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

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:

MedlinePlus related topics: Malaria

U.S. FDA Resources

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 in CL/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 administration(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

Estimated Enrollment:	40
Study Start Date:	March 2013
Estimated Study Completion Date:	March 2014
Estimated Primary Completion Date:	March 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

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

Contacts

Contact: Novartis Pharmaceuticals

+41 61 324 1111

Locations

Thailand
Novartis Investigative Site	Not yet recruiting
Bangkok, Thailand, 10400
Novartis Investigative Site	Not yet recruiting
Tak, Thailand, 63140
Novartis Investigative Site	Not yet recruiting
Tak, Thailand, 63110
Novartis Investigative Site	Not yet recruiting
Tak Province, Thailand, 63110

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

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:	January 24, 2013
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
Protozoan Infections
Parasitic Diseases

ClinicalTrials.gov processed this record on May 16, 2013