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Efficacy, Safety and Pharmacokinetics of Artemether-lumefantrine Dispersible Tablet in the Treatment of Malaria in Infants < 5 kg

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Novartis
Sponsor:
Collaborator:
Medicines for Malaria Venture
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01619878
First received: June 12, 2012
Last updated: July 9, 2014
Last verified: July 2014
  Purpose

The purpose of the study is to obtain efficacy, safety and pharmacokinetic (PK) data following treatment with artemether-lumefantrine dispersible tablet in infants < 5 kg of body weight (BW) with uncomplicated falciparum malaria.


Condition Intervention Phase
Acute Uncomplicated Falciparum Malaria
Drug: COA566
Drug: Artemether-lumefantrine dispersible tablet
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Polymerase Chain Reaction (PCR) corrected 28 day parasitological cure rate [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Percent of patients 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.


Secondary Outcome Measures:
  • Polymerase Chain Reaction (PCR) corrected parasitological cure rate at day 14 [ Time Frame: Baseline and day 14 ] [ Designated as safety issue: No ]
    Percent of patients with clearance of asexual parasites by day 7 after initiating study treatment without recrudescence at day 14, corrected for re-infection by Polymerase Chain Reaction (PCR) assay.

  • Polymerase Chain Reaction (PCR) corrected parasitological cure rate at day 42 [ Time Frame: Baseline and day 42 ] [ Designated as safety issue: No ]
    Percent of patients with clearance of asexual parasites by day 7 after initiating study treatment without recrudescence at day 42, corrected for re-infection by Polymerase Chain Reaction (PCR) assay.

  • Parasitological uncorrected cure rate at day 3 [ Time Frame: Baseline and day 3 ] [ Designated as safety issue: No ]
    Percent of patients with clearance of asexual parasites at day 3 after initiating study treatment.

  • Parasitological uncorrected cure rate at day 7 [ Time Frame: Baseline and day 7 ] [ Designated as safety issue: No ]
    Percent of patients with clearance of asexual parasites at day 7 after initiating study treatment.

  • Parasitological uncorrected cure rate at day 14 [ Time Frame: Baseline and day 14 ] [ Designated as safety issue: No ]
    Percent of patients with clearance of asexual parasites by day 7 after initiating study treatment without recrudescence at day 14.

  • Parasitological uncorrected cure rate at day 28 [ Time Frame: Baseline and day 28 ] [ Designated as safety issue: No ]
    Percent of patients with clearance of asexual parasites by day 7 after initiating study treatment without recrudescence at day 28.

  • Parasitological uncorrected cure rate at day 42 [ Time Frame: Baseline and day 42 ] [ Designated as safety issue: No ]
    Percent of patients with clearance of asexual parasites by day 7 after initiating study treatment without recrudescence at day 42.

  • Parasite reduction at 24 hours after treatment initiation [ Time Frame: Baseline and 24 hours ] [ Designated as safety issue: No ]
    Average percent change in parasite density at 24 hours from baseline.

  • Number of patients with parasitaemia at 72 hours after treatment initiation greater than or equal to 25 percent of count at baseline [ Time Frame: Baseline and 72 hours ] [ Designated as safety issue: No ]
    Percent of patients with parasite density at 72 hours after treatment initiation greater than or equal to 25 percent of parasite density at baseline.

  • Number of patients with parasitaemia at 48 hours after treatment initiation greater than at baseline [ Time Frame: Baseline and 48 hours ] [ Designated as safety issue: No ]
    Percent of patients with parasite density at 48 hours after treatment initiation greater than parasite density at baseline.

  • Time to parasite clearance (PCT) [ Time Frame: Up to 7 days ] [ Designated as safety issue: No ]
    Time from first dose until first total and continued disappearance of asexual parasite forms which remains at least a further 48 hours.

  • Time to fever clearance (FCT) [ Time Frame: Up to 7 days ] [ Designated as safety issue: No ]
    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.

  • Time to gametocyte clearance (GCT) [ Time Frame: Up to 7 days ] [ Designated as safety issue: No ]
    Time from first dose until first total and continued disappearance of gametocytes which remains at least a further 48 hours.

  • Gametocyte carriage over time [ Time Frame: Up to 42 days ] [ Designated as safety issue: No ]
    Number of patients with gametocyte carriage.

  • Incidence of serious adverse events (SAEs) [ Time Frame: up to day 365 ] [ Designated as safety issue: Yes ]
    Percent of patients with serious adverse events (SAEs).

  • Incidence of adverse events (AEs) [ Time Frame: Up to day 42 ] [ Designated as safety issue: Yes ]
    Percent of patients with adverse events (AEs).

  • Biochemical and haematological changes [ Time Frame: Up to day 42 ] [ Designated as safety issue: Yes ]
    Percent of patients with biochemical and haematological changes.


Estimated Enrollment: 40
Study Start Date: October 2012
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
Infants aged >28 days.
Drug: COA566
One dispersible tablet taken orally twice a day during 3 days.
Drug: Artemether-lumefantrine dispersible tablet
One dispersible tablet taken orally twice a day during 3 days.
Experimental: Cohort 2
Neonates of a term age 0 to ≤28 days
Drug: COA566
One dispersible tablet taken orally twice a day during 3 days.
Drug: Artemether-lumefantrine dispersible tablet
One dispersible tablet taken orally twice a day during 3 days.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Neonates / infants
  • Body weight < 5 kg
  • In cohort 1, infants aged > 28 days; in cohort 2, neonates of a term age 0 to ≤ 28 days
  • Microscopically confirmed diagnosis of acute uncomplicated Plasmodium falciparum malaria or mixed infections with an asexual Plasmodium falciparum parasitaemia of > 1,000 and < 100,000 parasites/µL

Exclusion Criteria:

  • Presence of severe malaria (according to World Health Organization definition)
  • Presence of the following signs of a critical condition: apnea-bradycardia, sustained bradycardia, tachycardia, desaturation, hypotension, hypothermia; or other severely deteriorated general condition (based on IMCI criteria in sick infants)
  • Presence of any clinically significant neurological condition
  • Presence of clinically significant abnormality of the hepatic and renal systems
  • Patients who sustained a significant blood volume loss (> 3% of calculated blood volume) in the past 30 days
  • Patients unable to swallow or whose drinking is impaired
  • Family history of congenital prolongation of the QTc interval or sudden death or with any other clinical condition known to be associated with prolongation of the QTc interval such as history of symptomatic cardiac arrhythmias, with clinically relevant bradycardia or with severe cardiac disease
  • Disturbances of electrolyte balance (e.g. hypokalaemia or hypomagnesaemia)
  • Presence of any age-adjusted clinically or hematologically relevant laboratory and blood chemistry abnormalities
  • Other protocol-defined inclusion/exclusion criteria may apply.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01619878

Contacts
Contact: Novartis Pharmaceuticals, Study Director +41613241111
Contact: Novartis Pharmaceuticals

Locations
Benin
Novartis Investigative Site Recruiting
Cotonou, Benin, 01 BP 107
Novartis investigative site Not yet recruiting
Cotonou, Benin
Burkina Faso
Novartis Investigative Site Recruiting
Burkina Faso, Burkina Faso, 2208
Novartis investigative site Not yet recruiting
Ouagadougou, Burkina Faso
Novartis Investigative Site Not yet recruiting
Ouagadougou 01, Burkina Faso
Congo
Novartis investigative site Not yet recruiting
Kinshasa, Congo
Nigeria
Novartis investigative site Not yet recruiting
Calabar, Nigeria
Togo
Novartis investigative site Not yet recruiting
Lome, Togo
Sponsors and Collaborators
Novartis Pharmaceuticals
Medicines for Malaria Venture
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01619878     History of Changes
Other Study ID Numbers: CCOA566B2306, 2011-005852-33, 2011-005858-33
Study First Received: June 12, 2012
Last Updated: July 9, 2014
Health Authority: United States: Food and Drug Administration
Burkina Faso: Ministère de la Santé S/C Direction générale de la pharmacie, du médicament et des laboratoires (DGPML).

Keywords provided by Novartis:
plasmodium
P. falciparum
malaria
infant
neonate

Additional relevant MeSH terms:
Malaria
Malaria, Falciparum
Parasitic Diseases
Protozoan Infections
Artemether
Artemether-lumefantrine combination
Artemisinins
Lumefantrine
Anthelmintics
Anti-Infective Agents
Antifungal Agents
Antimalarials
Antiparasitic Agents
Antiplatyhelmintic Agents
Antiprotozoal Agents
Coccidiostats
Pharmacologic Actions
Schistosomicides
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014