Anti-parasitic Activity and Safety Assessment of SAR97276A in Children With Uncomplicated Malaria - Full Text View

Purpose

Primary Objective:

To assess the antiparasitic activity of intramuscular (IM) SAR97276A based on parasite reduction ratio at 72 hours in pediatric patients with uncomplicated malaria

Secondary Objectives:

To assess the evolution of clinical signs and symptoms (including the need for a rescue therapy) in pediatric patients with uncomplicated malaria receiving SAR97276A with reference to Artemisinin-Based Combination Therapy (ACTs)
To assess the pharmacokinetics profile of SAR97276A in pediatric patients with uncomplicated malaria
To assess the safety profile of SAR97276A in pediatric patients with uncomplicated malaria
To assess the pharmacokinetic-pharmacodynamic relationship of SAR97276A

Condition	Intervention	Phase
Malaria	Drug: SAR97276A Drug: arthemeter + lumefantrine (ACTs)	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	An Open-label, Randomized Multicenter Study to Investigate the Anti-parasitic Activity, Pharmacokinetic and Safety of IM SAR97276A With Oral ACTs as Positive Control in Children Presenting With Symptomatic Plasmodium Falciparum Uncomplicated Malaria

Resource links provided by NLM:

MedlinePlus related topics: Malaria

Drug Information available for: Lumefantrine

U.S. FDA Resources

Further study details as provided by Sanofi:

Primary Outcome Measures:

Parasite Reduction Ratio (PRR) [ Time Frame: at 72 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Evolution of mean Parasitaemia over time (nb/µL) [ Time Frame: every 6 hours from baseline up to 72 hours (day 4) ] [ Designated as safety issue: No ]
Evolution of mean Gametocytes count over time (nb/µL) [ Time Frame: from baseline to end of study (day 28 ± 2) ] [ Designated as safety issue: No ]
Fever Clearance (time to reach Temperature < 38°C) [ Time Frame: every 6 hours from baseline up to 72 hours (day 4) ] [ Designated as safety issue: No ]
General conditions improvement: mean total symptom score over time [ Time Frame: every 6 hours from baseline up to 72 hours (day 4) ] [ Designated as safety issue: No ]
SAR97276 pharmacokinetic profile in plasma and blood [ Time Frame: from baseline up to 12 hours after the last study drug intake on (Day 3 ] [ Designated as safety issue: No ]

Enrollment:	20
Study Start Date:	October 2011
Study Completion Date:	January 2012
Primary Completion Date:	January 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Step 1 (SAR97276A od) 1 group of paediatric patients will receive 0.5 mg/kg SAR97276A administration once daily (od) for 3 days	Drug: SAR97276A Pharmaceutical form:solution for injection Route of administration: intramuscular
Experimental: Step 1 (SAR97276A bid) 1 group of paediatric patients will receive 0.25 mg/kg SAR97276A administration twice daily (bid) for 3 days	Drug: SAR97276A Pharmaceutical form:solution for injection Route of administration: intramuscular
Active Comparator: Step 1 (ACTs) 1 group of paediatric patients will receive arthemeter + lumefantrine (ACTs) bid for 3 days	Drug: arthemeter + lumefantrine (ACTs) Pharmaceutical form:tablet Route of administration: oral
Experimental: Step 2 (SAR97276A) 1 or 2 groups of paediatric patients will receive SAR97276A once daily (od) or twice a day (bid) administration for 3 days (the choice of the od or bid regimen will be based on the results obtained in step 1)	Drug: SAR97276A Pharmaceutical form:solution for injection Route of administration: intramuscular
Active Comparator: Step 2 (ACTs) 1 group of paediatric patients will receive arthemeter + lumefantrine (ACTs) bid for 3 days	Drug: arthemeter + lumefantrine (ACTs) Pharmaceutical form:tablet Route of administration: oral
Experimental: Step 3 (SAR97276A) 1 group of paediatric patients (2 to 11 years old) will receive: SAR97276A od or bid administration for 3 days (depending on results of step 1)	Drug: SAR97276A Pharmaceutical form:solution for injection Route of administration: intramuscular

Detailed Description:

The total duration per patients will last approximately 28 ± 2 days broken down as follows:

A screening phase up to 12-hours
A 28 ± 2 days study period

Eligibility

Ages Eligible for Study:	2 Years to 17 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria:

Patients diagnosed with symptomatic infection by Plasmodium falciparum microscopically confirmed in blood smear at Day-1 visit
Fever (tympanic or rectal temperature ≥ 38 C) or documented history of fever within the last 24h
Asexual parasitemia of ≥ 2 000 parasites/μL in blood smear at D-1 visit
Signed Informed Consent Form by the parents or legal guardian
Age: 12 to 17 years old for step 1
Age: 2 to 11 years old for step 2 and step 3

Exclusion criteria:

Participation in another clinical trial within the last 3 months or participation within a different cohort in this PDY11737 clinical trial or participation to previous trial with SAR97276
Documented history of adequate treatment with antimalarials expected to be effective within the preceding 72 hours
Severe concomitant disease (including concomitant febrile illnesses or infection)
Any sign suggestive of severe malaria
Severe malnutrition
Asexual parasitemia: Plasmodium falciparum > 100,000 parasites/μL in blood smear at D-1 visit
Previous treatment within 3 weeks prior to inclusion, and concomitant treatment with potent CYP3A4 inhibitors or CYP3A4 inducers or CYP2D6 substrates or potent CYP2D6 inhibitors
Known serious adverse event reaction or hypersensitivity to Artemisinin-Based Combination Therapy (ACTs) or any contraindications from the positive control therapy (Artemisinin Combined Treatments) or warning/precaution of use as defined in the respective National Product Labeling
Pregnant or breast-feeding women
Women of childbearing potential not protected by effective contraceptive method of birth control, or not willing to use an effective contraceptive(s) method(s) for the duration of the study (e.g.: double barrier method), and/or who are unwilling or unable to be tested for pregnancy,
CPK above 3 ULN,
Underlying hepatobiliary disease or ALT>3 ULN.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01445938

Locations

Benin
Investigational Site Number 204001
Cotonou, Benin
Burkina Faso
Investigational Site Number 854001
Ouagadougou, Burkina Faso
Gabon
Investigational Site Number 266001
Libreville, Gabon
Kenya
Investigational Site Number 404001
Kisumu, Kenya

Sponsors and Collaborators

Sanofi

Investigators

Study Director:

Clinical Sciences & Operations

Sanofi

More Information

No publications provided

Responsible Party:	Sanofi
ClinicalTrials.gov Identifier:	NCT01445938 History of Changes
Other Study ID Numbers:	PDY11737, 2010-021398-36, U1111-1118-0694
Study First Received:	September 26, 2011
Last Updated:	December 12, 2012
Health Authority:	Kenya: Pharmacy and Poisons Board

Additional relevant MeSH terms:

Malaria
Protozoan Infections
Parasitic Diseases
Antiparasitic Agents
Lumefantrine

Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimalarials
Antiprotozoal Agents

ClinicalTrials.gov processed this record on June 17, 2013