Back to resultsEfficacy, Safety, Tolerability and Pharmacokinetics of KAF156 in Adult Patients With Acute, Uncomplicated Plasmodium Falciparum or Vivax Malaria Mono-infection
Primary Purpose
Malaria
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
KAF156
Sponsored by
About this trial
This is an interventional treatment trial for Malaria focused on measuring acute malaria, KAF156
Eligibility Criteria
Inclusion Criteria:
-Male and female patients aged 20 to 60 years;Presence of mono-infection of P. falciparum or P. vivax; Weight between 40 kg to 90 kg.
Exclusion Criteria:
- Patients with signs and symptoms of severe/complicated malaria
- Infection with more than one parasite species
- Women of child-bearing potential; pregnant or nursing women
- Those who have taken any anti-malarial treatment in the preceding 14 days or other investigational drugs within 30 days or 5 half-lives
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Part 1 - Cohort 1: P. vivax: KAF156 400mg QD
Part 1 - Cohort 2: P. falciparum: KAF156 400mg QD
Part 2 - Cohort 3: P. falciparum: KAF156 800mg single dose
Arm Description
Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days.
Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days.
Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg.
Outcomes
Primary Outcome Measures
Time to Parasite Clearance
Parasite clearance was determined by assessing the parasite count in blood, using thin film, thick film and blood density assessments.
28-day Cure Rate - Part 2
28-day cure rate was defined as the percentage of participants with blood parasite count of zero after 28 days of treatment.
Secondary Outcome Measures
Area Under the Curve (AUC)0-24h - Part 1
AUC0-24h was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose. The 24h sampling of first post dose was taken before the second dose. On Day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Maximum Concentration (Cmax) - Part 1
Cmax was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose. The 24h sampling of first post dose should be taken before the second dose. On Day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Time to Maximum Concentration (Tmax) - Part 1
Tmax was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose. The 24h sampling of first post dose should be taken before the second dose. On Day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Area Under the Curve (AUC)Last - Part 1
AUClast was analyzed using parent drug in plasma samples. On Day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Area Under the Curve (AUC)Inf - Part 1
AUCinf was analyzed using parent drug in plasma samples. On Day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Half-life (T1/2) - Part 1
T1/2 was analyzed using parent drug in plasma samples. On day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Clearance (CL/F ) - Part 1
CL/F was analyzed using parent drug in plasma samples. On day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Apparent Volume of Distribution During the Terminal Elimination Phase Following Extravascular Administration (Vz/F) - Part 1
Vz/F was analyzed using parent drug in plasma samples. On Day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Accumulation Ratio (Racc) (=AUC0-24h, day3/AUC0-24h, day1) - Part 1
Racc was analyzed using parent drug in plasma samples. On day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
AUC0-24h - Part 2
AUC0-24h was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose.
AUC0-48h - Part 2
AUC0-48h was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
AUClast - Part 2
AUClast was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose
AUCinf - Part 2
AUCinf was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose
Cmax - Part 2
Cmax was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose.
Tmax - Part 2
Tmax was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose.
T1/2 - Part 2
T1/2 was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
CL/F - Part 2
CL/F was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Vz/F - Part 2
Vz/F was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Full Information
NCT ID
NCT01753323
First Posted
December 17, 2012
Last Updated
June 4, 2018
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT01753323
Brief Title
Efficacy, Safety, Tolerability and Pharmacokinetics of KAF156 in Adult Patients With Acute, Uncomplicated Plasmodium Falciparum or Vivax Malaria Mono-infection
Official Title
A Proof-of-concept, Open Label Study to Assess Efficacy, Safety, Tolerability and Pharmacokinetics of KAF156 in Adult Patients With Acute, Uncomplicated Plasmodium Falciparum or Vivax Malaria Mono-infection
Study Type
Interventional
2. Study Status
Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
March 2013 (undefined)
Primary Completion Date
August 2014 (Actual)
Study Completion Date
August 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will assess efficacy, safety , tolerability and PK in uncomplicated adult malaria patients with P. vivax or P. falciparum infection after 3 day dosing with KAF156 at 400 mg/day (Part 1) and single dosing with KAF156 at 800mg (Part 2)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria
Keywords
acute malaria, KAF156
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
43 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part 1 - Cohort 1: P. vivax: KAF156 400mg QD
Arm Type
Experimental
Arm Description
Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days.
Arm Title
Part 1 - Cohort 2: P. falciparum: KAF156 400mg QD
Arm Type
Experimental
Arm Description
Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days.
Arm Title
Part 2 - Cohort 3: P. falciparum: KAF156 800mg single dose
Arm Type
Experimental
Arm Description
Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg.
Intervention Type
Drug
Intervention Name(s)
KAF156
Intervention Description
KAF156 was supplied as tablets for oral use.
Primary Outcome Measure Information:
Title
Time to Parasite Clearance
Description
Parasite clearance was determined by assessing the parasite count in blood, using thin film, thick film and blood density assessments.
Time Frame
Day 5
Title
28-day Cure Rate - Part 2
Description
28-day cure rate was defined as the percentage of participants with blood parasite count of zero after 28 days of treatment.
Time Frame
Day 28
Secondary Outcome Measure Information:
Title
Area Under the Curve (AUC)0-24h - Part 1
Description
AUC0-24h was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose. The 24h sampling of first post dose was taken before the second dose. On Day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Time Frame
Days 1 and 3
Title
Maximum Concentration (Cmax) - Part 1
Description
Cmax was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose. The 24h sampling of first post dose should be taken before the second dose. On Day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Time Frame
Days 1 and 3
Title
Time to Maximum Concentration (Tmax) - Part 1
Description
Tmax was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose. The 24h sampling of first post dose should be taken before the second dose. On Day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Time Frame
Days 1 and 3
Title
Area Under the Curve (AUC)Last - Part 1
Description
AUClast was analyzed using parent drug in plasma samples. On Day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Time Frame
Day 3
Title
Area Under the Curve (AUC)Inf - Part 1
Description
AUCinf was analyzed using parent drug in plasma samples. On Day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Time Frame
Day 3
Title
Half-life (T1/2) - Part 1
Description
T1/2 was analyzed using parent drug in plasma samples. On day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Time Frame
Day 3
Title
Clearance (CL/F ) - Part 1
Description
CL/F was analyzed using parent drug in plasma samples. On day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Time Frame
Day 3
Title
Apparent Volume of Distribution During the Terminal Elimination Phase Following Extravascular Administration (Vz/F) - Part 1
Description
Vz/F was analyzed using parent drug in plasma samples. On Day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Time Frame
Day 3
Title
Accumulation Ratio (Racc) (=AUC0-24h, day3/AUC0-24h, day1) - Part 1
Description
Racc was analyzed using parent drug in plasma samples. On day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Time Frame
Day 3
Title
AUC0-24h - Part 2
Description
AUC0-24h was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose.
Time Frame
Day 1
Title
AUC0-48h - Part 2
Description
AUC0-48h was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Time Frame
Day 1
Title
AUClast - Part 2
Description
AUClast was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose
Time Frame
Day 1
Title
AUCinf - Part 2
Description
AUCinf was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose
Time Frame
Day 1
Title
Cmax - Part 2
Description
Cmax was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose.
Time Frame
Day 1
Title
Tmax - Part 2
Description
Tmax was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose.
Time Frame
Day 1
Title
T1/2 - Part 2
Description
T1/2 was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Time Frame
Day 1
Title
CL/F - Part 2
Description
CL/F was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Time Frame
Day 1
Title
Vz/F - Part 2
Description
Vz/F was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Time Frame
Day 1
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
-Male and female patients aged 20 to 60 years;Presence of mono-infection of P. falciparum or P. vivax; Weight between 40 kg to 90 kg.
Exclusion Criteria:
Patients with signs and symptoms of severe/complicated malaria
Infection with more than one parasite species
Women of child-bearing potential; pregnant or nursing women
Those who have taken any anti-malarial treatment in the preceding 14 days or other investigational drugs within 30 days or 5 half-lives
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Bangkok
ZIP/Postal Code
10400
Country
Thailand
Facility Name
Novartis Investigative Site
City
Srisaket
ZIP/Postal Code
33140
Country
Thailand
Facility Name
Novartis Investigative Site
City
Tak
ZIP/Postal Code
63110
Country
Thailand
Facility Name
Novartis Investigative Site
City
Tak
ZIP/Postal Code
63140
Country
Thailand
Facility Name
Novartis Investigative Site
City
Hanoi
ZIP/Postal Code
10000
Country
Vietnam
12. IPD Sharing Statement
Citations:
PubMed Identifier
27653565
Citation
White NJ, Duong TT, Uthaisin C, Nosten F, Phyo AP, Hanboonkunupakarn B, Pukrittayakamee S, Jittamala P, Chuthasmit K, Cheung MS, Feng Y, Li R, Magnusson B, Sultan M, Wieser D, Xun X, Zhao R, Diagana TT, Pertel P, Leong FJ. Antimalarial Activity of KAF156 in Falciparum and Vivax Malaria. N Engl J Med. 2016 Sep 22;375(12):1152-60. doi: 10.1056/NEJMoa1602250.
Results Reference
derived
Learn more about this trial
Efficacy, Safety, Tolerability and Pharmacokinetics of KAF156 in Adult Patients With Acute, Uncomplicated Plasmodium Falciparum or Vivax Malaria Mono-infection
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