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

Malaria Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01836458
• Other study ID #: CKAE609A2201
• Status: Completed
• Phase: Phase 2
• First received: April 17, 2013
• Last updated: February 3, 2016
• Start date: January 2014
• Est. completion date: March 2015

Study information

• Verified date: February 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Thailand: Ministry of Public HealthVietnam: Ministry of Health
• Study type: Interventional

Clinical Trial 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

Description:

There will be a total of approximately 45 patients recruited into this study and six doses of KAE609 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 information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 60 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Malaria
• Malaria, Falciparum

Intervention

Drug:
• KAE609
patients will receive KAE609 single dose of different dose level in each cohort.

Locations

Country	Name	City	State
Vietnam	Novartis Investigative Site	Ho Chi Minh

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Vietnam, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Minimum Inhibitory Concentration (MIC) 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.	within 72 hours after a single dose of KAE609	No
Secondary	Parasite clearance time	Parasite clearance time will be estimated using thick/thin blood films.	Day 1 to Day 5	No
Secondary	Fever clearance time	Fever is monitored on participants every 4 hours for the first 24 hours, then every 6 hours until negative reading obtained.	Day 1 to Day 5	No
Secondary	PCR-corrected cure rate on day 28, 35 and 42 days	PCR-corrected cure rate after a single dose of KAE609 at defined time points on day 28, 35 and 42 will be estimated.	42 days	No