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First in Man Clinical Trial of Emodepside (BAY 44-4400)

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ClinicalTrials.gov Identifier: NCT02661178
Recruitment Status : Completed
First Posted : January 22, 2016
Last Update Posted : August 25, 2017
Sponsor:
Collaborators:
Bayer
Bill and Melinda Gates Foundation
Information provided by (Responsible Party):
Drugs for Neglected Diseases

Brief Summary:
This study will investigate the safety, tolerability, and pharmacokinetics of single ascending doses of emodepside (BAY 44-4400) in healthy male volunteers. This study will also conduct an exploratory investigation of the relative bioavailability of emodepside administered as tablets and determine the effect of food on the pharmacokinetics.

Condition or disease Intervention/treatment Phase
Healthy Volunteers Drug: emodepside (BAY 44-4400) Drug: placebo Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 79 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: A Phase 1, Blinded, Randomized, Placebo Controlled, Parallel-Group, Single-Dose, Dose-Escalation Study to Investigate Safety, Tolerability, and Pharmacokinetics of Emodepside (BAY 44-4400) After Oral Dosing in Healthy Male Subjects
Actual Study Start Date : December 2015
Actual Primary Completion Date : March 27, 2017
Actual Study Completion Date : March 27, 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Emodepside

Arm Intervention/treatment
Experimental: emodepside (BAY 44-4400)
Up to 10 cohorts with single ascending dose
Drug: emodepside (BAY 44-4400)
Placebo Comparator: placebo of emodepside (BAY 44-4400)
Up to 10 cohorts with single ascending dose
Drug: placebo



Primary Outcome Measures :
  1. Safety and tolerability as measured by adverse events, physical and neurological examination findings, vital signs and 12-lead ECG, and clinical laboratory parameters ; in one cohort - ophthalmological examination findings [ Time Frame: up to 14 days post dose (may be extended to 21 days) ]

Secondary Outcome Measures :
  1. The AUC∞ (the area under the plasma drug concentration vs. time curve from time zero to infinity) of emodepside in plasma. [ Time Frame: from pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
  2. The AUC∞/D (the area under the plasma drug concentration vs. time curve from time zero to infinity, corrected for dose) of emodepside in plasma. [ Time Frame: from pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
  3. The Cmax (the observed maximum plasma concentration) of emodepside in plasma. [ Time Frame: from pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
  4. The Cmax/D (the observed maximum plasma concentration, corrected for dose) of emodepside in plasma. [ Time Frame: from pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
  5. The Cmax,norm (the observed maximum plasma concentration corrected by dose and body weight) of emodepside in plasma. [ Time Frame: from pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
  6. The Tmax (the time at which Cmax was apparent) of emodepside in plasma. [ Time Frame: from pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
  7. The t½ (the terminal half-life) of emodepside in plasma. [ Time Frame: from pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
  8. The MRT (the mean residence time) of emodepside in plasma. [ Time Frame: from pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
  9. The CL/F (the apparent total clearance from plasma) of emodepside in plasma. [ Time Frame: from pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
  10. The AUC∞,norm (the area under the concentration-time curve from time zero to infinity corrected by dose and body weight) of emodepside in plasma. [ Time Frame: from pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
  11. The AUCt (the area under the concentration-time curve from time zero (pre-dose) to the time of last quantifiable concentration) of emodepside in plasma. [ Time Frame: from pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
  12. The AUC t,norm (the area under the concentration-time curve from time zero (pre-dose) to the time of last quantifiable concentration corrected by dose and body weight) of emodepside in plasma. [ Time Frame: from pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
  13. The Vz/F (the apparent volume of distribution) of emodepside in plasma. [ Time Frame: from pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
  14. The lambda-z (the terminal rate constant) of emodepside in plasma. [ Time Frame: from pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
  15. The AUC t-∞ (the area under the concentration-time curve from time t to infinity) of emodepside in plasma. [ Time Frame: from pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
  16. The points terminal of emodepside in plasma. [ Time Frame: from pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
  17. The relative bioavailability (Frel) of the IR (immediate release) tablet of emodepside will be calculated (optionally). [ Time Frame: from pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
  18. The AUC∞ (the area under the plasma drug concentration vs. time curve from time zero to infinity) of metabolites of emodepside in plasma may be measured [ Time Frame: from pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
  19. The AUC∞/D (the area under the plasma drug concentration vs. time curve from time zero to infinity, corrected for dose) of metabolites of emodepside in plasma may be measured [ Time Frame: from pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
  20. The Cmax (the observed maximum plasma concentration) of metabolites of emodepside in plasma may be measured [ Time Frame: from pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
  21. The Cmax/D (the observed maximum plasma concentration, corrected for dose) of metabolites of emodepside in plasma may be measured [ Time Frame: from pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
  22. The Cmax,norm (the observed maximum plasma concentration corrected by dose and body weight) of metabolites of emodepside in plasma may be measured [ Time Frame: from pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
  23. The Tmax (the time at which Cmax was apparent) of metabolites of emodepside in plasma may be measured [ Time Frame: from pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
  24. The t½ (the terminal half-life) of metabolites of emodepside in plasma may be measured [ Time Frame: from pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
  25. The AUC∞,norm (the area under the concentration-time curve from time zero to infinity corrected by dose and body weight) of metabolites of emodepside in plasma may be measured [ Time Frame: from pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
  26. The AUCt (the area under the concentration-time curve from time zero (pre-dose) to the time of last quantifiable concentration) of metabolites of emodepside in plasma may be measured [ Time Frame: from pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
  27. The AUC t,norm (the area under the concentration-time curve from time zero (pre-dose) to the time of last quantifiable concentration corrected by dose and body weight) of metabolites of emodepside in plasma may be measured [ Time Frame: from pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
  28. The amount of emodepside, and possibly its metabolites, in urine. [ Time Frame: from pre-dose until 24h post-dose ]
  29. The concentration of emodepside, and possibly its metabolites, in urine. [ Time Frame: from pre-dose until 24h post-dose ]
  30. Possibility to determine the effect of food on the bioavailability of emodepside (BAY 44-4400) after single oral doses administered as solution or IR tablets. [ Time Frame: from pre-dose until 336h post-dose (may be extended to 504h post-dose) ]


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male, Caucasian volunteers, deemed healthy on the basis of a clinical history, physical examination, ECG, vital signs, and laboratory tests of blood and urine. Optionally, after further evaluation during the study, at the sponsor's discretion other ethnic groups may be recruited.
  • Aged 18 to 55 years.
  • With a body mass index (BMI; Quetelet index) in the range of 18 to 30.1 kg/m2 at screening.
  • 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.
  • 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

Exclusion Criteria:

  • Participation in another clinical trial within 3 months prior and during the study, or 5-times the half-life of the drug tested in the previous clinical trial, whichever is longer (time calculated relative to the last dose in the previous clinical trial)
  • Clinically relevant abnormal medical history, concurrent medical condition, acute or chronic illness or history of chronic illness sufficient to invalidate the subject's participation in the trial or make it unnecessarily hazardous.
  • Surgery (eg stomach bypass) or medical condition that might affect absorption of study drug taken orally.
  • Presence of abnormal physical findings, ECG, or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the subject.
  • Positive tests for hepatitis B & C, HIV
  • Presence or history of drug or alcohol abuse during the last 10 years, or intake of more than 21 units of alcohol weekly.
  • Regular daily consumption of more than one liter of xanthine-containing beverages
  • Regular daily consumption of more than 5 cigarettes daily, or use more than 3 grams (1/8 ounce) of tobacco
  • Use of a prescription medicine during the 28 days before the first dose of trial medication or use of an over-the-counter medicine, with the exception of acetaminophen (paracetamol), during the 7 days before the first dose of trial medication
  • Use of dietary supplements or herbal remedies (such as St John's Wort) known to interfere with the CYP3A4 and/or P-gp metabolic pathways during the 28 days before the first dose of trial medication (see list in Study Procedures Manual)

Additional exclusion criteria for cohort with ophthalmological assessments:

  • No contact lenses wear within 1 month prior to first dose of IMP. Contact lenses wear is not permitted during the study
  • Any ocular disorder for which topical ocular therapy is currently or chronically prescribed, including inflammatory eye disease (dry eye allergic conjunctivitis [seasonal allergic conjunctivitis, vernal keratoconjunctivitis, atopic keratoconjunctivitis], uveitis and glaucoma)
  • Past history of ocular disease requiring ongoing treatment
  • Past ocular surgery including laser or other refractive corneal surgery
  • Evidence of eye irritation, visual difficulties, corneal opacity, ocular surface (corneal or conjunctival damage, with or without ocular symptoms)
  • Evidence of narrow anterior chamber angles causing increased risk of acute glaucoma
  • Evidence of ocular media opacity including lens opacity/vitreous opacities
  • Evidence of retinal or optic nerve pathology
  • Evidence of pronounced colour blindness, as indicated by an Ishihara score of 9/13 or below

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02661178


Locations
United Kingdom
Hammersmith Medicines Research
London, United Kingdom, NW10 7EW
Sponsors and Collaborators
Drugs for Neglected Diseases
Bayer
Bill and Melinda Gates Foundation
Investigators
Principal Investigator: Malcolm Boyce, MD, BSc Hammersmith Medicines Research
Study Director: Frederic Monnot Drugs for Neglected Diseases Initiative

Responsible Party: Drugs for Neglected Diseases
ClinicalTrials.gov Identifier: NCT02661178     History of Changes
Other Study ID Numbers: DNDI-EMO-001
2015-003592-29 ( EudraCT Number )
First Posted: January 22, 2016    Key Record Dates
Last Update Posted: August 25, 2017
Last Verified: January 2017

Keywords provided by Drugs for Neglected Diseases:
Parasitic Diseases
Helminthiasis
Nematode Infections
Secernentea Infections
Spirurida Infections
Filariasis
Skin Diseases, Parasitic
Skin and Connective Tissue Diseases
Skin Diseases
Skin Diseases, Infectious
Depsipeptides
Emodepside
Neglected disease
Africa
New drug
Oral drug
Parasite
Anthelmintic drug
Cyclooctadepsipeptide
Single ascending dose
Volunteers
Phase 1
Safety
Tolerability
Pharmacokinetics
Relative bioavailability
Onchocerciasis