Malaria
Conditions
Keywords
acute malaria, KAF156
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)
Interventions
DRUGKAF156
KAF156 was supplied as tablets for oral use.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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 |
| 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 |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Thailand, Vietnam
Participant flow
Pre-assignment details
The enrollment of P. vivax malaria patients (Cohort 1) began first. Then the falciparum cohort began enrollment after four vivax patients had completed their dosing. Cohort 3 was enrolled after the completion of an interim analysis of safety, tolerability and efficacy data of seven completed patients in the second cohort of Part 1.
Participants by arm
| Arm | Count |
|---|---|
| Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days. | 11 |
| Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days. | 10 |
| Part 2 - Cohort 3: P. Falciparum: KAF156 800mg Single Dose Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg. | 22 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 |
| Overall Study | Lack of Efficacy | 0 | 0 | 8 |
| Overall Study | Protocol deviation | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD | Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD | Part 2 - Cohort 3: P. Falciparum: KAF156 800mg Single Dose | Total |
|---|---|---|---|---|
| Age, Continuous | 28.1 Years STANDARD_DEVIATION 8.42 | 36.7 Years STANDARD_DEVIATION 10.9 | 28.9 Years STANDARD_DEVIATION 7 | 31.2 Years STANDARD_DEVIATION 8.77 |
| Sex/Gender, Customized | 11 Participants | 10 Participants | 22 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 11 | 8 / 10 | 22 / 22 |
| serious Total, serious adverse events | 0 / 11 | 0 / 10 | 0 / 22 |
Outcome results
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.
Time frame: Day 28
Population: Intent-to-treat analysis set: the intent-to-treat analysis set included all randomized participants who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD | 28-day Cure Rate - Part 2 | 63.6 Percentage of participants |
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.
Time frame: Day 5
Population: Pharmacodynamic (PD) analysis set for Cohorts 1, 2 and 3: The PD set included all participants who received at least one dose of study medication except for 1 participant from Cohort 1, who was excluded due to a protocol deviation, and 1 participant from Cohort 3, who was withdrawn on Day 1.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD | Time to Parasite Clearance | 23.63 Hours |
| Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD | Time to Parasite Clearance | 44.97 Hours |
| Part 2 - Cohort 3: P. Falciparum: KAF156 800mg Single Dose | Time to Parasite Clearance | 48.75 Hours |
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.
Time frame: Day 3
Population: Pharmacokinetic (PK) analysis set for Cohorts 1 and 2: The PK set included all participants who received at least one dose of study medication except for 1 participant from Cohort 1, who was excluded due to a protocol deviation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD | Accumulation Ratio (Racc) (=AUC0-24h, day3/AUC0-24h, day1) - Part 1 | 2.16 ratio | Standard Deviation 0.256 |
| Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD | Accumulation Ratio (Racc) (=AUC0-24h, day3/AUC0-24h, day1) - Part 1 | 2.15 ratio | Standard Deviation 0.384 |
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.
Time frame: Day 3
Population: Pharmacokinetic (PK) analysis set for Cohorts 1 and 2: The PK set included all participants who received at least one dose of study medication except for 1 participant from Cohort 1, who was excluded due to a protocol deviation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD | Apparent Volume of Distribution During the Terminal Elimination Phase Following Extravascular Administration (Vz/F) - Part 1 | 1150 Liters | Standard Deviation 286 |
| Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD | Apparent Volume of Distribution During the Terminal Elimination Phase Following Extravascular Administration (Vz/F) - Part 1 | 1140 Liters | Standard Deviation 288 |
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.
Time frame: Days 1 and 3
Population: Pharmacokinetic (PK) analysis set for Cohorts 1 and 2: The PK set included all participants who received at least one dose of study medication except for 1 participant from Cohort 1, who was excluded due to a protocol deviation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD | Area Under the Curve (AUC)0-24h - Part 1 | Day 1 | 9470 (hr*ng/mL) | Standard Deviation 2140 |
| Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD | Area Under the Curve (AUC)0-24h - Part 1 | Day 3 | 20200 (hr*ng/mL) | Standard Deviation 3730 |
| Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD | Area Under the Curve (AUC)0-24h - Part 1 | Day 1 | 10100 (hr*ng/mL) | Standard Deviation 2440 |
| Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD | Area Under the Curve (AUC)0-24h - Part 1 | Day 3 | 21700 (hr*ng/mL) | Standard Deviation 6630 |
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.
Time frame: Day 3
Population: Pharmacokinetic (PK) analysis set for Cohorts 1 and 2: The PK set included all participants who received at least one dose of study medication except for 1 participant from Cohort 1, who was excluded due to a protocol deviation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD | Area Under the Curve (AUC)Inf - Part 1 | 58300 hr*ng/mL | Standard Deviation 14500 |
| Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD | Area Under the Curve (AUC)Inf - Part 1 | 56700 hr*ng/mL | Standard Deviation 24800 |
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.
Time frame: Day 3
Population: Pharmacokinetic (PK) analysis set for Cohorts 1 and 2: The PK set included all participants who received at least one dose of study medication except for 1 participant from Cohort 1, who was excluded due to a protocol deviation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD | Area Under the Curve (AUC)Last - Part 1 | 55800 hr*ng/mL | Standard Error 12800 |
| Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD | Area Under the Curve (AUC)Last - Part 1 | 54300 hr*ng/mL | Standard Error 22500 |
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.
Time frame: Day 1
Population: Pharmacokinetic (PK) analysis set analysis set for Cohort 3: The PK set for Cohort 3 included participants who received at least one dose of study medication except for 1 participant who was withdrawn on Day 1 and 3 participants who vomited before 3 hours.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD | AUC0-24h - Part 2 | 21700 hr*ng/mL | Standard Error 5680 |
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.
Time frame: Day 1
Population: Pharmacokinetic (PK) analysis set analysis set for Cohort 3: The PK set for Cohort 3 included participants who received at least one dose of study medication except for 1 participant who was withdrawn on Day 1 and 3 participants who vomited before 3 hours.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD | AUC0-48h - Part 2 | 33600 hr*ng/mL | Standard Error 9150 |
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
Time frame: Day 1
Population: Pharmacokinetic (PK) analysis set analysis set for Cohort 3: The PK set for Cohort 3 included participants who received at least one dose of study medication except for 1 participant who was withdrawn on Day 1 and 3 participants who vomited before 3 hours.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD | AUCinf - Part 2 | 58300 hr*ng/mL | Standard Deviation 18600 |
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
Time frame: Day 1
Population: Pharmacokinetic (PK) analysis set analysis set for Cohort 3: The PK set for Cohort 3 included participants who received at least one dose of study medication except for 1 participant who was withdrawn on Day 1 and 3 participants who vomited before 3 hours.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD | AUClast - Part 2 | 54900 hr*ng/mL | Standard Deviation 16600 |
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.
Time frame: Day 3
Population: Pharmacokinetic (PK) analysis set for Cohorts 1 and 2: The PK set included all participants who received at least one dose of study medication except for 1 participant from Cohort 1, who was excluded due to a protocol deviation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD | Clearance (CL/F ) - Part 1 | 20.4 L/hr | Standard Deviation 4.04 |
| Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD | Clearance (CL/F ) - Part 1 | 19.7 L/hr | Standard Deviation 5.12 |
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.
Time frame: Day 1
Population: Pharmacokinetic (PK) analysis set analysis set for Cohort 3: The PK set for Cohort 3 included participants who received at least one dose of study medication except for 1 participant who was withdrawn on Day 1 and 3 participants who who vomited before 3 hours.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD | CL/F - Part 2 | 15.1 L/hr | Standard Deviation 4.85 |
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.
Time frame: Day 1
Population: Pharmacokinetic (PK) analysis set analysis set for Cohort 3: The PK set for Cohort 3 included participants who received at least one dose of study medication except for 1 participant who was withdrawn on Day 1 and 3 participants who vomited before 3 hours.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD | Cmax - Part 2 | 1800 ng/mL | Standard Deviation 404 |
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.
Time frame: Day 3
Population: Pharmacokinetic (PK) analysis set for Cohorts 1 and 2: The PK set included all participants who received at least one dose of study medication except for 1 participant from Cohort 1, who was excluded due to a protocol deviation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD | Half-life (T1/2) - Part 1 | 39.0 hr | Standard Deviation 7.4 |
| Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD | Half-life (T1/2) - Part 1 | 40.8 hr | Standard Deviation 8.37 |
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.
Time frame: Days 1 and 3
Population: Pharmacokinetic (PK) analysis set for Cohorts 1 and 2: The PK set included all participants who received at least one dose of study medication except for 1 participant from Cohort 1, who was excluded due to a protocol deviation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD | Maximum Concentration (Cmax) - Part 1 | Day 1 | 795 ng/mL | Standard Error 182 |
| Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD | Maximum Concentration (Cmax) - Part 1 | Day 3 | 1440 ng/mL | Standard Error 299 |
| Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD | Maximum Concentration (Cmax) - Part 1 | Day 1 | 856 ng/mL | Standard Error 158 |
| Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD | Maximum Concentration (Cmax) - Part 1 | Day 3 | 1620 ng/mL | Standard Error 384 |
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.
Time frame: Day 1
Population: Pharmacokinetic (PK) analysis set analysis set for Cohort 3: The PK set for Cohort 3 included participants who received at least one dose of study medication except for 1 participant who was withdrawn on Day 1 and 3 participants who vomited before 3 hours.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD | T1/2 - Part 2 | 48.7 hours | Standard Deviation 7.85 |
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.
Time frame: Days 1 and 3
Population: Pharmacokinetic (PK) analysis set for Cohorts 1 and 2: The PK set included all participants who received at least one dose of study medication except for 1 participant from Cohort 1, who was excluded due to a protocol deviation.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD | Time to Maximum Concentration (Tmax) - Part 1 | Day 3 | 3.00 hour |
| Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD | Time to Maximum Concentration (Tmax) - Part 1 | Day 1 | 3.00 hour |
| Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD | Time to Maximum Concentration (Tmax) - Part 1 | Day 1 | 3.00 hour |
| Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD | Time to Maximum Concentration (Tmax) - Part 1 | Day 3 | 2.52 hour |
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.
Time frame: Day 1
Population: Pharmacokinetic (PK) analysis set analysis set for Cohort 3: The PK set for Cohort 3 included participants who received at least one dose of study medication except for 1 participant who was withdrawn on Day 1 and 3 participants who vomited before 3 hours.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD | Tmax - Part 2 | 3.52 hours |
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.
Time frame: Day 1
Population: Pharmacokinetic (PK) analysis set analysis set for Cohort 3: The PK set for Cohort 3 included participants who received at least one dose of study medication except for 1 participant who was withdrawn on Day 1 and 3 participants who vomited before 3 hours.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD | Vz/F - Part 2 | 1030 Liters | Standard Deviation 264 |