Efficacy, Safety, Tolerability and Pharmacokinetics of KAF156 in Adult Patients With Acute, Uncomplicated Plasmodium Falciparum or Vivax Malaria Mono-infection

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01753323
First received: December 17, 2012
Last updated: July 23, 2015
Last verified: July 2015
  Purpose

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)


Condition Intervention Phase
Malaria
Drug: KAF156
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Time to Parasite Clearance [ Time Frame: Day 5 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Days 1 and 3 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Days 1 and 3 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Days 1 and 3 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 3 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 3 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 3 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 3 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 3 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 3 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    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.


Enrollment: 43
Study Start Date: March 2013
Study Completion Date: August 2014
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1 - Cohort 1
Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days.
Drug: KAF156
KAF156 was supplied as tablets for oral use.
Experimental: Part 1 - Cohort 2
Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days.
Drug: KAF156
KAF156 was supplied as tablets for oral use.
Experimental: Part 2 - Cohort 3
Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg.
Drug: KAF156
KAF156 was supplied as tablets for oral use.

  Eligibility

Ages Eligible for Study:   20 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01753323

Locations
Thailand
Novartis Investigative Site
Bangkok, Thailand, 10400
Novartis Investigative Site
Srisaket, Thailand, 33140
Novartis Investigative Site
Tak, Thailand, 63110
Novartis Investigative Site
Tak, Thailand, 63140
Vietnam
Novartis Investigative Site
Hanoi, Vietnam, 10000
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01753323     History of Changes
Other Study ID Numbers: CKAF156X2201
Study First Received: December 17, 2012
Results First Received: July 23, 2015
Last Updated: July 23, 2015
Health Authority: Thailand: Institute for Development of Human Research Protection (IHRP)

Keywords provided by Novartis:
acute malaria, KAF156

Additional relevant MeSH terms:
Malaria
Malaria, Vivax
Parasitic Diseases
Protozoan Infections

ClinicalTrials.gov processed this record on August 26, 2015