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Study to Investigate the Clinical and Parasiticidal Activity and Pharmacokinetics of Different Doses of Artefenomel and Ferroquine in Patients With Uncomplicated Plasmodium Falciparum Malaria

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ClinicalTrials.gov Identifier: NCT03660839
Recruitment Status : Completed
First Posted : September 7, 2018
Results First Posted : December 2, 2020
Last Update Posted : December 2, 2020
Sponsor:
Collaborator:
Medicines for Malaria Venture
Information provided by (Responsible Party):
Sanofi

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Plasmodium Falciparum Infection
Interventions Drug: Artefenomel (OZ439)
Drug: Ferroquine (SSR97193)
Enrollment 140
Recruitment Details Study was conducted at 7 active sites in 5 countries. Total of 448 participants were screened between 11 September 2018 and 09 October 2019, of which 140 were randomized to 1 of 4 treatment arms and those who failed to meet inclusion criteria were considered as screen failure.
Pre-assignment Details All eligible participants were randomized via a centralized randomization system using interactive response technology to 1 of the 4 arms in 1:1:1:1 ratio. Day 0 (drug administration day, per protocol) was considered as Day 1 for all analysis using Safety population as per Clinical Data Interchange Standards Consortium convention.
Arm/Group Title Ferroquine (FQ) 400 Milligram (mg) Ferroquine 400 mg + Artefenomel (OZ439) 300 mg Ferroquine 400 mg + Artefenomel 600 mg Ferroquine 400 mg + Artefenomel 1000 mg
Hide Arm/Group Description On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition. On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension. On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension. On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension.
Period Title: Overall Study
Started 35 36 36 33
Completed [1] 35 36 36 33
Not Completed 0 0 0 0
[1]
Completed study treatment.
Arm/Group Title Ferroquine 400 mg Ferroquine 400 mg + Artefenomel 300 mg Ferroquine 400 mg + Artefenomel 600 mg Ferroquine 400 mg + Artefenomel 1000 mg Total
Hide Arm/Group Description On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition. On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension. On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension. On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension. Total of all reporting groups
Overall Number of Baseline Participants 35 36 36 33 140
Hide Baseline Analysis Population Description
Analysis was performed on all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 35 participants 36 participants 36 participants 33 participants 140 participants
25.4  (13.20) 21.8  (11.49) 20.7  (8.57) 22.2  (11.28) 22.5  (11.26)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 35 participants 36 participants 36 participants 33 participants 140 participants
Female
23
  65.7%
28
  77.8%
26
  72.2%
20
  60.6%
97
  69.3%
Male
12
  34.3%
8
  22.2%
10
  27.8%
13
  39.4%
43
  30.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 35 participants 36 participants 36 participants 33 participants 140 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
35
 100.0%
36
 100.0%
35
  97.2%
33
 100.0%
139
  99.3%
White
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
More than one race
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%
1
   2.8%
0
   0.0%
1
   0.7%
1.Primary Outcome
Title Percentage of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitological Response (ACPR) at Day 28 (ACPR28)
Hide Description ACPR:absence of parasitemia at Day 28, irrespective of axillary temperature(AT), participants not meeting any criteria of early therapy failure(ETF):Danger signs(DS)/symptoms of complicated(SoC)/severe malaria(SM) at Day 1, 2 or 3 in presence of parasitemia, concomitant to at least 1 positive parasitemia;or parasitemia on Day 2 >Day 0 irrespective of AT;or parasitemia on Day 3 with AT>=37.5 degree Celsius (°C);or parasitemia count on Day 3 >=25 percent (%) on Day 0, or late clinical failure (LCF):DS/SM in presence of parasitemia between Day 4 and 28,concomitant to at least one positive parasitemia;or presence of parasitemia and AT>=37.5°C on Day 4 to Day 28, or late parasitological failure(LPF):presence of parasitemia between Day 7 and 28 and AT<37.5°C and without rescue therapy. PCR-corrected ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with genotype identical to that present at Baseline), excluding participants with reinfection.
Time Frame Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic/Pharmacodynamic (PK/PD) efficacy population: who received at least 1 dose of OZ439/FQ with parasitologically confirmed Plasmodium falciparum at baseline with data post-randomization, 1 evaluable PK blood sample (OZ439/FQ) post dose, adequate documentation of dosing & sampling date, without any major protocol deviation related to drug administration (e.g. vomiting after drug intake). Here,"overall number of participants analyzed"=participants evaluable for this outcome measure.
Arm/Group Title Ferroquine 400 mg Ferroquine 400 mg + Artefenomel 300 mg Ferroquine 400 mg + Artefenomel 600 mg Ferroquine 400 mg + Artefenomel 1000 mg
Hide Arm/Group Description:
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension.
Overall Number of Participants Analyzed 26 31 33 31
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
80.8
(62.1 to 91.5)
90.3
(75.1 to 96.7)
90.9
(76.4 to 96.9)
87.1
(71.1 to 94.9)
2.Secondary Outcome
Title Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 28
Hide Description ACPR: absence of parasitemia at Day 28, irrespective of AT, in participants not meeting any criteria of ETF: DS/SoC/SM at Day 1, 2 or 3 in presence of parasitemia, concomitant to at least 1 positive parasitemia; or parasitemia on Day 2 > Day 0 irrespective of AT; or parasitemia on Day 3 with AT >=37.5°C; or parasitemia count on Day 3 >=25% on Day 0, or LCF: DS/SM in presence of parasitemia between Day 4 and 28, concomitant to at least one positive parasitemia; or presence of parasitemia and AT>=37.5°C on Day 4 to Day 28, or LPF: presence of parasitemia between Day 7 and 28 and AT<37.5°C or having rescue therapy for malaria. PCR-corrected ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with genotype identical to that present at Baseline), excluding participants with re-infection, whereas crude ACPR does not distinguish reinfection (new clone of parasite) or recrudescence.
Time Frame Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK/PD efficacy population.
Arm/Group Title Ferroquine 400 mg Ferroquine 400 mg + Artefenomel 300 mg Ferroquine 400 mg + Artefenomel 600 mg Ferroquine 400 mg + Artefenomel 1000 mg
Hide Arm/Group Description:
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension.
Overall Number of Participants Analyzed 31 33 36 32
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
64.5
(46.9 to 78.9)
81.8
(65.6 to 91.4)
77.8
(61.9 to 88.3)
78.1
(61.2 to 89)
3.Secondary Outcome
Title Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours
Hide Description Parasitemia (quantitative content of parasites present in the blood) at baseline until Day 7 (i.e. 168 hours) was assessed by optical microscope.
Time Frame Baseline, 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on modified intention-to-treat (mITT) population which included all randomized participants with parasitological confirmed P.falciparum malaria at baseline with parasitemia data post-randomization, received the single administration of OZ439/FQ. Here, "number analyzed" = participants with available data for each specified category.
Arm/Group Title Ferroquine 400 mg Ferroquine 400 mg + Artefenomel 300 mg Ferroquine 400 mg + Artefenomel 600 mg Ferroquine 400 mg + Artefenomel 1000 mg
Hide Arm/Group Description:
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension.
Overall Number of Participants Analyzed 35 36 36 33
Mean (Standard Deviation)
Unit of Measure: parasites per microliter
Baseline Number Analyzed 35 participants 36 participants 36 participants 33 participants
17496.0  (11889.55) 18799.6  (13559.14) 15171.9  (13012.53) 20546.8  (13835.31)
Change from baseline at 6 hours post-dose Number Analyzed 35 participants 36 participants 36 participants 32 participants
-1349.3  (11331.78) -96.9  (11699.28) 8515.4  (44264.14) 893.2  (21052.27)
Change from baseline at 12 hours post-dose Number Analyzed 35 participants 36 participants 35 participants 33 participants
-5721.5  (12441.39) -11471.6  (13399.27) -4156.6  (34663.71) -11319.4  (15490.43)
Change from baseline at 18 hours post-dose Number Analyzed 34 participants 36 participants 36 participants 33 participants
-9181.2  (11892.89) -17021.4  (13015.29) -9447.5  (32303.36) -18281.9  (13796.37)
Change from baseline at 24 hours post-dose Number Analyzed 34 participants 36 participants 36 participants 33 participants
-14238.4  (11402.25) -17939.0  (13061.86) -10674.6  (29868.45) -19461.9  (14049.02)
Change from baseline at 30 hours post-dose Number Analyzed 34 participants 35 participants 36 participants 32 participants
-16571.1  (12354.88) -19110.5  (13556.35) -13299.6  (17452.15) -19657.5  (14393.75)
Change from baseline at 36 hours post-dose Number Analyzed 34 participants 36 participants 36 participants 33 participants
-17036.9  (12307.57) -18792.2  (13548.16) -14573.9  (13623.86) -19587.9  (14051.82)
Change from baseline at 48 hours post-dose Number Analyzed 34 participants 36 participants 36 participants 33 participants
-17595.3  (12037.99) -17706.1  (13389.25) -14542.3  (13547.11) -20327.7  (13739.17)
Change from baseline at 72 hours post-dose Number Analyzed 33 participants 35 participants 34 participants 32 participants
-18231.8  (11801.65) -18396.3  (13091.47) -15333.7  (13382.41) -20314.2  (13980.12)
Change from baseline at 96 hours post-dose Number Analyzed 31 participants 33 participants 35 participants 31 participants
-18287.6  (12011.77) -19024.7  (13200.22) -15258.5  (13191.95) -20662.0  (14108.54)
Change from baseline at 120 hours post-dose Number Analyzed 29 participants 33 participants 35 participants 32 participants
-19280.0  (12145.86) -19024.7  (13200.22) -15265.3  (13190.14) -20350.4  (14010.21)
Change from baseline at 144 hours post-dose Number Analyzed 32 participants 33 participants 35 participants 31 participants
-18526.0  (11889.52) -19023.3  (13198.28) -15254.5  (13190.39) -20029.7  (14121.74)
Change from baseline at 168 hours post-dose Number Analyzed 31 participants 31 participants 34 participants 32 participants
-18962.8  (11813.20) -18922.2  (13141.19) -15268.5  (13388.49) -20349.5  (14010.98)
4.Secondary Outcome
Title Observed Parasite Reduction Ratio (PRR) at 24 Hours, 48 Hours, and 72 Hours
Hide Description The observed PRR was defined as the ratio of the number of parasites at time t=0 (baseline) divided by the parasite count at each specified time t (post-treatment). If the post dose parasite count = 0 (due to a negative parasitemia) then a value of 1 parasite per microliter was imputed to allow a parasite reduction ratio calculation.
Time Frame Baseline, 24, 48 and 72 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population. Here, 'number analyzed' = participants with available data for each specified category.
Arm/Group Title Ferroquine 400 mg Ferroquine 400 mg + Artefenomel 300 mg Ferroquine 400 mg + Artefenomel 600 mg Ferroquine 400 mg + Artefenomel 1000 mg
Hide Arm/Group Description:
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension.
Overall Number of Participants Analyzed 35 36 36 33
Mean (Standard Deviation)
Unit of Measure: ratio
At Hour 24 Number Analyzed 34 participants 36 participants 36 participants 33 participants
638.436  (2013.8609) 5921.197  (11566.1520) 5715.046  (9364.8892) 7929.720  (12675.8348)
At Hour 48 Number Analyzed 34 participants 36 participants 36 participants 33 participants
9709.093  (13987.7127) 17594.700  (13521.9507) 13120.409  (13182.3022) 19328.057  (14392.7604)
At Hour 72 Number Analyzed 33 participants 35 participants 35 participants 32 participants
15655.447  (12806.4644) 18069.583  (13409.1341) 14561.409  (13657.0665) 19125.715  (14516.8397)
5.Secondary Outcome
Title Time to 50% and 99% Parasite Reduction
Hide Description Time to 50% and 99% parasite reduction was defined as time needed for the parasitemia (quantitative content of parasites present in blood) to be reduced to 50% and 99% of the initial value, respectively.
Time Frame Up to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population. Here, "Overall Number of Participants Analyzed" = participants evaluable for this outcome measure.
Arm/Group Title Ferroquine 400 mg Ferroquine 400 mg + Artefenomel 300 mg Ferroquine 400 mg + Artefenomel 600 mg Ferroquine 400 mg + Artefenomel 1000 mg
Hide Arm/Group Description:
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension.
Overall Number of Participants Analyzed 21 28 28 25
Mean (Standard Deviation)
Unit of Measure: hours
Time to 50% Parasite reduction 14.07  (5.604) 7.74  (4.636) 7.78  (3.786) 9.47  (7.976)
Time to 99% Parasite reduction 36.92  (9.988) 19.33  (6.107) 18.34  (5.523) 22.95  (17.069)
6.Secondary Outcome
Title Parasite Clearance Time (PCT)
Hide Description PCT was defined as the time (in hours) from the start of study drug administration until the time of first negative blood film (no asexual parasites by microscopy). This first negative film was confirmed by a second negative film which was taken >=6 to <=12 hours of the first film. If the second film was performed <6 hours or >12 hours of the first film, then the parasite clearance was confirmed or invalidated by the third (thick) film following the second one, whatever the timing of this third film: If the third film was negative, then the clearance was considered confirmed and if the third film was positive, then the clearance was invalidated. Kaplan-Meier method was used for the estimation.
Time Frame From the start of study drug administration up to the time of the first negative blood film (up to Day 28)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population.
Arm/Group Title Ferroquine 400 mg Ferroquine 400 mg + Artefenomel 300 mg Ferroquine 400 mg + Artefenomel 600 mg Ferroquine 400 mg + Artefenomel 1000 mg
Hide Arm/Group Description:
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension.
Overall Number of Participants Analyzed 35 36 36 33
Median (95% Confidence Interval)
Unit of Measure: hours
56.1
(48.0 to 72.0)
30.0
(30.0 to 30.0)
30.0
(24.1 to 30.1)
30.0
(24.0 to 30.0)
7.Secondary Outcome
Title Parasite Clearance Rate
Hide Description Parasite clearance rate (k) is the minus slope of the natural logarithm parasitemia versus time linear relationship, after exclusion of outliers, lag phase and Tail, using the worldwide antimalarial resistance network, Parasite Clearance Estimator.
Time Frame Up to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population. Here, "Overall Number of Participants Analyzed" = participants evaluable for this outcome measure.
Arm/Group Title Ferroquine 400 mg Ferroquine 400 mg + Artefenomel 300 mg Ferroquine 400 mg + Artefenomel 600 mg Ferroquine 400 mg + Artefenomel 1000 mg
Hide Arm/Group Description:
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension.
Overall Number of Participants Analyzed 21 28 28 25
Mean (Standard Deviation)
Unit of Measure: 1 per hour
0.1956  (0.07627) 0.3609  (0.09963) 0.3962  (0.11983) 0.3581  (0.12484)
8.Secondary Outcome
Title Time to Re-emergence
Hide Description Time to re-emergence (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection irrespective of genotype. Re-emergence was confirmed by microscopy (positive blood smear). Participants with confirmed parasite clearance were included in the analysis and Kaplan-Meier method was used for estimation.
Time Frame Up to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population. Here, "overall number of participants analyzed" = participants evaluable for this outcome measure.
Arm/Group Title Ferroquine 400 mg Ferroquine 400 mg + Artefenomel 300 mg Ferroquine 400 mg + Artefenomel 600 mg Ferroquine 400 mg + Artefenomel 1000 mg
Hide Arm/Group Description:
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension.
Overall Number of Participants Analyzed 32 35 34 32
Median (95% Confidence Interval)
Unit of Measure: days
NA [1] 
(28.0 to NA)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
[1]
Median and upper limit of confidence interval (CI) was not estimable due to very low number of participants with events.
[2]
Median and 95% CI was not estimable due to very low number of participants with the events .
9.Secondary Outcome
Title Time to Recrudescence
Hide Description Time to recrudescence (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline. Recrudescence was confirmed by PCR analysis. Participants with confirmed parasite clearance were included in the analysis and Kaplan-Meier method was used for estimation.
Time Frame Up to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population. Here, "overall number of participants analyzed" = participants evaluable for this outcome measure.
Arm/Group Title Ferroquine 400 mg Ferroquine 400 mg + Artefenomel 300 mg Ferroquine 400 mg + Artefenomel 600 mg Ferroquine 400 mg + Artefenomel 1000 mg
Hide Arm/Group Description:
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension.
Overall Number of Participants Analyzed 32 35 34 32
Median (95% Confidence Interval)
Unit of Measure: days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Median and 95% CI was not estimable due to very low number of participants with the events.
10.Secondary Outcome
Title Time to Re-infection
Hide Description Time to re-infection (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection with a genotype that differed from that of parasites present at Baseline. Re-infection was confirmed by PCR analysis. Participants with confirmed parasite clearance were involved in the analysis and Kaplan-Maier method was used for estimation.
Time Frame Up to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population. Here, "overall number of participants analyzed" = participants evaluable for this outcome measure.
Arm/Group Title Ferroquine 400 mg Ferroquine 400 mg + Artefenomel 300 mg Ferroquine 400 mg + Artefenomel 600 mg Ferroquine 400 mg + Artefenomel 1000 mg
Hide Arm/Group Description:
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension.
Overall Number of Participants Analyzed 32 35 34 32
Median (95% Confidence Interval)
Unit of Measure: days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Median and 95% CI was not estimable due to very low number of participants with the events.
11.Secondary Outcome
Title Time Elapsed Below the Limit of Quantification (LOQ) of Parasitemia
Hide Description The time elapsed below LOQ (LOQ expressed in parasites/microliter) of parasitemia (quantitative content of parasites present in the blood) was defined as the time (in days) for which no parasites were seen i.e., time corresponding to PCT, up to the time of occurrence of a new malaria infection or recrudescence. If there was no occurrence of a new malaria infection or recrudescence, then this was the time corresponding to the first negative thick blood film, until the end of study. PCT (k) is the minus slope of the natural logarithm parasitemia versus time linear relationship, after exclusion of outliers, lag phase and Tail, using the worldwide antimalarial resistance network, Parasite clearance estimator. Participants with confirmed parasite clearance were involved in the analysis and Kaplan-Meier method was used for estimation.
Time Frame Up to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population. Here, "overall number of participants analyzed" = participants evaluable for this outcome measure.
Arm/Group Title Ferroquine 400 mg Ferroquine 400 mg + Artefenomel 300 mg Ferroquine 400 mg + Artefenomel 600 mg Ferroquine 400 mg + Artefenomel 1000 mg
Hide Arm/Group Description:
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension.
Overall Number of Participants Analyzed 32 35 34 32
Median (95% Confidence Interval)
Unit of Measure: days
25.0
(23.0 to 26.0)
26.0
(26.0 to 27.0)
26.5
(26.0 to 27.0)
26.0
(26.0 to 27.0)
12.Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)
Hide Description An AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. SAEs were any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment phase that was defined as the time from the start of study drug up to the Day 28. AE of special interest (AESI) was an AE (serious or non-serious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required.
Time Frame From Baseline up to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population: participants who received single administration of OZ439/FQ and were analyzed according to the treatment actually received.
Arm/Group Title Ferroquine 400 mg Ferroquine 400 mg + Artefenomel 300 mg Ferroquine 400 mg + Artefenomel 600 mg Ferroquine 400 mg + Artefenomel 1000 mg
Hide Arm/Group Description:
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension.
Overall Number of Participants Analyzed 35 36 36 33
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAE
18
  51.4%
21
  58.3%
24
  66.7%
24
  72.7%
Any treatment-emergent SAE
0
   0.0%
0
   0.0%
1
   2.8%
0
   0.0%
Any treatment-emergent AESI
0
   0.0%
1
   2.8%
0
   0.0%
1
   3.0%
Any TEAE led to treatment discontinuation
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Any TEAE led to death
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
13.Secondary Outcome
Title Pharmacokinetics (PK): Concentration of OZ439 in Plasma
Hide Description Concentrations of OZ439 in plasma was analyzed by liquid chromatography tandem mass spectroscopy (LC-MS/MS). The lower limit of quantification (LLOQ) was 1 nanograms per milliliter for analysis of OZ439. Data for this outcome measure was not planned to be collected and analyzed for "Ferroquine 400 mg" arm, since artefenomel was not administered.
Time Frame 1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK population which included all participants who received OZ439 and had at least one evaluable blood sample for PK OZ439 post study drug administration and with adequate documentation of date of dosing and date of sampling. Here, 'number analyzed' = participants with available data for each specified category.
Arm/Group Title Ferroquine 400 mg + Artefenomel 300 mg Ferroquine 400 mg + Artefenomel 600 mg Ferroquine 400 mg + Artefenomel 1000 mg
Hide Arm/Group Description:
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension.
Overall Number of Participants Analyzed 36 36 33
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms per milliliter
1 hour post-dose Number Analyzed 35 participants 35 participants 32 participants
88.641
(104.631%)
149.199
(87.153%)
188.423
(82.588%)
2 hours post-dose Number Analyzed 35 participants 34 participants 32 participants
269.075
(59.803%)
450.218
(58.642%)
655.851
(58.311%)
4 hours post-dose Number Analyzed 35 participants 35 participants 32 participants
349.134
(54.880%)
576.673
(54.357%)
978.649
(60.263%)
6 hours post-dose Number Analyzed 35 participants 35 participants 32 participants
234.375
(52.902%)
478.929
(87.523%)
865.581
(75.154%)
12 hours post-dose Number Analyzed 34 participants 35 participants 32 participants
92.614
(60.229%)
164.028
(99.433%)
369.335
(85.243%)
24 hours post-dose Number Analyzed 33 participants 33 participants 31 participants
17.526
(65.757%)
48.257
(107.605%)
84.167
(78.221%)
48 hours post-dose Number Analyzed 33 participants 33 participants 32 participants
6.097
(54.492%)
14.611
(95.627%)
29.554
(83.028%)
72 hours post-dose Number Analyzed 32 participants 33 participants 30 participants
3.224
(50.406%)
8.162
(77.493%)
16.665
(83.936%)
120 hours post-dose Number Analyzed 25 participants 32 participants 30 participants
2.144
(39.859%)
5.339
(61.816%)
8.596
(77.245%)
168 hours post-dose Number Analyzed 21 participants 32 participants 30 participants
1.745
(38.466%)
3.408
(73.232%)
5.903
(78.608%)
336 hours post-dose Number Analyzed 6 participants 21 participants 25 participants
1.227
(19.402%)
1.970
(66.212%)
3.149
(58.029%)
14.Secondary Outcome
Title Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood
Hide Description Concentrations of FQ and SSR97213 in blood was analyzed by LC-MS/MS. The LLOQ was 5 nanograms per milliliter for analysis of FQ and SSR97213.
Time Frame 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK population which included all participants who received FQ and had at least one evaluable blood sample for PK FQ post study drug administration and with adequate documentation of date of dosing and date of sampling. Here, 'number analyzed' = participants with available data for each specified category.
Arm/Group Title Ferroquine 400 mg Ferroquine 400 mg + Artefenomel 300 mg Ferroquine 400 mg + Artefenomel 600 mg Ferroquine 400 mg + Artefenomel 1000 mg
Hide Arm/Group Description:
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension.
Overall Number of Participants Analyzed 35 36 36 33
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms per milliliter
1 hour post-dose: FQ Number Analyzed 32 participants 33 participants 25 participants 25 participants
36.094
(80.476%)
27.214
(79.000%)
21.165
(55.491%)
26.599
(95.999%)
1 hour post-dose: SSR97213 Number Analyzed 8 participants 2 participants 2 participants 2 participants
13.209
(54.030%)
10.375
(15.713%)
6.161
(9.504%)
6.805
(28.203%)
4 hours post-dose: FQ Number Analyzed 35 participants 35 participants 35 participants 31 participants
64.934
(87.235%)
100.569
(61.578%)
79.656
(74.707%)
97.007
(72.230%)
4 hours post-dose: SSR97213 Number Analyzed 27 participants 27 participants 29 participants 26 participants
20.079
(90.358%)
29.632
(49.701%)
18.377
(98.310%)
17.559
(68.694%)
6 hours post-dose: FQ Number Analyzed 35 participants 35 participants 35 participants 32 participants
69.005
(75.045%)
92.657
(50.449%)
84.803
(75.544%)
95.062
(126.388%)
6 hours post-dose: SSR97213 Number Analyzed 30 participants 30 participants 29 participants 28 participants
23.170
(82.875%)
28.098
(53.438%)
25.954
(88.481%)
20.687
(70.211%)
8 hours post-dose: FQ Number Analyzed 34 participants 35 participants 35 participants 32 participants
64.293
(70.724%)
82.639
(49.891%)
78.196
(72.454%)
82.990
(69.989%)
8 hours post-dose: SSR97213 Number Analyzed 29 participants 29 participants 29 participants 29 participants
25.131
(66.944%)
29.319
(48.679%)
25.304
(78.822%)
20.299
(63.388%)
12 hours post-dose: FQ Number Analyzed 35 participants 35 participants 35 participants 32 participants
50.621
(57.540%)
68.384
(50.887%)
59.106
(70.461%)
71.743
(61.238%)
12 hours post-dose: SSR97213 Number Analyzed 31 participants 31 participants 30 participants 31 participants
19.957
(61.856%)
24.385
(48.408%)
20.615
(77.739%)
18.203
(64.197%)
24 hours post-dose: FQ Number Analyzed 34 participants 36 participants 35 participants 32 participants
44.351
(52.316%)
53.211
(48.834%)
47.568
(61.373%)
51.250
(75.940%)
24 hours post-dose: SSR97213 Number Analyzed 32 participants 33 participants 30 participants 31 participants
18.874
(56.412%)
22.967
(55.037%)
19.826
(70.907%)
16.763
(69.091%)
72 hours post-dose: FQ Number Analyzed 34 participants 35 participants 35 participants 31 participants
25.343
(35.315%)
31.161
(47.829%)
31.373
(70.287%)
29.792
(76.912%)
72 hours post-dose: SSR97213 Number Analyzed 32 participants 33 participants 30 participants 29 participants
16.757
(46.038%)
20.059
(45.134%)
21.315
(68.366%)
17.756
(82.612%)
168 hours post-dose: FQ Number Analyzed 31 participants 31 participants 34 participants 31 participants
16.973
(39.627%)
20.524
(39.625%)
21.543
(63.679%)
21.322
(62.951%)
168 hours post-dose: SSR97213 Number Analyzed 31 participants 30 participants 31 participants 30 participants
16.308
(52.300%)
19.196
(46.115%)
20.463
(55.587%)
19.108
(62.123%)
336 hours post-dose: FQ Number Analyzed 28 participants 31 participants 31 participants 29 participants
10.543
(36.770%)
11.678
(38.490%)
12.469
(48.236%)
11.263
(82.611%)
336 hours post-dose: SSR97213 Number Analyzed 31 participants 31 participants 31 participants 30 participants
13.612
(45.485%)
14.797
(46.036%)
15.647
(47.974%)
13.686
(72.213%)
672 hours post-dose: FQ Number Analyzed 11 participants 17 participants 20 participants 21 participants
6.737
(18.832%)
7.623
(28.348%)
7.601
(29.047%)
7.342
(53.998%)
672 hours post-dose: SSR97213 Number Analyzed 26 participants 30 participants 28 participants 25 participants
9.751
(41.862%)
10.324
(33.482%)
10.977
(34.251%)
12.014
(59.403%)
15.Secondary Outcome
Title Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of Artefenomel
Hide Description Cmax is the maximum observed plasma concentration of Artefenomel. Data for this outcome measure was not planned to be collected and analyzed for "Ferroquine 400 mg" arm, since artefenomel was not administered.
Time Frame Pre-dose, 1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK/PD efficacy population.
Arm/Group Title Ferroquine 400 mg + Artefenomel 300 mg Ferroquine 400 mg + Artefenomel 600 mg Ferroquine 400 mg + Artefenomel 1000 mg
Hide Arm/Group Description:
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension.
Overall Number of Participants Analyzed 33 36 32
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms per milliliter
277.3
(169%)
488.3
(232%)
920.6
(77%)
16.Secondary Outcome
Title Pharmacokinetics: Time to Reach Maximum Plasma Concentration (Tmax) of Artefenomel
Hide Description tmax is the time taken by the drug to reach the maximum plasma concentration. Data for this outcome measure was not planned to be collected and analyzed for "Ferroquine 400 mg" arm, since artefenomel was not administered.
Time Frame Pre-dose, 1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Focus of PK assessment was to support the analysis of exposure versus efficacy relationship (PK and PD). Since tmax was not considered relevant to the objective of exposure-response analysis, data for this outcome measure were not collected and reported.
Arm/Group Title Ferroquine 400 mg + Artefenomel 300 mg Ferroquine 400 mg + Artefenomel 600 mg Ferroquine 400 mg + Artefenomel 1000 mg
Hide Arm/Group Description:
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
17.Secondary Outcome
Title Pharmacokinetics: Plasma Concentration at 168 Hours Post-dose (C168h) of Artefenomel
Hide Description The observed plasma concentration of artefenomel post 168 hours of drug administration. Data for this outcome measure was not planned to be collected and analyzed for "Ferroquine 400 mg" arm, since artefenomel was not administered.
Time Frame At 168 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK/PD efficacy population.
Arm/Group Title Ferroquine 400 mg + Artefenomel 300 mg Ferroquine 400 mg + Artefenomel 600 mg Ferroquine 400 mg + Artefenomel 1000 mg
Hide Arm/Group Description:
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension.
Overall Number of Participants Analyzed 33 36 32
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms per milliliter
0.9251
(110%)
2.152
(202%)
4.445
(165%)
18.Secondary Outcome
Title Pharmacokinetics: Area Under the Concentration Curve (AUC) Form Time 0 to Infinity (AUC0-inf]) of Artefenomel
Hide Description Area under the plasma concentration versus time curve from time 0 to infinity. Data for this outcome measure was not planned to be collected and analyzed for "Ferroquine 400 mg" arm, since artefenomel was not administered.
Time Frame Pre-dose, 1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK/PD efficacy population.
Arm/Group Title Ferroquine 400 mg + Artefenomel 300 mg Ferroquine 400 mg + Artefenomel 600 mg Ferroquine 400 mg + Artefenomel 1000 mg
Hide Arm/Group Description:
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension.
Overall Number of Participants Analyzed 33 36 32
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: micrograms*hour per milliliter
3.269
(113%)
6.46
(181%)
13.05
(114%)
19.Secondary Outcome
Title Pharmacokinetics: Terminal Half-life (t1/2) of Artefenomel
Hide Description Terminal t1/2 is defined as the time required for the plasma concentration of a drug to decrease by half of its initial concentration. Data for this outcome measure was not planned to be collected and analyzed for "Ferroquine 400 mg" arm, since artefenomel was not administered.
Time Frame Pre-dose, 1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Focus of PK assessment was to support the analysis of exposure versus efficacy relationship (PK and PD). Since terminal t1/2 was not considered relevant to the objective of exposure-response analysis, therefore data for this outcome measure were not collected and reported.
Arm/Group Title Ferroquine 400 mg + Artefenomel 300 mg Ferroquine 400 mg + Artefenomel 600 mg Ferroquine 400 mg + Artefenomel 1000 mg
Hide Arm/Group Description:
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
20.Secondary Outcome
Title Pharmacokinetics: Maximum Observed Plasma Concentration of Ferroquine and Its Active Metabolite SSR97213
Hide Description Cmax is the maximum observed plasma concentration of Ferroquine.
Time Frame Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK/PD efficacy population.
Arm/Group Title Ferroquine 400 mg Ferroquine 400 mg + Artefenomel 300 mg Ferroquine 400 mg + Artefenomel 600 mg Ferroquine 400 mg + Artefenomel 1000 mg
Hide Arm/Group Description:
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension.
Overall Number of Participants Analyzed 31 33 36 32
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms per milliliter
FQ
80.99
(61%)
79.95
(93%)
72.64
(88%)
82.45
(95%)
SSR97213
24.58
(61%)
22.65
(83%)
19.14
(99%)
19.76
(78%)
21.Secondary Outcome
Title Pharmacokinetics: Time to Reach Maximum Plasma Concentration of Ferroquine and Its Active Metabolite SSR97213
Hide Description tmax is the time taken by the drug to reach the maximum plasma concentration.
Time Frame Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Focus of PK assessment was to support the analysis of exposure versus efficacy relationship (PK and PD). Since tmax was not considered relevant to the objective of exposure-response analysis, therefore data for this outcome measure were not collected and reported.
Arm/Group Title Ferroquine 400 mg Ferroquine 400 mg + Artefenomel 300 mg Ferroquine 400 mg + Artefenomel 600 mg Ferroquine 400 mg + Artefenomel 1000 mg
Hide Arm/Group Description:
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension.
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
22.Secondary Outcome
Title Pharmacokinetics: Plasma Concentration at 168 Hours Post-dose of Ferroquine and Its Active Metabolite SSR97213
Hide Description The observed plasma concentration of FQ and SSR97213 post 168 hours of FQ administration.
Time Frame At 168 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK/PD efficacy population.
Arm/Group Title Ferroquine 400 mg Ferroquine 400 mg + Artefenomel 300 mg Ferroquine 400 mg + Artefenomel 600 mg Ferroquine 400 mg + Artefenomel 1000 mg
Hide Arm/Group Description:
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension.
Overall Number of Participants Analyzed 31 33 36 32
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms per milliliter
FQ
15.86
(44%)
18.32
(42%)
18.69
(52%)
17.83
(60%)
SSR97213
16.15
(51%)
16.03
(68%)
15.2
(78%)
14.95
(86%)
23.Secondary Outcome
Title Pharmacokinetics: Area Under the Concentration Curve Form Time 0 to Day 28 (AUC0-28) of Ferroquine and Its Active Metabolite SSR97213
Hide Description Area under the plasma concentration versus time curve from time 0 to Day 28 (i.e. 672 hours).
Time Frame Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK/PD efficacy population.
Arm/Group Title Ferroquine 400 mg Ferroquine 400 mg + Artefenomel 300 mg Ferroquine 400 mg + Artefenomel 600 mg Ferroquine 400 mg + Artefenomel 1000 mg
Hide Arm/Group Description:
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension.
Overall Number of Participants Analyzed 31 33 36 32
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: micrograms*hour per milliliter
FQ
8.874
(42%)
10.33
(40%)
10.13
(51%)
10.14
(56%)
SSR97213
8.878
(48%)
9.051
(56%)
8.483
(68%)
8.487
(71%)
24.Secondary Outcome
Title Pharmacokinetics: Area Under the Concentration Curve From Time 0 to Infinity of Ferroquine and Its Active Metabolite SSR97213
Hide Description Area under the plasma concentration versus time curve from time 0 to infinity.
Time Frame Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PK/PD efficacy population.
Arm/Group Title Ferroquine 400 mg Ferroquine 400 mg + Artefenomel 300 mg Ferroquine 400 mg + Artefenomel 600 mg Ferroquine 400 mg + Artefenomel 1000 mg
Hide Arm/Group Description:
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension.
Overall Number of Participants Analyzed 31 33 36 32
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: micrograms*hour per milliliter
FQ
15.5
(47%)
17.81
(43%)
16.3
(63%)
16.87
(59%)
SSR97213
19.58
(53%)
20.09
(48%)
17.94
(69%)
18.32
(68%)
25.Secondary Outcome
Title Pharmacokinetics: Terminal Half-life of Ferroquine
Hide Description Terminal t1/2 is defined as the time required for the plasma concentration of a drug to decrease by half of its initial concentration.
Time Frame Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose
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Hide Analysis Population Description
Focus of PK assessment was to support the analysis of exposure versus efficacy relationship (PK and PD). Since terminal t1/2 was not considered relevant to the objective of exposure-response analysis, therefore data for this outcome measure were not collected and reported.
Arm/Group Title Ferroquine 400 mg Ferroquine 400 mg + Artefenomel 300 mg Ferroquine 400 mg + Artefenomel 600 mg Ferroquine 400 mg + Artefenomel 1000 mg
Hide Arm/Group Description:
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension.
On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension.
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame From Baseline up to Day 28
Adverse Event Reporting Description Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.
 
Arm/Group Title Ferroquine 400 mg Ferroquine 400 mg + Artefenomel 300 mg Ferroquine 400 mg + Artefenomel 600 mg Ferroquine 400 mg + Artefenomel 1000 mg
Hide Arm/Group Description On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition. On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension. On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension. On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension.
All-Cause Mortality
Ferroquine 400 mg Ferroquine 400 mg + Artefenomel 300 mg Ferroquine 400 mg + Artefenomel 600 mg Ferroquine 400 mg + Artefenomel 1000 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/35 (0.00%)      0/36 (0.00%)      0/36 (0.00%)      0/33 (0.00%)    
Hide Serious Adverse Events
Ferroquine 400 mg Ferroquine 400 mg + Artefenomel 300 mg Ferroquine 400 mg + Artefenomel 600 mg Ferroquine 400 mg + Artefenomel 1000 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/35 (0.00%)      0/36 (0.00%)      1/36 (2.78%)      0/33 (0.00%)    
Infections and infestations         
Malaria  1  0/35 (0.00%)  0 0/36 (0.00%)  0 1/36 (2.78%)  1 0/33 (0.00%)  0
1
Term from vocabulary, MedDRA 22.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ferroquine 400 mg Ferroquine 400 mg + Artefenomel 300 mg Ferroquine 400 mg + Artefenomel 600 mg Ferroquine 400 mg + Artefenomel 1000 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   13/35 (37.14%)      17/36 (47.22%)      17/36 (47.22%)      22/33 (66.67%)    
Blood and lymphatic system disorders         
Anaemia  1  0/35 (0.00%)  0 2/36 (5.56%)  2 1/36 (2.78%)  1 0/33 (0.00%)  0
Thrombocytopenia  1  2/35 (5.71%)  2 0/36 (0.00%)  0 0/36 (0.00%)  0 0/33 (0.00%)  0
Gastrointestinal disorders         
Abdominal pain  1  1/35 (2.86%)  1 4/36 (11.11%)  4 0/36 (0.00%)  0 2/33 (6.06%)  2
Constipation  1  0/35 (0.00%)  0 2/36 (5.56%)  2 0/36 (0.00%)  0 0/33 (0.00%)  0
Diarrhoea  1  0/35 (0.00%)  0 1/36 (2.78%)  1 0/36 (0.00%)  0 2/33 (6.06%)  2
Nausea  1  1/35 (2.86%)  1 1/36 (2.78%)  1 2/36 (5.56%)  3 2/33 (6.06%)  2
Vomiting  1  3/35 (8.57%)  3 3/36 (8.33%)  3 5/36 (13.89%)  5 10/33 (30.30%)  10
General disorders         
Pyrexia  1  0/35 (0.00%)  0 2/36 (5.56%)  2 1/36 (2.78%)  1 4/33 (12.12%)  4
Infections and infestations         
Malaria  1  7/35 (20.00%)  7 6/36 (16.67%)  6 7/36 (19.44%)  7 6/33 (18.18%)  6
Rhinitis  1  0/35 (0.00%)  0 1/36 (2.78%)  1 2/36 (5.56%)  2 2/33 (6.06%)  3
Nervous system disorders         
Dizziness  1  0/35 (0.00%)  0 0/36 (0.00%)  0 2/36 (5.56%)  2 4/33 (12.12%)  4
Headache  1  3/35 (8.57%)  3 6/36 (16.67%)  10 1/36 (2.78%)  1 7/33 (21.21%)  9
Skin and subcutaneous tissue disorders         
Pruritus  1  2/35 (5.71%)  2 0/36 (0.00%)  0 0/36 (0.00%)  0 1/33 (3.03%)  1
1
Term from vocabulary, MedDRA 22.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
Results Point of Contact
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Name/Title: Trial Transparency Team
Organization: Sanofi
Phone: 800-633-1610 ext 1#
EMail: Contact-US@sanofi.com
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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT03660839    
Other Study ID Numbers: ACT14655
U1111-1191-5573 ( Other Identifier: UTN )
First Submitted: August 20, 2018
First Posted: September 7, 2018
Results First Submitted: November 5, 2020
Results First Posted: December 2, 2020
Last Update Posted: December 2, 2020