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: August 7, 2014
Last verified: August 2014
  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 400 mg
Drug: KAF156 800 mg
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:
  • Parasite clearance time [ Time Frame: baseline and up to 5 days ] [ Designated as safety issue: No ]
    Change in calculated parasite count in blood, using thin film, thick film and blood density assessments.

  • 28-day cure rate [ Time Frame: day 28 ] [ Designated as safety issue: No ]
    Percent of patients with blood parasite count of zero after 28 days of treatment.


Secondary Outcome Measures:
  • ECG monitoring [ Time Frame: Days 1, 2, 3 and 5 ] [ Designated as safety issue: Yes ]
    ECGs will be monitored at 3 hours post dose on day 1; pre-dose, and 3 hours post dose on Day 2; pre-dose, 3, 5, 24, 48 hours post dose on Day 3 and at study completion.

  • Area under the curve (AUC) 0-24h [ Time Frame: Days 1 and 3 ] [ Designated as safety issue: No ]
    Change in AUC 0-24h will be analyzed using parent drug in plasma samples. On Day 1: 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: 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) [ Time Frame: Day s 1 and 3 ] [ Designated as safety issue: No ]
    Change in accumulation ratio will be analyzed using parent drug in plasma samples. On Day 1: 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: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose

  • Maximum concentration (Cmax) [ Time Frame: Days 1 and 3 (Part 1); Day 1 (Part 2) ] [ Designated as safety issue: No ]
    Changes in Cmax will be analyzed using parent drug in plasma samples. On Day 1 of Part 1: 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 of Part 1 and Day 1 of Part 2: 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) [ Time Frame: Days 1 and 3 of (Part 1); Day 1 (Part 2) ] [ Designated as safety issue: No ]
    Change in Tmax will be analyzed using parent drug in plasma samples. On Day 1 of Part 1: 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 of Part 1 and Day 1 of Part 2: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose

  • Half-life (T1/2) [ Time Frame: Day 3 (Part 1); Day 1 (Part 2) ] [ Designated as safety issue: No ]
    Changes in half life will be analyzed using parent drug in plasma samples. On Day 3 of Part 1 and Day 1 of Part 2: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose

  • Clearance (CL/F ) [ Time Frame: Day 3 (Part 1); Day 1 (Part 2) ] [ Designated as safety issue: No ]
    Changes inCL/F will be analyzed using parent drug in plasma samples . On Day 3 of Part 1 and Day 1 of Part 2: 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 administrationi(Vz/F) [ Time Frame: Day 3 of Part 1; Day 1 of Part 2 ] [ Designated as safety issue: No ]
    Changes in apparent volume of distribution will be analyzed using parent drug in plasma samples. On Day 3 of Part 1 and Day 1 of Part 2: 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 [ Time Frame: Day 3 (Part 1); Day 1 (Part 2) ] [ Designated as safety issue: No ]
    Changes in AUC -last will be analyzed using parent drug in plasma samples. On Day 3 of Part 1 and Day 1 of Part 2: 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) 0-t [ Time Frame: Day 1 (Part 2) ] [ Designated as safety issue: No ]
    Changes in AUC 0-t will be analyzed using parent drug in plasma samples On Day 1 of Part 2: 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 [ Time Frame: Day 1 (Part 2) ] [ Designated as safety issue: No ]
    Changes in AUC inf will be analyzed using parent drug in plasma samples. On Day 1 of Part 2: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose

  • Lab evaluation - hematology [ Time Frame: Days 2, 3, 5, study completion ] [ Designated as safety issue: Yes ]
    Changes in hematology will be measured.

  • Lab evaluation - blood chemistry [ Time Frame: Day 2, 3, 5, study completion ] [ Designated as safety issue: Yes ]
    Changes in blood chemistry will be measured.

  • Lab evaluation - urinalysis [ Time Frame: Day 2, 3, 5, study completion ] [ Designated as safety issue: Yes ]
    Changes in urinalysis will be measured


Enrollment: 40
Study Start Date: March 2013
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
Approximately 10 subjects with Plasmodium vivax malaria will receive KAF156 400 mg once a day for three days
Drug: KAF156 400 mg
KAF156 will be supplied as tablets for oral use.
Experimental: Cohort 2
Approximately 10 subjects with Plasmodium falciparum malaria will receive KAF156 400mg once a day for three days
Drug: KAF156 400 mg
KAF156 will be supplied as tablets for oral use.
Experimental: Cohort 3
Approximately 20 subjects with Plasmodium falciparum malaria will receive single dose of KAF156 800mg
Drug: KAF156 800 mg
KAF156 will be 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, 63140
Novartis Investigative Site
Tak, Thailand, 63110
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
Last Updated: August 7, 2014
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 October 23, 2014