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

Phase 2

Completed

Conditions: Malaria

Interventions: Drug: KAF156

Registration Number: NCT01753323

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: 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)

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 43

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Part 1 - Cohort 2: P. falciparum: KAF156 400mg QD	KAF156	Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days.
Part 1 - Cohort 1: P. vivax: KAF156 400mg QD	KAF156	Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days.
Part 2 - Cohort 3: P. falciparum: KAF156 800mg single dose	KAF156	Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg.

Primary Outcome Measures

Name	Time	Method
Time to Parasite Clearance	Day 5	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	Day 28	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

Name	Time	Method
Area Under the Curve (AUC)0-24h - Part 1	Days 1 and 3	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	Days 1 and 3	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	Days 1 and 3	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	Day 3	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	Day 3	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.
Accumulation Ratio (Racc) (=AUC0-24h, day3/AUC0-24h, day1) - Part 1	Day 3	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.
AUC0-48h - Part 2	Day 1	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.
Cmax - Part 2	Day 1	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.
Half-life (T1/2) - Part 1	Day 3	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	Day 3	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	Day 3	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.
AUClast - Part 2	Day 1	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
AUC0-24h - Part 2	Day 1	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.
AUCinf - Part 2	Day 1	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
Tmax - Part 2	Day 1	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	Day 1	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	Day 1	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	Day 1	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.