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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03167242
• Collaborator: Medicines for Malaria Venture (Other)
• Enrollment: 524
• Locations: 11
• Arms: 12
• Actual Duration (Months): 46.9
• Patients Per Site: 47.6
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

This study was designed to determine the most effective and tolerable dose at the shortest dosing regimen of the investigational drug KAF156 in combination with a solid dispersion formulation of lumefantrine (LUM-SDF) in adult/adolescent and pediatric patients with uncomplicated Plasmodium falciparum malaria.

There is unmet medical need for anti-malarial treatment with new mechanism of action to reduce probability of developing resistance, and for duration shorter than 3 days of treatment and/or reduced pill burden.

Condition or Disease	Intervention/Treatment	Phase
Acute Uncomplicated Plasmodium Falciparum Malaria	Drug: KAF156; Drug: Coartem; Drug: Lumefantrine Solid Dispersion Formulation	Phase 2

Detailed Description

This was a Phase 2 multi-center and open-label study with a single cohort pharmacokinetic (PK) Run-in Part followed by 2 randomized parallel-group parts, Part A and Part B, in adults and children with confirmed and uncomplicated Plasmodium falciparum malaria. Each part (PK Run-in, Part A and Part B) had the same design structure: A screening phase of up to 24 hours where participants were evaluated for eligibility and randomized (Part A and B) into different cohorts. A treatment phase of up to 3 days where participants were treated for 1, 2 or 3 consecutive days. Finally, participants were followed up until Day 43, where the rescue medication was the local standard at the discretion of the Investigator and participants

PK Run-in part: Adult/adolescent participants (≥ 12 years old) were dosed with a single dose of 200 mg KAF156 and 960 mg LUM-SDF at Day 1. The purpose of this part was to assess potential PK interactions between the compounds when dosed together.

Part A: Adult/adolescent participants (≥ 12 years old) were randomized into one of seven cohorts in a 2:2:2:2:2:2:1 ratio: six KAF156 and LUM-SDF cohorts at starting doses of 400 mg and 480 mg once daily (QD) for 1 day respectively and a control arm (Coartem twice a day (BID) for 3 days). Upon completion of Part A, all the dosing groups were evaluated in an interim assessment to determine the effective and tolerated KAF156 and LUM-SDF dosing regimen and dosages to be used in Part B.

Part B: Children participants (2 to < 12 years old) were randomized to three KAF156 and LUM-SDF cohorts at dosages and dosing regimens selected from Part A and the control arm (Coartem) in a 2:2:2:1 ratio.

Study Design

• Study Type: Interventional
• Actual Enrollment: 524 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Interventional, Multicenter, Randomized Open Label Study to Determine the Effective and Tolerable Dose of KAF156 and Lumefantrine Solid Dispersion Formulation in Combination, Given Once Daily for 1, 2 and 3-days to Adults and Children With Uncomplicated Plasmodium Falciparum Malaria
• Actual Study Start Date: Aug 2, 2017
• Actual Primary Completion Date: Jun 14, 2021
• Actual Study Completion Date: Jun 28, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: KAF156; KAF156 comes in 100 mg tablets for oral administration. KAF156 was administered in combination with LUM-SDF once daily (QD) for 1, 2 or 3 days at 200 mg, 400 mg or 800 mg doses.; Other Names: KAF ; Drug: Lumefantrine Solid Dispersion Formulation; LUM-SDF comes in 240 mg or 480 mg sachets for oral administration. LUM-SDF was administered in combination with KAF156 once daily (QD) for 1, 2 or 3 days at 480 mg or 960 mg doses.; Other Names: LUM-SDF and LUM
Experimental: 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	Drug: KAF156; KAF156 comes in 100 mg tablets for oral administration. KAF156 was administered in combination with LUM-SDF once daily (QD) for 1, 2 or 3 days at 200 mg, 400 mg or 800 mg doses.; Other Names: KAF ; Drug: Lumefantrine Solid Dispersion Formulation; LUM-SDF comes in 240 mg or 480 mg sachets for oral administration. LUM-SDF was administered in combination with KAF156 once daily (QD) for 1, 2 or 3 days at 480 mg or 960 mg doses.; Other Names: LUM-SDF and LUM
Experimental: 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	Drug: KAF156; KAF156 comes in 100 mg tablets for oral administration. KAF156 was administered in combination with LUM-SDF once daily (QD) for 1, 2 or 3 days at 200 mg, 400 mg or 800 mg doses.; Other Names: KAF ; Drug: Lumefantrine Solid Dispersion Formulation; LUM-SDF comes in 240 mg or 480 mg sachets for oral administration. LUM-SDF was administered in combination with KAF156 once daily (QD) for 1, 2 or 3 days at 480 mg or 960 mg doses.; Other Names: LUM-SDF and LUM
Experimental: 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	Drug: KAF156; KAF156 comes in 100 mg tablets for oral administration. KAF156 was administered in combination with LUM-SDF once daily (QD) for 1, 2 or 3 days at 200 mg, 400 mg or 800 mg doses.; Other Names: KAF ; Drug: Lumefantrine Solid Dispersion Formulation; LUM-SDF comes in 240 mg or 480 mg sachets for oral administration. LUM-SDF was administered in combination with KAF156 once daily (QD) for 1, 2 or 3 days at 480 mg or 960 mg doses.; Other Names: LUM-SDF and LUM
Experimental: 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	Drug: KAF156; KAF156 comes in 100 mg tablets for oral administration. KAF156 was administered in combination with LUM-SDF once daily (QD) for 1, 2 or 3 days at 200 mg, 400 mg or 800 mg doses.; Other Names: KAF ; Drug: Lumefantrine Solid Dispersion Formulation; LUM-SDF comes in 240 mg or 480 mg sachets for oral administration. LUM-SDF was administered in combination with KAF156 once daily (QD) for 1, 2 or 3 days at 480 mg or 960 mg doses.; Other Names: LUM-SDF and LUM
Experimental: 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	Drug: KAF156; KAF156 comes in 100 mg tablets for oral administration. KAF156 was administered in combination with LUM-SDF once daily (QD) for 1, 2 or 3 days at 200 mg, 400 mg or 800 mg doses.; Other Names: KAF ; Drug: Lumefantrine Solid Dispersion Formulation; LUM-SDF comes in 240 mg or 480 mg sachets for oral administration. LUM-SDF was administered in combination with KAF156 once daily (QD) for 1, 2 or 3 days at 480 mg or 960 mg doses.; Other Names: LUM-SDF and LUM
Active Comparator: Part A - Cohort 7: Coartem Participants received Coartem twice daily via oral administration for 3 days	Drug: Coartem; Coartem comes as 20/120 mg dispersible tablets or 80/480 mg tablets for oral administration. Coartem was administered twice daily for 3 days as active comparator.
Experimental: 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	Drug: KAF156; KAF156 comes in 100 mg tablets for oral administration. KAF156 was administered in combination with LUM-SDF once daily (QD) for 1, 2 or 3 days at 200 mg, 400 mg or 800 mg doses.; Other Names: KAF ; Drug: Lumefantrine Solid Dispersion Formulation; LUM-SDF comes in 240 mg or 480 mg sachets for oral administration. LUM-SDF was administered in combination with KAF156 once daily (QD) for 1, 2 or 3 days at 480 mg or 960 mg doses.; Other Names: LUM-SDF and LUM
Experimental: 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	Drug: KAF156; KAF156 comes in 100 mg tablets for oral administration. KAF156 was administered in combination with LUM-SDF once daily (QD) for 1, 2 or 3 days at 200 mg, 400 mg or 800 mg doses.; Other Names: KAF ; Drug: Lumefantrine Solid Dispersion Formulation; LUM-SDF comes in 240 mg or 480 mg sachets for oral administration. LUM-SDF was administered in combination with KAF156 once daily (QD) for 1, 2 or 3 days at 480 mg or 960 mg doses.; Other Names: LUM-SDF and LUM
Experimental: 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	Drug: KAF156; KAF156 comes in 100 mg tablets for oral administration. KAF156 was administered in combination with LUM-SDF once daily (QD) for 1, 2 or 3 days at 200 mg, 400 mg or 800 mg doses.; Other Names: KAF ; Drug: Lumefantrine Solid Dispersion Formulation; LUM-SDF comes in 240 mg or 480 mg sachets for oral administration. LUM-SDF was administered in combination with KAF156 once daily (QD) for 1, 2 or 3 days at 480 mg or 960 mg doses.; Other Names: LUM-SDF and LUM
Experimental: 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	Drug: KAF156; KAF156 comes in 100 mg tablets for oral administration. KAF156 was administered in combination with LUM-SDF once daily (QD) for 1, 2 or 3 days at 200 mg, 400 mg or 800 mg doses.; Other Names: KAF ; Drug: Lumefantrine Solid Dispersion Formulation; LUM-SDF comes in 240 mg or 480 mg sachets for oral administration. LUM-SDF was administered in combination with KAF156 once daily (QD) for 1, 2 or 3 days at 480 mg or 960 mg doses.; Other Names: LUM-SDF and LUM
Active Comparator: Part B - Cohort 4: Coartem Participants received Coartem twice daily via oral administration for 3 days	Drug: Coartem; Coartem comes as 20/120 mg dispersible tablets or 80/480 mg tablets for oral administration. Coartem was administered twice daily for 3 days as active comparator.

Outcome Measures

Primary Outcome Measures

1. Part A and Part B: Number of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitological Response (ACPR) at Day 29 [28 days post first dose]

   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.

2. PK Run-in: Area Under the Blood Concentration-time Curve Over the Last 24 Hours After Treatment Dose (AUC0-24h) of KAF156 [0, 1, 3, 6, 12, 18 and 24 hours post-dose]

   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.

Secondary Outcome Measures

1. Part A and Part B: Number of Participants With Polymerase Chain Reaction (PCR)-Uncorrected Adequate Clinical and Parasitological Response (ACPR) [14, 28 and 42 days post first dose]

   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.

2. Part A and Part B: Number of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitological Response (ACPR) [14 and 42 days post first dose]

   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.

3. Part A and Part B: Number of Participants With Recrudescence Events [42 days post first dose]

   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.

4. Part A and Part B: Number of Participants With Reinfection Events [42 days post first dose]

   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.

5. Part A and Part B: Fever Clearance Time (FCT) [42 days post first dose]

   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.

6. PK Run-in, Part A and Part B: Parasite Clearance Time (PCT) [42 days post first dose]

   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.

7. PK Run-in, Part A and Part B: Number of Participants With Parasitaemia [12, 24 and 48 hours post last dose]

   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.

8. 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 [3, 6, 18 and 24 hours post last dose]

   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.

9. Part A and Part B: Maximum Peak Observed Concentration (Cmax) of KAF156 [3, 6, 18, 24, 27, 30, 48, 51, 54, 68, 72 and 168 hours post last dose]

   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.

10. PK Run-in and Part A: Elimination Half-life (T½) of KAF156 [0, 1, 3, 6, 12, 18, 24, 27, 30, 36, 48, 72, 96 and 168 hours post last dose]

    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.

11. PK Run-in and Part A (Cohorts 1 and 2): Time to Reach Maximum Blood Concentrations (Tmax) of KAF156 [0, 1, 3, 6, 12, 18, 24, 30, 48, 96 and 168 hours post last dose]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Part A: male and female patients ≥ 12 years and with a body weight ≥ 35.0 kg. Part B: after determining the effective/tolerated doses and regimens in adolescent and adult patients, male and female patients ≥ 2 and < 12 years and with a body weight ≥ 10.0 kg will be included.

• Microscopic confirmation of P. falciparum by Giemsa-stained thick and thin films.

• 1. falciparum parasitaemia of more than 1000 and less than 150 000 parasites/µL at the time of pre-screening (i.e., Study Visit 1).

• Axillary temperature ≥ 37.5 ºC or oral/tympanic/rectal temperature ≥ 38.3 ºC; or similar history of fever during the previous 24 hours (history of fever must be documented).

• Written informed consent must be obtained before any assessment is performed. If the patient is unable to read and write, then a witnessed consent according to local ethical standards is permitted. Patients < 18 years old, who are capable of providing assent, must provide assent with parental/legal guardian consent or as per local ethical guidelines.

Exclusion Criteria:

• Mixed Plasmodium infections.

• Signs and symptoms of severe malaria according to WHO (World Health Organization) 2015 criteria unless characterized by high parasitaemia only.

• Patients with concurrent febrile illnesses (e.g., typhoid fever).

• Severe vomiting, defined as more than 3 times in the 24 hours prior to inclusion in the study or severe diarrhea defined as more than 3 watery stools per day.

• Pregnant or nursing (lactating) women.

• Clinically relevant abnormalities of electrolyte balance which require correction, e.g., hypokalemia, hypocalcemia or hypomagnesemia.

• Anemia (Hemoglobin level < 8 g/dL).

• Patients with prior antimalarial therapy or antibiotics with antimalarial activity within minimum of their five (5) plasma half-lives (or within 4 weeks of screening if half-life is unknown).

• History or family history of long QT syndrome or sudden cardiac death, or any other clinical condition known to prolong the QTc (heart rate-corrected QT) interval, such as history of symptomatic cardiac arrhythmias, clinically relevant bradycardia or severe heart disease.

• Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the patient in case of participation in the study. The investigator should make this determination in consideration of the patient's medical history and/or clinical or laboratory evidence of any of the following:

• AST/ALT > 2 x the upper limit of normal range (ULN), regardless of the level of total bilirubin

• AST/ALT > 1.5 and ≤ 2 x ULN and total bilirubin is > ULN

• Total bilirubin > 2 x ULN, regardless of the level of AST/ALT

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Nanoro		Burkina Faso
2	Novartis Investigative Site	Lambarene		Gabon
3	Novartis Investigative Site	Ranchi	Jharkhand	India	834009
4	Novartis Investigative Site	Kombewa		Kenya
5	Novartis Investigative Site	Siaya		Kenya	2300
6	Novartis Investigative Site	Sotuba		Mali
7	Novartis Investigative Site	Chokwe		Mozambique
8	Novartis Investigative Site	Tak		Thailand	63140
9	Novartis Investigative Site	Masaka		Uganda
10	Novartis Investigative Site	Tororo		Uganda
11	Novartis Investigative Site	Binh Phuoc Province	VNM	Vietnam	830000

Sponsors and Collaborators

• Novartis Pharmaceuticals
• Medicines for Malaria Venture

Investigators

• Study Director: Study Director, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Apr 13, 2018
• Statistical Analysis Plan - Nov 8, 2021

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03167242
• Other Study ID Numbers: CKAF156A2202; 2020-003284-25
• First Posted: May 25, 2017
• Last Update Posted: Feb 10, 2022
• Last Verified: Dec 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Malaria; Malaria, Falciparum; Lumefantrine; Artemether, Lumefantrine Drug Combination

Study Results

Participant Flow

Recruitment Details	Participants were recruited from 13 sites in 10 countries.
Pre-assignment Detail	Before being enrolled in the study, participants underwent a prescreening evaluation to ascertain the Plasmodium falciparum parasitemia count.

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

Baseline Characteristics

Arm/Group Title	PK Run-in Cohort: KAF 200 mg and LUM 960 mg QD for 1 Day	Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day	Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 Day	Part A - Cohort 3: KAF 400 mg and LUM 960 mg QD for 2 Days	Part A - Cohort 4: KAF 200 mg and LUM 480 mg QD for 3 Days	Part A - Cohort 5: KAF 400 mg and LUM 480 mg QD for 3 Days	Part A - Cohort 6: KAF 400 mg and LUM 960 mg QD for 3 Days	Part A - Cohort 7: Coartem	Part B - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day	Part B - Cohort 2: KAF 400 mg and LUM 960 mg QD for 2 Days	Part B - Cohort 3: KAF 400 mg and LUM 960 mg QD for 3 Days	Part B - Cohort 4: Coartem	Total
Arm/Group Description	Participants received a single oral dose of KAF156 200 mg and LUM-SDF 960 mg	Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Participants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Participants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Participants received Coartem twice daily via oral administration for 3 days	Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Participants received Coartem twice daily via oral administration for 3 days	Total of all reporting groups
Overall Participants	12	51	51	51	54	51	52	27	53	53	45	24	524
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	17.8 (10.25)	22.3 (13.53)	21.3 (10.69)	21.1 (11.09)	23.3 (14.68)	20.3 (11.90)	20.0 (9.49)	20.9 (12.28)	6.6 (2.86)	6.2 (2.90)	6.9 (2.60)	5.9 (2.21)	16.3 (12.10)
Sex: Female, Male (Count of Participants)
Female	6 50%	26 51%	24 47.1%	21 41.2%	26 48.1%	25 49%	20 38.5%	13 48.1%	31 58.5%	29 54.7%	20 44.4%	15 62.5%	256 48.9%
Male	6 50%	25 49%	27 52.9%	30 58.8%	28 51.9%	26 51%	32 61.5%	14 51.9%	22 41.5%	24 45.3%	25 55.6%	9 37.5%	268 51.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	7 13.7%	7 13.7%	7 13.7%	9 16.7%	7 13.7%	7 13.5%	4 14.8%	1 1.9%	1 1.9%	0 0%	0 0%	50 9.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	12 100%	44 86.3%	44 86.3%	43 84.3%	45 83.3%	44 86.3%	45 86.5%	23 85.2%	52 98.1%	52 98.1%	45 100%	24 100%	473 90.3%
White	0 0%	0 0%	0 0%	1 2%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.2%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Part A and Part B: Number of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitological Response (ACPR) at Day 29
Description	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.
Time Frame	28 days post first dose

Outcome Measure Data

Analysis Population Description

All participants comprised in Per-protocol Set (PPS)

Arm/Group Title	Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day	Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 Day	Part A - Cohort 3: KAF 400 mg and LUM 960 mg QD for 2 Days	Part A - Cohort 4: KAF 200 mg and LUM 480 mg QD for 3 Days	Part A - Cohort 5: KAF 400 mg and LUM 480 mg QD for 3 Days	Part A - Cohort 6: KAF 400 mg and LUM 960 mg QD for 3 Days	Part A - Cohort 7: Coartem	Part B - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day	Part B - Cohort 2: KAF 400 mg and LUM 960 mg QD for 2 Days	Part B - Cohort 3: KAF 400 mg and LUM 960 mg QD for 3 Days	Part B - Cohort 4: Coartem
Arm/Group Description	Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Participants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Participants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Participants received Coartem twice daily via oral administration for 3 days	Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Participants received Coartem twice daily via oral administration for 3 days
Measure Participants	50	48	48	47	44	43	25	48	46	40	22
Count of Participants [Participants]	46 383.3%	45 88.2%	47 92.2%	47 92.2%	44 81.5%	42 82.4%	25 48.1%	37 137%	42 79.2%	38 71.7%	21 46.7%

2. Primary Outcome

Title	PK Run-in: Area Under the Blood Concentration-time Curve Over the Last 24 Hours After Treatment Dose (AUC0-24h) of KAF156
Description	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.
Time Frame	0, 1, 3, 6, 12, 18 and 24 hours post-dose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	PK Run-in Cohort: KAF 200 mg and LUM 960 mg QD for 1 Day
Arm/Group Description	Participants received a single oral dose of KAF156 200 mg and LUM-SDF 960 mg
Measure Participants	11
Geometric Mean (Geometric Coefficient of Variation) [hours*μg/mL]	5.35 (34.8)

3. Secondary Outcome

Title	Part A and Part B: Number of Participants With Polymerase Chain Reaction (PCR)-Uncorrected Adequate Clinical and Parasitological Response (ACPR)
Description	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.
Time Frame	14, 28 and 42 days post first dose

Outcome Measure Data

Analysis Population Description

All participants comprised in Full Analysis Set (FAS)

Arm/Group Title	Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day	Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 Day	Part A - Cohort 3: KAF 400 mg and LUM 960 mg QD for 2 Days	Part A - Cohort 4: KAF 200 mg and LUM 480 mg QD for 3 Days	Part A - Cohort 5: KAF 400 mg and LUM 480 mg QD for 3 Days	Part A - Cohort 6: KAF 400 mg and LUM 960 mg QD for 3 Days	Part A - Cohort 7: Coartem	Part B - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day	Part B - Cohort 2: KAF 400 mg and LUM 960 mg QD for 2 Days	Part B - Cohort 3: KAF 400 mg and LUM 960 mg QD for 3 Days	Part B - Cohort 4: Coartem
Arm/Group Description	Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Participants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Participants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Participants received Coartem twice daily via oral administration for 3 days	Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Participants received Coartem twice daily via oral administration for 3 days
Measure Participants	51	51	51	54	51	52	27	52	53	45	24
Day 14 post first dose	49 408.3%	47 92.2%	51 100%	53 103.9%	50 92.6%	51 100%	27 51.9%	51 188.9%	52 98.1%	43 81.1%	24 53.3%
Day 28 post first dose	46 383.3%	40 78.4%	48 94.1%	51 100%	45 83.3%	47 92.2%	26 50%	34 125.9%	41 77.4%	36 67.9%	15 33.3%
Day 42 post first dose	42 350%	36 70.6%	45 88.2%	45 88.2%	41 75.9%	45 88.2%	19 36.5%	29 107.4%	33 62.3%	31 58.5%	11 24.4%

4. Secondary Outcome

Title	Part A and Part B: Number of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitological Response (ACPR)
Description	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.
Time Frame	14 and 42 days post first dose

Outcome Measure Data

Analysis Population Description

All participants comprised in Per-protocol Set (PPS)

Arm/Group Title	Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day	Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 Day	Part A - Cohort 3: KAF 400 mg and LUM 960 mg QD for 2 Days	Part A - Cohort 4: KAF 200 mg and LUM 480 mg QD for 3 Days	Part A - Cohort 5: KAF 400 mg and LUM 480 mg QD for 3 Days	Part A - Cohort 6: KAF 400 mg and LUM 960 mg QD for 3 Days	Part A - Cohort 7: Coartem	Part B - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day	Part B - Cohort 2: KAF 400 mg and LUM 960 mg QD for 2 Days	Part B - Cohort 3: KAF 400 mg and LUM 960 mg QD for 3 Days	Part B - Cohort 4: Coartem
Arm/Group Description	Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Participants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Participants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Participants received Coartem twice daily via oral administration for 3 days	Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Participants received Coartem twice daily via oral administration for 3 days
Measure Participants	50	48	48	47	44	43	25	48	46	40	22
Day 14 post first dose	48 400%	46 90.2%	48 94.1%	47 92.2%	44 81.5%	43 84.3%	25 48.1%	47 174.1%	45 84.9%	40 75.5%	22 48.9%
Day 42 post first dose	45 375%	44 86.3%	46 90.2%	46 90.2%	43 79.6%	41 80.4%	24 46.2%	36 133.3%	37 69.8%	37 69.8%	20 44.4%

5. Secondary Outcome

Title	Part A and Part B: Number of Participants With Recrudescence Events
Description	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.
Time Frame	42 days post first dose

Outcome Measure Data

Analysis Population Description

All participants comprised in Full Analysis Set (FAS).

Arm/Group Title	Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day	Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 Day	Part A - Cohort 3: KAF 400 mg and LUM 960 mg QD for 2 Days	Part A - Cohort 4: KAF 200 mg and LUM 480 mg QD for 3 Days	Part A - Cohort 5: KAF 400 mg and LUM 480 mg QD for 3 Days	Part A - Cohort 6: KAF 400 mg and LUM 960 mg QD for 3 Days	Part A - Cohort 7: Coartem	Part B - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day	Part B - Cohort 2: KAF 400 mg and LUM 960 mg QD for 2 Days	Part B - Cohort 3: KAF 400 mg and LUM 960 mg QD for 3 Days	Part B - Cohort 4: Coartem
Arm/Group Description	Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Participants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Participants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Participants received Coartem twice daily via oral administration for 3 days	Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Participants received Coartem twice daily via oral administration for 3 days
Measure Participants	51	51	51	54	51	52	27	52	53	45	24
Count of Participants [Participants]	4 33.3%	3 5.9%	1 2%	1 2%	0 0%	2 3.9%	0 0%	12 44.4%	7 13.2%	3 5.7%	2 4.4%

6. Secondary Outcome

Title	Part A and Part B: Number of Participants With Reinfection Events
Description	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.
Time Frame	42 days post first dose

Outcome Measure Data

Analysis Population Description

All participants comprised in Full Analysis Set (FAS).

Arm/Group Title	Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day	Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 Day	Part A - Cohort 3: KAF 400 mg and LUM 960 mg QD for 2 Days	Part A - Cohort 4: KAF 200 mg and LUM 480 mg QD for 3 Days	Part A - Cohort 5: KAF 400 mg and LUM 480 mg QD for 3 Days	Part A - Cohort 6: KAF 400 mg and LUM 960 mg QD for 3 Days	Part A - Cohort 7: Coartem	Part B - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day	Part B - Cohort 2: KAF 400 mg and LUM 960 mg QD for 2 Days	Part B - Cohort 3: KAF 400 mg and LUM 960 mg QD for 3 Days	Part B - Cohort 4: Coartem
Arm/Group Description	Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Participants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Participants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Participants received Coartem twice daily via oral administration for 3 days	Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Participants received Coartem twice daily via oral administration for 3 days
Measure Participants	51	51	51	54	51	52	27	52	53	45	24
Count of Participants [Participants]	3 25%	7 13.7%	4 7.8%	7 13.7%	8 14.8%	2 3.9%	8 15.4%	11 40.7%	10 18.9%	9 17%	10 22.2%

7. Secondary Outcome

Title	Part A and Part B: Fever Clearance Time (FCT)
Description	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.
Time Frame	42 days post first dose

Outcome Measure Data

Analysis Population Description

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.

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

8. Secondary Outcome

Title	PK Run-in, Part A and Part B: Parasite Clearance Time (PCT)
Description	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.
Time Frame	42 days post first dose

Outcome Measure Data

Analysis Population Description

All participants comprised in Full Analysis Set (FAS).

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

9. Secondary Outcome

Title	PK Run-in, Part A and Part B: Number of Participants With Parasitaemia
Description	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.
Time Frame	12, 24 and 48 hours post last dose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	PK Run-in Cohort: KAF 200 mg and LUM 960 mg QD for 1 Day	Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day	Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 Day	Part A - Cohort 3: KAF 400 mg and LUM 960 mg QD for 2 Days	Part A - Cohort 4: KAF 200 mg and LUM 480 mg QD for 3 Days	Part A - Cohort 5: KAF 400 mg and LUM 480 mg QD for 3 Days	Part A - Cohort 6: KAF 400 mg and LUM 960 mg QD for 3 Days	Part A - Cohort 7: Coartem	Part B - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day	Part B - Cohort 2: KAF 400 mg and LUM 960 mg QD for 2 Days	Part B - Cohort 3: KAF 400 mg and LUM 960 mg QD for 3 Days	Part B - Cohort 4: Coartem
Arm/Group Description	Participants received a single oral dose of KAF156 200 mg and LUM-SDF 960 mg	Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Participants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Participants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Participants received Coartem twice daily via oral administration for 3 days	Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Participants received Coartem twice daily via oral administration for 3 days
Measure Participants	12	51	51	51	54	51	52	27	52	53	45	24
12 hours post last dose	12 100%	46 90.2%	46 90.2%	44 86.3%	52 96.3%	49 96.1%	49 94.2%	22 81.5%	48 90.6%	48 90.6%	42 93.3%	22 91.7%
24 hours post last dose	11 91.7%	39 76.5%	41 80.4%	38 74.5%	46 85.2%	42 82.4%	34 65.4%	14 51.9%	41 77.4%	42 79.2%	36 80%	17 70.8%
48 hours post last dose	3 25%	13 25.5%	9 17.6%	8 15.7%	12 22.2%	10 19.6%	11 21.2%	4 14.8%	4 7.5%	10 18.9%	5 11.1%	1 4.2%

10. Secondary Outcome

Title	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
Description	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.
Time Frame	3, 6, 18 and 24 hours post last dose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day	Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 Day	Part A - Cohort 3: KAF 400 mg and LUM 960 mg QD for 2 Days	Part A - Cohort 4: KAF 200 mg and LUM 480 mg QD for 3 Days	Part A - Cohort 5: KAF 400 mg and LUM 480 mg QD for 3 Days	Part A - Cohort 6: KAF 400 mg and LUM 960 mg QD for 3 Days	Part B - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day	Part B - Cohort 2: KAF 400 mg and LUM 960 mg QD for 2 Days	Part B - Cohort 3: KAF 400 mg and LUM 960 mg QD for 3 Days
Arm/Group Description	Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Participants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Participants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days
Measure Participants	38	44	41	43	36	41	48	0	0
Geometric Mean (Geometric Coefficient of Variation) [hours*μg/mL]	9.84 (41.5)	21.7 (41.7)	9.95 (131.9)	5.91 (29.2)	11 (79.3)	10.9 (57.4)	11 (47.7)

11. Secondary Outcome

Title	Part A and Part B: Maximum Peak Observed Concentration (Cmax) of KAF156
Description	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.
Time Frame	3, 6, 18, 24, 27, 30, 48, 51, 54, 68, 72 and 168 hours post last dose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day	Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 Day	Part A - Cohort 3: KAF 400 mg and LUM 960 mg QD for 2 Days	Part A - Cohort 4: KAF 200 mg and LUM 480 mg QD for 3 Days	Part A - Cohort 5: KAF 400 mg and LUM 480 mg QD for 3 Days	Part A - Cohort 6: KAF 400 mg and LUM 960 mg QD for 3 Days	Part B - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day	Part B - Cohort 2: KAF 400 mg and LUM 960 mg QD for 2 Days	Part B - Cohort 3: KAF 400 mg and LUM 960 mg QD for 3 Days
Arm/Group Description	Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Participants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Participants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days	Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days
Measure Participants	39	44	40	43	36	41	48	46	41
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	653 (43.9)	1470 (46.5)	1060 (83.9)	665 (30.3)	1470 (30.9)	1320 (32.7)	714 (49.4)	1060 (48.4)	1380 (29.7)

12. Secondary Outcome

Title	PK Run-in and Part A: Elimination Half-life (T½) of KAF156
Description	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.
Time Frame	0, 1, 3, 6, 12, 18, 24, 27, 30, 36, 48, 72, 96 and 168 hours post last dose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	PK Run-in Cohort: KAF 200 mg and LUM 960 mg QD for 1 Day	Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day	Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 Day	Part A - Cohort 3: KAF 400 mg and LUM 960 mg QD for 2 Days	Part A - Cohort 4: KAF 200 mg and LUM 480 mg QD for 3 Days	Part A - Cohort 5: KAF 400 mg and LUM 480 mg QD for 3 Days	Part A - Cohort 6: KAF 400 mg and LUM 960 mg QD for 3 Days
Arm/Group Description	Participants received a single oral dose of KAF156 200 mg and LUM-SDF 960 mg	Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days	Participants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Participants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days	Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days
Measure Participants	11	4	6	4	2	9	2
Mean (Standard Deviation) [Hours]	25.0 (8.81)	25.4 (5.32)	29.9 (9.95)	31.0 (3.86)	35.8 (19.4)	28.4 (3.49)	26.6 (4.15)

13. Secondary Outcome

Title	PK Run-in and Part A (Cohorts 1 and 2): Time to Reach Maximum Blood Concentrations (Tmax) of KAF156
Description	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.
Time Frame	0, 1, 3, 6, 12, 18, 24, 30, 48, 96 and 168 hours post last dose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PK Run-in Cohort: KAF 200 mg and LUM 960 mg QD for 1 Day	Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 Day	Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 Day
Arm/Group Description	Participants received a single oral dose of KAF156 200 mg and LUM-SDF 960 mg	Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg	Participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg
Measure Participants	12	5	6
Mean (Standard Deviation) [Hours]	4.23 (1.55)	39.8 (77.3)	5.99 (3.11)

Adverse Events

Time Frame	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.
Adverse Event Reporting Description	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.
Arm/Group Title	PK Run-in: KAF 200 mg and LUM 960 mg QD for 1 Day		Part A: KAF 800 mg and LUM 960 mg QD for 1 Day		Part A: KAF 200 mg and LUM 480 mg QD for 3 Days		Part A: KAF 400 mg and LUM 480 mg QD for 3 Days		Part A and Part B: KAF 400 mg and LUM 960 mg QD for 1 Day		Part A and Part B: KAF 400 mg and LUM 960 mg QD for 2 Days		Part A and Part B: KAF 400 mg and LUM 960 mg QD for 3 Days		Part A and Part B: Coartem
Arm/Group Description	PK Run-in participants received a single oral dose of KAF156 200 mg and LUM-SDF 960 mg		Part A - Cohort 2 participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg		Part A - Cohort 4 participants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days		Part A - Cohort 5 participants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days		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 - 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 - 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 - Cohort 7 and Part B - Cohort 4 participants received Coartem twice daily via oral administration for 3 days
All Cause Mortality
	PK Run-in: KAF 200 mg and LUM 960 mg QD for 1 Day		Part A: KAF 800 mg and LUM 960 mg QD for 1 Day		Part A: KAF 200 mg and LUM 480 mg QD for 3 Days		Part A: KAF 400 mg and LUM 480 mg QD for 3 Days		Part A and Part B: KAF 400 mg and LUM 960 mg QD for 1 Day		Part A and Part B: KAF 400 mg and LUM 960 mg QD for 2 Days		Part A and Part B: KAF 400 mg and LUM 960 mg QD for 3 Days		Part A and Part B: Coartem
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/51 (0%)		0/54 (0%)		0/51 (0%)		0/103 (0%)		0/104 (0%)		0/97 (0%)		0/51 (0%)
Serious Adverse Events
	PK Run-in: KAF 200 mg and LUM 960 mg QD for 1 Day		Part A: KAF 800 mg and LUM 960 mg QD for 1 Day		Part A: KAF 200 mg and LUM 480 mg QD for 3 Days		Part A: KAF 400 mg and LUM 480 mg QD for 3 Days		Part A and Part B: KAF 400 mg and LUM 960 mg QD for 1 Day		Part A and Part B: KAF 400 mg and LUM 960 mg QD for 2 Days		Part A and Part B: KAF 400 mg and LUM 960 mg QD for 3 Days		Part A and Part B: Coartem
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		1/51 (2%)		2/54 (3.7%)		1/51 (2%)		7/103 (6.8%)		5/104 (4.8%)		2/97 (2.1%)		3/51 (5.9%)
Blood and lymphatic system disorders
Anaemia	0/12 (0%)		0/51 (0%)		0/54 (0%)		1/51 (2%)		0/103 (0%)		1/104 (1%)		0/97 (0%)		0/51 (0%)
Hepatobiliary disorders
Hepatitis acute	0/12 (0%)		0/51 (0%)		0/54 (0%)		0/51 (0%)		1/103 (1%)		0/104 (0%)		0/97 (0%)		0/51 (0%)
Jaundice	0/12 (0%)		0/51 (0%)		0/54 (0%)		0/51 (0%)		1/103 (1%)		0/104 (0%)		0/97 (0%)		0/51 (0%)
Infections and infestations
COVID-19	0/12 (0%)		0/51 (0%)		0/54 (0%)		0/51 (0%)		0/103 (0%)		1/104 (1%)		0/97 (0%)		0/51 (0%)
Plasmodium falciparum infection	0/12 (0%)		1/51 (2%)		0/54 (0%)		0/51 (0%)		0/103 (0%)		0/104 (0%)		0/97 (0%)		0/51 (0%)
Pneumonia	0/12 (0%)		0/51 (0%)		0/54 (0%)		0/51 (0%)		0/103 (0%)		0/104 (0%)		1/97 (1%)		0/51 (0%)
Sepsis	0/12 (0%)		0/51 (0%)		0/54 (0%)		0/51 (0%)		0/103 (0%)		1/104 (1%)		0/97 (0%)		0/51 (0%)
Injury, poisoning and procedural complications
Road traffic accident	0/12 (0%)		0/51 (0%)		0/54 (0%)		0/51 (0%)		1/103 (1%)		0/104 (0%)		0/97 (0%)		0/51 (0%)
Investigations
Alanine aminotransferase increased	0/12 (0%)		0/51 (0%)		0/54 (0%)		0/51 (0%)		0/103 (0%)		0/104 (0%)		0/97 (0%)		1/51 (2%)
Aspartate aminotransferase	0/12 (0%)		0/51 (0%)		1/54 (1.9%)		0/51 (0%)		0/103 (0%)		0/104 (0%)		0/97 (0%)		0/51 (0%)
Blood alkaline phosphatase increased	0/12 (0%)		0/51 (0%)		1/54 (1.9%)		0/51 (0%)		3/103 (2.9%)		2/104 (1.9%)		0/97 (0%)		3/51 (5.9%)
Blood bilirubin increased	0/12 (0%)		0/51 (0%)		0/54 (0%)		0/51 (0%)		2/103 (1.9%)		2/104 (1.9%)		1/97 (1%)		2/51 (3.9%)
Skin and subcutaneous tissue disorders
Petechiae	0/12 (0%)		0/51 (0%)		0/54 (0%)		0/51 (0%)		0/103 (0%)		0/104 (0%)		1/97 (1%)		0/51 (0%)
Other (Not Including Serious) Adverse Events
	PK Run-in: KAF 200 mg and LUM 960 mg QD for 1 Day		Part A: KAF 800 mg and LUM 960 mg QD for 1 Day		Part A: KAF 200 mg and LUM 480 mg QD for 3 Days		Part A: KAF 400 mg and LUM 480 mg QD for 3 Days		Part A and Part B: KAF 400 mg and LUM 960 mg QD for 1 Day		Part A and Part B: KAF 400 mg and LUM 960 mg QD for 2 Days		Part A and Part B: KAF 400 mg and LUM 960 mg QD for 3 Days		Part A and Part B: Coartem
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/12 (58.3%)		37/51 (72.5%)		30/54 (55.6%)		32/51 (62.7%)		69/103 (67%)		68/104 (65.4%)		59/97 (60.8%)		30/51 (58.8%)
Blood and lymphatic system disorders
Anaemia	0/12 (0%)		0/51 (0%)		1/54 (1.9%)		1/51 (2%)		5/103 (4.9%)		3/104 (2.9%)		5/97 (5.2%)		1/51 (2%)
Eosinophilia	0/12 (0%)		2/51 (3.9%)		3/54 (5.6%)		2/51 (3.9%)		0/103 (0%)		1/104 (1%)		3/97 (3.1%)		0/51 (0%)
Thrombocytopenia	0/12 (0%)		3/51 (5.9%)		1/54 (1.9%)		5/51 (9.8%)		1/103 (1%)		1/104 (1%)		0/97 (0%)		2/51 (3.9%)
Cardiac disorders
Sinus bradycardia	0/12 (0%)		4/51 (7.8%)		1/54 (1.9%)		0/51 (0%)		4/103 (3.9%)		1/104 (1%)		3/97 (3.1%)		0/51 (0%)
Gastrointestinal disorders
Abdominal pain	0/12 (0%)		3/51 (5.9%)		2/54 (3.7%)		7/51 (13.7%)		3/103 (2.9%)		5/104 (4.8%)		4/97 (4.1%)		0/51 (0%)
Diarrhoea	0/12 (0%)		4/51 (7.8%)		1/54 (1.9%)		2/51 (3.9%)		1/103 (1%)		3/104 (2.9%)		3/97 (3.1%)		0/51 (0%)
Vomiting	0/12 (0%)		8/51 (15.7%)		2/54 (3.7%)		3/51 (5.9%)		8/103 (7.8%)		9/104 (8.7%)		8/97 (8.2%)		2/51 (3.9%)
General disorders
Pyrexia	0/12 (0%)		5/51 (9.8%)		4/54 (7.4%)		6/51 (11.8%)		20/103 (19.4%)		18/104 (17.3%)		9/97 (9.3%)		13/51 (25.5%)
Treatment failure	0/12 (0%)		3/51 (5.9%)		3/54 (5.6%)		2/51 (3.9%)		3/103 (2.9%)		0/104 (0%)		1/97 (1%)		2/51 (3.9%)
Infections and infestations
Bronchitis	1/12 (8.3%)		0/51 (0%)		0/54 (0%)		0/51 (0%)		2/103 (1.9%)		3/104 (2.9%)		2/97 (2.1%)		0/51 (0%)
Infection parasitic	1/12 (8.3%)		0/51 (0%)		1/54 (1.9%)		0/51 (0%)		0/103 (0%)		0/104 (0%)		0/97 (0%)		1/51 (2%)
Malaria	0/12 (0%)		8/51 (15.7%)		4/54 (7.4%)		6/51 (11.8%)		28/103 (27.2%)		25/104 (24%)		16/97 (16.5%)		18/51 (35.3%)
Upper respiratory tract infection	0/12 (0%)		6/51 (11.8%)		5/54 (9.3%)		3/51 (5.9%)		15/103 (14.6%)		12/104 (11.5%)		12/97 (12.4%)		5/51 (9.8%)
Investigations
Blood phosphorus increased	4/12 (33.3%)		0/51 (0%)		1/54 (1.9%)		0/51 (0%)		0/103 (0%)		0/104 (0%)		0/97 (0%)		0/51 (0%)
Electrocardiogram QT prolonged	1/12 (8.3%)		5/51 (9.8%)		9/54 (16.7%)		9/51 (17.6%)		5/103 (4.9%)		6/104 (5.8%)		9/97 (9.3%)		3/51 (5.9%)
Nervous system disorders
Headache	0/12 (0%)		10/51 (19.6%)		15/54 (27.8%)		7/51 (13.7%)		16/103 (15.5%)		13/104 (12.5%)		14/97 (14.4%)		7/51 (13.7%)
Respiratory, thoracic and mediastinal disorders
Cough	0/12 (0%)		3/51 (5.9%)		3/54 (5.6%)		5/51 (9.8%)		7/103 (6.8%)		10/104 (9.6%)		6/97 (6.2%)		4/51 (7.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.