A Study to Find the Minimum Inhibitory Concentration of KAE609 in Adult Male Patients With P. Falciparum Monoinfection

Phase 2

Completed

Conditions: Malaria

Interventions: Drug: KAE609

Registration Number: NCT01836458

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: This study aims to determine the Minimum Inhibitory Concentration of KAE609 in adult male patients with acute, uncomplicated malaria due to P.falciparum monoinfection after single dosing with KAE609

Detailed Description: There will be a total of approximately 45 patients recruited into this study and six doses of KAE609 and will be investigated.The dose groups will run in sequence. Patient will be given a single dose of KAE609 and be followed up for 42 days.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 25

Inclusion Criteria

Monoinfection with P. falciparum confirmed by microscopy
Asexual P. falciparum parasitemia count of 5,000 to 50,000/µL
Axillary temperature ≥37.5 ºC or oral/tympanic/rectal temperature ≥38 ºC; or similar documented temperature during the previous 24 hours
Body weight between 40 to 90 kg

Key

Exclusion Criteria

Signs and symptoms of severe malaria according to World Health Organization (WHO) 2010 criteria
Mixed Plasmodium infection, i.e. infection with more than one species of malaria parasites
Use of other investigational drugs within 30 days or within 5 half-lives of enrollment, whichever is longer
History of antimalarial use within 2 months of screening
Use of any antibiotics with antimalarial activity or other prohibited medication within 14 days of screening
Long QT syndrome or QTc using Fridericia's formula >430 msec
History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
Hemoglobin level <10 g/dL
Liver disease or injury as indicated by elevated liver tests such as SGPT (ALT) or SGOT (AST) >2 times the upper limit of normal
Renal dysfunction as indicated by serum creatinine >2 times the upper limit of normal in the absence of dehydration; in case of dehydration, serum creatinine should be <2 times the upper limit of normal after oral or parental rehydration
Known to be immunocompromised (including HIV infection) or are receiving immunosuppressive therapy at the time or enrollment; HIV testing is not required
Known history of hepatitis B or C; testing is not required
Febrile condition due to diseases other than malaria (e.g. acute lower respiratory tract infection), known underlying chronic or severe disease (e.g. cardiac, hepatic, renal, gastrointestinal, neurologic, or psychiatric disease), or any condition precluding enrollment into this study according to the investigator
Severe vomiting defined as >3 times during the previous 24 hours or inability to tolerate oral medication; severe diarrhea defined as ≥3 watery stools during the previous 24 hours
Severe malnutrition defined by a body mass index (BMI) <18.5 kg/m2 or unintentional loss of weight ≥10% with evidence of suboptimal intake resulting in loss of subcutaneous fat and/or severe muscle wasting
Active tuberculosis or history of taking anti-tuberculosis medications within 24 months prior to screening

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dose 1: 30 mg	KAE609	Single dose of KAE609 30 mg
Dose 2: 20 mg	KAE609	Single dose of KAE609 20 mg
Dose 4: 15 mg	KAE609	Single dose of KAE609 15 mg
Dose 3: 10 mg	KAE609	Single dose of KAE609 10 mg

Primary Outcome Measures

Name	Time	Method
Minimum Inhibitory Concentration (MIC) of KAE609	Up to Day 8 after a single dose of KAE609	To observe the exposure-response (PK/PD) relationship for a single dose of KAE609. The key parameter is MIC, defined as the concentration at which the relative rate of change in parasitemia is equal to zero. Approximation of MIC will assist in identifying the optimal dose of KAE609, which will be one component of a future combination antimalarial. MIC could not be determined due to small sample size no data was collected from any participants.

Secondary Outcome Measures

Name	Time	Method
Median Time to Parasite Clearance	pre-dose, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 54, 60, 66, 72 hours post dose of KAE609	Parasite clearance time will be estimated using thick/thin blood films.
Median Time to Fever Clearance	Day 1 to Day 5	Fever is monitored on participants every 4 hours for the first 24 hours, then every 6 hours until negative reading obtained.
Percentage of Patients PCR-corrected Cure Rate by Day 28, Day 35 & Day 42	Day 28, Day 35 & Day 42	PCR-corrected cure rate after a single dose of KAE609 by Day 28, Day 35 \& Day 42. PCR-corrected cure rate accounts for failures due to reappearance of parasites that were present in the blood before treatment (i.e. recrudescent infection) but not for failures due to a post-treatment inoculation (i.e. new infection).