Overview
Platform study to evaluate the efficacy and safety of anti-malarial agents in patients with uncomplicated Plasmodium falciparum malaria
Description
The purpose of this platform study is to evaluate the parasiticidal effect and potential for cure with different anti-malarial agents administered as monotherapy and/or in combination therapy with other anti-malarial agents in adults, adolescents, and children with uncomplicated Plasmodium falciparum malaria. Additionally, the safety, tolerability, and pharmacokinetics of these anti-malarial agents will be evaluated for dose selection for future studies.
Eligibility
Inclusion Criteria:
- Male and female patients ≥18 years of age for Part A, ≥12 years of age for Part B and 2 to \<12 years of age 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.
- Axillary temperature ≥ 37.5ºC or oral/tympanic/rectal temperature ≥ 38.0ºC; or history of fever during the previous 24 hours.
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 \< 8 g/dL), or known chronic underlying disease such as sickle cell disease at screening
- Known clinically significant liver disease (e.g., chronic hepatitis, liver cirrhosis (compensated or decompensated), history of hepatitis B or C, hepatitis A or B vaccination in the last 3 months, known gallbladder or bile duct disease, acute or chronic pancreatitis. Clinical or laboratory evidence of any of the following at screening:
- AST/ALT \> 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 effective contraception, 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
Other protocol-defined inclusion/exclusion criteria may apply.
