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

Novartis Pharmaceuticals43 enrolled

Overview

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)

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Malaria

Interventions

KAF156DRUG

KAF156 was supplied as tablets for oral use.

Eligibility

Sex: ALLMin age: 20 YearsMax age: 60 Years

Medical Language ↔ Plain English

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

Locations (5)

Novartis Investigative Site

Bangkok, Thailand

Novartis Investigative Site

Si Sa Ket, Thailand

Novartis Investigative Site

Tak, Thailand

Novartis Investigative Site

Tak, Thailand

Novartis Investigative Site

Outcomes

Primary Outcomes

Time to Parasite Clearance

Parasite clearance was determined by assessing the parasite count in blood, using thin film, thick film and blood density assessments.

Time frame: Day 5

28-day Cure Rate - Part 2

28-day cure rate was defined as the percentage of participants with blood parasite count of zero after 28 days of treatment.

Time frame: Day 28

Secondary Outcomes

Area Under the Curve (AUC)0-24h - Part 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. 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.

Time frame: Days 1 and 3

Maximum Concentration (Cmax) - Part 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. 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 frame: Days 1 and 3

Time to Maximum Concentration (Tmax) - Part 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. 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 frame: Days 1 and 3

Area Under the Curve (AUC)Last - Part 1

Data from ClinicalTrials.gov

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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

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.

Time frame: Day 3

Half-life (T1/2) - Part 1

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.

Time frame: Day 3

Clearance (CL/F ) - Part 1

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.

Time frame: Day 3

Apparent Volume of Distribution During the Terminal Elimination Phase Following Extravascular Administration (Vz/F) - Part 1

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.

Time frame: Day 3

Accumulation Ratio (Racc) (=AUC0-24h, day3/AUC0-24h, day1) - Part 1

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.

Time frame: Day 3

AUC0-24h - Part 2

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.

Time frame: Day 1

AUC0-48h - Part 2

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.

Time frame: Day 1

AUClast - Part 2

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

Time frame: Day 1

AUCinf - Part 2

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

Time frame: Day 1

Cmax - Part 2

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.

Time frame: Day 1

Tmax - Part 2

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.

Time frame: Day 1

T1/2 - Part 2

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.

Time frame: Day 1

CL/F - Part 2

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.

Time frame: Day 1

Vz/F - Part 2

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.

Time frame: Day 1