Clinical trial NCT01836458: A Study to Find the Minimum Inhibitory Concentration of KAE609 in Adult Male Patients With P. Falciparum Monoinfection
Official title: An Open-label Study to Find the Minimum Inhibitory Concentration(MIC) of KAE609 in Adult Male Patients With Acute, Uncomplicated Malaria Due to Plasmodium Falciparum Monoinfection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malaria
Keywords: Malaria, KAE609
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2013-04-19
Enrollment: 25
Sex: ALL
Minimum age (years): 20
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Key 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

Primary outcomes:
measure: Minimum Inhibitory Concentration (MIC) of KAE609
timeFrame: Up to Day 8 after a single dose of KAE609
Secondary outcomes:
measure: Median Time to Parasite Clearance
timeFrame: 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
measure: Median Time to Fever Clearance
timeFrame: Day 1 to Day 5
measure: Percentage of Patients PCR-corrected Cure Rate by Day 28, Day 35 & Day 42
timeFrame: Day 28, Day 35 & Day 42
Other outcomes:
Locations:
city: Ho Chi Minh
country: Vietnam
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Hien TT, White NJ, Thuy-Nhien NT, Hoa NT, Thuan PD, Tarning J, Nosten F, Magnusson B, Jain JP, Hamed K. Estimation of the In Vivo MIC of Cipargamin in Uncomplicated Plasmodium falciparum Malaria. Antimicrob Agents Chemother. 2017 Jan 24;61(2):e01940-16. doi: 10.1128/AAC.01940-16. Print 2017 Feb.