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

January 30, 2012
May 9, 2013
January 2012
June 2012   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01524341 on ClinicalTrials.gov Archive Site
  • 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
  • Safety and tolerability [ Time Frame: vital signs: Days 1 through 6; ECG: Days1, 2, 3; Labs: Days 2, 3, 5, study completion ] [ Designated as safety issue: Yes ]

    Determined by vital signs, ECG evaluations, laboratory evaluations and adverse events.

    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 administrationi(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
Not Provided
Not Provided
 
Efficacy, Safety, Tolerability and Pharmacokinetics of KAE609 in Adult Patients With Acute, Uncomplicated Plasmodium Falciparum or Vivax Malaria Mono-infection
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

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

Not Provided
Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Malaria
Drug: KAE609
KAE609 was supplied as capsules for oral use.
  • Experimental: Cohort 1
    10 subjects with Plasmodium vivax malaria will receive 30 mg KAE609 once a day for three days
    Intervention: Drug: KAE609
  • Experimental: Cohort 2
    10 subjects with Plasmodium falciparum malaria will receive 30 mg KAE609 once a day for three days
    Intervention: Drug: KAE609
White NJ, Pukrittayakamee S, Phyo AP, Rueangweerayut R, Nosten F, Jittamala P, Jeeyapant A, Jain JP, Lefèvre G, Li R, Magnusson B, Diagana TT, Leong FJ. Spiroindolone KAE609 for falciparum and vivax malaria. N Engl J Med. 2014 Jul 31;371(5):403-10. doi: 10.1056/NEJMoa1315860.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
27
June 2012
June 2012   (final data collection date for primary outcome measure)

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.

Both
20 Years to 60 Years
No
Contact information is only displayed when the study is recruiting subjects
Thailand
 
NCT01524341
CKAE609X2201
Not Provided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP