Clinical Trial Results:
An open-label, single-arm study to evaluate the efficacy, safety and PK of artemether-lumefantrine dispersible tablet in the treatment of acute uncomplicated Plasmodium falciparum malaria in infants <5 kg body weight
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Summary
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EudraCT number |
2011-005852-33 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
08 Jul 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
15 Jul 2016
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First version publication date |
15 Jul 2016
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CCOA566B2306
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01619878 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Novartis Pharma AG
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Sponsor organisation address |
CH-4002, Basel, Switzerland,
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Public contact |
Clinical Disclosure Office, Novartis Pharma AG, 41 613241111,
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Scientific contact |
Clinical Disclosure Office, Novartis Pharma AG, 41 613241111,
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000777-PIP01-09 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
08 Jul 2014
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
08 Jul 2014
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The primary objective was to evaluate the efficacy of a 3-day regimen of artemether-lumefantrine
dispersible tablet (1 tablet twice daily) in infants <5 kg of BW with acute uncomplicated P. falciparum
malaria using the polymerase chain reaction (PCR)-corrected 28-day parasitological cure rate.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
08 Oct 2012
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
12 Months | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Benin: 4
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Country: Number of subjects enrolled |
Burkina Faso: 16
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Worldwide total number of subjects |
20
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
20
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||
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Pre-assignment
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Screening details |
The participant that did not complete in the "6 week follow-up phase" was also included in "Follow-up at 12 Months of Age" and was lost to follow-up | ||||||||||||||||
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Period 1
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Period 1 title |
Cohort 1- 6 week / 12 month follow-up (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||
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Arms
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Arm title
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Cohort 1 | ||||||||||||||||
Arm description |
One Artemether-lumefantrine (COA566) dispersible tablet taken orally twice a day during 3 days. Infants age >28 days. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
Artemether-lumefantrine
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Investigational medicinal product code |
COA566
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Other name |
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Pharmaceutical forms |
Dispersible tablet
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Routes of administration |
Oral use
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Dosage and administration details |
20 mg artemether/ 120 mg dispersible tablet was given twice daily for 3 consecutive days. Each tablet was dispersed in water (approximately 10 mL) and given orally.
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| Notes [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: The participant that did not complete in the "6 week follow-up phase" was also included in "Follow-up at 12 Months of Age" and was lost to follow-up |
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Baseline characteristics reporting groups
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Reporting group title |
Cohort 1
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Reporting group description |
One Artemether-lumefantrine (COA566) dispersible tablet taken orally twice a day during 3 days. Infants age >28 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Cohort 1
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Reporting group description |
One Artemether-lumefantrine (COA566) dispersible tablet taken orally twice a day during 3 days. Infants age >28 days. | ||
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End point title |
Polymerase Chain Reaction (PCR) corrected 28 day parasitological cure rate [1] | ||||||
End point description |
Number of participants with clearance of asexual parasites by day 7 after initiating study treatment without recrudescence at day 28, corrected for re-infection by Polymerase Chain Reaction (PCR) assay. “No statistical analysis was planned for this primary outcome.”
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End point type |
Primary
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End point timeframe |
28 days
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this primary outcome. |
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| No statistical analyses for this end point | |||||||
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End point title |
Polymerase Chain Reaction (PCR) corrected parasitological cure rate at day 14 and 42 | ||||||||||
End point description |
Number of participants with clearance of asexual parasites by day 7 after initiating study treatment without recrudescence at day 14 and day 42, corrected for re-infection by Polymerase Chain Reaction (PCR) assay.
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End point type |
Secondary
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End point timeframe |
Day 14 and 42
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| No statistical analyses for this end point | |||||||||||
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End point title |
Number of participants with parasitological uncorrected cure rate at day 3, 7, 14, 28 and 42 | ||||||||||||||||
End point description |
Number of patients with clearance of asexual parasites at day 3, 7, 14, 28 and 42 after initiating study treatment.
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End point type |
Secondary
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End point timeframe |
Day 3, 7, 14, 28 and 42
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Percent Change of parasite count from baseline at 24 hours | ||||||||
End point description |
Percent change of parasite count from baseline at 24 hours
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End point type |
Secondary
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End point timeframe |
baseline, 24 hours
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of participants with parasitaemia at 48 hours after treatment initiation greater than at baseline | ||||||
End point description |
Number of participants with parasite density at 48 hours after treatment initiation greater than parasite density at baseline.
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End point type |
Secondary
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End point timeframe |
48 hours
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| No statistical analyses for this end point | |||||||
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End point title |
Number of participants with parasitaemia at 72 hours after treatment initiation greater than or equal to 25 percent of count at baseline | ||||||
End point description |
Number of participants with parasite density at 72 hours after treatment initiation greater than or equal to 25 percent of parasite density at baseline.
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End point type |
Secondary
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End point timeframe |
72 hours
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| No statistical analyses for this end point | |||||||
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End point title |
Time to parasite clearance (PCT) | ||||||||
End point description |
Time from first dose until first total and continued disappearance of asexual parasite forms which remains at least a further 48 hours.
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End point type |
Secondary
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End point timeframe |
Up to 7 days
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to fever clearance (FCT) | ||||||||
End point description |
Time from first dose to the first time the axillary body temperature decreased below and remained below 37.5° C for at least 48 hours.
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End point type |
Secondary
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End point timeframe |
Up to 7 days
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to gametocyte clearance (GCT) | ||||||||
End point description |
Time from first dose until first total and continued disappearance of gametocytes which remains at least a further 48 hours.
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End point type |
Secondary
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End point timeframe |
Up to 7 days
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit
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Adverse event reporting additional description |
Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.1
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Reporting groups
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Reporting group title |
Cohort 1
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Reporting group description |
Cohort 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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27 May 2013 |
Amendment 1: issued 33 weeks after study start of patients, introduced the following changes: Bioanalytics laboratory and corresponding shipping address for pharmacokinetic samples were changed from WuXi AppTec Co., China to Swiss BioQuant AG, Switzerland; Corresponding adjustments were made in the timings for delivery of shipment of pharmacokinetic samples. This amendment was not considered to have affected the interpretation of study results as these changes were minor and mainly administrative |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| interim review after Cohort 1 6-week follow-up period the joint DMC recommended not to continue with the initiation of Cohort 2. The study therefore concluded when Cohort 1 patients completed their follow-up visit at 12 months of age. | |||
