Back to resultsLumefantrine in Venous Plasma Versus Dried Capillary Blood Spot
Primary Purpose
Malaria
Status
Completed
Phase
Phase 4
Locations
Switzerland
Study Type
Interventional
Intervention
Artemether + lumefantrine
Sponsored by
About this trial
This is an interventional other trial for Malaria focused on measuring antimalarials, blood samples, drug concentrations, pharmacokinetics, lumefantrine, healthy volunteers
Eligibility Criteria
Inclusion Criteria:
- Absence of current drug treatment (except hormonal contraception, an additional barrier method is strongly advised)
- 12-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.
Exclusion Criteria:
- 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
- Psychological status which could have an impact on subject's ability to give informed consent
- Any feature of subject's medical history or present condition which, in the investigator's opinion, could confound the results of the study, complicate their interpretation or represent a potential risk for the subject
Sites / Locations
- Division of Clinical Pharmacology
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Artemether + lumefantrine
Arm Description
One single adult dose of artemether + lumefantrine 80 + 480 mg
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Concordance of concentrations of desbutyl-lumefantrine measured in DBS and in plasma
Concordance of lumefantrine and desbutyl-lumefantrine concentrations measured in dried venous blood spot samples and in plasma
Concordance of concentration of lumefantrine and desbutyl-lumefantrine measured in whole venous blood and in plasma
Determination of a ratio of intra-erythrocyte and plasma concentrations of lumefantrine and desbutyl-lumefantrine over time (corrected for hematocrit)
Determination of a ratio of unbound plasma concentration and total plasma concentration of lumefantrine and desbutyl-lumefantrine over time
Determination of the limit of quantification of artemether and dihydroartemisinin in dried blood spots samples, using the standard method of a calibration curve
Determination the relative precision of lumefantrine and desbutyl-lumefantrine concentrations in dried blood spots versus in plasma, using triplicate measurements and a hierarchical non-linear regression model
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02742285
Brief Title
Lumefantrine in Venous Plasma Versus Dried Capillary Blood Spot
Official Title
Comparison of Lumefantrine Concentrations Measured in Venous Plasma Versus in Dried Capillary Blood Spot Samples in Healthy Volunteers.
Study Type
Interventional
2. Study Status
Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
May 2016 (undefined)
Primary Completion Date
July 2016 (Actual)
Study Completion Date
September 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Thierry Buclin
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
Detailed Description
(Details available on request)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria
Keywords
antimalarials, blood samples, drug concentrations, pharmacokinetics, lumefantrine, healthy volunteers
7. Study Design
Primary Purpose
Other
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Artemether + lumefantrine
Arm Type
Other
Arm Description
One single adult dose of artemether + lumefantrine 80 + 480 mg
Intervention Type
Drug
Intervention Name(s)
Artemether + lumefantrine
Other Intervention Name(s)
(Riamet)
Intervention Description
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.
Primary Outcome Measure Information:
Title
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.
Time Frame
Within the first two weeks after drug intake
Secondary Outcome Measure Information:
Title
Concordance of concentrations of desbutyl-lumefantrine measured in DBS and in plasma
Time Frame
Within the first two weeks after drug intake
Title
Concordance of lumefantrine and desbutyl-lumefantrine concentrations measured in dried venous blood spot samples and in plasma
Time Frame
Within the first two weeks after drug intake
Title
Concordance of concentration of lumefantrine and desbutyl-lumefantrine measured in whole venous blood and in plasma
Time Frame
Within the first two weeks after drug intake
Title
Determination of a ratio of intra-erythrocyte and plasma concentrations of lumefantrine and desbutyl-lumefantrine over time (corrected for hematocrit)
Time Frame
Within the first two weeks after drug intake
Title
Determination of a ratio of unbound plasma concentration and total plasma concentration of lumefantrine and desbutyl-lumefantrine over time
Time Frame
Within the first two weeks after drug intake
Title
Determination of the limit of quantification of artemether and dihydroartemisinin in dried blood spots samples, using the standard method of a calibration curve
Time Frame
Within the first 24 hours after drug intake
Title
Determination the relative precision of lumefantrine and desbutyl-lumefantrine concentrations in dried blood spots versus in plasma, using triplicate measurements and a hierarchical non-linear regression model
Time Frame
Within the first two weeks after drug intake
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Absence of current drug treatment (except hormonal contraception, an additional barrier method is strongly advised)
12-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.
Exclusion Criteria:
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
Psychological status which could have an impact on subject's ability to give informed consent
Any feature of subject's medical history or present condition which, in the investigator's opinion, could confound the results of the study, complicate their interpretation or represent a potential risk for the subject
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thierry Buclin, Professor
Organizational Affiliation
Division of Clinical Pharmacology, University Hospital, Lausanne, Switzerland
Official's Role
Principal Investigator
Facility Information:
Facility Name
Division of Clinical Pharmacology
City
Lausanne
State/Province
Vaud
ZIP/Postal Code
1011
Country
Switzerland
12. IPD Sharing Statement
Plan to Share IPD
Yes
Learn more about this trial
Lumefantrine in Venous Plasma Versus Dried Capillary Blood Spot
We'll reach out to this number within 24 hrs