Relative Bioavailability Study of Emodepside IR-tablets and Solution
Condition: Filariasis
MeSH terms: Filariasis
Intervention: Emodepside (BAY 44-4400)
Intervention description: 2 tablets compared to the liquid formulation
Intervention MeSH terms: Praziquantel; Emodepside; Toltrazuril
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This is a single-centre, open-label, randomized, parallel-group relative bioavailability study in healthy men. The study will be done in 2 parts, as follows:
Part 1 - single oral doses of 5 mg emodepside will be tested:
Part 1a - the LSF (reference formulation) and 2 new IR-tablet formulations (test formulations) will be administered in the fasted state.
Part 1b - the 2 new IR-tablet formulations will be administered in the fed state (high-fat, high-calorie meal).
Part 2 - single oral doses of 10 mg emodepside will be tested: depending on the results from Part 1, one or both IR-tablet formulations will be administered in the fasted state.
Masking: None (Open Label)
Enrollment: 77.0
Sex: Male
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This study evaluates 2 new immediate release (IR)-tablet formulations of emodepside and they
      will be compared to the oral liquid service formulation (LSF) used in the FIH Single
      Ascending Dose study (DNDi-EMO-001 study) (CT.gov identifier: NCT02661178)
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male, Caucasian volunteers, deemed healthy based on a clinical history, physical
             examination, ECG, vital signs, and laboratory tests of blood and urine.

          2. 18 to 45 years of age

          3. Normal body weight (Body Mass Index (BMI); Quetelet index) in the range 18.0 to 30.1
             kg/m2 at screening

          4. Mean blood pressure and heart rate (from the triplicate readings) in the supine
             position at the screening assessment outside one (or more) of the ranges: 90-140 mm Hg
             systolic BP 60-90 mm Hg diastolic BP 45-100 beats/min HR

          5. Sufficient intelligence to understand the nature of the trial and any hazards of
             participating in it. Ability to communicate satisfactorily with the Investigator and
             to participate in, and comply with the requirements of, the entire trial

          6. Willingness to give written consent to participate, after reading the information and
             consent form, and after having the opportunity to discuss the trial with the
             Investigator or his delegate

          7. Willingness to give written consent to have data entered into The Overvolunteering
             Prevention System (TOPS)

          8. Willingness to follow contraception requirements of the study, from the first dose of
             the IMP until 90 days after dosing and inform HMR as soon as possible if their partner
             becomes pregnant in the 90 days after dosing

             Exclusion Criteria:

          9. Administration of a licensed or unlicensed medicinal product as part of another
             clinical trial in the 3 months before the first dose of study medication, or within 5
             half-lives of administration of a medicinal product given in the previous study
             (whichever is longer), or otherwise in the follow-up period for any clinical trial

         10. Clinically relevant abnormal medical history, concurrent medical condition, acute or
             chronic illness, or history of chronic illness (such as diabetes mellitus or other
             abnormalities of glucose homeostasis) sufficient to invalidate the subject's
             participation in the trial or make it unnecessarily hazardous

         11. Past surgery (e.g. stomach bypass) or medical condition that might affect absorption
             of the study drug when taken orally

         12. Presence of abnormal physical findings, ECG, or laboratory values at the screening
             assessment that could interfere with the objectives of the trial or the safety of the
             subject

         13. Loss of more than 400 mL of blood within the 3 months before admission

         14. Clinically relevant history of vital organ disease, or other organ or central nervous
             system disease (e.g. diabetes mellitus, liver disease, seizures, etc.)

         15. Current or previous medical or psychiatric disorder that, in the opinion of the
             Investigator or the Sponsor, would increase the risk and ability to participate in
             and/or complete the study

         16. Positive test for hepatitis B, hepatitis C or HIV

         17. Febrile illness (e.g. fever) within 1 week before the first dose of study medication

         18. History of a severe allergy, non-allergic drug reaction, severe adverse reaction to
             any drug, or multiple drug allergies

         19. Hypersensitivity to any ingredient of the study medication, including the active
             ingredient (emodepside)

         20. Presence or history of drug or alcohol abuse in the last year, or intake of more than
             21 units (1 unit = 1/2 pint of beer, 1 small glass of wine or 1 measure of spirits) of
             alcohol weekly

         21. Regular daily consumption of more than one litre of beverages containing xanthine

         22. Daily consumption of more than 10 cigarettes or more than 6 grams (1/4 ounce) of
             tobacco

         23. Use of a prescription medicine during the 28 days before the dose of study medication,
             or use of an over-the-counter medicine (with exception of acetaminophen
             (paracetamol)), during the 7 days before the dose of study medication

         24. Use, within 14 days before the dose of study medication, of dietary supplements or
             herbal remedies (such as St John's Wort) that are known to be inducers or inhibitors
             of CYP3A4, or other co-medications known to be relevant substrates of CYP3A4 (see list
             in the Study Procedures Manual)

         25. Use, within 14 days before the dose of study medication, of dietary supplements or
             herbal remedies that are known to be strong inhibitors of P-gp, or other
             co-medications known to be relevant substrates of P-gp (see list in the Study
             Procedures Manual)

         26. Relevant pathological abnormalities in the ECG at screening, such as:

             second or third-degree atrioventricular (AV) block prolongation of the QRS complex >
             120 msec, QTc-interval (QTcB or QTcF) > 450 msec. The mean of the triplicate ECG
             readings will be used to assess eligibility.

         27. Evidence of drug abuse (via urine testing) at the screening assessment or admission to
             the ward

         28. Use of excluded therapies that may impact on the interpretation of study results in
             the opinion of the Investigator or Sponsor

         29. Objection by General Practitioner (GP) to subject entering trial

         30. History of residing for 6 or more continuous months during the last 3 years in regions
             with endemic parasitic infections, as determined by the Investigator

         31. Possibility that subject will not cooperate with the requirements of the protocol