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Safety, Tolerability and PK of Multiple-ascending Doses of Emodepside

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: NCT03383614
Recruitment Status : Completed
First Posted : December 26, 2017
Results First Posted : April 15, 2020
Last Update Posted : April 15, 2020
Sponsor:
Collaborators:
Bayer
Bill and Melinda Gates Foundation
Information provided by (Responsible Party):
Drugs for Neglected Diseases

Brief Summary:
The study evaluates safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of emodepside, after administration as a Liquid Service Formulation (LSF), over 10 days, in healthy male caucasian subjects.

Condition or disease Intervention/treatment Phase
Filariasis Drug: LSF emodepside (BAY 44-4400) or matching placebo Phase 1

Detailed Description:

There is an urgent need for a macrofilaricidal drug, killing or sterilizing permanently O. volvulus adult worms, which could be used in individual case management and, after appropriate testing, as an alternative drug to ivermectin in Mass Drug Administration (MDA) programs. Emodepside is a promising candidate to kill the adult and sexually mature O. volvulus as explained below. Emodepside was shown to be macrofilaricidal against a variety of filarial nematodes and is a registered drug for animal health, commercialized by Bayer AG under the name of Profender® (in combination with praziquantel) or Procox® (in combination with toltrazuril).

A first-in-human (FIH) double-blind, placebo-controlled study of single ascending doses of emodepside in healthy Caucasian men has been conducted and the preliminary results are favourable, supporting continuation of the Phase I development program. In the present repeat dose study, PK as well as safety and tolerability of the liquid service formulation of emodepside, given over 10 days, will be tested.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1, Single-Blind, Randomized, Placebo Controlled, Parallel-Group, Multiple-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 : November 14, 2017
Actual Primary Completion Date : October 15, 2018
Actual Study Completion Date : October 15, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Emodepside

Arm Intervention/treatment
Experimental: cohort 1 (8 subjects)
6 subjects with LSF emodepside 5mg, OD 2 subjects with matching placebo
Drug: LSF emodepside (BAY 44-4400) or matching placebo
Emodepside administered as an LSF oral solution (1mg/mL)

Experimental: cohort 2 (8 subjects)
6 subjects with LSF emodepside 10mg, OD 2 subjects with matching placebo
Drug: LSF emodepside (BAY 44-4400) or matching placebo
Emodepside administered as an LSF oral solution (1mg/mL)

Experimental: cohort 3 (8 subjects)
6 subjects with LSF emodepside 10mg, BID 2 subjects with matching placebo
Drug: LSF emodepside (BAY 44-4400) or matching placebo
Emodepside administered as an LSF oral solution (1mg/mL)




Primary Outcome Measures :
  1. Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Adverse Events [ Time Frame: up to 120 days ]
    Death, serious adverse events (SAEs) and treatment-emergent adverse events (TEAEs).

  2. Safety and Tolerability of Emodepside After Multiple Doses as Measured by Adverse Event Severity [ Time Frame: Up to 120 days ]
    Number of subjects with a TEAE, by highest level of severity.

  3. Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Vital Signs Findings [ Time Frame: up to 120 days ]
    Vital signs included heart rate, systolic and diastolic blood pressure and temperature.

  4. Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With 12-lead Electrocardiogram Findings [ Time Frame: up to 30 days ]
    The following variables were recorded in 12-lead ECGs: ventricular rate, PR interval, QRS interval, QTcB and QTcF interval.

  5. Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Clinical Laboratory Tests Findings [ Time Frame: up to 120 days ]
    Clinical laboratory parameters included clinical chemistry, hematology, coagulation and urinalysis.

  6. Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Ophthalmology Assessment Findings [ Time Frame: up to 10 days ]
    Ophthalmological examinations at Screening Visit 2 and Day 10 were done at a specialist eye hospital by a Consultant Ophthalmologist, or their assistant. Examinations included: ocular symptoms and history, autorefraction, best correct visual acuity, colour vision, Amsler grid, ocular alignment and motility, confrontation visual field, slit-lamp, measurement of intraocular pressure and an optical coherence tomography test.

  7. Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Physical Examination Findings [ Time Frame: up to 120 days ]
    Abnormal or clinically significant physical examination findings during the study or reported as an adverse event.

  8. Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Neurological Examination Findings [ Time Frame: up to 120 days ]
    Abnormal or clinically significant neurological examination findings during the study or reported as an adverse event.


Secondary Outcome Measures :
  1. Geometric Mean Emodepside Plasma Pharmacokinetic Concentration−Time Data During the Repeated Dosing Period [ Time Frame: From Day 1, pre-dose to Day 9, 24 hours post-dose ]

    Summary of geometric mean emodepside plasma pharmacokinetic concentration−time data (ng/mL) during the repeated dosing period (Days 0-9) in healthy men.

    Subjects in the 10 mg emodepside BID dosing group had twice-daily doses on Days 0-8 and a single dose on the morning of Day 9. Therefore, the Day 9, 24 h post-dose value was not comparable to the previous value in that dosing group.


  2. The AUClast of Emodepside in Plasma [ Time Frame: AUClast in plasma after the last dose (Day 9) ]

    Summary of AUClast of emodepside after the last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population.

    Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120h (Day 14) after the morning dose.

    AUClast: the area under the concentration-time curve from time zero (pre-dose) to the time of last quantifiable concentration.

    PK=pharmacokinetic. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).


  3. The AUClast/D of Emodepside in Plasma [ Time Frame: AUClast /D in plasma after the last dose (Day 9) ]

    Summary of AUClast/D of emodepside after the last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population.

    Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120h (Day 14) after the morning dose.

    AUClast/D: the area under the concentration-time curve from time zero (pre-dose) to the time of last quantifiable concentration corrected for dose.

    The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).


  4. The AUClast,Norm of Emodepside in Plasma [ Time Frame: AUClast,norm in plasma after the last (Day 9) dose ]

    Summary of AUClast,norm of emodepside after the last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population.

    Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120h (Day 14) after the morning dose.

    AUClast,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.

    The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).


  5. The AUC12 of Emodepside in Plasma [ Time Frame: AUC12 in plasma after the first (Day 0) and last (Day 9) dose ]

    Summary of AUC12 of emodepside after the first (Day 0) and last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population.

    Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15h after the morning dose. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120h (Day 14) after the morning dose.

    AUC12: the area under the concentration-time curve from time zero (pre-dose) to 12h.

    Note: AUC12 was calculated only in Cohort 3. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).


  6. The AUC12/D of Emodepside in Plasma [ Time Frame: AUC12/D in plasma after the first (Day 0) and last (Day 9) dose ]

    Summary of AUC12/D of emodepside after the first (Day 0) and last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population.

    Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15h after the morning dose. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120h (Day 14) after the morning dose.

    AUC12/D: the area under the concentration-time curve from time zero (pre-dose) to 12h, corrected for dose.

    Note: AUC12/D was collected only in Cohort 3. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).


  7. The AUC12,Norm of Emodepside in Plasma [ Time Frame: AUC12,norm in plasma after the first (Day 0) and last (Day 9) dose ]

    Summary of AUC12,norm of emodepside after the first (Day 0) and last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population.

    Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15 h after the morning dose. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose.

    AUC12,norm: the area under the concentration−time curve from time zero (pre-dose) to 12 h corrected by dose and body weight.

    Note: AUC12,norm was calculated only in Cohort 3. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).


  8. The AUC24 of Emodepside in Plasma [ Time Frame: AUC24 in plasma after the first (Day 0) and last (Day 9) dose ]

    Summary of AUC24 of emodepside after the first (Day 0) and last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population.

    Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15 h after the morning dose. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose.

    AUC24: the area under the concentration-time curve from time zero (pre-dose) to 24 h.

    The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).


  9. The AUC24/D of Emodepside in Plasma [ Time Frame: AUC24/D in plasma after the first (Day 0) and last (Day 9) dose ]

    Summary of AUC24/D of emodepside after the first (Day 0) and last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population.

    Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15 h after the morning dose. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose.

    AUC24/D: the area under the concentration-time curve from time zero (pre-dose) to 24h corrected for dose.

    The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).


  10. The AUC24,Norm of Emodepside in Plasma [ Time Frame: AUC24,norm in plasma at Day 0 and Day 9 ]

    Summary of AUC24,norm of emodepside after the first (Day 0) and last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population.

    Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15h after the morning dose. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120h (Day 14) after the morning dose.

    AUC24,norm: the area under the concentration-time curve from time zero (pre-dose) to 24h corrected by dose and body weight.

    The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).


  11. The Cmax of Emodepside in Plasma [ Time Frame: Cmax in plasma after the first (Day 0) and last (Day 9) dose ]

    Summary of Cmax of emodepside after the first (Day 0) and last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population.

    Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15 h after the morning dose. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose.

    Cmax: the observed maximum plasma concentration measured in a subject after dosing identified by inspection of the drug concentration vs. time data.

    The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).


  12. The Cmax/D of Emodepside in Plasma [ Time Frame: Cmax/D in plasma after the first (Day 0) and last (Day 9) dose ]

    Summary of Cmax/D of emodepside after the first (Day 0) and last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population.

    Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15 h after the morning dose. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose.

    Cmax/D: the observed maximum plasma concentration measured in a subject after dosing identified by inspection of the drug concentration vs. time data, corrected for dose.

    The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).


  13. The Cmax,Norm of Emodepside in Plasma [ Time Frame: Cmax,norm in plasma after the first (Day 0) and last (Day 9) dose ]

    Summary of Cmax,norm of emodepside after the first (Day 0) and last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population.

    Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15 h after the morning dose. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose.

    Cmax,norm: the observed maximum plasma concentration measured in a subject after dosing identified by inspection of the drug concentration vs. time data, corrected for dose and body weight.

    The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).


  14. The Ctrough of Emodepside in Plasma [ Time Frame: Ctrough in plasma after the last (Day 9) dose ]

    Summary of Ctrough (log-transformed) of emodepside after last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population.

    Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose.

    Ctrough: trough plasma concentration (measured concentration at the end of a dosing interval on Day 9 [taken directly before next administration]) obtained directly from the concentration-time data.

    The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).


  15. The Tmax of Emodepside in Plasma [ Time Frame: tmax in plasma after the first (Day 0) and last (Day 9) dose ]

    Summary of tmax of emodepside after the first (Day 0) and last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population.

    Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15 h after the morning dose. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose.

    tmax: the time at which Cmax was apparent, identified by inspection of the drug concentration vs. time data.


  16. The t1/2 of Emodepside in Plasma [ Time Frame: t1/2 in plasma after the last (Day 9) dose ]

    Summary of t1/2 of emodepside after the last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population.

    Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose.

    t1/2: terminal half-life. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).


  17. The t1/2,(0-24) of Emodepside in Plasma [ Time Frame: t1/2,(0-24) in plasma after the last (Day 9) dose ]

    Summary of t1/2,(0-24) of emodepside after the last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population.

    Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose.

    t1/2,(0-24): half-life calculated from the terminal slope of the log concentration-time (0-24h) curve.

    The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).


  18. The λz of Emodepside in Plasma [ Time Frame: λz in plasma after the last (Day 9) dose ]

    Summary of λz of emodepside after the last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population.

    Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose.

    λz: terminal rate constant. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).


  19. The CLss/F of Emodepside in Plasma [ Time Frame: CLss/F in plasma after the last (Day 9) dose ]

    Summary of CLss/F of emodepside after the last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population.

    Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose.

    CLss/F: apparent total clearance from plasma on Day 9. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).


  20. The Vz/F of Emodepside in Plasma [ Time Frame: Vz/F in plasma after the last (Day 9) dose ]

    Summary of Vz/F of emodepside after the last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population.

    Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose.

    Vz/F: apparent volume of distribution on Day 9. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).


  21. The MRTlast of Emodepside in Plasma [ Time Frame: MRTlast in plasma after the first (Day 0) dose ]

    Summary of MRTlast of emodepside after the first (Day 0) dose for 10-day oral treatment courses in healthy men: PK parameter population.

    Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15 h after the morning dose.

    MRTlast: mean residence time from time zero (pre-dose) to the time of last quantifiable concentration (measurable up to 24h after dosing on Day 0).

    The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).


  22. The Rac(AUC12) of Emodepside in Plasma [ Time Frame: Rac(AUC12) after 10 days' repeated doses of 10 mg emodepside (Day 9) ]

    Summary of emodepside plasma Rac(AUC12) after 10 days' repeated doses of 10 mg emodepside (Day 9): PK parameter population.

    Rac(AUC12): accumulation ratio calculated from AUC12, where AUC12 is the area under the concentration−time curve from time zero (pre-dose) to 12h.

    Note: measure of dispersion is 'percentage coefficient of variation' (the between-subject coefficient of variation [%CVb]).

    Note: Rac(AUC12) was calculated only in Cohort 3.


  23. The Rac(AUC24) of Emodepside in Plasma [ Time Frame: Rac(AUC24) after 10 days' repeated doses of 10 mg emodepside (Day 9) ]

    Summary of emodepside plasma Rac(AUC24) after 10 days' repeated doses of 10 mg emodepside (Day 9): PK parameter population.

    Rac(AUC24): accumulation ratio calculated from AUC24, where AUC24 is the area under the concentration-time curve from time zero (pre-dose) to 24h.

    Note: measure of dispersion is 'percentage coefficient of variation' (the between-subject coefficient of variation [%CVb]).


  24. The Rac(Cmax) of Emodepside in Plasma [ Time Frame: Rac(Cmax) after 10 days' repeated doses of 10 mg emodepside (Day 9) ]

    Summary of emodepside plasma Rac(Cmax) after 10 days' repeated doses of 10 mg emodepside (Day 9): PK parameter population.

    Rac(Cmax): accumulation ratio calculated from Cmax, where Cmax is the observed maximum plasma concentration measured in a subject after dosing identified by inspection of the drug concentration vs. time data.

    Note: measure of dispersion is 'percentage coefficient of variation' (the between-subject coefficient of variation [%CVb]).


  25. Mean Glucose Concentration at Day -1 [ Time Frame: Mean glucose at Day -1 after repeated once or twice daily dosing ]
    Mean glucose concentrations (mmol/L) after repeated once or twice daily dosing with up to 10 mg emodepside or placebo at Day -1.

  26. Mean Glucose Concentration at Day 0 [ Time Frame: Mean glucose after repeated once or twice daily dosing for up to 10 days ]

    Mean glucose concentrations (mmol/L) after repeated once or twice daily dosing with up to 10 mg emodepside or placebo at Day 0.

    Baseline=predose on Day 0.


  27. Mean Glucose Concentration at Day 9 [ Time Frame: Mean glucose at Day 9 after repeated once or twice daily dosing ]
    Mean glucose concentrations (mmol/L) after repeated once or twice daily dosing with up to 10 mg emodepside or placebo at Day 9.

  28. Mean Glucose Concentration at Day 30 [ Time Frame: Mean glucose at Day 30 after repeated once or twice daily dosing ]
    Mean glucose concentrations (mmol/L) after repeated once or twice daily dosing with up to 10 mg emodepside or placebo at Day 30.

  29. Mean Insulin Concentration at Day -1 [ Time Frame: Mean insulin concentration at Day-1 after repeated once or twice daily dosing ]
    Mean insulin concentration (pmol/L) after repeated once or twice daily dosing with up to 10 mg emodepside or placebo at Day -1.

  30. Mean Insulin Concentration at Day 0 [ Time Frame: Mean insulin concentration at Day 0 after repeated once or twice daily dosing ]

    Mean insulin concentration (pmol/L) after repeated once or twice daily dosing with up to 10 mg emodepside or placebo at Day 0.

    Baseline=predose on Day 0.


  31. Mean Insulin Concentration at Day 9 [ Time Frame: Mean insulin concentration at Day 9 after repeated once or twice daily dosing ]
    Mean insulin concentration (pmol/L) after repeated once or twice daily dosing with up to 10 mg emodepside or placebo at Day 9.

  32. Mean Insulin Concentration at Day 30 [ Time Frame: Mean insulin concentration at Day 30 after repeated once or twice daily dosing ]
    Mean insulin concentration (pmol/L) after repeated once or twice daily dosing with up to 10 mg emodepside or placebo at Day 30.

  33. Mean Serum Glucose Concentration at Day -2 [ Time Frame: Mean serum glucose concentration at Day -2, before and up to 4 hours after intake of a high-glucose solution ]

    Oral glucose tolerance test: mean serum glucose concentration at Day -2, before and up to 4 hours after intake of a high-glucose solution, in subjects receiving repeated doses of emodepside or placebo for 10 days (Days 0-9).

    Baseline=pre-glucose intake on each respective day.


  34. Mean Serum Glucose Concentration at Day 1 [ Time Frame: Mean serum glucose concentration at Day 1, before and up to 4 hours after intake of a high-glucose solution ]

    Oral glucose tolerance test: mean serum glucose concentration at Day 1, before and up to 4 hours after intake of a high-glucose solution, in subjects receiving repeated doses of emodepside or placebo for 10 days (Days 0-9).

    Baseline=pre-glucose intake on each respective day.


  35. Mean Serum Glucose Concentration at Day 8 [ Time Frame: Mean serum glucose concentration at Day 8, before and up to 4 hours after intake of a high-glucose solution ]

    Oral glucose tolerance test: mean serum glucose concentration at Day 8, before and up to 4 hours after intake of a high-glucose solution, in subjects receiving repeated doses of emodepside or placebo for 10 days (Days 0-9).

    Baseline=pre-glucose intake on each respective day.


  36. Mean Serum Glucose Concentration at Day 120 [ Time Frame: Mean serum glucose concentration at Day 120, before and up to 4 hours after intake of a high-glucose solution ]

    Oral glucose tolerance test: mean serum glucose concentration at Day 120, before and up to 4 hours after intake of a high-glucose solution, in subjects receiving repeated doses of emodepside or placebo for 10 days (Days 0-9).

    Baseline=pre-glucose intake on each respective day. Note: At Day 120, serum glucose concentration was only measured in Cohort 3 (10 mg BID)


  37. Mean Serum Insulin Concentration at Day -2 [ Time Frame: Mean serum insulin concentration at Day -2, before and up to 4 hours after intake of a high-glucose solution ]

    Oral glucose tolerance test: mean serum insulin concentration at Day -2, before and up to 4 hours after intake of a high-glucose solution, in subjects receiving repeated doses of emodepside or placebo for 10 days (Days 0-9).

    Baseline=pre-glucose intake on each respective day.


  38. Mean Serum Insulin Concentration at Day 1 [ Time Frame: Mean serum insulin concentration at Day 1, before and up to 4 hours after intake of a high-glucose solution ]

    Oral glucose tolerance test: mean serum insulin concentration at Day 1, before and up to 4 hours after intake of a high-glucose solution, in subjects receiving repeated doses of emodepside or placebo for 10 days (Days 0-9).

    Baseline=pre-glucose intake on each respective day.


  39. Mean Serum Insulin Concentration at Day 8 [ Time Frame: Mean serum insulin concentration at Day 8, before and up to 4 hours after intake of a high-glucose solution ]

    Oral glucose tolerance test: mean serum insulin concentration at Day 8, before and up to 4 hours after intake of a high-glucose solution, in subjects receiving repeated doses of emodepside or placebo for 10 days (Days 0-9).

    Baseline=pre-glucose intake on each respective day.


  40. Mean Serum Insulin Concentration at Day 120 [ Time Frame: Mean serum insulin concentration at Day 120, before and up to 4 hours after intake of a high-glucose solution ]

    Oral glucose tolerance test: mean serum insulin concentration at Day 120, before and up to 4 hours after intake of a high-glucose solution, in subjects receiving repeated doses of emodepside or placebo for 10 days (Days 0-9).

    Baseline=pre-glucose intake on each respective day. Note: At Day 120, serum glucose concentration was only measured in Cohort 3 (10 mg BID)



Other Outcome Measures:
  1. Drug-related Adverse Events [ Time Frame: Drug-related AEs were reported throughout the study ]

    Subjects presenting drug-related treatment-emergent adverse events listed by preferred term.

    Note: subjects with ≥1 adverse event are counted only once per preferred term.




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.


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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   only male subjects will be included
Accepts Healthy Volunteers:   Yes
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 (BMI; Quetelet index) in the range 18 to 30.1 kg/m2 at screening.
  4. Blood pressure and heart rate in the supine position prior to randomisation must be within the ranges 90-140 mm Hg systolic, 60-90 mm Hg diastolic; heart rate 45-100 beats/min.
  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.
  8. Willingness to agree to the contraceptive requirements of the study from the first dose until 120 days after the last dose of study medication.

Exclusion Criteria:

  1. Administration of a licensed or unlicensed medicinal product as part of another clinical trial within the 3 months before, or within 5 half-lives of, their first dose of study medication, whichever is longer, or is currently in the follow-up period for any clinical trial.
  2. 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.
  3. Past surgery (e.g., stomach bypass) or medical condition that might affect absorption of study drug taken orally.
  4. 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.
  5. Loss of more than 400 mL of blood within 3 months before admission.
  6. Clinically relevant history of vital organ disease or other disease of an organ or the central nervous system.
  7. Current or previous medical or psychiatric disorder, condition or history of such (e.g., seizures) that, in the opinion of the Investigator or the Sponsor, would increase the risk associated with study participation, or impair the subject's ability to participate or complete this study.
  8. Positive test for hepatitis B, hepatitis C or HIV.
  9. Febrile illness within 1 week before the first dose of study medication.
  10. History of severe allergy, non-allergic drug reactions, severe adverse reaction to any drug, or multiple drug allergies.
  11. Subjects with hypersensitivity to any ingredient of the study medication, including the active ingredient, emodepside.
  12. Presence or history of drug or alcohol abuse in the last 10 years, or intake of more than 21 units of alcohol weekly.
  13. Regular daily consumption of more than one liter of xanthine-containing beverages.
  14. Regular daily consumption of more than 5 cigarettes daily, or use more than 3 grams (1/8 ounce) of tobacco.
  15. Use of a prescription medicine during the 28 days before the first dose of study medication or use of an over-the-counter medicine (with exception of acetaminophen [paracetamol]), during the 7 days before the first dose of study medication.
  16. Use 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, during the 28 days before the first dose of study medication (see list in the Study Procedures Manual).
  17. Use of dietary supplements or herbal remedies (such as St John's Wort) that are known to be strong inhibitors of P-gp, or other co-medications known to be relevant substrates of P-gp, during the 28 days before the first dose of study medication (see list in the Study Procedures Manual).
  18. Relevant pathological abnormalities in the ECG at screening, such as a second or third-degree atrioventricular (AV) block or prolongation of the QRS complex over 120 msec or QTc-interval over 450 msec (corrected using Bazett's [QTcB] or Fridericia's [QTcF] formulae).
  19. Evidence of drug abuse (via urine testing) at the screening assessment or admission to the ward.
  20. Use of excluded therapies that may impact on the interpretation of study results in the opinion of the Investigator or Sponsor.
  21. Objection by General Practitioner (GP) to subject entering trial.
  22. History of residing for 6 or more continuous months, within the last 3 years, in regions with endemic parasitic infections as determined by the Investigator.
  23. Possibility that subject will not cooperate with the requirements of the protocol.
  24. No contact lenses wear within 1 month before dosing. Wearing contact lenses is not permitted during the study.
  25. 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).
  26. Past history of ocular disease requiring ongoing treatment.
  27. Past ocular surgery including laser or other refractive corneal surgery.
  28. Evidence of eye irritation, visual difficulties, corneal opacity, ocular surface (corneal or conjunctival damage, with or without ocular symptoms).
  29. Evidence of narrow anterior chamber angles causing increased risk of acute glaucoma.
  30. Evidence of ocular media opacity including lens opacity/vitreous opacities.
  31. Evidence of retinal or optic nerve pathology.
  32. 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): NCT03383614


Locations
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United Kingdom
Hammersmith Medicines Research Limited
London, United Kingdom, NW10 7EW
Sponsors and Collaborators
Drugs for Neglected Diseases
Bayer
Bill and Melinda Gates Foundation
Investigators
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Principal Investigator: Jeremy Dennison, PhD MBChB Hammersmith Medicines Research Limited
  Study Documents (Full-Text)

Documents provided by Drugs for Neglected Diseases:
Study Protocol  [PDF] July 25, 2018
Statistical Analysis Plan  [PDF] August 29, 2018

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Responsible Party: Drugs for Neglected Diseases
ClinicalTrials.gov Identifier: NCT03383614    
Other Study ID Numbers: DNDI-EMO-02
2017-003020-75 ( EudraCT Number )
First Posted: December 26, 2017    Key Record Dates
Results First Posted: April 15, 2020
Last Update Posted: April 15, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Filariasis
Spirurida Infections
Secernentea Infections
Nematode Infections
Helminthiasis
Parasitic Diseases
Emodepside
Antiparasitic Agents
Anti-Infective Agents