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Trial record 38 of 48 for:    ( Map: Gabon )

Phase II Efficacy Study of Artefenomel & Piperaquine in Adults & Children With P. Falciparum Malaria.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02083380
Recruitment Status : Completed
First Posted : March 11, 2014
Results First Posted : January 30, 2017
Last Update Posted : March 10, 2017
Sponsor:
Information provided by (Responsible Party):
Medicines for Malaria Venture

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Uncomplicated Plasmodium Falciparum Malaria
Interventions Drug: Artefenomel 800mg: piperaquine 640mg
Drug: Artefenomel 800mg: piperaquine 960mg
Drug: Artefenomel 800mg: piperaquine 1440mg
Enrollment 448
Recruitment Details Randomized double blind study. Conduct was July 2014-August 2015 in Africa (Benin, Burkina Faso, Democratic Republic of Congo, Gabon, Mozambique and Uganda) and Vietnam. Following informed consent patients were recruited to the study. Patients below the age to give legal Informed Consent were consented according local customs / legal requirements.
Pre-assignment Details Patients were assigned a screening number and underwent screening procedures to assess eligibility. Eligible patients were randomized through an Interactive web-response system and followed for efficacy and safety up to 42 days post dose and 63 days at selected centers. Patients were consented separately to remain in the study up to Day 63.
Arm/Group Title A) Artefenomel 800mg: Piperaquine 640mg B) Artefenomel 800mg: Piperaquine 960mg C) Artefenomel 800mg: Piperaquine 1440mg
Hide Arm/Group Description Artefenomel 800mg: Piperaquine phosphate 640mg loose combination Artefenomel 800mg: Piperaquine phosphate 960mg loose combination Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
Period Title: Overall Study
Started 148 [1] 151 [2] 149 [2]
Completed [3] 57 56 65
Not Completed 91 95 84
Reason Not Completed
Lack of Efficacy             68             79             64
Withdrawal by Subject             9             3             7
Physician Decision             1             6             3
Adverse Event             0             0             1
Lost to Follow-up             5             3             3
Other             8             4             6
[1]
5 subjects excluded from safety / ITT population - no drug administered
[2]
3 subjects excluded from safety / ITT population - no drug administered
[3]
Lack of Efficacy = Received rescue treatment therefore linked with the efficacy endpoint ACPR
Arm/Group Title A) Artefenomel 800mg: PQP 640mg B) Artefenomel 800mg: PQP 960mg C) Artefenomel 800mg: PQP 1440mg Total
Hide Arm/Group Description Artefenomel 800mg: Piperaquine 640mg Artefenomel 800mg: Piperaquine 960mg Artefenomel 800mg: Piperaquine 1440mg Total of all reporting groups
Overall Number of Baseline Participants 143 148 146 437
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 143 participants 148 participants 146 participants 437 participants
> 15 years 41 42 41 124
> 5 to <= 15 years 8 8 9 25
> 2 to <= 5 years 69 72 70 211
>= 0.5 to <= 2 years 25 26 26 77
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 143 participants 148 participants 146 participants 437 participants
Female
83
  58.0%
85
  57.4%
98
  67.1%
266
  60.9%
Male
60
  42.0%
63
  42.6%
48
  32.9%
171
  39.1%
1.Primary Outcome
Title PCR-adjusted ACPR at Day 28 in the PP Population (All Patients)
Hide Description

Polymerase chain reaction (PCR)-adjusted adequate clinical and parasitological response (ACPR) at Day 28: defined as: absence of parasitaemia on Day 28, irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure (ETF), late clinical failure (LCF) or late parasitological failure (LPF). Definition of ETF, LCF and LPF according to a modified standard WHO classification. Per protocol population (PP).

95% Clopper-Pearson 2-sided Confidence Interval (CI) constructed around the single binomial proportion per treatment arm and total.

Time Frame Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Primary analysis population was the per protocol population defined as all patients comprising the ITT set and without major protocol deviations. Including insufficient evidence of study indication, no baseline parasitemia and non-compliance with study drug administration.
Arm/Group Title A) Artefenomel 800mg: Piperaquine 640mg B) Artefenomel 800mg: Piperaquine 960mg C) Artefenomel 800mg: Piperaquine 1440mg
Hide Arm/Group Description:
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
Overall Number of Participants Analyzed 106 117 117
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: % ACPR PCR-adjusted
70.8
(61.13 to 79.19)
68.4
(59.13 to 76.66)
78.6
(70.09 to 85.67)
2.Primary Outcome
Title PCR-adjusted ACPR at Day 28 in the PP Population: Asia (All Ages)
Hide Description

PCR-adjusted adequate clinical and parasitological response (ACPR) at Day 28: defined as: absence of parasitaemia on Day 28, irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure (ETF), late clinical failure (LCF) or late parasitological failure (LPF). Definition of ETF, LCF and LPF according to a modified standard WHO classification.

95% Clopper-Pearson 2-sided CI constructed around the single binomial proportion per treatment arm and total.

Time Frame Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Primary analysis population was the per protocol population defined as all patients comprising the ITT set and without major protocol deviations. Including insufficient evidence of study indication, no baseline parasitemia and non-compliance with study drug administration.
Arm/Group Title A) Artefenomel 800mg: Piperaquine 640mg B) Artefenomel 800mg: Piperaquine 960mg C) Artefenomel 800mg: Piperaquine 1440mg
Hide Arm/Group Description:
Artefenomel 800mg: Piperaquine phosphate 640mg loose combination
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
Overall Number of Participants Analyzed 25 25 27
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: % ACPR PCR-adjusted
64
(42.52 to 82.03)
64
(42.52 to 82.03)
70.4
(49.82 to 86.25)
3.Primary Outcome
Title PCR-adjusted ACPR at Day 28 in the PP Population: Africa (All Ages)
Hide Description

PCR-adjusted adequate clinical and parasitological response (ACPR) at Day 28: defined as: absence of parasitaemia on Day 28, irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure (ETF), late clinical failure (LCF) or late parasitological failure (LPF). Definition of ETF, LCF and LPF according to a modified standard WHO classification.

95% Clopper-Pearson 2-sided CI constructed around the single binomial proportion per treatment arm and total.

Time Frame Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Primary analysis population was the per protocol population defined as all patients comprising the ITT set and without major protocol deviations. Including insufficient evidence of study indication, no baseline parasitemia and non-compliance with study drug administration.
Arm/Group Title A) Artefenomel 800mg: Piperaquine 640mg B) Artefenomel 800mg: Piperaquine 960mg C) Artefenomel 800mg: Piperaquine 1440mg
Hide Arm/Group Description:
Artefenomel 800mg: Piperaquine phosphate 640mg loose combination
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
Overall Number of Participants Analyzed 81 92 90
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: % ACPR PCR-adjusted
72.8
(61.81 to 82.13)
69.6
(59.10 to 78.73)
81.1
(71.49 to 88.59)
4.Primary Outcome
Title PCR-adjusted ACPR at Day 28 in the PP Population: Africa (> Than 5 Years)
Hide Description

PCR-adjusted adequate clinical and parasitological response (ACPR) at Day 28: defined as: absence of parasitaemia on Day 28, irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure (ETF), late clinical failure (LCF) or late parasitological failure (LPF). Definition of ETF, LCF and LPF according to a modified standard WHO classification.

95% Clopper-Pearson 2-sided CI constructed around the single binomial proportion per treatment arm and total.

Time Frame Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Primary analysis population was the per protocol population defined as all patients comprising the ITT set and without major protocol deviations. Including insufficient evidence of study indication, no baseline parasitemia and non-compliance with study drug administration.
Arm/Group Title A) Artefenomel 800mg: Piperaquine 640mg B) Artefenomel 800mg: Piperaquine 960mg C) Artefenomel 800mg: Piperaquine 1440mg
Hide Arm/Group Description:
Artefenomel 800mg: Piperaquine phosphate 640mg loose combination
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
Overall Number of Participants Analyzed 18 21 19
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: % ACPR PCR-adjusted
77.8
(52.36 to 93.59)
90.5
(69.62 to 98.83)
89.5
(66.86 to 98.70)
5.Primary Outcome
Title PCR-adjusted ACPR at Day 28 in the PP Population: Africa (< = 5 Years)
Hide Description

PCR-adjusted adequate clinical and parasitological response (ACPR) at Day 28: defined as: absence of parasitaemia on Day 28, irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure (ETF), late clinical failure (LCF) or late parasitological failure (LPF). Definition of ETF, LCF and LPF according to a modified standard WHO classification.

95% Clopper-Pearson 2-sided CI constructed around the single binomial proportion per treatment arm and total.

Time Frame Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Primary analysis population was the per protocol population defined as all patients comprising the ITT set and without major protocol deviations. Including insufficient evidence of study indication, no baseline parasitemia and non-compliance with study drug administration.
Arm/Group Title A) Artefenomel 800mg: Piperaquine 640mg B) Artefenomel 800mg: Piperaquine 960mg C) Artefenomel 800mg: Piperaquine 1440mg
Hide Arm/Group Description:
Artefenomel 800mg: Piperaquine phosphate 640mg loose combination
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
Overall Number of Participants Analyzed 63 71 71
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: % ACPR PCR-adjusted
71.4
(58.65 to 82.11)
63.4
(51.10 to 74.50)
78.9
(67.56 to 87.67)
6.Primary Outcome
Title PCR-adjusted ACPR at Day 28 in the PP Population: Africa (>2 to <= 5 Years)
Hide Description

PCR-adjusted adequate clinical and parasitological response (ACPR) at Day 28: defined as: absence of parasitaemia on Day 28, irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure (ETF), late clinical failure (LCF) or late parasitological failure (LPF). Definition of ETF, LCF and LPF according to a modified standard WHO classification.

95% Clopper-Pearson 2-sided CI constructed around the single binomial proportion per treatment arm and total.

Time Frame Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Primary analysis population was the per protocol population defined as all patients comprising the ITT set and without major protocol deviations. Including insufficient evidence of study indication, no baseline parasitemia and non-compliance with study drug administration.
Arm/Group Title A) Artefenomel 800mg: Piperaquine 640mg B) Artefenomel 800mg: Piperaquine 960mg C) Artefenomel 800mg: Piperaquine 1440mg
Hide Arm/Group Description:
Artefenomel 800mg: Piperaquine phosphate 640mg loose combination
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
Overall Number of Participants Analyzed 45 50 55
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: % ACPR PCR-adjusted
75.6
(60.46 to 87.12)
74.0
(59.66 to 85.37)
83.6
(71.20 to 92.23)
7.Primary Outcome
Title PCR-adjusted ACPR at Day 28 in the PP Population: Africa (>= 0.5 to <= 2 Years)
Hide Description

PCR-adjusted adequate clinical and parasitological response (ACPR) at Day 28: defined as: absence of parasitaemia on Day 28, irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure (ETF), late clinical failure (LCF) or late parasitological failure (LPF). Definition of ETF, LCF and LPF according to a modified standard WHO classification.

95% Clopper-Pearson 2-sided CI constructed around the single binomial proportion per treatment arm and total.

Time Frame Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Primary analysis population was the per protocol population defined as all patients comprising the ITT set and without major protocol deviations. Including insufficient evidence of study indication, no baseline parasitemia and non-compliance with study drug administration.
Arm/Group Title A) Artefenomel 800mg: Piperaquine 640mg B) Artefenomel 800mg: Piperaquine 960mg C) Artefenomel 800mg: Piperaquine 1440mg
Hide Arm/Group Description:
Artefenomel 800mg: Piperaquine phosphate 640mg loose combination
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
Overall Number of Participants Analyzed 18 21 16
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: % ACPR PCR-adjusted
61.1
(35.75 to 82.70)
38.1
(18.11 to 61.56)
62.5
(35.43 to 84.80)
8.Secondary Outcome
Title PCR - Adjusted ACPR at Day 42 in the PP Population
Hide Description PCR - adjusted adequate clinical and parasitological response at Day 42
Time Frame Days 42
Hide Outcome Measure Data
Hide Analysis Population Description
Primary analysis population was the per protocol population defined as all patients comprising the ITT set and without major protocol deviations. Including insufficient evidence of study indication, no baseline parasitemia and non-compliance with study drug administration.
Arm/Group Title A) Artefenomel 800mg: Piperaquine 640mg B) Artefenomel 800mg: Piperaquine 960mg C) Artefenomel 800mg: Piperaquine 1440mg
Hide Arm/Group Description:
Artefenomel 800mg: Piperaquine phosphate 640mg loose combination
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
Overall Number of Participants Analyzed 100 108 100
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: % ACPR PCR-adjusted
65.0
(54.82 to 74.27)
65.7
(55.99 to 74.60)
72.0
(62.13 to 80.52)
9.Secondary Outcome
Title PCR-adjusted ACPR at Day 63 in the PP Population
Hide Description PCR-adjusted adequate clinical and parasitological response at Day 63
Time Frame Day 63
Hide Outcome Measure Data
Hide Analysis Population Description
Primary analysis population was the per protocol population defined as all patients comprising the ITT set and without major protocol deviations. Including insufficient evidence of study indication, no baseline parasitemia and non-compliance with study drug administration.
Arm/Group Title A) Artefenomel 800mg: Piperaquine 640mg B) Artefenomel 800mg: Piperaquine 960mg C) Artefenomel 800mg: Piperaquine 1440mg
Hide Arm/Group Description:
Artefenomel 800mg: Piperaquine phosphate 640mg loose combination
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
Overall Number of Participants Analyzed 83 90 84
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: % ACPR PCR-adjusted
57.8
(46.49 to 68.60)
58.9
(48.02 to 69.16)
69.0
(58.02 to 78.69)
10.Secondary Outcome
Title Crude ACPR at Day 28 in the PP Population
Hide Description Crude adequate clinical and parasitological response at Day 28
Time Frame Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Primary analysis population was the per protocol population defined as all patients comprising the ITT set and without major protocol deviations. Including insufficient evidence of study indication, no baseline parasitemia and non-compliance with study drug administration. The PP population comprised 93.3% of the randomized population.
Arm/Group Title A) Artefenomel 800mg: Piperaquine 640mg B) Artefenomel 800mg: Piperaquine 960mg C) Artefenomel 800mg: Piperaquine 1440mg
Hide Arm/Group Description:
Artefenomel 800mg: Piperaquine phosphate 640mg loose combination
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
C) Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
Overall Number of Participants Analyzed 129 136 133
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: % ACPR unadjusted (crude)
57.4
(48.36 to 66.03)
56.6
(47.85 to 65.09)
66.9
(58.23 to 74.83)
11.Secondary Outcome
Title Crude ACPR at Day 42 in the PP Population
Hide Description Crude adequate clinical and parasitological response at Day 42
Time Frame Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
Primary analysis population was the per protocol population defined as all patients comprising the ITT set and without major protocol deviations. Including insufficient evidence of study indication, no baseline parasitemia and non-compliance with study drug administration.
Arm/Group Title A) Artefenomel 800mg: Piperaquine 640mg B) Artefenomel 800mg: Piperaquine 960mg C) Artefenomel 800mg: Piperaquine 1440mg
Hide Arm/Group Description:
Artefenomel 800mg: Piperaquine phosphate 640mg loose combination
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
Overall Number of Participants Analyzed 127 134 130
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: % ACPR unajusted (crude)
48.0
(39.09 to 57.07)
48.5
(39.79 to 57.29)
51.5
(42.62 to 60.39)
12.Secondary Outcome
Title Crude ACPR at Day 63 in the PP Population
Hide Description Crude adequate clinical and parasitological response at Day 63
Time Frame Day 63
Hide Outcome Measure Data
Hide Analysis Population Description
Primary analysis population was the per protocol population defined as all patients comprising the ITT set and without major protocol deviations. Including insufficient evidence of study indication, no baseline parasitemia and non-compliance with study drug administration. The PP population comprised 93.3% of the randomized population.
Arm/Group Title A) Artefenomel 800mg: Piperaquine 640mg B) Artefenomel 800mg: Piperaquine 960mg C) Artefenomel 800mg: Piperaquine 1440mg
Hide Arm/Group Description:
Artefenomel 800mg: Piperaquine phosphate 640mg loose combination
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
Overall Number of Participants Analyzed 114 122 116
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: % ACPR unadjusted (crude)
42.1
(32.92 to 51.71)
39.3
(30.62 to 48.59)
49.1
(39.74 to 58.58)
13.Secondary Outcome
Title PCR-adjusted ACPR at Day 28 in the ITT Population
Hide Description PCR-adjusted adequate clinical and parasitological response at Day 28. Intent to Treat ( ITT) population.
Time Frame Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) population : all patients who provided written informed consent, were randomised, received the single dose combination of OZ439/PQP study drug (or part thereof), and had a confirmed positive blood film for P. falciparum asexual parasitaemia at inclusion.
Arm/Group Title A) Artefenomel 800mg: Piperaquine 640mg B) Artefenomel 800mg: Piperaquine 960mg C) Artefenomel 800mg: Piperaquine 1440mg
Hide Arm/Group Description:
Artefenomel 800mg: Piperaquine phosphate 640mg loose combination
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
Overall Number of Participants Analyzed 143 148 146
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: % ACPR PCR-adjusted
53.8
(45.32 to 62.21)
55.4
(47.02 to 63.57)
65.1
(56.75 to 72.76)
14.Secondary Outcome
Title PCR-adjusted ACPR at Day 42 in the ITT Population
Hide Description PCR-adjusted adequate clinical and parasitological response at Day 42 in the ITT population
Time Frame Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) population : all patients who provided written informed consent, were randomised, received the single dose combination of OZ439/PQP study drug (or part thereof), and had a confirmed positive blood film for P. falciparum asexual parasitaemia at inclusion.
Arm/Group Title A) Artefenomel 800mg: Piperaquine 640mg B) Artefenomel 800mg: Piperaquine 960mg C) Artefenomel 800mg: Piperaquine 1440mg
Hide Arm/Group Description:
Artefenomel 800mg: Piperaquine phosphate 640mg loose combination
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
Overall Number of Participants Analyzed 143 148 146
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: % ACPR PCR-adjusted
46.9
(38.47 to 55.37)
48.6
(40.36 to 56.99)
50.0
(41.62 to 58.38)
15.Secondary Outcome
Title PCR-adjusted ACPR at Day 63 in the ITT Population
Hide Description PCR-adjusted adequate clinical and parasitological response at Day 63 in the ITT population
Time Frame Day 63
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) population : all patients who provided written informed consent, were randomised, received the single dose combination of OZ439/PQP study drug (or part thereof), and had a confirmed positive blood film for P. falciparum asexual parasitaemia at inclusion.
Arm/Group Title A) Artefenomel 800mg: Piperaquine 640mg B) Artefenomel 800mg: Piperaquine 960mg C) Artefenomel 800mg: Piperaquine 1440mg
Hide Arm/Group Description:
Artefenomel 800mg: Piperaquine phosphate 640mg loose combination
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
Overall Number of Participants Analyzed 136 140 135
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: % ACPR PCR-adjusted
36.8
(28.67 to 45.45)
38.6
(30.47 to 47.16)
43.7
(35.19 to 52.50)
16.Secondary Outcome
Title Crude ACPR at Day 28 in the ITT Population
Hide Description Crude adequate clinical and parasitological response at Day 28 in the ITT population
Time Frame Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) population : all patients who provided written informed consent, were randomised, received the single dose combination of OZ439/PQP study drug (or part thereof), and had a confirmed positive blood film for P. falciparum asexual parasitaemia at inclusion.
Arm/Group Title A) Artefenomel 800mg: Piperaquine 640mg B) Artefenomel 800mg: Piperaquine 960mg C) Artefenomel 800mg: Piperaquine 1440mg
Hide Arm/Group Description:
Artefenomel 800mg: Piperaquine phosphate 640mg loose combination
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
Overall Number of Participants Analyzed 143 148 146
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: % ACPR unadjusted (crude)
53.1
(44.63 to 61.53)
53.4
(45.01 to 61.61)
63.0
(54.64 to 70.85)
17.Secondary Outcome
Title Crude ACPR at Day 42 in the ITT Population
Hide Description Crude adequate clinical and parasitological response at Day 42 in the ITT population
Time Frame Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) population : all patients who provided written informed consent, were randomised, received the single dose combination of OZ439/PQP study drug (or part thereof), and had a confirmed positive blood film for P. falciparum asexual parasitaemia at inclusion.
Arm/Group Title A) Artefenomel 800mg: Piperaquine 640mg B) Artefenomel 800mg: Piperaquine 960mg C) Artefenomel 800mg: Piperaquine 1440mg
Hide Arm/Group Description:
Artefenomel 800mg: Piperaquine phosphate 640mg loose combination
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
Overall Number of Participants Analyzed 143 148 146
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: % ACPR unadjusted (crude)
44.1
(35.77 to 52.59)
44.6
(36.43 to 52.98)
46.6
(38.29 to 55.01)
18.Secondary Outcome
Title Crude ACPR at Day 63 in the ITT Population
Hide Description Crude adequate clinical and parasitological response at Day 63 in the ITT population
Time Frame Day 63
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) population : all patients who provided written informed consent, were randomised, received the single dose combination of OZ439/PQP study drug (or part thereof), and had a confirmed positive blood film for P. falciparum asexual parasitaemia at inclusion.
Arm/Group Title A) Artefenomel 800mg: Piperaquine 640mg B) Artefenomel 800mg: Piperaquine 960mg C) Artefenomel 800mg: Piperaquine 1440mg
Hide Arm/Group Description:
Artefenomel 800mg: Piperaquine phosphate 640mg loose combination
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
Overall Number of Participants Analyzed 136 140 135
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: % ACPR unadjusted (crude)
36.8
(28.67 to 45.45)
35.0
(27.14 to 43.51)
43.0
(34.48 to 51.76)
19.Secondary Outcome
Title Kaplan-Meier Estimate of Recurrence
Hide Description Kaplan-Meier estimate of number of recurrent infections (either recrudescence or new infection)
Time Frame Day 63
Hide Outcome Measure Data
Hide Analysis Population Description
modified Intent to Treat (mITT) population : all patients who provided written informed consent, were randomised, were compliant with the single dose combination of OZ439/PQP study drug and had a confirmed positive blood film for P. falciparum asexual parasitaemia at inclusion.
Arm/Group Title A) Artefenomel 800mg: Piperaquine 640mg B) Artefenomel 800mg: Piperaquine 960mg C) Artefenomel 800mg: Piperaquine 1440mg
Hide Arm/Group Description:
Artefenomel 800mg: Piperaquine phosphate 640mg loose combination
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
Overall Number of Participants Analyzed 141 141 140
Measure Type: Number
Unit of Measure: % population recurring
44.7 54.6 43.6
20.Secondary Outcome
Title Kaplan-Meier Estimate of Recrudescence
Hide Description Kaplan-Meier estimate of number of patients with recrudescence
Time Frame Day 63
Hide Outcome Measure Data
Hide Analysis Population Description
modified Intent to Treat (mITT) population : all patients who provided written informed consent, were randomised, were compliant with the single dose combination of OZ439/PQP study drug and had a confirmed positive blood film for P. falciparum asexual parasitaemia at inclusion.
Arm/Group Title A) Arttefenomel 800mg: Piperaquine 640mg B) Artefenomel 800mg: Piperaquine 960mg C) Artefenomel 800mg: Piperaquine 1440mg
Hide Arm/Group Description:
Artefenomel 800mg: Piperaquine phosphate 640mg loose combination
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
Overall Number of Participants Analyzed 141 141 140
Measure Type: Number
Unit of Measure: % patients with recrudescence
22.7 29.1 18.6
21.Secondary Outcome
Title Kaplan-Meier Estimate of New Infection Rate
Hide Description Kaplan-Meier estimate of number of patients with new infections
Time Frame Day 63
Hide Outcome Measure Data
Hide Analysis Population Description
modified Intent to Treat (mITT) population : all patients who provided written informed consent, were randomised, were compliant with the single dose combination of OZ439/PQP study drug and had a confirmed positive blood film for P. falciparum asexual parasitaemia at inclusion.
Arm/Group Title A) Artefenomel 800mg: Piperaquine 640mg B) Artefenomel 800mg: Piperaquine 960mg C) Artefenomel 800mg: Piperaquine 1440mg
Hide Arm/Group Description:
Artefenomel 800mg: Piperaquine phosphate 640mg loose combination
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
Overall Number of Participants Analyzed 141 141 140
Measure Type: Number
Unit of Measure: % population with new infection
11.3 16.3 13.6
22.Secondary Outcome
Title Parasite Clearance Time
Hide Description Time post dose to parasite clearance
Time Frame 0, 6, 12, 18, 24, 30, 36, 48 and 72 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
Primary analysis population was the per protocol population defined as all patients comprising the ITT set and without major protocol deviations. Including insufficient evidence of study indication, no baseline parasitemia and non-compliance with study drug administration.
Arm/Group Title A) Artefenomel 800mg: Piperaquine 640mg B) Artefenomel 800mg: Piperaquine 960mg C) Artefenomel 800mg: Piperaquine 1440mg
Hide Arm/Group Description:
Artefenomel 800mg: Piperaquine phosphate 640mg loose combination
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
Overall Number of Participants Analyzed 139 140 139
Median (95% Confidence Interval)
Unit of Measure: hours
36.1
(36.0 to 36.1)
36.0
(36.0 to 36.1)
36.1
(36.0 to 36.1)
23.Secondary Outcome
Title Fever Clearance Time
Hide Description Time to fever clearance (hours)
Time Frame Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
Primary analysis population was the per protocol population defined as all patients comprising the ITT set and without major protocol deviations. Including insufficient evidence of study indication, no baseline parasitemia and non-compliance with study drug administration.
Arm/Group Title A) Artefenomel 800mg: Piperaquine 640mg B) Artefenomel 800mg: Piperaquine 960mg C) Artefenomel 800mg: Piperaquine 1440mg
Hide Arm/Group Description:
Artefenomel 800mg: Piperaquine phosphate 640mg loose combination
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
Overall Number of Participants Analyzed 139 140 139
Median (95% Confidence Interval)
Unit of Measure: hours
1.0
(1.0 to 2.6)
1.2
(1.0 to 2.1)
1.1
(1.0 to 2.0)
24.Secondary Outcome
Title PRR48
Hide Description Parasite reduction ratio at 48 hours post dose
Time Frame 0, 6, 12, 18, 24, 30, 36 and 48 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
Primary analysis population was the per protocol population defined as all patients comprising the ITT set and without major protocol deviations. Including insufficient evidence of study indication, no baseline parasitemia and non-compliance with study drug administration. Subjects with sufficient data points to determine PRR48
Arm/Group Title A) Artefenomel 800mg: Piperaquine 640mg B) Artefenomel 800mg: Piperaquine 960mg C) Artefenomel 800mg: Piperaquine 1440mg
Hide Arm/Group Description:
Artefenomel 800mg: Piperaquine phosphate 640mg loose combination
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
Overall Number of Participants Analyzed 97 103 99
Median (Inter-Quartile Range)
Unit of Measure: ratio
9.120
(6.900 to 12.970)
9.300
(7.660 to 13.340)
8.690
(6.850 to 12.260)
25.Other Pre-specified Outcome
Title Piperaquine: Cday7 Asia (All Ages)
Hide Description Piperaquine concentration at Day7 in Asian patients all ages
Time Frame Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title A) Artefenomel 800mg: Piperaquine 640mg B) Artefenomel 800mg: Piperaquine 960mg C) Artefenomel 800mg: Piperaquine 1440mg
Hide Arm/Group Description:
Artefenomel 800mg: Piperaquine phosphate 640mg loose combination
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
Overall Number of Participants Analyzed 27 28 28
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
4.2
(72%)
6.9
(61%)
9.3
(78%)
26.Other Pre-specified Outcome
Title Piperaquine: Cday7 Africa (> 5 Years)
Hide Description Piperaquine concentration at Day7 in African patients > 5 years
Time Frame Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title A) Artefenomel 800mg: Piperaquine 640mg B) Artefenomel 800mg: Piperaquine 960mg C) Artefenomel 800mg: Piperaquine 1440mg
Hide Arm/Group Description:
Artefenomel 800mg: Piperaquine phosphate 640mg loose combination
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
Overall Number of Participants Analyzed 21 22 21
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
5.6
(113%)
8.8
(105%)
12.1
(103%)
27.Other Pre-specified Outcome
Title Piperaquine: Cday7 Africa (>2 to <= 5 Years)
Hide Description Piperaquine concentration at Day7 in African patients > 2 and <= 5years
Time Frame Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title A) Artefenomel 800mg: Piperaquine 640mg B) Artefenomel 800mg: Piperaquine 960mg C) Artefenomel 800mg: Piperaquine 1440mg
Hide Arm/Group Description:
Artefenomel 800mg: Piperaquine phosphate 640mg loose combination
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
Overall Number of Participants Analyzed 43 42 33
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
6.3
(71%)
9.2
(87%)
10.9
(92%)
28.Other Pre-specified Outcome
Title Piperaquine: Cday7 Africa (>=0.5 to <= 2 Years)
Hide Description Piperaquine concentration at Day7 in African patients >= 0.5 and <= 2 years
Time Frame Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title A) Artefenomel 800mg: Piperaquine 640mg B) Artefenomel 800mg: Piperaquine 960mg C) Artefenomel 800mg: Piperaquine 1440mg
Hide Arm/Group Description:
Artefenomel 800mg: Piperaquine phosphate 640mg loose combination
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
Overall Number of Participants Analyzed 51 52 59
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
5.0
(63%)
5.9
(70%)
9.0
(94%)
29.Other Pre-specified Outcome
Title Artefenomel Cday7 Asian Patients (All Ages)
Hide Description Artefenomel concentration on Day 7 in Asian Patients (all ages). All Treatment arms.
Time Frame Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title A) Artefenomel 800mg: PQP 640mg, 960mg & 1440mg
Hide Arm/Group Description:

Artefenomel 800mg: Piperaquine phosphate 640mg, 960mg & 1440mg combined

Artefenomel 800mg: PQP 640mg, 960mg & 1440mg

Overall Number of Participants Analyzed 82
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
5.1
(95%)
30.Other Pre-specified Outcome
Title Artefenomel Cday7 African Patients (> 5 Years)
Hide Description Artefenomel concentration on Day 7 in African Patients > 5 years. All Treatment arms.
Time Frame Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title A) Artefenomel 800mg: PQP 640mg, 960mg & 1440mg
Hide Arm/Group Description:
Artefenomel 800mg: Piperaquine phosphate 640mg, 960mg & 1440mg combined
Overall Number of Participants Analyzed 64
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
3.3
(141%)
31.Other Pre-specified Outcome
Title Artefenomel Cday7 African Patients (>2 to <= 5 Years)
Hide Description Artefenomel concentration on Day 7 in African Patients >2 to <= 5 years. All Treatment arms.
Time Frame Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title A) Artefenomel 800mg: PQP 640mg, 960mg & 1440mg
Hide Arm/Group Description:
Artefenomel 800mg: Piperaquine phosphate 640mg, 960mg & 1440mg combined
Overall Number of Participants Analyzed 120
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
3.3
(142%)
32.Other Pre-specified Outcome
Title Artefenomel Cday7 African Patients (>=0.5 to <= 2 Years)
Hide Description Artefenomel concentration on Day 7 in African Patients >= 0.5 to <=2 years. All Treatment arms.
Time Frame Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title A) Artefenomel 800mg: PQP 640mg, 960mg & 1440mg
Hide Arm/Group Description:
Artefenomel 800mg: Piperaquine phosphate 640mg, 960mg & 1440mg combined
Overall Number of Participants Analyzed 161
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
2.0
(147%)
Time Frame From screening up to Day 63 post dose
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title A) Artefenomel 800mg: PQP 640mg B) Artefenomel 800mg: PQP 960mg C) Artefenomel 800mg: PQP 1440mg
Hide Arm/Group Description Artefenomel 800mg: Piperaquine phosphate 640mg Artefenomel 800mg: Piperaquine 960mg Artefenomel 800mg: Piperaquine 1440mg
All-Cause Mortality
A) Artefenomel 800mg: PQP 640mg B) Artefenomel 800mg: PQP 960mg C) Artefenomel 800mg: PQP 1440mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
A) Artefenomel 800mg: PQP 640mg B) Artefenomel 800mg: PQP 960mg C) Artefenomel 800mg: PQP 1440mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/146 (0.68%)      1/148 (0.68%)      2/143 (1.40%)    
Investigations       
Transaminase elevation  1 [1]  0/146 (0.00%)  0 0/148 (0.00%)  0 1/143 (0.70%)  2
Anemia  1  0/146 (0.00%)  0 0/148 (0.00%)  0 1/143 (0.70%)  1
Hemoglobin drop < 5 g/dL  1  1/146 (0.68%)  1 0/148 (0.00%)  0 0/143 (0.00%)  0
Nervous system disorders       
Febrile convulsion * 1  0/146 (0.00%)  0 1/148 (0.68%)  1 0/143 (0.00%)  0
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (Unspecified)
[1]
Two reversible SAEs of possibly related reversible transaminase elevation in one subject
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
A) Artefenomel 800mg: PQP 640mg B) Artefenomel 800mg: PQP 960mg C) Artefenomel 800mg: PQP 1440mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   122/146 (83.56%)      127/148 (85.81%)      115/143 (80.42%)    
Gastrointestinal disorders       
Diarrhoea * 1  20/146 (13.70%)  20 21/148 (14.19%)  21 11/143 (7.69%)  12
Vomiting  1  16/146 (10.96%)  16 20/148 (13.51%)  20 14/143 (9.79%)  14
Abdominal pain * 1  12/146 (8.22%)  13 8/148 (5.41%)  9 5/143 (3.50%)  5
General disorders       
Pyrexia  1  9/146 (6.16%)  11 12/148 (8.11%)  13 5/143 (3.50%)  5
Infections and infestations       
malaria  1  34/146 (23.29%)  34 45/148 (30.41%)  48 43/143 (30.07%)  44
Bronchitis * 1  10/146 (6.85%)  11 13/148 (8.78%)  19 13/143 (9.09%)  16
Rhinitis * 1  10/146 (6.85%)  10 9/148 (6.08%)  10 11/143 (7.69%)  11
Plasmodium Falciparum Infection  1  7/146 (4.79%)  7 10/148 (6.76%)  10 9/143 (6.29%)  9
Investigations       
Electrocardiumgram QT prolonged  1  44/146 (30.14%)  56 41/148 (27.70%)  48 27/143 (18.88%)  29
Neutrophil count decreased  1  12/146 (8.22%)  13 11/148 (7.43%)  11 18/143 (12.59%)  18
Haemoglobin decreased  1  11/146 (7.53%)  11 20/148 (13.51%)  22 9/143 (6.29%)  9
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (Unspecified)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Associate Professor Dr Michael Ramharter
Organization: Medical University of Vienna, Division of Infectious Diseases and Tropical Medicine
Phone: +43140400-44400
EMail: michael.ramharter@meduniwien.ac.at
Layout table for additonal information
Responsible Party: Medicines for Malaria Venture
ClinicalTrials.gov Identifier: NCT02083380     History of Changes
Other Study ID Numbers: MMV_OZ439_13_003
First Submitted: March 7, 2014
First Posted: March 11, 2014
Results First Submitted: December 5, 2016
Results First Posted: January 30, 2017
Last Update Posted: March 10, 2017