Physiologically-based Pharmacokinetic Modeling of Ivermectin in Healthy Human Volunteers (IVMPBPK)
Primary Purpose
Malaria
Status
Completed
Phase
Phase 1
Locations
Switzerland
Study Type
Interventional
Intervention
Ivermectin
Sponsored by
About this trial
This is an interventional basic science trial for Malaria
Eligibility Criteria
Inclusion criteria
- Age 18-65 years old
- Caucasian male or female volunteers
- Body mass index (BMI) 18-30 kg/m2, weight ≥ 50 kg
- Full mental and legal capacity
- Signed informed consent prior to any study related procedure
- Ability to communicate in German or English, sufficient to comprehend and adhere to study protocol
- Normal physical examination, vital signs, laboratory workup, and electrocardiogram (ECG) (in the opinion of investigator)
- No history or presence of surgical or medical conditions that might interfere with absorption, distribution, metabolism, and / or elimination of study drug, and / or which might increase its toxic effects (in the opinion of investigator)
- No ongoing or recent (one month) participation in another clinical trial
- No loss of blood ≥ 250 ml within the last three months
- No known hypersensitivity to study drug or any of its constituents
- No other conditions or circumstances that might interfere with compliance with study protocol (in the opinion of investigator)
Exclusion criteria
- History or presence of hepatic or biliary disease
- History of gastrointestinal surgery, specifically cholecystectomy
- History or presence of alcohol or drug abuse
- History or presence of neurological or psychiatric comorbidities, including psychological therapy
- Other clinically significant concomitant disease states (e.g., renal disease, cardiovascular disease, etc.)
- Intake of prescribed or over-the-counter medications, herbal preparations, and / or vitamin / dietary supplements
- Clinically relevant history or presence of allergy or asthma (in the opinion of investigator)
- Female volunteers: pregnancy as confirmed by laboratory assessment; breast-feeding
- Known hypersensitivity or allergy to class of drugs or the study product
- Women with intention to become pregnant during the course of the study,
- Lack of safe contraception, defined as: female participants of childbearing potential, not using and not willing to continue using two medically reliable methods of contraception for the entire study duration, or who are not using any other method considered sufficiently reliable by the investigator in individual cases, for the duration of the study from screening visit to 30 days after end-of-study-examination.
- Please note that female participants who are surgically sterilised / hysterectomised or post-menopausal for longer than 2 years are not considered as being of child bearing potential.
- Known or suspected non-compliance, drug or alcohol abuse,
- Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant.
Sites / Locations
- University Hospital Basel
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Ivermectin
Arm Description
Single dose of ivermectin 12 mg (as 4 tablets of Stromectol (R) 3 mg) orally
Outcomes
Primary Outcome Measures
Maximum concentration (Cmax) of ivermectin in whole blood, plasma, and capillary blood
Time to maximum concentration (Tmax) of ivermectin in whole blood, plasma, and capillary blood
Area under the curve (AUC) of ivermectin in whole blood, plasma, and capillary blood
Secondary Outcome Measures
Occurence of adverse events
adverse events (treatment-emergent and/or leading to premature study drug discontinuation).
Laboratory changes
Change from baseline for clinical laboratory tests at the end of the study.
Changes in electrocardiogram (ECG)
Change from baseline in resting 12-channel electrocardiogram (ECG) at the end of the study.
Full Information
NCT ID
NCT02963324
First Posted
November 4, 2016
Last Updated
January 31, 2017
Sponsor
University Hospital, Basel, Switzerland
1. Study Identification
Unique Protocol Identification Number
NCT02963324
Brief Title
Physiologically-based Pharmacokinetic Modeling of Ivermectin in Healthy Human Volunteers
Acronym
IVMPBPK
Official Title
Physiologically-based Pharmacokinetic Modeling of Ivermectin in Healthy Human Volunteers - a Single-center, Open-label Pharmacokinetics Study
Study Type
Interventional
2. Study Status
Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
November 2016 (undefined)
Primary Completion Date
December 2016 (Actual)
Study Completion Date
January 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Basel, Switzerland
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The present study assesses the pharmacokinetic profile of Ivermectin (IVM) in healthy human volunteers and aims to create a physiologically-based pharmacokinetic model. Planned indication is the prevention of malaria transmission.
Detailed Description
Ivermectin (IVM) is a broad spectrum antiparasitic drug. Recent research indicates that IVM could potentially be used in malaria vector control.
The present study assesses the pharmacokinetic profile of IVM in healthy human volunteers and aims to create a physiologically-based pharmacokinetic model. This model will be used to characterize enterohepatic circulation, serve as a basis for drug-drug and drug-disease-state interaction studies, and simulations of IVM disposition in different populations, with special regard given to adolescents and children. With this, safety in individual administrations can be increased, and mass drug administration programs, e.g. oral IVM as malaria vector control, be simulated and planned to maximize the share of a population that can be included. Capillary blood concentration profiles will also be determined to assess the amount of IVM delivered to mosquitos in malaria vector control programs. Furthermore, this study will validate dried blood spot analytics of IVM which will allow easier procurement of pharmacokinetics (PK) data in the field.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ivermectin
Arm Type
Experimental
Arm Description
Single dose of ivermectin 12 mg (as 4 tablets of Stromectol (R) 3 mg) orally
Intervention Type
Drug
Intervention Name(s)
Ivermectin
Other Intervention Name(s)
Stromectol
Primary Outcome Measure Information:
Title
Maximum concentration (Cmax) of ivermectin in whole blood, plasma, and capillary blood
Time Frame
Intermittent sampling for 72 hours after dosing
Title
Time to maximum concentration (Tmax) of ivermectin in whole blood, plasma, and capillary blood
Time Frame
Intermittent sampling for 72 hours after dosing
Title
Area under the curve (AUC) of ivermectin in whole blood, plasma, and capillary blood
Time Frame
Intermittent sampling for 72 hours after dosing
Secondary Outcome Measure Information:
Title
Occurence of adverse events
Description
adverse events (treatment-emergent and/or leading to premature study drug discontinuation).
Time Frame
For 72 hours after dosing
Title
Laboratory changes
Description
Change from baseline for clinical laboratory tests at the end of the study.
Time Frame
For 72 hours after dosing
Title
Changes in electrocardiogram (ECG)
Description
Change from baseline in resting 12-channel electrocardiogram (ECG) at the end of the study.
Time Frame
For 72 hours after dosing
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion criteria
Age 18-65 years old
Caucasian male or female volunteers
Body mass index (BMI) 18-30 kg/m2, weight ≥ 50 kg
Full mental and legal capacity
Signed informed consent prior to any study related procedure
Ability to communicate in German or English, sufficient to comprehend and adhere to study protocol
Normal physical examination, vital signs, laboratory workup, and electrocardiogram (ECG) (in the opinion of investigator)
No history or presence of surgical or medical conditions that might interfere with absorption, distribution, metabolism, and / or elimination of study drug, and / or which might increase its toxic effects (in the opinion of investigator)
No ongoing or recent (one month) participation in another clinical trial
No loss of blood ≥ 250 ml within the last three months
No known hypersensitivity to study drug or any of its constituents
No other conditions or circumstances that might interfere with compliance with study protocol (in the opinion of investigator)
Exclusion criteria
History or presence of hepatic or biliary disease
History of gastrointestinal surgery, specifically cholecystectomy
History or presence of alcohol or drug abuse
History or presence of neurological or psychiatric comorbidities, including psychological therapy
Other clinically significant concomitant disease states (e.g., renal disease, cardiovascular disease, etc.)
Intake of prescribed or over-the-counter medications, herbal preparations, and / or vitamin / dietary supplements
Clinically relevant history or presence of allergy or asthma (in the opinion of investigator)
Female volunteers: pregnancy as confirmed by laboratory assessment; breast-feeding
Known hypersensitivity or allergy to class of drugs or the study product
Women with intention to become pregnant during the course of the study,
Lack of safe contraception, defined as: female participants of childbearing potential, not using and not willing to continue using two medically reliable methods of contraception for the entire study duration, or who are not using any other method considered sufficiently reliable by the investigator in individual cases, for the duration of the study from screening visit to 30 days after end-of-study-examination.
Please note that female participants who are surgically sterilised / hysterectomised or post-menopausal for longer than 2 years are not considered as being of child bearing potential.
Known or suspected non-compliance, drug or alcohol abuse,
Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephan Krähenbühl, MD PhD
Organizational Affiliation
University Hospital, Basel, Switzerland
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Basel
City
Basel
ZIP/Postal Code
4031
Country
Switzerland
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Physiologically-based Pharmacokinetic Modeling of Ivermectin in Healthy Human Volunteers
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