Trial Outcomes & Findings for Efficacy and Safety of KAF156 in Combination With LUM-SDF in Adults and Children With Uncomplicated Plasmodium Falciparum Malaria (NCT NCT03167242)

Results Overview

PCR-corrected ACPR defined as the absence of parasitaemia was evaluated at Day 29 (i.e., 28 days post first dose) based on the short half-life of the study drugs. Microscopic species identification was confirmed and determined by PCR genotyping methods to establish malaria recrudescence/reinfection. A participant was considered as PCR-corrected ACPR at Day 29 if the participant did not meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure and was absence of parasitaemia on Day 29 irrespective of axillary temperature unless the presence of parasitaemia after 7 days was due to reinfection based on PCR. A presence of parasitaemia after 7 days of treatment initiation was considered as a reinfection only if the parasitaemia was clear before Day 8 and none of the parasite strain(s) detected on Day 8 or later matched with the parasite strain at baseline based on PCR.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

524 participants

Primary outcome timeframe

28 days post first dose

Results posted on

2022-02-10

Participant Flow

Participants were recruited from 13 sites in 10 countries.

Before being enrolled in the study, participants underwent a prescreening evaluation to ascertain the Plasmodium falciparum parasitemia count.

Participant milestones

Participant milestones
Measure	PK Run-in Cohort: KAF 200 mg and LUM 960 mg QD for 1 Day Participants received a single oral dose of KAF156 200 mg and LUM-SDF 960 mg	Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 Day Participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg	Part A - Cohort 3: KAF 400 mg and LUM 960 mg QD for 2 Days Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part A - Cohort 4: KAF 200 mg and LUM 480 mg QD for 3 Days Participants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 5: KAF 400 mg and LUM 480 mg QD for 3 Days Participants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 6: KAF 400 mg and LUM 960 mg QD for 3 Days Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part A - Cohort 7: Coartem Participants received Coartem twice daily via oral administration for 3 days	Part B - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part B - Cohort 2: KAF 400 mg and LUM 960 mg QD for 2 Days Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part B - Cohort 3: KAF 400 mg and LUM 960 mg QD for 3 Days Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part B - Cohort 4: Coartem Participants received Coartem twice daily via oral administration for 3 days
Overall Study STARTED	12	51	51	51	54	51	52	27	53	53	45	24
Overall Study Full Analysis Set (FAS)	12	51	51	51	54	51	52	27	52	53	45	24
Overall Study Pharmacokinetics (PK) Analysis Set	12	47	51	46	48	46	45	24	48	46	41	24
Overall Study Per-Protocol Set (PPS)	12	50	48	48	47	44	43	25	48	46	40	22
Overall Study Rich Pharmacokinetics (PK) Analysis Subset	12	5	6	6	6	12	5	0	0	0	0	0
Overall Study COMPLETED	12	50	48	50	53	49	50	26	52	53	43	23
Overall Study NOT COMPLETED	0	1	3	1	1	2	2	1	1	0	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 Day Participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg	Part A - Cohort 3: KAF 400 mg and LUM 960 mg QD for 2 Days Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part A - Cohort 4: KAF 200 mg and LUM 480 mg QD for 3 Days Participants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 5: KAF 400 mg and LUM 480 mg QD for 3 Days Participants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 6: KAF 400 mg and LUM 960 mg QD for 3 Days Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part A - Cohort 7: Coartem Participants received Coartem twice daily via oral administration for 3 days	Part B - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part B - Cohort 3: KAF 400 mg and LUM 960 mg QD for 3 Days Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part B - Cohort 4: Coartem Participants received Coartem twice daily via oral administration for 3 days
Overall Study Patient/Guardian Decision	1	2	1	1	1	0	0	0	1	0
Overall Study Lost to Follow-up	0	1	0	0	1	2	1	0	1	1
Overall Study Reason not provided	0	0	0	0	0	0	0	1	0	0

Baseline Characteristics

Efficacy and Safety of KAF156 in Combination With LUM-SDF in Adults and Children With Uncomplicated Plasmodium Falciparum Malaria

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PK Run-in Cohort: KAF 200 mg and LUM 960 mg QD for 1 Day n=12 Participants Participants received a single oral dose of KAF156 200 mg and LUM-SDF 960 mg	Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day n=51 Participants Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 Day n=51 Participants Participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg	Part A - Cohort 3: KAF 400 mg and LUM 960 mg QD for 2 Days n=51 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part A - Cohort 4: KAF 200 mg and LUM 480 mg QD for 3 Days n=54 Participants Participants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 5: KAF 400 mg and LUM 480 mg QD for 3 Days n=51 Participants Participants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 6: KAF 400 mg and LUM 960 mg QD for 3 Days n=52 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part A - Cohort 7: Coartem n=27 Participants Participants received Coartem twice daily via oral administration for 3 days	Part B - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day n=53 Participants Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part B - Cohort 2: KAF 400 mg and LUM 960 mg QD for 2 Days n=53 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part B - Cohort 3: KAF 400 mg and LUM 960 mg QD for 3 Days n=45 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part B - Cohort 4: Coartem n=24 Participants Participants received Coartem twice daily via oral administration for 3 days	Total n=524 Participants Total of all reporting groups
Age, Continuous	17.8 Years STANDARD_DEVIATION 10.25 • n=5 Participants	22.3 Years STANDARD_DEVIATION 13.53 • n=7 Participants	21.3 Years STANDARD_DEVIATION 10.69 • n=5 Participants	21.1 Years STANDARD_DEVIATION 11.09 • n=4 Participants	23.3 Years STANDARD_DEVIATION 14.68 • n=21 Participants	20.3 Years STANDARD_DEVIATION 11.90 • n=10 Participants	20.0 Years STANDARD_DEVIATION 9.49 • n=115 Participants	20.9 Years STANDARD_DEVIATION 12.28 • n=24 Participants	6.6 Years STANDARD_DEVIATION 2.86 • n=42 Participants	6.2 Years STANDARD_DEVIATION 2.90 • n=42 Participants	6.9 Years STANDARD_DEVIATION 2.60 • n=42 Participants	5.9 Years STANDARD_DEVIATION 2.21 • n=42 Participants	16.3 Years STANDARD_DEVIATION 12.10 • n=36 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	26 Participants n=7 Participants	24 Participants n=5 Participants	21 Participants n=4 Participants	26 Participants n=21 Participants	25 Participants n=10 Participants	20 Participants n=115 Participants	13 Participants n=24 Participants	31 Participants n=42 Participants	29 Participants n=42 Participants	20 Participants n=42 Participants	15 Participants n=42 Participants	256 Participants n=36 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	25 Participants n=7 Participants	27 Participants n=5 Participants	30 Participants n=4 Participants	28 Participants n=21 Participants	26 Participants n=10 Participants	32 Participants n=115 Participants	14 Participants n=24 Participants	22 Participants n=42 Participants	24 Participants n=42 Participants	25 Participants n=42 Participants	9 Participants n=42 Participants	268 Participants n=36 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	7 Participants n=7 Participants	7 Participants n=5 Participants	7 Participants n=4 Participants	9 Participants n=21 Participants	7 Participants n=10 Participants	7 Participants n=115 Participants	4 Participants n=24 Participants	1 Participants n=42 Participants	1 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	50 Participants n=36 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Black or African American	12 Participants n=5 Participants	44 Participants n=7 Participants	44 Participants n=5 Participants	43 Participants n=4 Participants	45 Participants n=21 Participants	44 Participants n=10 Participants	45 Participants n=115 Participants	23 Participants n=24 Participants	52 Participants n=42 Participants	52 Participants n=42 Participants	45 Participants n=42 Participants	24 Participants n=42 Participants	473 Participants n=36 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	1 Participants n=36 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=36 Participants

PRIMARY outcome

Timeframe: 28 days post first dose

Population: All participants comprised in Per-protocol Set (PPS)

PCR-corrected ACPR defined as the absence of parasitaemia was evaluated at Day 29 (i.e., 28 days post first dose) based on the short half-life of the study drugs. Microscopic species identification was confirmed and determined by PCR genotyping methods to establish malaria recrudescence/reinfection. A participant was considered as PCR-corrected ACPR at Day 29 if the participant did not meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure and was absence of parasitaemia on Day 29 irrespective of axillary temperature unless the presence of parasitaemia after 7 days was due to reinfection based on PCR. A presence of parasitaemia after 7 days of treatment initiation was considered as a reinfection only if the parasitaemia was clear before Day 8 and none of the parasite strain(s) detected on Day 8 or later matched with the parasite strain at baseline based on PCR.

Outcome measures

Outcome measures
Measure	Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day n=50 Participants Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 Day n=48 Participants Participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg	Part A - Cohort 3: KAF 400 mg and LUM 960 mg QD for 2 Days n=48 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part A - Cohort 4: KAF 200 mg and LUM 480 mg QD for 3 Days n=47 Participants Participants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 5: KAF 400 mg and LUM 480 mg QD for 3 Days n=44 Participants Participants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 6: KAF 400 mg and LUM 960 mg QD for 3 Days n=43 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part A - Cohort 7: Coartem n=25 Participants Participants received Coartem twice daily via oral administration for 3 days	Part B - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day n=48 Participants Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part B - Cohort 2: KAF 400 mg and LUM 960 mg QD for 2 Days n=46 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part B - Cohort 3: KAF 400 mg and LUM 960 mg QD for 3 Days n=40 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part B - Cohort 4: Coartem n=22 Participants Participants received Coartem twice daily via oral administration for 3 days	Part B - Cohort 4: Coartem Participants received Coartem twice daily via oral administration for 3 days
Part A and Part B: Number of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitological Response (ACPR) at Day 29	46 Participants	45 Participants	47 Participants	47 Participants	44 Participants	42 Participants	25 Participants	37 Participants	42 Participants	38 Participants	21 Participants	—

PRIMARY outcome

Timeframe: 0, 1, 3, 6, 12, 18 and 24 hours post-dose

Population: Pharmacokinetics (PK) Analysis Set. Only participants with available PK data at the specified time point were included in the analysis.

Pharmacokinetic (PK) parameters were calculated based on KAF156 blood concentrations determined by a validated liquid chromatography and tandem mass spectrometry (LC-MS/MS) method. AUC0-24h was determined using non-compartmental methods.

Outcome measures

Outcome measures
Measure	Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day n=11 Participants Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 Day Participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg	Part A - Cohort 3: KAF 400 mg and LUM 960 mg QD for 2 Days Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part A - Cohort 4: KAF 200 mg and LUM 480 mg QD for 3 Days Participants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 5: KAF 400 mg and LUM 480 mg QD for 3 Days Participants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 6: KAF 400 mg and LUM 960 mg QD for 3 Days Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part A - Cohort 7: Coartem Participants received Coartem twice daily via oral administration for 3 days	Part B - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part B - Cohort 2: KAF 400 mg and LUM 960 mg QD for 2 Days Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part B - Cohort 3: KAF 400 mg and LUM 960 mg QD for 3 Days Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part B - Cohort 4: Coartem Participants received Coartem twice daily via oral administration for 3 days	Part B - Cohort 4: Coartem Participants received Coartem twice daily via oral administration for 3 days
PK Run-in: Area Under the Blood Concentration-time Curve Over the Last 24 Hours After Treatment Dose (AUC0-24h) of KAF156	5.35 hours*μg/mL Geometric Coefficient of Variation 34.8	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 14, 28 and 42 days post first dose

Population: All participants comprised in Full Analysis Set (FAS)

PCR-uncorrected ACPR defined as the absence of parasitaemia was evaluated at days 15, 29 and 43 (i.e., 14, 28 and 42 days post first dose). A participant was considered as PCR-uncorrected ACPR at Days 15, 29 or 43 if the participant did not meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure and was absence of parasitaemia on Days 15, 29 or 43 irrespective of axillary temperature.

Outcome measures

Outcome measures
Measure	Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day n=51 Participants Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 Day n=51 Participants Participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg	Part A - Cohort 3: KAF 400 mg and LUM 960 mg QD for 2 Days n=51 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part A - Cohort 4: KAF 200 mg and LUM 480 mg QD for 3 Days n=54 Participants Participants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 5: KAF 400 mg and LUM 480 mg QD for 3 Days n=51 Participants Participants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 6: KAF 400 mg and LUM 960 mg QD for 3 Days n=52 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part A - Cohort 7: Coartem n=27 Participants Participants received Coartem twice daily via oral administration for 3 days	Part B - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day n=52 Participants Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part B - Cohort 2: KAF 400 mg and LUM 960 mg QD for 2 Days n=53 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part B - Cohort 3: KAF 400 mg and LUM 960 mg QD for 3 Days n=45 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part B - Cohort 4: Coartem n=24 Participants Participants received Coartem twice daily via oral administration for 3 days	Part B - Cohort 4: Coartem Participants received Coartem twice daily via oral administration for 3 days
Part A and Part B: Number of Participants With Polymerase Chain Reaction (PCR)-Uncorrected Adequate Clinical and Parasitological Response (ACPR) Day 42 post first dose	42 Participants	36 Participants	45 Participants	45 Participants	41 Participants	45 Participants	19 Participants	29 Participants	33 Participants	31 Participants	11 Participants	—
Part A and Part B: Number of Participants With Polymerase Chain Reaction (PCR)-Uncorrected Adequate Clinical and Parasitological Response (ACPR) Day 14 post first dose	49 Participants	47 Participants	51 Participants	53 Participants	50 Participants	51 Participants	27 Participants	51 Participants	52 Participants	43 Participants	24 Participants	—
Part A and Part B: Number of Participants With Polymerase Chain Reaction (PCR)-Uncorrected Adequate Clinical and Parasitological Response (ACPR) Day 28 post first dose	46 Participants	40 Participants	48 Participants	51 Participants	45 Participants	47 Participants	26 Participants	34 Participants	41 Participants	36 Participants	15 Participants	—

SECONDARY outcome

Timeframe: 14 and 42 days post first dose

Population: All participants comprised in Per-protocol Set (PPS)

PCR-corrected ACPR defined as the absence of parasitaemia was evaluated at days 15 and 43 (i.e., 14 and 42 days post first dose). Microscopic species identification was confirmed and determined by PCR genotyping methods to establish malaria recrudescence/reinfection. A participant was considered as PCR-corrected ACPR at Day 15 or Day 43 if the participant did not meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure and was absence of parasitaemia on Day 15 or Day 43 irrespective of axillary temperature unless the presence of parasitaemia after 7 days was due to reinfection based on PCR. A presence of parasitaemia after 7 days of treatment initiation was considered as a reinfection only if the parasitaemia was clear before Day 8 and none of the parasite strain(s) detected on Day 8 or later matched with the parasite strain at baseline based on PCR.

Outcome measures

Outcome measures
Measure	Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day n=50 Participants Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 Day n=48 Participants Participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg	Part A - Cohort 3: KAF 400 mg and LUM 960 mg QD for 2 Days n=48 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part A - Cohort 4: KAF 200 mg and LUM 480 mg QD for 3 Days n=47 Participants Participants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 5: KAF 400 mg and LUM 480 mg QD for 3 Days n=44 Participants Participants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 6: KAF 400 mg and LUM 960 mg QD for 3 Days n=43 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part A - Cohort 7: Coartem n=25 Participants Participants received Coartem twice daily via oral administration for 3 days	Part B - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day n=48 Participants Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part B - Cohort 2: KAF 400 mg and LUM 960 mg QD for 2 Days n=46 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part B - Cohort 3: KAF 400 mg and LUM 960 mg QD for 3 Days n=40 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part B - Cohort 4: Coartem n=22 Participants Participants received Coartem twice daily via oral administration for 3 days	Part B - Cohort 4: Coartem Participants received Coartem twice daily via oral administration for 3 days
Part A and Part B: Number of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitological Response (ACPR) Day 14 post first dose	48 Participants	46 Participants	48 Participants	47 Participants	44 Participants	43 Participants	25 Participants	47 Participants	45 Participants	40 Participants	22 Participants	—
Part A and Part B: Number of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitological Response (ACPR) Day 42 post first dose	45 Participants	44 Participants	46 Participants	46 Participants	43 Participants	41 Participants	24 Participants	36 Participants	37 Participants	37 Participants	20 Participants	—

SECONDARY outcome

Timeframe: 42 days post first dose

Population: All participants comprised in Full Analysis Set (FAS).

Recrudescence is defined as appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at baseline. Recrudescence must be confirmed by PCR analysis.

Outcome measures

Outcome measures
Measure	Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day n=51 Participants Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 Day n=51 Participants Participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg	Part A - Cohort 3: KAF 400 mg and LUM 960 mg QD for 2 Days n=51 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part A - Cohort 4: KAF 200 mg and LUM 480 mg QD for 3 Days n=54 Participants Participants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 5: KAF 400 mg and LUM 480 mg QD for 3 Days n=51 Participants Participants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 6: KAF 400 mg and LUM 960 mg QD for 3 Days n=52 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part A - Cohort 7: Coartem n=27 Participants Participants received Coartem twice daily via oral administration for 3 days	Part B - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day n=52 Participants Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part B - Cohort 2: KAF 400 mg and LUM 960 mg QD for 2 Days n=53 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part B - Cohort 3: KAF 400 mg and LUM 960 mg QD for 3 Days n=45 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part B - Cohort 4: Coartem n=24 Participants Participants received Coartem twice daily via oral administration for 3 days	Part B - Cohort 4: Coartem Participants received Coartem twice daily via oral administration for 3 days
Part A and Part B: Number of Participants With Recrudescence Events	4 Participants	3 Participants	1 Participants	1 Participants	0 Participants	2 Participants	0 Participants	12 Participants	7 Participants	3 Participants	2 Participants	—

SECONDARY outcome

Timeframe: 42 days post first dose

Population: All participants comprised in Full Analysis Set (FAS).

Reinfection is defined as appearance of asexual parasites after clearance of initial infection with a genotype different from those parasites present at baseline. Reinfection must be confirmed by PCR analysis.

Outcome measures

Outcome measures
Measure	Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day n=51 Participants Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 Day n=51 Participants Participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg	Part A - Cohort 3: KAF 400 mg and LUM 960 mg QD for 2 Days n=51 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part A - Cohort 4: KAF 200 mg and LUM 480 mg QD for 3 Days n=54 Participants Participants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 5: KAF 400 mg and LUM 480 mg QD for 3 Days n=51 Participants Participants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 6: KAF 400 mg and LUM 960 mg QD for 3 Days n=52 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part A - Cohort 7: Coartem n=27 Participants Participants received Coartem twice daily via oral administration for 3 days	Part B - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day n=52 Participants Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part B - Cohort 2: KAF 400 mg and LUM 960 mg QD for 2 Days n=53 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part B - Cohort 3: KAF 400 mg and LUM 960 mg QD for 3 Days n=45 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part B - Cohort 4: Coartem n=24 Participants Participants received Coartem twice daily via oral administration for 3 days	Part B - Cohort 4: Coartem Participants received Coartem twice daily via oral administration for 3 days
Part A and Part B: Number of Participants With Reinfection Events	3 Participants	7 Participants	4 Participants	7 Participants	8 Participants	2 Participants	8 Participants	11 Participants	10 Participants	9 Participants	10 Participants	—

SECONDARY outcome

Timeframe: 42 days post first dose

Population: Full Analysis Set (FAS). Only participants with fever at baseline and post-baseline assessment of fever clearance at the time point were included in the analysis.

Fever Clearance Time (FCT) is defined as the time from the first dose until the first time the axillary body temperature decreased below and remained below 37.5°C axillary or 38.0°C oral/tympanic/rectal for at least a further 24 hours. In case a participant received rescue medication before (fever) clearance, the time to event was censored at the first use of rescue medication.

Outcome measures

Outcome measures
Measure	Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day n=16 Participants Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 Day n=7 Participants Participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg	Part A - Cohort 3: KAF 400 mg and LUM 960 mg QD for 2 Days n=8 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part A - Cohort 4: KAF 200 mg and LUM 480 mg QD for 3 Days n=15 Participants Participants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 5: KAF 400 mg and LUM 480 mg QD for 3 Days n=13 Participants Participants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 6: KAF 400 mg and LUM 960 mg QD for 3 Days n=9 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part A - Cohort 7: Coartem n=5 Participants Participants received Coartem twice daily via oral administration for 3 days	Part B - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day n=9 Participants Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part B - Cohort 2: KAF 400 mg and LUM 960 mg QD for 2 Days n=11 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part B - Cohort 3: KAF 400 mg and LUM 960 mg QD for 3 Days n=10 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part B - Cohort 4: Coartem n=5 Participants Participants received Coartem twice daily via oral administration for 3 days	Part B - Cohort 4: Coartem Participants received Coartem twice daily via oral administration for 3 days
Part A and Part B: Fever Clearance Time (FCT)	18.7 Hours Standard Error 3.09	22.5 Hours Standard Error 6.09	20.3 Hours Standard Error 4.92	16.6 Hours Standard Error 3.48	17.5 Hours Standard Error 2.65	19.2 Hours Standard Error 2.92	26.3 Hours Standard Error 7.67	23.5 Hours Standard Error 10.26	17.3 Hours Standard Error 7.4	13.8 Hours Standard Error 3.68	22.9 Hours Standard Error 12.78	—

SECONDARY outcome

Timeframe: 42 days post first dose

Population: All participants comprised in Full Analysis Set (FAS).

Parasite Clearance Time (PCT) is defined as the time from the first dose until the first total and continued disappearance of asexual parasite forms which remained at least a further 48 hours. In case a participant received rescue medication before (parasite) clearance, the time to event was censored at the first use of rescue medication.

Outcome measures

Outcome measures
Measure	Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day n=12 Participants Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 Day n=51 Participants Participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg	Part A - Cohort 3: KAF 400 mg and LUM 960 mg QD for 2 Days n=51 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part A - Cohort 4: KAF 200 mg and LUM 480 mg QD for 3 Days n=51 Participants Participants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 5: KAF 400 mg and LUM 480 mg QD for 3 Days n=54 Participants Participants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 6: KAF 400 mg and LUM 960 mg QD for 3 Days n=51 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part A - Cohort 7: Coartem n=52 Participants Participants received Coartem twice daily via oral administration for 3 days	Part B - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day n=27 Participants Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part B - Cohort 2: KAF 400 mg and LUM 960 mg QD for 2 Days n=52 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part B - Cohort 3: KAF 400 mg and LUM 960 mg QD for 3 Days n=53 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part B - Cohort 4: Coartem n=45 Participants Participants received Coartem twice daily via oral administration for 3 days	Part B - Cohort 4: Coartem n=24 Participants Participants received Coartem twice daily via oral administration for 3 days
PK Run-in, Part A and Part B: Parasite Clearance Time (PCT)	49.9 Hours Standard Error 4.35	48.4 Hours Standard Error 3.5	46.6 Hours Standard Error 3.93	39.9 Hours Standard Error 2.46	51.4 Hours Standard Error 3.97	49.7 Hours Standard Error 3.72	48.1 Hours Standard Error 4.24	50.0 Hours Standard Error 12.82	42.6 Hours Standard Error 2.62	47.0 Hours Standard Error 2.79	41.9 Hours Standard Error 2.58	35.6 Hours Standard Error 2.82

SECONDARY outcome

Timeframe: 12, 24 and 48 hours post last dose

Population: Full Analysis Set (FAS). Only participants with assessment of parasitaemia at the timepoint were included in the analysis.

Parasitaemia is the quantitative content of parasites in the blood determined by microscopy examination validated methods. Only Plasmodium Falciparum asexual form is used for parasitaemia assessments.

Outcome measures

Outcome measures
Measure	Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day n=12 Participants Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 Day n=51 Participants Participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg	Part A - Cohort 3: KAF 400 mg and LUM 960 mg QD for 2 Days n=51 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part A - Cohort 4: KAF 200 mg and LUM 480 mg QD for 3 Days n=51 Participants Participants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 5: KAF 400 mg and LUM 480 mg QD for 3 Days n=54 Participants Participants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 6: KAF 400 mg and LUM 960 mg QD for 3 Days n=51 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part A - Cohort 7: Coartem n=52 Participants Participants received Coartem twice daily via oral administration for 3 days	Part B - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day n=27 Participants Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part B - Cohort 2: KAF 400 mg and LUM 960 mg QD for 2 Days n=52 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part B - Cohort 3: KAF 400 mg and LUM 960 mg QD for 3 Days n=53 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part B - Cohort 4: Coartem n=45 Participants Participants received Coartem twice daily via oral administration for 3 days	Part B - Cohort 4: Coartem n=24 Participants Participants received Coartem twice daily via oral administration for 3 days
PK Run-in, Part A and Part B: Number of Participants With Parasitaemia 12 hours post last dose	12 Participants	46 Participants	46 Participants	44 Participants	52 Participants	49 Participants	49 Participants	22 Participants	48 Participants	48 Participants	42 Participants	22 Participants
PK Run-in, Part A and Part B: Number of Participants With Parasitaemia 24 hours post last dose	11 Participants	39 Participants	41 Participants	38 Participants	46 Participants	42 Participants	34 Participants	14 Participants	41 Participants	42 Participants	36 Participants	17 Participants
PK Run-in, Part A and Part B: Number of Participants With Parasitaemia 48 hours post last dose	3 Participants	13 Participants	9 Participants	8 Participants	12 Participants	10 Participants	11 Participants	4 Participants	4 Participants	10 Participants	5 Participants	1 Participants

SECONDARY outcome

Timeframe: 3, 6, 18 and 24 hours post last dose

Population: Pharmacokinetics (PK) Analysis Set. Only participants with available PK data at the specified time point were included in the analysis. As per study design, AUC0-24h was not determined for Part B cohorts 2 and 3.

Pharmacokinetic (PK) parameters were calculated based on KAF156 blood concentrations determined by a validated liquid chromatography and tandem mass spectrometry (LC-MS/MS) method. AUC0-24h was determined using non-compartmental methods.

Outcome measures

Outcome measures
Measure	Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day n=38 Participants Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 Day n=44 Participants Participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg	Part A - Cohort 3: KAF 400 mg and LUM 960 mg QD for 2 Days n=41 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part A - Cohort 4: KAF 200 mg and LUM 480 mg QD for 3 Days n=43 Participants Participants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 5: KAF 400 mg and LUM 480 mg QD for 3 Days n=36 Participants Participants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 6: KAF 400 mg and LUM 960 mg QD for 3 Days n=41 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part A - Cohort 7: Coartem n=48 Participants Participants received Coartem twice daily via oral administration for 3 days	Part B - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part B - Cohort 2: KAF 400 mg and LUM 960 mg QD for 2 Days Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part B - Cohort 3: KAF 400 mg and LUM 960 mg QD for 3 Days Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part B - Cohort 4: Coartem Participants received Coartem twice daily via oral administration for 3 days	Part B - Cohort 4: Coartem Participants received Coartem twice daily via oral administration for 3 days
Part A and Part B: Area Under the Blood Concentration-time Curve Over the Last 24 Hours After Last Treatment Dose (AUC0-24h) of KAF156	9.84 hours*μg/mL Geometric Coefficient of Variation 41.5	21.7 hours*μg/mL Geometric Coefficient of Variation 41.7	9.95 hours*μg/mL Geometric Coefficient of Variation 131.9	5.91 hours*μg/mL Geometric Coefficient of Variation 29.2	11 hours*μg/mL Geometric Coefficient of Variation 79.3	10.9 hours*μg/mL Geometric Coefficient of Variation 57.4	11 hours*μg/mL Geometric Coefficient of Variation 47.7	—	—	—	—	—

SECONDARY outcome

Timeframe: 3, 6, 18, 24, 27, 30, 48, 51, 54, 68, 72 and 168 hours post last dose

Population: Pharmacokinetics (PK) Analysis Set. Only participants with available PK data at the specified time point were included in the analysis.

Pharmacokinetic (PK) parameters were calculated based on KAF156 blood concentrations determined by a validated liquid chromatography and tandem mass spectrometry (LC-MS/MS) method. Cmax was determined using non-compartmental methods.

Outcome measures

Outcome measures
Measure	Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day n=39 Participants Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 Day n=44 Participants Participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg	Part A - Cohort 3: KAF 400 mg and LUM 960 mg QD for 2 Days n=40 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part A - Cohort 4: KAF 200 mg and LUM 480 mg QD for 3 Days n=43 Participants Participants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 5: KAF 400 mg and LUM 480 mg QD for 3 Days n=36 Participants Participants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 6: KAF 400 mg and LUM 960 mg QD for 3 Days n=41 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part A - Cohort 7: Coartem n=48 Participants Participants received Coartem twice daily via oral administration for 3 days	Part B - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day n=46 Participants Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part B - Cohort 2: KAF 400 mg and LUM 960 mg QD for 2 Days n=41 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part B - Cohort 3: KAF 400 mg and LUM 960 mg QD for 3 Days Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part B - Cohort 4: Coartem Participants received Coartem twice daily via oral administration for 3 days	Part B - Cohort 4: Coartem Participants received Coartem twice daily via oral administration for 3 days
Part A and Part B: Maximum Peak Observed Concentration (Cmax) of KAF156	653 ng/mL Geometric Coefficient of Variation 43.9	1470 ng/mL Geometric Coefficient of Variation 46.5	1060 ng/mL Geometric Coefficient of Variation 83.9	665 ng/mL Geometric Coefficient of Variation 30.3	1470 ng/mL Geometric Coefficient of Variation 30.9	1320 ng/mL Geometric Coefficient of Variation 32.7	714 ng/mL Geometric Coefficient of Variation 49.4	1060 ng/mL Geometric Coefficient of Variation 48.4	1380 ng/mL Geometric Coefficient of Variation 29.7	—	—	—

SECONDARY outcome

Timeframe: 0, 1, 3, 6, 12, 18, 24, 27, 30, 36, 48, 72, 96 and 168 hours post last dose

Population: Rich Pharmacokinetics (PK) Analysis subset. Only participants with available PK data at the specified time point were included in the analysis.

Pharmacokinetic (PK) parameters were calculated based on KAF156 blood concentrations determined by a validated liquid chromatography and tandem mass spectrometry (LC-MS/MS) method. T½ was determined using non-compartmental methods.

Outcome measures

Outcome measures
Measure	Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day n=11 Participants Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 Day n=4 Participants Participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg	Part A - Cohort 3: KAF 400 mg and LUM 960 mg QD for 2 Days n=6 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part A - Cohort 4: KAF 200 mg and LUM 480 mg QD for 3 Days n=4 Participants Participants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 5: KAF 400 mg and LUM 480 mg QD for 3 Days n=2 Participants Participants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 6: KAF 400 mg and LUM 960 mg QD for 3 Days n=9 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part A - Cohort 7: Coartem n=2 Participants Participants received Coartem twice daily via oral administration for 3 days	Part B - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part B - Cohort 2: KAF 400 mg and LUM 960 mg QD for 2 Days Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part B - Cohort 3: KAF 400 mg and LUM 960 mg QD for 3 Days Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part B - Cohort 4: Coartem Participants received Coartem twice daily via oral administration for 3 days	Part B - Cohort 4: Coartem Participants received Coartem twice daily via oral administration for 3 days
PK Run-in and Part A: Elimination Half-life (T½) of KAF156	25.0 Hours Standard Deviation 8.81	25.4 Hours Standard Deviation 5.32	29.9 Hours Standard Deviation 9.95	31.0 Hours Standard Deviation 3.86	35.8 Hours Standard Deviation 19.4	28.4 Hours Standard Deviation 3.49	26.6 Hours Standard Deviation 4.15	—	—	—	—	—

SECONDARY outcome

Timeframe: 0, 1, 3, 6, 12, 18, 24, 30, 48, 96 and 168 hours post last dose

Population: Rich Pharmacokinetics (PK) Analysis subset. Only participants with available PK data at the specified time point were included in the analysis. As per study design, Tmax was only determined per PK Run-in and Part A cohorts 1 and 2.

Pharmacokinetic (PK) parameters were calculated based on KAF156 blood concentrations determined by a validated liquid chromatography and tandem mass spectrometry (LC-MS/MS) method. Tmax was determined using non-compartmental methods.

Outcome measures

Outcome measures
Measure	Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day n=12 Participants Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 Day n=5 Participants Participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg	Part A - Cohort 3: KAF 400 mg and LUM 960 mg QD for 2 Days n=6 Participants Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part A - Cohort 4: KAF 200 mg and LUM 480 mg QD for 3 Days Participants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 5: KAF 400 mg and LUM 480 mg QD for 3 Days Participants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A - Cohort 6: KAF 400 mg and LUM 960 mg QD for 3 Days Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part A - Cohort 7: Coartem Participants received Coartem twice daily via oral administration for 3 days	Part B - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part B - Cohort 2: KAF 400 mg and LUM 960 mg QD for 2 Days Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part B - Cohort 3: KAF 400 mg and LUM 960 mg QD for 3 Days Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part B - Cohort 4: Coartem Participants received Coartem twice daily via oral administration for 3 days	Part B - Cohort 4: Coartem Participants received Coartem twice daily via oral administration for 3 days
PK Run-in and Part A (Cohorts 1 and 2): Time to Reach Maximum Blood Concentrations (Tmax) of KAF156	4.23 Hours Standard Deviation 1.55	39.8 Hours Standard Deviation 77.3	5.99 Hours Standard Deviation 3.11	—	—	—	—	—	—	—	—	—

Adverse Events

PK Run-in: KAF 200 mg and LUM 960 mg QD for 1 Day

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Part A: KAF 800 mg and LUM 960 mg QD for 1 Day

Serious events: 1 serious events

Other events: 37 other events

Deaths: 0 deaths

Part A: KAF 200 mg and LUM 480 mg QD for 3 Days

Serious events: 2 serious events

Other events: 30 other events

Deaths: 0 deaths

Part A: KAF 400 mg and LUM 480 mg QD for 3 Days

Serious events: 1 serious events

Other events: 32 other events

Deaths: 0 deaths

Part A and Part B: KAF 400 mg and LUM 960 mg QD for 1 Day

Serious events: 7 serious events

Other events: 69 other events

Deaths: 0 deaths

Part A and Part B: KAF 400 mg and LUM 960 mg QD for 2 Days

Serious events: 5 serious events

Other events: 68 other events

Deaths: 0 deaths

Part A and Part B: KAF 400 mg and LUM 960 mg QD for 3 Days

Serious events: 2 serious events

Other events: 59 other events

Deaths: 0 deaths

Part A and Part B: Coartem

Serious events: 3 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	PK Run-in: KAF 200 mg and LUM 960 mg QD for 1 Day n=12 participants at risk PK Run-in participants received a single oral dose of KAF156 200 mg and LUM-SDF 960 mg	Part A: KAF 800 mg and LUM 960 mg QD for 1 Day n=51 participants at risk Part A - Cohort 2 participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg	Part A: KAF 200 mg and LUM 480 mg QD for 3 Days n=54 participants at risk Part A - Cohort 4 participants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A: KAF 400 mg and LUM 480 mg QD for 3 Days n=51 participants at risk Part A - Cohort 5 participants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A and Part B: KAF 400 mg and LUM 960 mg QD for 1 Day n=103 participants at risk Part A - Cohort 1 and Part B - Cohort 1 participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part A and Part B: KAF 400 mg and LUM 960 mg QD for 2 Days n=104 participants at risk Part A - Cohort 3 and Part B - Cohort 2 participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part A and Part B: KAF 400 mg and LUM 960 mg QD for 3 Days n=97 participants at risk Part A - Cohort 6 and Part B - Cohort 3 participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part A and Part B: Coartem n=51 participants at risk Part A - Cohort 7 and Part B - Cohort 4 participants received Coartem twice daily via oral administration for 3 days
Blood and lymphatic system disorders Anaemia	0.00% 0/12 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/54 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	2.0% 1/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/103 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.96% 1/104 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/97 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.
Hepatobiliary disorders Hepatitis acute	0.00% 0/12 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/54 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.97% 1/103 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/104 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/97 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.
Hepatobiliary disorders Jaundice	0.00% 0/12 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/54 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.97% 1/103 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/104 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/97 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.
Infections and infestations COVID-19	0.00% 0/12 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/54 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/103 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.96% 1/104 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/97 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.
Infections and infestations Plasmodium falciparum infection	0.00% 0/12 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	2.0% 1/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/54 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/103 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/104 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/97 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.
Infections and infestations Pneumonia	0.00% 0/12 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/54 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/103 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/104 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	1.0% 1/97 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.
Infections and infestations Sepsis	0.00% 0/12 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/54 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/103 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.96% 1/104 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/97 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/12 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/54 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.97% 1/103 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/104 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/97 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.
Investigations Alanine aminotransferase increased	0.00% 0/12 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/54 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/103 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/104 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/97 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	2.0% 1/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.
Investigations Aspartate aminotransferase	0.00% 0/12 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	1.9% 1/54 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/103 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/104 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/97 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.
Investigations Blood alkaline phosphatase increased	0.00% 0/12 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	1.9% 1/54 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	2.9% 3/103 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	1.9% 2/104 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/97 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	5.9% 3/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.
Investigations Blood bilirubin increased	0.00% 0/12 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/54 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	1.9% 2/103 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	1.9% 2/104 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	1.0% 1/97 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	3.9% 2/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.
Skin and subcutaneous tissue disorders Petechiae	0.00% 0/12 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/54 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/103 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/104 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	1.0% 1/97 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.

Other adverse events

Other adverse events
Measure	PK Run-in: KAF 200 mg and LUM 960 mg QD for 1 Day n=12 participants at risk PK Run-in participants received a single oral dose of KAF156 200 mg and LUM-SDF 960 mg	Part A: KAF 800 mg and LUM 960 mg QD for 1 Day n=51 participants at risk Part A - Cohort 2 participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg	Part A: KAF 200 mg and LUM 480 mg QD for 3 Days n=54 participants at risk Part A - Cohort 4 participants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A: KAF 400 mg and LUM 480 mg QD for 3 Days n=51 participants at risk Part A - Cohort 5 participants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Part A and Part B: KAF 400 mg and LUM 960 mg QD for 1 Day n=103 participants at risk Part A - Cohort 1 and Part B - Cohort 1 participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Part A and Part B: KAF 400 mg and LUM 960 mg QD for 2 Days n=104 participants at risk Part A - Cohort 3 and Part B - Cohort 2 participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Part A and Part B: KAF 400 mg and LUM 960 mg QD for 3 Days n=97 participants at risk Part A - Cohort 6 and Part B - Cohort 3 participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Part A and Part B: Coartem n=51 participants at risk Part A - Cohort 7 and Part B - Cohort 4 participants received Coartem twice daily via oral administration for 3 days
Blood and lymphatic system disorders Anaemia	0.00% 0/12 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	1.9% 1/54 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	2.0% 1/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	4.9% 5/103 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	2.9% 3/104 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	5.2% 5/97 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	2.0% 1/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.
Blood and lymphatic system disorders Eosinophilia	0.00% 0/12 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	3.9% 2/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	5.6% 3/54 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	3.9% 2/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/103 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.96% 1/104 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	3.1% 3/97 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/12 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	5.9% 3/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	1.9% 1/54 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	9.8% 5/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.97% 1/103 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.96% 1/104 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/97 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	3.9% 2/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.
Cardiac disorders Sinus bradycardia	0.00% 0/12 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	7.8% 4/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	1.9% 1/54 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	3.9% 4/103 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.96% 1/104 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	3.1% 3/97 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.
Gastrointestinal disorders Abdominal pain	0.00% 0/12 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	5.9% 3/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	3.7% 2/54 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	13.7% 7/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	2.9% 3/103 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	4.8% 5/104 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	4.1% 4/97 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.
Gastrointestinal disorders Diarrhoea	0.00% 0/12 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	7.8% 4/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	1.9% 1/54 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	3.9% 2/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.97% 1/103 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	2.9% 3/104 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	3.1% 3/97 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.
Gastrointestinal disorders Vomiting	0.00% 0/12 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	15.7% 8/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	3.7% 2/54 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	5.9% 3/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	7.8% 8/103 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	8.7% 9/104 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	8.2% 8/97 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	3.9% 2/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.
General disorders Pyrexia	0.00% 0/12 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	9.8% 5/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	7.4% 4/54 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	11.8% 6/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	19.4% 20/103 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	17.3% 18/104 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	9.3% 9/97 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	25.5% 13/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.
General disorders Treatment failure	0.00% 0/12 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	5.9% 3/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	5.6% 3/54 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	3.9% 2/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	2.9% 3/103 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/104 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	1.0% 1/97 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	3.9% 2/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.
Infections and infestations Bronchitis	8.3% 1/12 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/54 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	1.9% 2/103 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	2.9% 3/104 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	2.1% 2/97 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.
Infections and infestations Infection parasitic	8.3% 1/12 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	1.9% 1/54 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/103 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/104 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/97 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	2.0% 1/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.
Infections and infestations Malaria	0.00% 0/12 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	15.7% 8/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	7.4% 4/54 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	11.8% 6/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	27.2% 28/103 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	24.0% 25/104 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	16.5% 16/97 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	35.3% 18/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.
Infections and infestations Upper respiratory tract infection	0.00% 0/12 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	11.8% 6/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	9.3% 5/54 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	5.9% 3/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	14.6% 15/103 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	11.5% 12/104 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	12.4% 12/97 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	9.8% 5/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.
Investigations Blood phosphorus increased	33.3% 4/12 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	1.9% 1/54 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/103 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/104 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/97 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	0.00% 0/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.
Investigations Electrocardiogram QT prolonged	8.3% 1/12 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	9.8% 5/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	16.7% 9/54 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	17.6% 9/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	4.9% 5/103 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	5.8% 6/104 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	9.3% 9/97 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	5.9% 3/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.
Nervous system disorders Headache	0.00% 0/12 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	19.6% 10/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	27.8% 15/54 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	13.7% 7/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	15.5% 16/103 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	12.5% 13/104 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	14.4% 14/97 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	13.7% 7/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/12 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	5.9% 3/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	5.6% 3/54 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	9.8% 5/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	6.8% 7/103 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	9.6% 10/104 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	6.2% 6/97 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.	7.8% 4/51 • Adverse events were reported from Day 1 to Day 43, where Day 43 could be 42, 41 or 40 days after end of treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Any sign or symptom that occurs during the study treatment plus the 40, 41 or 42 days post treatment depending on whether the participant received treatment during 1, 2 or 3 consecutive days respectively. Part A and Part B safety data was pooled for safety analysis since Part B cohorts 1, 2 and 3 dosages and dosing regimens match with Part A cohorts 1, 3 and 6 respectively. Part B dosages and dosing regimens were selected based on the outcome of the interim assessment in Part A.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: + 1 862 778 8300

Email: [email protected]

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.
Publication restrictions are in place

Restriction type: OTHER