Malaria
Conditions
Interventions
Cohort A1 INE963 Dose Level 1
Cohort A1 INE963 Dose Level 2
Cohort A1 INE963 Dose Level 3
Cohort B1 INE963 and KAE609
Cohort B1 Coartem
Cohort B2 KLU156 and KAE609
Cohort B2 Coartem
Cohort C2 KLU156 and KAE609
Cohort C2 Coartem
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Signed informed consent must be obtained prior to participation in the study Male and female patients =18 years of age for Part A, =12 years of age for Part B, and =2 years and <12 years for Part C at screening Patients must have acute uncomplicated P. falciparum malaria mono infection at screening confirmed by a parasite count between 5,000 to 150,000 asexual parasite count/µl of blood for P. falciparum for Part A and between 1,000 to 150,000 asexual parasite count/µl of blood for Parts B and C Patients in Part A must weigh between 40 kg and 90 kg. Patients in Part B must weigh between 35 kg and 90 kg at screening. Patients in Part C must weigh at least 10 kg at screening. Patients must be able to swallow oral medications Able to communicate well with the investigator, to understand and comply with the requirements of the study
Exclusion criteria
Exclusion criteria: Patients with signs and symptoms of severe/complicated malaria at screening or mixed Plasmodium infection (i.e., infection with more than one malaria species) at screening Moderate to severe anemia, chronic hemoglobinopathy (Hemoglobin level 3 x the upper limit of normal range (ULN), regardless of the level of total bilirubin AST/ALT > 1.5 and = 2 x ULN and total bilirubin is > ULN Total bilirubin > 2 x ULN, regardless of the level of AST/ALT Any known/suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection at screening. Pregnant or nursing (lactating) women, women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using methods of contraception as outlined in Section 12, and sexually active patients not willing to practice effective contraception. History or current diagnosis of ECG abnormalities indicating significant risk of safety for patients participating in the study such as: Concomitant clinically significant cardiac arrhythmias, e.g., sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker History of familial long QT syndrome or known family history of Torsades de Pointe. Resting heart rate (physical exam or 12 lead ECG) < 50 bpm For full list, please reference protocol section 5.2
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Parts B and C- cure rate of an anti-malarial agent administered orally as combination therapy versus the standard of care in patients with uncomplicated P. falciparum malaria by using polymerase chain reaction PCR corrected adequate clinical and parasitological response ACPR. ACPR is defined as the absence of parasitemia on Study Day 29 irrespective of axillary temperature, without previously meeting any of the criteria of Early Treatment Failure (ETF) or Late Clinical Failure (LCF) or Late Parasitological Failure (LPF).;Part A - Parasite clearance time of oral doses of anti-malarial agents administered as monotherapy in patients with uncomplicated Plasmodium falciparum malaria. PCT is defined as the time from the first positive blood slide at inclusion to the time of the first negative slide followed by two consecutive slides. | — |
Secondary
| Measure | Time frame |
|---|---|
| T1/2 - the elimination half-life associated with the terminal slope of a semi-logarithmic concentration-time curve.;CL - the total body clearance of drug from the plasma.;Vz/F - the apparent volume of distribution during terminal phase.;Incidence and severity of AEs and SAEs by treatment group, including changes in vital signs, electrocardiograms (ECGs), and laboratory results qualifying and reported as AEs.;Part A - cure rate of an anti-malarial agent administered orally as monotherapy in patients with uncomplicated P. falciparum malaria by using polymerase chain reaction PCR corrected adequate clinical and parasitological response ACPR;Parts B and C - Parasite clearance time of oral doses of anti-malarial agents administered as monotherapy in patients with uncomplicated Plasmodium falciparum malaria;Parts B and C - cure rate of an anti-malarial agent administered orally as combination therapy versus the standard of care in patients with uncomplicated P. falciparum malaria by using polymerase chain reaction PCR uncorrected adequate clinical and parasitological response ACPR;AUClast - Area under the serum concentration-time curve from time zero to the time of last measurable concentration sample time;AUCinf - Area under the concentration time curve from time zero (pre-dose) to infinity.;Cmax - the maximum (peak) observed plasma, blood, serum, or other blood fluid drug concentration after single dose administration.;Tmax - the time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration. | — |
Countries
Burkina Faso, Cote Divoire, Gabon, Ghana, Kenya, Rwanda, Uganda
Contacts
Public ContactAmanda Nguyen
Clinical Scientist
Outcome results
None listed