Clinical trial NCT02963324: Physiologically-based Pharmacokinetic Modeling of Ivermectin in Healthy Human Volunteers
Official title: Physiologically-based Pharmacokinetic Modeling of Ivermectin in Healthy Human Volunteers - a Single-center, Open-label Pharmacokinetics Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Malaria
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2016-11-15
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

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.

Primary outcomes:
measure: Maximum concentration (Cmax) of ivermectin in whole blood, plasma, and capillary blood
timeFrame: Intermittent sampling for 72 hours after dosing
measure: Time to maximum concentration (Tmax) of ivermectin in whole blood, plasma, and capillary blood
timeFrame: Intermittent sampling for 72 hours after dosing
measure: Area under the curve (AUC) of ivermectin in whole blood, plasma, and capillary blood
timeFrame: Intermittent sampling for 72 hours after dosing
Secondary outcomes:
measure: Occurence of adverse events
timeFrame: For 72 hours after dosing
measure: Laboratory changes
timeFrame: For 72 hours after dosing
measure: Changes in electrocardiogram (ECG)
timeFrame: For 72 hours after dosing
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Stephan Krähenbühl, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: