
Conditions
Sponsors
GlaxoSmithKline Research And Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male and female patients aged 18 to 65 years. • Presence of malaria due to mono-infection with P. falciparum confirmed by: – Fever, as defined by axillary temperature >=37.5°C or oral/tympanic temperature >=38°C and, – Microscopically confirmed P. falciparum malaria parasite mono-infection, – A parasite count between 2,000 to 60,000 asexual parasite count/µL of blood for P. falciparum. • Have a BMI between >=18 and <=30 kg/m2. • Able to swallow oral medication. • Signed informed consent, acknowledging understanding and willingness to comply with the requirements of the study. If the patient is unable to write, thumb print consent, signed by an impartial witness is permitted according to local ethical considerations. • Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. • A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: - Is a woman of non-childbearing potential (WONCBP) or - Is a woman of childbearing potential (WOCBP) and using an acceptable contraceptive method, from Study Day 1, and during the study intervention period (40 +/-3 days).
Exclusion criteria
Exclusion criteria: • Patients with signs and symptoms of severe/complicated malaria according to the WHO 2024 Criteria. • Mixed Plasmodium infection, i.e., infection with more than one malaria (plasmodium) species (by microscopy; participant to be withdrawn from study treatment if PCR subsequently indicates presence of mixed infection). • Abnormal values: QTcF >450 msec or QTcF >480 msec for patients with bundle branch block. • Any clinically significant ECG abnormalities at Screening unrelated to malaria (including but not limited to, second degree AV block (Mobitz Type 2), complete heart block, ST changes, atrial fibrillation, atrial flutter, supraventricular tachycardia, ventricular tachycardia, prolonged QT interval. • History of malignancy (or current malignancy) of any organ system (other than localized carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. • Creatinine >=2 x ULN. • Significant illness within two weeks prior to screening. • Positive HIV antibody test at screening, or history of HIV infection based on past positive test result, clinical record or current treatment. • Severe vomiting, defined as more than 3 times in the 24 hours before screening or inability to tolerate oral treatment. • Severe diarrhoea defined as more than 3 watery stools per day in the 24 hours before screening. • Known history or evidence (based on clinical examination or investigation) of uncontrolled active cardiovascular disease (including hypertension), respiratory disease (including active tuberculosis even if treatment is ongoing), liver cirrhosis or liver disease (based on prior investigation, clinical signs and/or interpretation of liver enzymes), other active hepatic, renal, gastrointestinal, immunological, neurological, endocrine, infectious, or psychiatric disease. • Anaemia (Hb 2.0 x ULN. • Total bilirubin >1.5 x ULN; Participants with Gilbert’s syndrome can be included with total bilirubin >1.5xULN as long as direct bilirubin is <=1.5xULN. • Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones). • Presence of hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study int
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants with serious adverse events (SAEs) overall, treatment related, and by severity A SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant; abnormal pregnancy outcomes; or any other situation according to medical or scientific judgment. The intensity of SAEs is assessed as per the Division of Acquired Immunodeficiency Syndrome (DAIDS) criteria Version 2.1 where grades are defined based on numeric criteria as follows Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: potentially life-threatening; Grade 5: death. A higher grade indicates greater severity. Any = occurrence of the event regardless of intensity grade and treatment relationship. Treatment related = occurrence of the event which, in the investigator’s opinion, is related to the administered treatment regardless of the intensity grade. ;Number of participants with non-serious AEs overall, treatment related, and by severity An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. The intensity of non-serious AEs is assessed using the DAIDS criteria Version 2.1 where grades are defined based on numeric criteria as follows Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: potentially life-threatening; Grade 5: death. A higher grade indicates greater severity. Any = occurrence of the event regardless of intensity grade and treatment relationship. Treatment related = occurrence of the event which, in the investigator’s opinion, is related to the administered treatment regardless of the intensity grade. | — |
Secondary
| Measure | Time frame |
|---|---|
| Observed accumulation ratio of GSK3772701 based on Cmax (RCmax) following multiple doses Cmax (RCmax) is defined as the accumulation ratio for Cmax comparing last day of dosing to Day 1. ;Area under the concentration (AUC) - time curve (AUC[0-t]) of GSK3772701 AUC(0-t) is defined as the area under the concentration-time curve from time zero to the time of the last evaluable concentration. ;AUC(0-t) extrapolated to infinity (AUC[0-inf]) of GSK3772701 AUC(0-inf) is defined as the area under the concentration-time curve extrapolated to infinity calculated as: AUC(0-inf) = AUC(0-t) + C(t) / ?z. ;Maximum observed concentration (Cmax) of GSK3772701 ;Time to maximum observed drug concentration (Tmax) of GSK3772701 Tmax is defined as time to reach the Cmax. ;Apparent terminal half-life (t1/2) of GSK3772701 Apparent terminal phase half-life in plasma (and blood), calculated as loge (2)/?z. ;Trough concentration (Ctau) of GSK3772701 following multiple dose administration Ctau is defined as the trough/pre-dose concentration after dosing interval, tau. ;Observed accumulation ratio (R) of GSK3772701 for AUC [AUC(Ro)] following multiple dose administration AUC-tau (Ro) is defined as the accumulation ratio for AUC(0-tau) comparing last day of dosing to Day 1. | — |
Countries
Gabon, Uganda
Contacts
Public ContactMichelle Botha
Regulatory
Outcome results
None listed