Exploratory Ph I Trial of the Active IMP in Healthy Volunteers in Relation to COVID-19
Condition: Covid19
MeSH terms: COVID-19
Intervention: Ivermectin; Placebo
Intervention description: Ivermectin: Investigation of the safety, tolerability and the pharmacokinetic profile of the active IMP in an exploratory study; Matching Placebo to the Active IMP.
Intervention MeSH terms: Ivermectin
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention 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 (Participant, Investigator)
Masking description: The study is double-blinded. Patients will be randomised to receive 1 of 3 doses of the Active IMP or a matching placebo.
Enrollment: 24.0
Sex: Male
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers

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.
    

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.