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

Malaria Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01753323
• Other study ID #: CKAF156X2201
• Status: Completed
• Phase: Phase 2
• Start date: March 2013
• Est. completion date: August 2014

Study information

• Verified date: June 2018
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: August 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Malaria
• Malaria, Vivax

Intervention

Drug:
• KAF156
KAF156 was supplied as tablets for oral use.

Locations

Country	Name	City	State
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Srisaket
Thailand	Novartis Investigative Site	Tak
Thailand	Novartis Investigative Site	Tak
Vietnam	Novartis Investigative Site	Hanoi

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Thailand,  Vietnam, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Parasite Clearance	Parasite clearance was determined by assessing the parasite count in blood, using thin film, thick film and blood density assessments.	Day 5
Primary	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.	Day 28
Secondary	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.	Days 1 and 3
Secondary	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.	Days 1 and 3
Secondary	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.	Days 1 and 3
Secondary	Area Under the Curve (AUC)Last - Part 1	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.	Day 3
Secondary	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.	Day 3
Secondary	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.	Day 3
Secondary	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.	Day 3
Secondary	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.	Day 3
Secondary	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.	Day 3
Secondary	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.	Day 1
Secondary	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.	Day 1
Secondary	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	Day 1
Secondary	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	Day 1
Secondary	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.	Day 1
Secondary	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.	Day 1
Secondary	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.	Day 1
Secondary	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.	Day 1
Secondary	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.	Day 1