Efficacy, Safety, Tolerability and Pharmacokinetics of KAE609 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:
NCT01524341
First received: January 30, 2012
Last updated: May 9, 2013
Last verified: May 2013
  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 KAE609 at 30 mg/day


Condition Intervention Phase
Malaria
Drug: KAE609
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, 3-day Repeated Dose Study to Assess Efficacy, Safety, Tolerability and Pharmacokinetics of KAE609 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: From baseline to the time point when the blood parasite count is zero(up to a maximum of 5 days) ] [ Designated as safety issue: No ]
    Calculated based on parasite count in blood. In thin film, use actual WBCs/µl, of blood to calculate parasite density by using the following formula: parasites/µl= #parasites× actual WBC/#WBCs counted. In thick film, assume that there are 250 RBCs per HPF, RBC count from 8 HPF equal 2000 RBC, Use actual RBCs/µl blood to calculate parasite density by using the following formula: parasites/µl= # of parasites in 8HPF/2000)× actual RBC.


Secondary Outcome Measures:
  • Number of participants with adverse events [ Time Frame: vital signs: Days 1 through 6; ECG: Days1, 2, 3; Labs: Days 2, 3, 5, study completion ] [ Designated as safety issue: Yes ]
    Number of participants with adverse events determined by Vital sign(body temperature, blood pressure and pulse rate): pre dose, 4, 8, 12, 16, 20, 24 hours post dose on Day 1: then 6, 12, 18, 24 hours post dose on each day during domiciles period until at least two consecutive normal temperature readings are obtained, then it will measure daily until Day 6. ECG: 3-4 hours post dose on day1; pre dose, 3-4 hours post dose on Day 2; pre dose, 3-4 hours post dose on Day 3 and study completion. Lab evaluation: Day 2, Day3 and Day5, study completion.

  • Area under the curve (AUC)0-24h on Day 1 and Day 3 [ Time Frame: Day 1 and Day 3 ] [ Designated as safety issue: No ]

    The parent drug in plasma samples will be analyzed. 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, 36, 48, 72, 96, 144, and 192 hours post dose


  • The accumulation ratio (Racc) (=AUC0-24h, day3/AUC0-24h, day1) [ Time Frame: Day 1 and Day 3 ] [ Designated as safety issue: No ]

    The parent drug in plasma samples will be analyzed. 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, 36, 48, 72, 96, 144, and 192 hours post dose


  • Maximum concentration (Cmax) on Day 1 and Day 3 [ Time Frame: Day 1 and Day 3 ] [ Designated as safety issue: No ]

    The parent drug in plasma samples will be analyzed. 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, 36, 48, 72, 96, 144, and 192 hours post dose


  • Time to maximum concentration (Tmax) on Day 1 and Day 3 [ Time Frame: Day 1 and Day 3 ] [ Designated as safety issue: No ]

    The parent drug in plasma samples will be analyzed. 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, 36, 48, 72, 96, 144, and 192 hours post dose


  • Half-life (T1/2) [ Time Frame: Day 3 ] [ Designated as safety issue: No ]
    The parent drug in plasma samples will be analyzed On Day 3: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, and 192 hours post dose

  • Clearance (CL/F ) [ Time Frame: Day 3 ] [ Designated as safety issue: No ]
    The parent drug in plasma samples will be analyzed On Day 3: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, and 192 hours post dose

  • The apparent volume of distribution during the terminal elimination phase following extravascular administration (Vz/F) [ Time Frame: Day 3 ] [ Designated as safety issue: No ]
    The parent drug in plasma samples will be analyzed. On Day 3: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, and 192 hours post dose


Enrollment: 27
Study Start Date: January 2012
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
10 subjects with Plasmodium vivax malaria will receive 30 mg KAE609 once a day for three days
Drug: KAE609
KAE609 was supplied as capsules for oral use.
Experimental: Cohort 2
10 subjects with Plasmodium falciparum malaria will receive 30 mg KAE609 once a day for three days
Drug: KAE609
KAE609 was supplied as capsules 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
  • Mixed Plasmodium infection
  • Presence of other serious or chronic clinical condition requiring hospitalization.
  • Severe malnutrition
  • Significant chronic medical conditions which in the opinion of the investigator preclude enrollment into the study

Other protocol-defined inclusion/exclusion criteria may apply.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01524341

Locations
Thailand
Novartis Investigative Site
Bangkok, Thailand, 10400
Novartis Investigative Site
Tak, Thailand, 63110
Novartis Investigative Site
Tak Province, Thailand, 63110
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: NCT01524341     History of Changes
Other Study ID Numbers: CKAE609X2201
Study First Received: January 30, 2012
Last Updated: May 9, 2013
Health Authority: United States: Food and Drug Administration
Thailand: Ministry of Public Health

Keywords provided by Novartis:
Acute malaria
KAE609

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

ClinicalTrials.gov processed this record on April 21, 2014