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

NCT01836458 | Completed Phase 2 Results

• 1 other identifier: CKAE609A2201
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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

Conditions

Malaria

Keywords

Malaria, KAE609

Outcome Measures

Primary Outcomes (1)

• 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. MIC could not be determined due to small sample size no data was collected from any participants.

  Up to Day 8 after a single dose of KAE609

Secondary Outcomes (3)

• 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

• Median Time to Fever Clearance

  Day 1 to Day 5

• Percentage of Patients PCR-corrected Cure Rate by Day 28, Day 35 & Day 42

  Day 28, Day 35 & Day 42

Study Arms (4)

Dose 1: 30 mg

EXPERIMENTAL

Single dose of KAE609 30 mg

Drug: KAE609

Dose 2: 20 mg

EXPERIMENTAL

Single dose of KAE609 20 mg

Drug: KAE609

Dose 3: 10 mg

EXPERIMENTAL

Single dose of KAE609 10 mg

Drug: KAE609

Dose 4: 15 mg

EXPERIMENTAL

Single dose of KAE609 15 mg

Drug: KAE609

Interventions

KAE609 DRUG

Patients will receive KAE609 single dose at a different dose level in each cohort.

Dose 1: 30 mg; Dose 2: 20 mg; Dose 3: 10 mg; Dose 4: 15 mg

Eligibility Criteria

• Age: 20 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis Investigative Site

Ho Chi Minh City, Vietnam

Location

Related Publications (1)

• 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.

  PMID: 27872070 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

NITD 609

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2013
• First Posted: April 19, 2013
• Study Start: January 1, 2014
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: October 31, 2016
• Results First Posted: October 31, 2016

Record last verified: 2016-09

Locations

VN (1)