Lumefantrine in Venous Plasma Versus Dried Capillary Blood Spot

NCT02742285 | Completed Phase 4

• 1 other identifier: DBS-ALU
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Measurement of the concentration of antimalarials in the blood of the general population helps estimating the overall drug pressure and is used in efficacy studies. The current sampling standard for drug measurement is plasma obtained by venous puncture. The use of a Dried Blood Spots (DBS) sampling strategy can make some aspects of field trials conditions easier, but concordance with usual venous sampling is not yet established. The current work will allow validating the concentrations of lumefantrine measured in the DBS samples collected during the field trials and validate the use of DBS for future studies. In addition, bearing in mind the substantial deployment of artemether-lumefantrine combinations supplies throughout most malaria endemic countries, this study may improve our understanding of lumefantrine and artemether distribution in the blood compartments and generate knowledge for further developing analytical methods for drug measurement. The overall purpose of this study is to validate the dried blood spots as a sampling method for the analysis of lumefantrine. The primary objective is to assess the concordance between lumefantrine plasma and dried blood spots (DBS) concentrations. The investigators also aim at describing lumefantrine's distribution in the different blood compartments: binding to plasma proteins, total in plasma, inside the red blood cells, total in whole blood.

Conditions

Malaria

Keywords

antimalarials; blood samples; drug concentrations; pharmacokinetics; lumefantrine; healthy volunteers

Outcome Measures

Primary Outcomes (1)

• Concordance of concentrations of lumefantrine measured in dried capillary blood spot samples (DBS) and in plasma, at different time-points after the administration of a single oral adult dose of artemether-lumefantrine.

  Within the first two weeks after drug intake

Secondary Outcomes (7)

• Concordance of concentrations of desbutyl-lumefantrine measured in DBS and in plasma

  Within the first two weeks after drug intake

• Concordance of lumefantrine and desbutyl-lumefantrine concentrations measured in dried venous blood spot samples and in plasma

  Within the first two weeks after drug intake

• Concordance of concentration of lumefantrine and desbutyl-lumefantrine measured in whole venous blood and in plasma

  Within the first two weeks after drug intake

• Determination of a ratio of intra-erythrocyte and plasma concentrations of lumefantrine and desbutyl-lumefantrine over time (corrected for hematocrit)

  Within the first two weeks after drug intake

• Determination of a ratio of unbound plasma concentration and total plasma concentration of lumefantrine and desbutyl-lumefantrine over time

  Within the first two weeks after drug intake

Study Arms (1)

Artemether + lumefantrine

OTHER

One single adult dose of artemether + lumefantrine 80 + 480 mg

Drug: Artemether + lumefantrine

Interventions

Artemether + lumefantrine DRUG

A single adult dose of artemether-lumefantrine will be administered on a unique occasion together with food. Venous and capillary blood samples will be collected at 6 to 10 time points, as defined before drug administration with each volunteer.

Also known as: (Riamet)

Artemether + lumefantrine

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Absence of current drug treatment (except hormonal contraception, an additional barrier method is strongly advised)
• lead ECG without significant abnormalities
• The subject understands the procedures, agrees to participate and is willing to give written informed consent
• The subject agrees to be available for at least 5 blood sampling after drug administration, at scheduled time points.

You may not qualify if:

• History of any major medical disorder
• Any recent acute illness which could expose the subject to a higher risk or might confound the results of the study
• Current pregnancy or breast-feeding
• Congenital prolongation of the QT interval (e.g., long QT syndrome) or any other clinical condition known to prolong the corrected QT interval
• Family history of congenital prolongation of the QT interval or sudden death
• Known disturbances of electrolyte balance
• Known liver disorder of any type, even if no medical treatment is needed. Gilbert syndrome will be tolerated, if mild
• Treatment in the previous three months with any drug known to have well-defined potential for toxicity to a major organ
• History of hypersensitivity to any component of the drug
• History of hypersensitivity to any drug if considered as serious
• History of alcohol or drug abuse
• Present consumption of a large quantity of alcohol or wine (\>0.5 L wine/day) or equivalent. Consumption of reasonable amount of wine (0.3 L) or of beer is acceptable, except between Day -1 to Day 3 of drug administration
• Use of any medication the week prior to study or as based on 5 plasma half-life rule and up to 48 hours post drug administration
• Participation in a clinical trial in the previous 3 months unless no treatment provided and low amount of blood collected
• Occupation which might interfere with visits and blood sampling during the study

Sponsors & Collaborators

• Thierry Buclin: lead

Study Sites (1)

Division of Clinical Pharmacology

Lausanne, Canton of Vaud, 1011, Switzerland

Location

MeSH Terms

Conditions

Malaria

Interventions

Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Thierry Buclin, Professor

  Division of Clinical Pharmacology, University Hospital, Lausanne, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 1, 2016
• First Posted: April 19, 2016
• Study Start: May 1, 2016
• Primary Completion: July 1, 2016
• Study Completion: September 1, 2016
• Last Updated: January 16, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will share

Locations

CH (1)