Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02661178
Recruitment Status : Completed
First Posted : January 22, 2016
Results First Posted : April 13, 2020
Last Update Posted : April 13, 2020
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

Layout table for study information
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 [ Time Frame: Up to 14 days post dose (may be extended to 21 days) ]
    Deaths, serious adverse events (SAEs) and treatment-emergent adverse events (TEAEs)

  2. Safety and Tolerability as Measured by Physical and Neurological Examination Findings [ Time Frame: Up to 14 days post dose (may be extended to 21 days) ]
    Abnormal or clinically significant neurological examination findings during the study or reported as an AE

  3. Safety and Tolerability as Measured by Vital Signs [ Time Frame: Up to 14 days post dose (may be extended to 21 days) ]
    Vital signs included heart rate, systolic and diastolic blood pressure,

  4. Safety and Tolerability as Measured by 12-lead ECG [ Time Frame: Up to 14 days post dose (may be extended to 21 days) ]
    The following variables were recorded in 12-lead ECGs and extracted from continuous 12-lead ECG recordings: ventricular rate, PR interval, QRS interval, QTcB and QTcF interval.

  5. Safety and Tolerability as Measured by Clinical Laboratory Parameters [ Time Frame: Up to 14 days post dose (may be extended to 21 days) ]
    Clinical laboratory parameters included hematology, biochemistry, serology and coagulation in blood samples and urinalysis in urine samples

  6. Safety and Tolerability as Measured by Ophthalmological Examination Findings in One Study Arm Only [ Time Frame: Up to 14 days post dose (may be extended to 21 days) ]
    Subjects attended a specialist eye hospital for ophthalmology assessments by a Consultant Ophthalmologist. Opthalmology assessments included:ocular symptoms, past ocular history, auto-refraction, best corrected distance visual acuity, color vision assessment, amsler grid assessment, ocular alignment and ocular motility assessment, confrontation visual field assessment, slit lamp examination (anterior segment), intraocular pressure (Goldmann Tonometry), optical coherence scanning of tomography, post mydriatic ocular media (at Screening visit 2 only) and retinal examination with slit lamp and lens.


Secondary Outcome Measures :
  1. The AUC∞ of Emodepside in Plasma [ Time Frame: From pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
    The area under the plasma drug concentration versus time curve from time zero to infinity (AUC∞)

  2. The AUC∞/D of Emodepside in Plasma [ Time Frame: From pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
    Dose-normalized area under the plasma drug concentration versus time curve from time zero to infinity (AUC∞/D), calculated as AUC∞/Dose administered.

  3. The Cmax of Emodepside in Plasma [ Time Frame: From pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
    Maximum observed plasma concentration (Cmax) was obtained directly from the concentration-time data

  4. The Cmax/D of Emodepside in Plasma [ Time Frame: From pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
    Dose-normalized observed maximum plasma concentration (Cmax/D) was calculated as Cmax/Dose administered

  5. The Cmax, Norm of Emodepside in Plasma [ Time Frame: From pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
    The observed maximum plasma concentration (Cmax) normalized by dose and body weight was calculated as Cmax/(Dose administered*body weight)

  6. The Tmax of Emodepside in Plasma [ Time Frame: From pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
    Time to reach maximum plasma concentration (Tmax) was obtained directly from the concentration-time data

  7. The t½ of Emodepside in Plasma [ Time Frame: From pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
    Terminal half-life (t½), calculated according to the equation t½ = ln2/λz, where λz is the apparent terminal elimination rate constant, estimated by linear regression of log-transformed concentration versus time data

  8. The MRT of Emodepside in Plasma [ Time Frame: From pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
    The mean residence time (MRT) was calculated as MRT = AUMC/AUC∞, where AUMC is the area under the first moment of the concentration-time curve from zero time (pre-dose) extrapolated to infinite time

  9. The CL/F of Emodepside in Plasma [ Time Frame: From pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
    Apparent total clearance from plasma (CL/F) was calculated as CL/F = Dose/AUC∞

  10. The AUC 0-24 of Emodepside in Plasma [ Time Frame: From pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
    Area under the plasma concentration-time curve from time zero (pre-dose) to 24 h was calculated using the trapezoidal method

  11. The AUC 0-24/D of Emodepside in Plasma [ Time Frame: From pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
    Dose-normalized area under the concentration-time curve (AUC) from time zero (pre-dose) to 24 h was calculated as AUC0-24/Dose administered

  12. The AUC 24, Norm of Emodepside in Plasma [ Time Frame: From pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
    Area under the concentration-time curve from time zero (pre-dose) to 24 h, normalized by dose and body weight (AUC 24, norm) was calculated as AUC0-24/(Dose administered*body weight)

  13. The Vz/F of Emodepside in Plasma [ Time Frame: From pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
    Apparent volume of distribution (Vz/F) was calculated as Vz/F = Dose/(λz × AUC∞), where λz is the apparent terminal elimination rate constant, estimated by linear regression of log-transformed concentration versus time data

  14. The AUC Last of Emodepside in Plasma [ Time Frame: From pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
    The area under the concentration-time curve from time zero (pre-dose) to the time of last quantifiable concentration (t), calculated using the linear trapezoidal method for increasing concentrations and the log trapezoidal method for decreasing concentrations

  15. Frel of the IR (Immediate Release) Tablet of Emodepside [ Time Frame: From pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
    The average relative bioavailability (Frel) of the IR tablet was calculated

  16. The AUC Last, Norm of Emodepside in Plasma [ Time Frame: From pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
    The area under the concentration-time curve from time zero (pre-dose) to the time of last quantifiable concentration normalized by dose and body weight (AUClast/(Dose administered*body weight))

  17. Effect of Food on the Bioavailability (Cmax) of Emodepside (BAY 44-4400) After Single Oral Dose Administered as Solution or IR Tablets in One Arm Only [ Time Frame: From pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
    Results of the statistical analysis of the effect of food on Emodepside exposure, after a single dose of 10 mg Emodepside LSF solution.

  18. Effect of Food on the Bioavailability (AUC24) of Emodepside (BAY 44-4400) After Single Oral Dose Administered as Solution or IR Tablets in One Arm Only [ Time Frame: From pre-dose until 336h post-dose (may be extended to 504h post-dose) ]
    Results of the statistical analysis of the effect of food on Emodepside exposure, after a single dose of 10 mg Emodepside LSF solution.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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
Layout table for location information
United Kingdom
Hammersmith Medicines Research
London, United Kingdom, NW10 7EW
Sponsors and Collaborators
Drugs for Neglected Diseases
Bayer
Bill and Melinda Gates Foundation
Investigators
Layout table for investigator information
Principal Investigator: Malcolm Boyce, MD, BSc Hammersmith Medicines Research
Study Director: Frederic Monnot Drugs for Neglected Diseases Initiative
  Study Documents (Full-Text)

Documents provided by Drugs for Neglected Diseases:
Study Protocol  [PDF] January 18, 2017
Statistical Analysis Plan  [PDF] March 10, 2017

Layout table for additonal information
Responsible Party: Drugs for Neglected Diseases
ClinicalTrials.gov Identifier: NCT02661178    
Other Study ID Numbers: DNDI-EMO-001
2015-003592-29 ( EudraCT Number )
First Posted: January 22, 2016    Key Record Dates
Results First Posted: April 13, 2020
Last Update Posted: April 13, 2020
Last Verified: October 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Emodepside
Antiparasitic Agents
Anti-Infective Agents