Trial Outcomes & Findings for Efficacy, Safety, Tolerability and Pharmacokinetics of KAF156 in Adult Patients With Acute, Uncomplicated Plasmodium Falciparum or Vivax Malaria Mono-infection (NCT NCT01753323)
NCT ID: NCT01753323
Last Updated: 2018-06-07
Results Overview
Parasite clearance was determined by assessing the parasite count in blood, using thin film, thick film and blood density assessments.
COMPLETED
PHASE2
43 participants
Day 5
2018-06-07
Participant Flow
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.
Participant milestones
| Measure |
Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD
Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days.
|
Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD
Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days.
|
Part 2 - Cohort 3: P. Falciparum: KAF156 800mg Single Dose
Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg.
|
|---|---|---|---|
|
Overall Study
STARTED
|
11
|
10
|
22
|
|
Overall Study
Pharmacodynamic (PD) Set
|
10
|
10
|
21
|
|
Overall Study
Pharmacokinetic(PK) Set
|
10
|
10
|
21
|
|
Overall Study
Safety Set
|
11
|
10
|
22
|
|
Overall Study
Intent-to-treat Analysis Set
|
11
|
10
|
22
|
|
Overall Study
COMPLETED
|
10
|
10
|
13
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
9
|
Reasons for withdrawal
| Measure |
Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD
Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days.
|
Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD
Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days.
|
Part 2 - Cohort 3: P. Falciparum: KAF156 800mg Single Dose
Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg.
|
|---|---|---|---|
|
Overall Study
Lack of Efficacy
|
0
|
0
|
8
|
|
Overall Study
Protocol deviation
|
1
|
0
|
0
|
|
Overall Study
Adverse Event
|
0
|
0
|
1
|
Baseline Characteristics
Efficacy, Safety, Tolerability and Pharmacokinetics of KAF156 in Adult Patients With Acute, Uncomplicated Plasmodium Falciparum or Vivax Malaria Mono-infection
Baseline characteristics by cohort
| Measure |
Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD
n=11 Participants
Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days.
|
Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD
n=10 Participants
Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days.
|
Part 2 - Cohort 3: P. Falciparum: KAF156 800mg Single Dose
n=22 Participants
Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg.
|
Total
n=43 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
28.1 Years
STANDARD_DEVIATION 8.42 • n=5 Participants
|
36.7 Years
STANDARD_DEVIATION 10.90 • n=7 Participants
|
28.9 Years
STANDARD_DEVIATION 7.00 • n=5 Participants
|
31.2 Years
STANDARD_DEVIATION 8.77 • n=4 Participants
|
|
Sex/Gender, Customized
|
11 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
43 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Day 5Population: 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.
Parasite clearance was determined by assessing the parasite count in blood, using thin film, thick film and blood density assessments.
Outcome measures
| Measure |
Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD
n=10 Participants
Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days.
|
Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD
n=10 Participants
Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days.
|
Part 2 - Cohort 3: P. Falciparum: KAF156 800mg Single Dose
n=21 Participants
Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg.
|
|---|---|---|---|
|
Time to Parasite Clearance
|
23.63 Hours
Interval 16.0 to 30.02
|
44.97 Hours
Interval 36.25 to 47.98
|
48.75 Hours
Interval 42.0 to 53.95
|
PRIMARY outcome
Timeframe: Day 28Population: Intent-to-treat analysis set: the intent-to-treat analysis set included all randomized participants who received at least one dose of study medication.
28-day cure rate was defined as the percentage of participants with blood parasite count of zero after 28 days of treatment.
Outcome measures
| Measure |
Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD
n=22 Participants
Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days.
|
Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD
Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days.
|
Part 2 - Cohort 3: P. Falciparum: KAF156 800mg Single Dose
Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg.
|
|---|---|---|---|
|
28-day Cure Rate - Part 2
|
63.6 Percentage of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1 and 3Population: 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.
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.
Outcome measures
| Measure |
Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD
n=10 Participants
Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days.
|
Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD
n=10 Participants
Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days.
|
Part 2 - Cohort 3: P. Falciparum: KAF156 800mg Single Dose
Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg.
|
|---|---|---|---|
|
Area Under the Curve (AUC)0-24h - Part 1
Day 1
|
9470 (hr*ng/mL)
Standard Deviation 2140
|
10100 (hr*ng/mL)
Standard Deviation 2440
|
—
|
|
Area Under the Curve (AUC)0-24h - Part 1
Day 3
|
20200 (hr*ng/mL)
Standard Deviation 3730
|
21700 (hr*ng/mL)
Standard Deviation 6630
|
—
|
SECONDARY outcome
Timeframe: Days 1 and 3Population: 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.
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.
Outcome measures
| Measure |
Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD
n=10 Participants
Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days.
|
Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD
n=10 Participants
Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days.
|
Part 2 - Cohort 3: P. Falciparum: KAF156 800mg Single Dose
Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg.
|
|---|---|---|---|
|
Maximum Concentration (Cmax) - Part 1
Day 1
|
795 ng/mL
Standard Error 182
|
856 ng/mL
Standard Error 158
|
—
|
|
Maximum Concentration (Cmax) - Part 1
Day 3
|
1440 ng/mL
Standard Error 299
|
1620 ng/mL
Standard Error 384
|
—
|
SECONDARY outcome
Timeframe: Days 1 and 3Population: 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.
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.
Outcome measures
| Measure |
Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD
n=10 Participants
Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days.
|
Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD
n=10 Participants
Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days.
|
Part 2 - Cohort 3: P. Falciparum: KAF156 800mg Single Dose
Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg.
|
|---|---|---|---|
|
Time to Maximum Concentration (Tmax) - Part 1
Day 1
|
3.00 hour
Interval 2.0 to 6.0
|
3.00 hour
Interval 1.0 to 4.03
|
—
|
|
Time to Maximum Concentration (Tmax) - Part 1
Day 3
|
3.00 hour
Interval 2.0 to 5.98
|
2.52 hour
Interval 2.0 to 3.02
|
—
|
SECONDARY outcome
Timeframe: Day 3Population: 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.
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.
Outcome measures
| Measure |
Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD
n=10 Participants
Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days.
|
Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD
n=10 Participants
Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days.
|
Part 2 - Cohort 3: P. Falciparum: KAF156 800mg Single Dose
Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg.
|
|---|---|---|---|
|
Area Under the Curve (AUC)Last - Part 1
|
55800 hr*ng/mL
Standard Error 12800
|
54300 hr*ng/mL
Standard Error 22500
|
—
|
SECONDARY outcome
Timeframe: Day 3Population: 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.
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.
Outcome measures
| Measure |
Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD
n=10 Participants
Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days.
|
Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD
n=10 Participants
Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days.
|
Part 2 - Cohort 3: P. Falciparum: KAF156 800mg Single Dose
Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg.
|
|---|---|---|---|
|
Area Under the Curve (AUC)Inf - Part 1
|
58300 hr*ng/mL
Standard Deviation 14500
|
56700 hr*ng/mL
Standard Deviation 24800
|
—
|
SECONDARY outcome
Timeframe: Day 3Population: 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.
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.
Outcome measures
| Measure |
Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD
n=10 Participants
Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days.
|
Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD
n=10 Participants
Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days.
|
Part 2 - Cohort 3: P. Falciparum: KAF156 800mg Single Dose
Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg.
|
|---|---|---|---|
|
Half-life (T1/2) - Part 1
|
39.0 hr
Standard Deviation 7.40
|
40.8 hr
Standard Deviation 8.37
|
—
|
SECONDARY outcome
Timeframe: Day 3Population: 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.
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.
Outcome measures
| Measure |
Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD
n=10 Participants
Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days.
|
Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD
n=10 Participants
Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days.
|
Part 2 - Cohort 3: P. Falciparum: KAF156 800mg Single Dose
Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg.
|
|---|---|---|---|
|
Clearance (CL/F ) - Part 1
|
20.4 L/hr
Standard Deviation 4.04
|
19.7 L/hr
Standard Deviation 5.12
|
—
|
SECONDARY outcome
Timeframe: Day 3Population: 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.
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.
Outcome measures
| Measure |
Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD
n=10 Participants
Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days.
|
Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD
n=10 Participants
Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days.
|
Part 2 - Cohort 3: P. Falciparum: KAF156 800mg Single Dose
Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg.
|
|---|---|---|---|
|
Apparent Volume of Distribution During the Terminal Elimination Phase Following Extravascular Administration (Vz/F) - Part 1
|
1150 Liters
Standard Deviation 286
|
1140 Liters
Standard Deviation 288
|
—
|
SECONDARY outcome
Timeframe: Day 3Population: 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.
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.
Outcome measures
| Measure |
Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD
n=10 Participants
Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days.
|
Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD
n=10 Participants
Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days.
|
Part 2 - Cohort 3: P. Falciparum: KAF156 800mg Single Dose
Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg.
|
|---|---|---|---|
|
Accumulation Ratio (Racc) (=AUC0-24h, day3/AUC0-24h, day1) - Part 1
|
2.16 ratio
Standard Deviation 0.256
|
2.15 ratio
Standard Deviation 0.384
|
—
|
SECONDARY outcome
Timeframe: Day 1Population: 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.
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.
Outcome measures
| Measure |
Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD
n=18 Participants
Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days.
|
Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD
Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days.
|
Part 2 - Cohort 3: P. Falciparum: KAF156 800mg Single Dose
Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg.
|
|---|---|---|---|
|
AUC0-24h - Part 2
|
21700 hr*ng/mL
Standard Error 5680
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1Population: 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.
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.
Outcome measures
| Measure |
Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD
n=18 Participants
Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days.
|
Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD
Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days.
|
Part 2 - Cohort 3: P. Falciparum: KAF156 800mg Single Dose
Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg.
|
|---|---|---|---|
|
AUC0-48h - Part 2
|
33600 hr*ng/mL
Standard Error 9150
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1Population: 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.
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
Outcome measures
| Measure |
Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD
n=18 Participants
Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days.
|
Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD
Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days.
|
Part 2 - Cohort 3: P. Falciparum: KAF156 800mg Single Dose
Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg.
|
|---|---|---|---|
|
AUClast - Part 2
|
54900 hr*ng/mL
Standard Deviation 16600
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1Population: 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.
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
Outcome measures
| Measure |
Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD
n=18 Participants
Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days.
|
Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD
Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days.
|
Part 2 - Cohort 3: P. Falciparum: KAF156 800mg Single Dose
Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg.
|
|---|---|---|---|
|
AUCinf - Part 2
|
58300 hr*ng/mL
Standard Deviation 18600
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1Population: 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.
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.
Outcome measures
| Measure |
Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD
n=18 Participants
Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days.
|
Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD
Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days.
|
Part 2 - Cohort 3: P. Falciparum: KAF156 800mg Single Dose
Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg.
|
|---|---|---|---|
|
Cmax - Part 2
|
1800 ng/mL
Standard Deviation 404
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1Population: 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.
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.
Outcome measures
| Measure |
Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD
n=18 Participants
Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days.
|
Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD
Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days.
|
Part 2 - Cohort 3: P. Falciparum: KAF156 800mg Single Dose
Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg.
|
|---|---|---|---|
|
Tmax - Part 2
|
3.52 hours
Interval 2.0 to 11.6
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1Population: 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.
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.
Outcome measures
| Measure |
Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD
n=18 Participants
Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days.
|
Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD
Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days.
|
Part 2 - Cohort 3: P. Falciparum: KAF156 800mg Single Dose
Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg.
|
|---|---|---|---|
|
T1/2 - Part 2
|
48.7 hours
Standard Deviation 7.85
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1Population: 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.
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.
Outcome measures
| Measure |
Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD
n=18 Participants
Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days.
|
Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD
Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days.
|
Part 2 - Cohort 3: P. Falciparum: KAF156 800mg Single Dose
Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg.
|
|---|---|---|---|
|
CL/F - Part 2
|
15.1 L/hr
Standard Deviation 4.85
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1Population: 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.
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.
Outcome measures
| Measure |
Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD
n=18 Participants
Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days.
|
Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD
Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days.
|
Part 2 - Cohort 3: P. Falciparum: KAF156 800mg Single Dose
Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg.
|
|---|---|---|---|
|
Vz/F - Part 2
|
1030 Liters
Standard Deviation 264
|
—
|
—
|
Adverse Events
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
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD
n=11 participants at risk
Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days.
|
Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD
n=10 participants at risk
Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days.
|
Part 2 - Cohort 3: P. Falciparum: KAF156 800mg Single Dose
n=22 participants at risk
Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/11
|
10.0%
1/10
|
31.8%
7/22
|
|
Blood and lymphatic system disorders
Lymphopenia
|
0.00%
0/11
|
0.00%
0/10
|
4.5%
1/22
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/11
|
0.00%
0/10
|
18.2%
4/22
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/11
|
10.0%
1/10
|
59.1%
13/22
|
|
Cardiac disorders
Atrioventricular block first degree
|
0.00%
0/11
|
0.00%
0/10
|
4.5%
1/22
|
|
Cardiac disorders
Palpitations
|
0.00%
0/11
|
10.0%
1/10
|
0.00%
0/22
|
|
Cardiac disorders
Sinus bradycardia
|
9.1%
1/11
|
30.0%
3/10
|
63.6%
14/22
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/11
|
20.0%
2/10
|
4.5%
1/22
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/11
|
0.00%
0/10
|
18.2%
4/22
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/11
|
10.0%
1/10
|
18.2%
4/22
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/11
|
10.0%
1/10
|
27.3%
6/22
|
|
General disorders
Fatigue
|
0.00%
0/11
|
0.00%
0/10
|
9.1%
2/22
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.00%
0/11
|
10.0%
1/10
|
18.2%
4/22
|
|
Infections and infestations
Malaria
|
0.00%
0/11
|
0.00%
0/10
|
4.5%
1/22
|
|
Investigations
Alanine aminotransferase increased
|
9.1%
1/11
|
10.0%
1/10
|
22.7%
5/22
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/11
|
10.0%
1/10
|
13.6%
3/22
|
|
Investigations
Blood thyroid stimulating hormone decreased
|
0.00%
0/11
|
10.0%
1/10
|
0.00%
0/22
|
|
Investigations
Electrocardiogram QT prolonged
|
9.1%
1/11
|
0.00%
0/10
|
13.6%
3/22
|
|
Investigations
Eosinophil count increased
|
9.1%
1/11
|
0.00%
0/10
|
0.00%
0/22
|
|
Investigations
Monocyte count decreased
|
0.00%
0/11
|
10.0%
1/10
|
0.00%
0/22
|
|
Investigations
Monocyte count increased
|
18.2%
2/11
|
0.00%
0/10
|
0.00%
0/22
|
|
Investigations
Thyroxine free increased
|
0.00%
0/11
|
10.0%
1/10
|
0.00%
0/22
|
|
Investigations
White blood cell count decreased
|
0.00%
0/11
|
0.00%
0/10
|
18.2%
4/22
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/11
|
10.0%
1/10
|
22.7%
5/22
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/11
|
10.0%
1/10
|
0.00%
0/22
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/11
|
10.0%
1/10
|
50.0%
11/22
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/11
|
0.00%
0/10
|
4.5%
1/22
|
|
Nervous system disorders
Dizziness
|
0.00%
0/11
|
10.0%
1/10
|
9.1%
2/22
|
|
Renal and urinary disorders
Glycosuria
|
0.00%
0/11
|
10.0%
1/10
|
0.00%
0/22
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/11
|
0.00%
0/10
|
13.6%
3/22
|
|
Skin and subcutaneous tissue disorders
Dermatitis allergic
|
0.00%
0/11
|
10.0%
1/10
|
0.00%
0/22
|
|
Vascular disorders
Hypotension
|
0.00%
0/11
|
0.00%
0/10
|
9.1%
2/22
|
Additional Information
Study Director
Novartis Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER