Exploratory Ph I Trial of the Active IMP in Healthy Volunteers in Relation to COVID-19

Study Overview
=================
Brief Summary
-----------------
An early stage trial to check how safe and tolerable, as well as how the body handles continuous daily use of Active IMP over 28 days in healthy volunteers.

Detailed Description
-----------------
Detailed information restricted because this is a Phase 1 clinical trial.

Official Title
-----------------
A Randomised, Double-Blind, Placebo-Controlled, Exploratory Phase I Trial Assessing the Pharmacokinetic Profile, Safety and Tolerability of a Continuous Daily Dosing Regimen of Active IMP in Healthy Volunteers

Conditions
-----------------
Covid19

Intervention / Treatment
-----------------
* Drug: Ivermectin
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Important Inclusion Criteria: Subject is male of any ethnic origin. Subject is aged between 18 to 45 years, inclusive. Subject has a body mass index (BMI) of 18.5 to 32.0 kg/m2, inclusive. Subject is ≥50 kg. Negative reverse transcription polymerase chain reaction (RT-PCR) Test for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) at Screening and negative lateral flow immunoassay test for SARS-CoV-2 at Day -1. Healthy as determined by a responsible physician, based on medical evaluation including medical history, physical examinations, neurological examinations, concomitant medication, vital signs, 12-lead ECG and clinical laboratory evaluations. Male subjects must use a condom during the study and for 3 months after their final dose of study medication, if their partner is a woman of childbearing potential. In addition, their female partner of childbearing potential must use an additional method of highly effective contraception from first dosing until 3 months following final dosing. Important Exclusion Criteria: Clinically relevant history of abnormal physical or mental health (defined as any subject requiring medical, psychological or pharmacotherapeutic intervention for mental illness) interfering with the study as determined by medical history and physical examinations obtained during Screening and Day -1 as judged by the Investigator (including [but not limited to], neurological, psychiatric, endocrine, cardiovascular, respiratory, gastrointestinal, hepatic, or renal disorder). Any other concomitant disease or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study as outlined in this Protocol, or that would, in the opinion of the Investigator, pose an unacceptable risk to the subject in this study. Evidence of previous SARS-CoV-2 infection from medical history. Ophthalmologic disorder (moderate and sever retina or optic nerve pathology; cataracts excluded). Subjects with a diagnosis of asthma or any other respiratory conditions. A neurologic disorder that may compromise blood brain barrier permeability (stroke within 90 days, brain tumour, multiple sclerosis, or other neuroinflammatory condition, a neurodegenerative disorder, epilepsy) or history of seizures. Positive test for hepatitis B surface antigen (HBsAg), anti-hepatitis C antibody (anti-HCV) or human immunodeficiency virus I and II (anti-HIV I/II) at Screening. The subject has participated in a clinical study and has received a medication or a new chemical entity within 3 months or 5 half-lives (whichever is longer) prior to first dosing of current study medication. Use of any drugs that are known substrates of CYP3A4, P-glycoprotein (P-gp) from within 4 weeks of Screening and unable to refrain from them until the end of the study (e.g., rifampicin, quinidine, amiodarone, diltiazem, spironolactone, verapamil, clarithromycin, erythromycin, itraconazole, ketoconazole, cyclosporine, tacrolimus, indinavir, ritonavir or cobicistat). Use of critical CYP3A4 substrate drugs such as warfarin or coumarin anticoagulants. Recent or expected microfilaricidal drug use, including ivermectin, or travel history to areas that are endemic for Loa loa or onchocerciasis (Angola, Cameroon, Central African Republic, Chad, Democratic Republic of Congo, Ethiopia, Equatorial, Guinea, Gabon, Republic of Congo, Nigeria and Sudan). Use of medications having potential activity against SARS-CoV-2 such as hydroxychloroquine, chloroquine, lopinavir, ritonavir, remdesivir, azithromycin, in the 30 days prior to Screening and unable to refrain from them until the end of the study. Consumption of any food or drinks containing cranberry, pomegranate, starfruit, grapefruit, pomelos, exotic citrus fruits or Seville oranges (including marmalade and juices made from these fruits) within 14 days prior to first dosing until the end of the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: The study is a placebo-controlled, double-blinded exploratory study to investigate safety, Pk and tolerability of a continuous daily dosing of the active drugs (at 3 different doses) in healthy participants.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 50mcg/kg (oral)<br>Ivermectin loading dose of 200 mcg/kg followed by daily doses of 50mcg/kg from D2 to D28 | Drug: Ivermectin<br>* Ivermectin: Investigation of the safety, tolerability and the pharmacokinetic profile of the active IMP in an exploratory study<br>|
| Experimental: 75mcg/kg (oral)<br>Ivermectin loading dose of 200 mcg/kg followed by daily doses of 75mcg/kg from D2 to D28 | Drug: Ivermectin<br>* Ivermectin: Investigation of the safety, tolerability and the pharmacokinetic profile of the active IMP in an exploratory study<br>|
| Experimental: 100mcg/kg (oral)<br>Ivermectin loading dose of 200 mcg/kg followed by daily doses of 100mcg/kg from D2 to D28 | Drug: Ivermectin<br>* Ivermectin: Investigation of the safety, tolerability and the pharmacokinetic profile of the active IMP in an exploratory study<br>|
| Placebo Comparator: Matching Placebo (oral)<br>Placebo using tablets identical to the Active IMP | Drug: Placebo<br>* Matching Placebo to the Active IMP.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Concentrations - (Maximum Plasma Concentration [Cmax]) | Maximum plasma concentration (Cmax) | D1, D2 and D28 | 
| Pharmacokinetic Concentrations - (Time to Reach Cmax [Tmax]) | Time to reach Cmax (Tmax) | D1, D2 and D28 | 
| Pharmacokinetic Concentrations - (Area Under the Plasma Concentration-time Curve From Zero to 24 Hours [AUC0-24hr]) | area under the plasma concentration-time curve from zero to 24 hours (AUC0-24hr) concentration-time curve from zero to 24 hours (AUC0-24hr) | D1, D2 and D28 | 
| Pharmacokinetic Concentrations - (Apparent Terminal Half-Life [T1/2]) | apparent terminal half-life (t1/2) | D28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability - Treatment Emergent Adverse Events (TEAEs) | Clinical safety data from adverse event (AE) reporting | From Screening (Day -28) to Follow up visit (Day +42) plus 7 additional days. |