Physiologically-based Pharmacokinetic Modeling of Ivermectin in Healthy Human Volunteers

Study Overview
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Brief Summary
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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
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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.

Official Title
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Physiologically-based Pharmacokinetic Modeling of Ivermectin in Healthy Human Volunteers - a Single-center, Open-label Pharmacokinetics Study

Conditions
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Malaria

Intervention / Treatment
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* Drug: Ivermectin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ivermectin<br>Single dose of ivermectin 12 mg (as 4 tablets of Stromectol (R) 3 mg) orally | Drug: Ivermectin<br> <br> * Other names: Stromectol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum concentration (Cmax) of ivermectin in whole blood, plasma, and capillary blood |  | Intermittent sampling for 72 hours after dosing | 
| Time to maximum concentration (Tmax) of ivermectin in whole blood, plasma, and capillary blood |  | Intermittent sampling for 72 hours after dosing | 
| Area under the curve (AUC) of ivermectin in whole blood, plasma, and capillary blood |  | Intermittent sampling for 72 hours after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurence of adverse events | adverse events (treatment-emergent and/or leading to premature study drug discontinuation). | For 72 hours after dosing | 
| Laboratory changes | Change from baseline for clinical laboratory tests at the end of the study. | For 72 hours after dosing | 
| Changes in electrocardiogram (ECG) | Change from baseline in resting 12-channel electrocardiogram (ECG) at the end of the study. | For 72 hours after dosing |