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

• Sponsor: Drugs for Neglected Diseases (Other)
• Overall Status: Completed
• CT.gov ID: NCT03383614
• Collaborator: Bayer (Industry), Bill and Melinda Gates Foundation (Other)
• Enrollment: 24
• Location: 1
• Arms: 3
• Actual Duration (Months): 11
• Patients Per Site Per Month: 2.2

Study Details

Study Description

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.

Study Design

• Study Type: Interventional
• 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: Nov 14, 2017
• Actual Primary Completion Date: Oct 15, 2018
• Actual Study Completion Date: Oct 15, 2018

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures

1. Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Adverse Events [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hammersmith Medicines Research Limited	London		United Kingdom	NW10 7EW

Sponsors and Collaborators

• Drugs for Neglected Diseases
• Bayer
• Bill and Melinda Gates Foundation

Investigators

• Principal Investigator: Jeremy Dennison, PhD MBChB, Hammersmith Medicines Research Limited

Study Documents (Full-Text)

• Study Protocol - Jul 25, 2018
• Statistical Analysis Plan - Aug 29, 2018

More Information

Publications

None provided.

• Responsible Party: Drugs for Neglected Diseases
• ClinicalTrials.gov Identifier: NCT03383614
• Other Study ID Numbers: DNDI-EMO-02; 2017-003020-75
• First Posted: Dec 26, 2017
• Last Update Posted: Apr 15, 2020
• Last Verified: Apr 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Filariasis; Emodepside

Study Results

Participant Flow

Pre-assignment Detail	24 healthy subjects were randomized and received study drug or matching placebo.

Arm/Group Title	Cohort 1: 5mg EMODEPSIDE OD	Cohort 2: 10mg EMODEPSIDE OD	Cohort 3: 10mg EMODEPSIDE BID	Placebo Group
Arm/Group Description	6 subjects with LSF emodepside 5mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, BID LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with matching placebo (2 subjects per dose group)
Period Title: Overall Study
STARTED	6	6	6	6
COMPLETED	6	5	6	6
NOT COMPLETED	0	1	0	0

Baseline Characteristics

Arm/Group Title	Cohort 1: 5mg EMODEPSIDE OD	Cohort 2: 10mg EMODEPSIDE OD	Cohort 3: 10mg EMODEPSIDE BID	Placebo Group	Total
Arm/Group Description	6 subjects with LSF emodepside 5mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, BID LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with matching placebo (2 subjects per dose group)	Total of all reporting groups
Overall Participants	6	6	6	6	24
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	6 100%	6 100%	6 100%	6 100%	24 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	31.0	33.3	28.0	32.7	31.3
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%
Male	6 100%	6 100%	6 100%	6 100%	24 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	6 100%	6 100%	6 100%	6 100%	24 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%
White	6 100%	6 100%	6 100%	6 100%	24 100%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United Kingdom	6 100%	6 100%	6 100%	6 100%	24 100%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	179.3 (4.18)	179.7 (4.59)	181.8 (6.74)	182.7 (8.80)	180.9 (6.10)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	72.18 (6.204)	77.70 (17.570)	75.23 (9.520)	74.73 (8.999)	74.96 (10.807)
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	22.48 (2.520)	23.88 (4.392)	22.72 (2.111)	22.33 (0.882)	22.85 (2.664)
Smokers (Count of Participants)
Count of Participants [Participants]	2 33.3%	1 16.7%	1 16.7%	0 0%	4 16.7%
Weekly alcohol consumption (units) (units/week) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units/week]	8.3 (3.79)	3.3 (2.31)	7.0 (3.46)	5.8 (2.17)	6.1 (3.11)
Xanthine (mL/day) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL/day]	441.7 (245.80)	562.5 (239.36)	283.3 (104.08)	300.0 (122.47)	397.4 (209.15)

Outcome Measures

1. Primary Outcome

Title	Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Adverse Events
Description	Death, serious adverse events (SAEs) and treatment-emergent adverse events (TEAEs).
Time Frame	up to 120 days

Outcome Measure Data

Analysis Population Description

Adverse events were determined in the Safety population. Adverse events were monitored from Screening (Day -28 and until Day -3) to Follow-up (up to Day 120 ±2 days). AE=adverse event; OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: 5mg EMODEPSIDE OD	Cohort 2: 10mg EMODEPSIDE OD	Cohort 3: 10mg EMODEPSIDE BID	Placebo Group
Arm/Group Description	6 subjects with LSF emodepside 5mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, BID LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with matching placebo (2 subjects per dose group)
Measure Participants	6	6	6	6
AEs	5 83.3%	6 100%	6 100%	4 66.7%
TEAEs	5 83.3%	6 100%	6 100%	4 66.7%
Drug-related TEAEs	2 33.3%	1 16.7%	3 50%	1 16.7%
SAEs	1 16.7%	0 0%	0 0%	0 0%
Deaths	0 0%	0 0%	0 0%	0 0%
Withdrawals from the study owing to a TEAE	0 0%	0 0%	0 0%	0 0%

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Adverse events were determined in the Safety population. Adverse events were monitored from Screening (Day -28 and until Day -3) to Follow-up (up to Day 120 ±2 days). AE=adverse event; OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: 5mg EMODEPSIDE OD	Cohort 2: 10mg EMODEPSIDE OD	Cohort 3: 10mg EMODEPSIDE BID	Placebo Group
Arm/Group Description	6 subjects with LSF emodepside 5mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, BID LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with matching placebo (2 subjects per dose group)
Measure Participants	6	6	6	6
Mild	2 33.3%	3 50%	4 66.7%	3 50%
Moderate	2 33.3%	3 50%	2 33.3%	1 16.7%
Severe	1 16.7%	0 0%	0 0%	0 0%

3. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Vital signs were measured pre-dose on Day -1, at regular time points until Follow-up (Day 30), and at each long-term follow-up visit. OD=once daily; BID=twice daily; HR=heart rate; BP=blood pressure.

Arm/Group Title	Cohort 1: 5mg EMODEPSIDE OD	Cohort 2: 10mg EMODEPSIDE OD	Cohort 3: 10mg EMODEPSIDE BID	Placebo Group
Arm/Group Description	6 subjects with LSF emodepside 5mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, BID LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with matching placebo (2 subjects per dose group)
Measure Participants	6	6	6	6
Clinically significant change in HR	0 0%	0 0%	0 0%	0 0%
Clinically significant change in systolic BP	0 0%	0 0%	0 0%	0 0%
Clinically significant change in diastolic BP	0 0%	0 0%	0 0%	0 0%
Clinically significant change in temperature	0 0%	0 0%	0 0%	0 0%

4. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Twelve-lead ECG assessments were made predose on Day -1 and at regular timepoints until Follow-up (Day 30). ECG=electrocardiogram; OD=once daily; BID=twice daily; PR=PR interval.

Arm/Group Title	Cohort 1: 5mg EMODEPSIDE OD	Cohort 2: 10mg EMODEPSIDE OD	Cohort 3: 10mg EMODEPSIDE BID	Placebo Group
Arm/Group Description	6 subjects with LSF emodepside 5mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, BID LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with matching placebo (2 subjects per dose group)
Measure Participants	6	6	6	6
Clinically significant changes in ventricular rate	0 0%	0 0%	0 0%	0 0%
Clinically significant changes in PR interval	0 0%	0 0%	0 0%	0 0%
Clinically significant changes in QRS interval	0 0%	0 0%	0 0%	0 0%
Clinically significant changes in QTcB interval	0 0%	0 0%	0 0%	0 0%

5. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Clinical laboratory parameters were measured pre-dose on Day -1, at regular time points until Follow-up (Day 30), and at each long-term follow-up visit. OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: 5mg EMODEPSIDE OD	Cohort 2: 10mg EMODEPSIDE OD	Cohort 3: 10mg EMODEPSIDE BID	Placebo Group
Arm/Group Description	6 subjects with LSF emodepside 5mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, BID LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with matching placebo (2 subjects per dose group)
Measure Participants	6	6	6	6
Clinically significant clinical chemistry changes	0 0%	0 0%	1 16.7%	0 0%
Clinically significant hematology changes	0 0%	0 0%	0 0%	0 0%
Clinically significant coagulation changes	0 0%	0 0%	0 0%	0 0%
Clinically significant urinalysis changes	0 0%	0 0%	0 0%	0 0%

6. Primary Outcome

Title	Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Ophthalmology Assessment Findings
Description	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.
Time Frame	up to 10 days

Outcome Measure Data

Analysis Population Description

Ophthalmological assessments were performed at the second screening visit after all other eligibility criteria had been met and on Day 10. OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: 5mg EMODEPSIDE OD	Cohort 2: 10mg EMODEPSIDE OD	Cohort 3: 10mg EMODEPSIDE BID	Placebo Group
Arm/Group Description	6 subjects with LSF emodepside 5mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, BID LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with matching placebo (2 subjects per dose group)
Measure Participants	6	6	6	6
Clinically significant ocular symptoms	3 50%	0 0%	3 50%	1 16.7%
Clinically significant Amsler grid assessment	1 16.7%	0 0%	0 0%	0 0%

7. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Physical and neurological examinations were measured pre-dose on Day -1, at regular time points until Follow-up (Day 30), and at each long-term follow-up visit. Results are reported for subjects experiencing abnormal result/AE, as opposed to individual events. OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: 5mg EMODEPSIDE OD	Cohort 2: 10mg EMODEPSIDE OD	Cohort 3: 10mg EMODEPSIDE BID	Placebo Group
Arm/Group Description	6 subjects with LSF emodepside 5mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, BID LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with matching placebo (2 subjects per dose group)
Measure Participants	6	6	6	6
Abnormal physical examination	2 33.3%	1 16.7%	2 33.3%	0 0%
Physical examination reported as an AE	2 33.3%	1 16.7%	1 16.7%	0 0%

8. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Neurological examinations were measured pre-dose on Day -1, at regular time points until Follow-up (Day 30), and at each long-term follow-up visit. OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: 5mg EMODEPSIDE OD	Cohort 2: 10mg EMODEPSIDE OD	Cohort 3: 10mg EMODEPSIDE BID	Placebo Group
Arm/Group Description	6 subjects with LSF emodepside 5mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, BID LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with matching placebo (2 subjects per dose group)
Measure Participants	6	6	6	6
Abnormal neurological examination	2 33.3%	1 16.7%	1 16.7%	1 16.7%
Neurological examination reported as an AE	1 16.7%	1 16.7%	1 16.7%	1 16.7%

9. Secondary Outcome

Title	Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period
Description	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.
Time Frame	From Day 1, pre-dose to Day 9, 24 hours post-dose

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: Emodepside 5 mg OD	Cohort 2: Emodepside 10 mg OD	Cohort 3: Emodepside 10 mg BID
Arm/Group Description	Emodepside (BAY 44-4400) 5 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, twice a day (morning and evening) in fasted state.
Measure Participants	6	6	6
Day 1, pre-dose	8.77 (35.8)	15.78 (42.9)	45.94 (35.1)
Day 2, pre-dose	15.24 (31.1)	28.80 (40.0)	64.62 (38.5)
Day 3, pre-dose	21.22 (35.0)	39.08 (45.6)	84.65 (37.7)
Day 4, pre-dose	24.81 (37.4)	47.38 (42.2)	98.01 (32.0)
Day 5, pre-dose	31.46 (36.3)	60.07 (42.9)	120.98 (31.1)
Day 6, pre-dose	36.68 (36.7)	70.88 (39.6)	137.60 (35.2)
Day 7, pre-dose	40.57 (31.4)	83.31 (43.0)	149.41 (33.3)
Day 8, pre-dose	46.91 (36.8)	91.63 (42.4)	179.90 (35.3)
Day 9, pre-dose	49.73 (35.1)	97.11 (44.0)	184.94 (37.1)
Day 9, 24 hour post-dose	51.76 (36.6)	108.17 (49.1)	176.10 (39.8)

10. Secondary Outcome

Title	The AUClast of Emodepside in Plasma
Description	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).
Time Frame	AUClast in plasma after the last dose (Day 9)

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: Emodepside 5 mg OD	Cohort 2: Emodepside 10 mg OD	Cohort 3: Emodepside 10 mg BID
Arm/Group Description	Emodepside (BAY 44-4400) 5 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, twice a day (morning and evening) in fasted state.
Measure Participants	6	6	6
Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]	19359 (29.9)	40655 (43.5)	59554 (29.1)

11. Secondary Outcome

Title	The AUClast/D of Emodepside in Plasma
Description	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).
Time Frame	AUClast /D in plasma after the last dose (Day 9)

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: Emodepside 5 mg OD	Cohort 2: Emodepside 10 mg OD	Cohort 3: Emodepside 10 mg BID
Arm/Group Description	Emodepside (BAY 44-4400) 5 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, twice a day (morning and evening) in fasted state.
Measure Participants	6	6	6
Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL/mg]	3872 (29.9)	4065 (43.5)	5955 (29.1)

12. Secondary Outcome

Title	The AUClast,Norm of Emodepside in Plasma
Description	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).
Time Frame	AUClast,norm in plasma after the last (Day 9) dose

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: Emodepside 5 mg OD	Cohort 2: Emodepside 10 mg OD	Cohort 3: Emodepside 10 mg BID
Arm/Group Description	Emodepside (BAY 44-4400) 5 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, twice a day (morning and evening) in fasted state.
Measure Participants	6	6	6
Geometric Mean (Geometric Coefficient of Variation) [(h*ng/mL)/(mg*kg)]	53.9 (33.1)	52.9 (69.5)	79.1 (40.6)

13. Secondary Outcome

Title	The AUC12 of Emodepside in Plasma
Description	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).
Time Frame	AUC12 in plasma after the first (Day 0) and last (Day 9) dose

Outcome Measure Data

Analysis Population Description

BID=twice daily.

Arm/Group Title	Cohort 3: Emodepside 10 mg BID
Arm/Group Description	Emodepside (BAY 44-4400) 10 mg orally, twice a day (morning and evening) in fasted state.
Measure Participants	6
Day 0	742 (29.4)
Day 9	2810 (35.0)

14. Secondary Outcome

Title	The AUC12/D of Emodepside in Plasma
Description	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).
Time Frame	AUC12/D in plasma after the first (Day 0) and last (Day 9) dose

Outcome Measure Data

Analysis Population Description

BID=twice daily.

Arm/Group Title	Cohort 3: Emodepside 10 mg BID
Arm/Group Description	Emodepside (BAY 44-4400) 10 mg orally, twice a day (morning and evening) in fasted state.
Measure Participants	6
Day 0	74.2 (29.4)
Day 9	281 (35.0)

15. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

BID=twice daily.

Arm/Group Title	Cohort 3: Emodepside 10 mg BID
Arm/Group Description	Emodepside (BAY 44-4400) 10 mg orally, twice a day (morning and evening) in fasted state.
Measure Participants	6
Day 0	0.985 (39.2)
Day 9	3.73 (46.6)

16. Secondary Outcome

Title	The AUC24 of Emodepside in Plasma
Description	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).
Time Frame	AUC24 in plasma after the first (Day 0) and last (Day 9) dose

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: Emodepside 5 mg OD	Cohort 2: Emodepside 10 mg OD	Cohort 3: Emodepside 10 mg BID
Arm/Group Description	Emodepside (BAY 44-4400) 5 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, twice a day (morning and evening) in fasted state.
Measure Participants	6	6	6
Day 0	574 (19.7)	1135 (32.7)	1428 (26.5)
Day 9	1689 (31.3)	3487 (44.2)	4897 (35.8)

17. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: Emodepside 5 mg OD	Cohort 2: Emodepside 10 mg OD	Cohort 3: Emodepside 10 mg BID
Arm/Group Description	Emodepside (BAY 44-4400) 5 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, twice a day (morning and evening) in fasted state.
Measure Participants	6	6	6
Day 0	115 (19.7)	113 (32.7)	71.4 (26.5)
Day 9	338 (31.3)	349 (44.2)	490 (35.8)

18. Secondary Outcome

Title	The AUC24,Norm of Emodepside in Plasma
Description	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).
Time Frame	AUC24,norm in plasma at Day 0 and Day 9

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: Emodepside 5 mg OD	Cohort 2: Emodepside 10 mg OD	Cohort 3: Emodepside 10 mg BID
Arm/Group Description	Emodepside (BAY 44-4400) 5 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, twice a day (morning and evening) in fasted state.
Measure Participants	6	6	6
Day 0	1.60 (21.5)	1.48 (56.7)	0.948 (36.5)
Day 9	4.70 (34.1)	4.54 (69.7)	6.50 (47.7)

19. Secondary Outcome

Title	The Cmax of Emodepside in Plasma
Description	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).
Time Frame	Cmax in plasma after the first (Day 0) and last (Day 9) dose

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: Emodepside 5 mg OD	Cohort 2: Emodepside 10 mg OD	Cohort 3: Emodepside 10 mg BID
Arm/Group Description	Emodepside (BAY 44-4400) 5 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, twice a day (morning and evening) in fasted state.
Measure Participants	6	6	6
Day 0	93.8 (17.8)	186 (21.3)	160 (20.4)
Day 9	149 (17.9)	287 (39.7)	349 (27.1)

20. Secondary Outcome

Title	The Cmax/D of Emodepside in Plasma
Description	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).
Time Frame	Cmax/D in plasma after the first (Day 0) and last (Day 9) dose

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: Emodepside 5 mg OD	Cohort 2: Emodepside 10 mg OD	Cohort 3: Emodepside 10 mg BID
Arm/Group Description	Emodepside (BAY 44-4400) 5 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, twice a day (morning and evening) in fasted state.
Measure Participants	6	6	6
Day 0	18.8 (17.8)	18.6 (21.3)	16.0 (20.4)
Day 9	29.9 (17.9)	28.7 (39.7)	34.9 (27.1)

21. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: Emodepside 5 mg OD	Cohort 2: Emodepside 10 mg OD	Cohort 3: Emodepside 10 mg BID
Arm/Group Description	Emodepside (BAY 44-4400) 5 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, twice a day (morning and evening) in fasted state.
Measure Participants	6	6	6
Day 0	0.261 (18.4)	0.242 (42.8)	0.212 (28.7)
Day 9	0.416 (20.6)	0.374 (65.4)	0.464 (38.2)

22. Secondary Outcome

Title	The Ctrough of Emodepside in Plasma
Description	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).
Time Frame	Ctrough in plasma after the last (Day 9) dose

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: Emodepside 5 mg OD	Cohort 2: Emodepside 10 mg OD	Cohort 3: Emodepside 10 mg BID
Arm/Group Description	Emodepside (BAY 44-4400) 5 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, twice a day (morning and evening) in fasted state.
Measure Participants	6	6	6
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	49.7 (36.8)	97.1 (50.8)	185 (39.5)

23. Secondary Outcome

Title	The Tmax of Emodepside in Plasma
Description	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.
Time Frame	tmax in plasma after the first (Day 0) and last (Day 9) dose

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: Emodepside 5 mg OD	Cohort 2: Emodepside 10 mg OD	Cohort 3: Emodepside 10 mg BID
Arm/Group Description	Emodepside (BAY 44-4400) 5 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, twice a day (morning and evening) in fasted state.
Measure Participants	6	6	6
Day 0	1.00	1.25	1.00
Day 9	1.00	1.25	1.50

24. Secondary Outcome

Title	The t1/2 of Emodepside in Plasma
Description	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).
Time Frame	t1/2 in plasma after the last (Day 9) dose

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: Emodepside 5 mg OD	Cohort 2: Emodepside 10 mg OD	Cohort 3: Emodepside 10 mg BID
Arm/Group Description	Emodepside (BAY 44-4400) 5 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, twice a day (morning and evening) in fasted state.
Measure Participants	6	6	6
Geometric Mean (Geometric Coefficient of Variation) [Hours]	419 (42.6)	450 (30.6)	508 (56.9)

25. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: Emodepside 5 mg OD	Cohort 2: Emodepside 10 mg OD	Cohort 3: Emodepside 10 mg BID
Arm/Group Description	Emodepside (BAY 44-4400) 5 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, twice a day (morning and evening) in fasted state.
Measure Participants	6	6	6
Geometric Mean (Geometric Coefficient of Variation) [Hours]	26.9 (52.4)	18.4 (30.0)	33.2 (55.0)

26. Secondary Outcome

Title	The λz of Emodepside in Plasma
Description	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).
Time Frame	λz in plasma after the last (Day 9) dose

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: Emodepside 5 mg OD	Cohort 2: Emodepside 10 mg OD	Cohort 3: Emodepside 10 mg BID
Arm/Group Description	Emodepside (BAY 44-4400) 5 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, twice a day (morning and evening) in fasted state.
Measure Participants	6	6	6
Geometric Mean (Geometric Coefficient of Variation) [1/h]	0.00166 (42.6)	0.00154 (30.6)	0.00137 (56.9)

27. Secondary Outcome

Title	The CLss/F of Emodepside in Plasma
Description	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).
Time Frame	CLss/F in plasma after the last (Day 9) dose

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: Emodepside 5 mg OD	Cohort 2: Emodepside 10 mg OD	Cohort 3: Emodepside 10 mg BID
Arm/Group Description	Emodepside (BAY 44-4400) 5 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, twice a day (morning and evening) in fasted state.
Measure Participants	6	6	6
Geometric Mean (Geometric Coefficient of Variation) [L/h]	2.96 (31.3)	2.87 (44.2)	3.56 (35.0)

28. Secondary Outcome

Title	The Vz/F of Emodepside in Plasma
Description	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).
Time Frame	Vz/F in plasma after the last (Day 9) dose

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: Emodepside 5 mg OD	Cohort 2: Emodepside 10 mg OD	Cohort 3: Emodepside 10 mg BID
Arm/Group Description	Emodepside (BAY 44-4400) 5 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, twice a day (morning and evening) in fasted state.
Measure Participants	6	6	6
Geometric Mean (Geometric Coefficient of Variation) [litre(s)]	1788 (74.2)	1861 (68.5)	2607 (102.1)

29. Secondary Outcome

Title	The MRTlast of Emodepside in Plasma
Description	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).
Time Frame	MRTlast in plasma after the first (Day 0) dose

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: Emodepside 5 mg OD	Cohort 2: Emodepside 10 mg OD	Cohort 3: Emodepside 10 mg BID
Arm/Group Description	Emodepside (BAY 44-4400) 5 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, twice a day (morning and evening) in fasted state.
Measure Participants	6	6	6
Geometric Mean (Geometric Coefficient of Variation) [Hours]	7.28 (10.7)	7.00 (11.0)	10.8 (2.8)

30. Secondary Outcome

Title	The Rac(AUC12) of Emodepside in Plasma
Description	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.
Time Frame	Rac(AUC12) after 10 days' repeated doses of 10 mg emodepside (Day 9)

Outcome Measure Data

Analysis Population Description

BID=twice daily.

Arm/Group Title	Cohort 3: Emodepside 10 mg BID
Arm/Group Description	Emodepside (BAY 44-4400) 10 mg orally, twice a day (morning and evening) in fasted state.
Measure Participants	6
Mean (Standard Deviation) [Ratio]	3.83 (15.5)

31. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: Emodepside 5 mg OD	Cohort 2: Emodepside 10 mg OD	Cohort 3: Emodepside 10 mg BID
Arm/Group Description	Emodepside (BAY 44-4400) 5 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, twice a day (morning and evening) in fasted state.
Measure Participants	6	6	6
Mean (Standard Deviation) [Ratio]	2.97 (16.1)	3.09 (11.3)	3.47 (17.1)

32. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: Emodepside 5 mg OD	Cohort 2: Emodepside 10 mg OD	Cohort 3: Emodepside 10 mg BID
Arm/Group Description	Emodepside (BAY 44-4400) 5 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, once daily in fasted state.	Emodepside (BAY 44-4400) 10 mg orally, twice a day (morning and evening) in fasted state.
Measure Participants	6	6	6
Mean (Standard Deviation) [Ratio]	1.61 (16.5)	1.58 (24.1)	2.21 (17.4)

33. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: 5mg EMODEPSIDE OD	Cohort 2: 10mg EMODEPSIDE OD	Cohort 3: 10mg EMODEPSIDE BID	Placebo Group
Arm/Group Description	6 subjects with LSF emodepside 5mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, BID LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with matching placebo (2 subjects per dose group)
Measure Participants	6	6	6	6
-24 h	4.72 (0.286)	4.68 (0.349)	4.80 (0.245)	4.77 (0.468)
-23 h	4.90 (0.308)	4.85 (0.259)	4.85 (0.281)	4.92 (0.313)
-22 h	4.77 (0.378)	4.72 (0.371)	4.72 (0.279)	4.82 (0.360)
-20 h	4.63 (0.388)	4.57 (0.207)	4.55 (0.207)	4.73 (0.480)
-12 h	5.17 (0.712)	5.55 (0.451)	5.52 (0.556)	5.48 (0.806)

34. Secondary Outcome

Title	Mean Glucose Concentration at Day 0
Description	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.
Time Frame	Mean glucose after repeated once or twice daily dosing for up to 10 days

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: 5mg EMODEPSIDE OD	Cohort 2: 10mg EMODEPSIDE OD	Cohort 3: 10mg EMODEPSIDE BID	Placebo Group
Arm/Group Description	6 subjects with LSF emodepside 5mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, BID LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with matching placebo (2 subjects per dose group)
Measure Participants	6	6	6	6
Predose (Baseline)	4.96 (0.321)	4.85 (0.409)	4.85 (0.351)	4.85 (0.288)
1 h	5.07 (0.367)	5.57 (0.816)	5.42 (0.445)	4.78 (0.214)
2 h	5.05 (0.327)	5.28 (0.508)	5.27 (0.472)	4.70 (0.310)
4 h	4.73 (0.378)	4.75 (0.274)	4.82 (0.279)	4.70 (0.276)
12 h	5.68 (0.268)	6.22 (0.343)	5.57 (0.554)	6.27 (0.761)
24 h	5.07 (0.314)	4.88 (0.264)	4.87 (0.273)	4.97 (0.288)

35. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: 5mg EMODEPSIDE OD	Cohort 2: 10mg EMODEPSIDE OD	Cohort 3: 10mg EMODEPSIDE BID	Placebo Group
Arm/Group Description	6 subjects with LSF emodepside 5mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, BID LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with matching placebo (2 subjects per dose group)
Measure Participants	6	6	6	6
Predose	4.52 (0.306)	4.95 (0.362)	4.97 (0.314)	4.67 (0.234)
1 h	5.10 (0.352)	5.98 (1.972)	5.65 (0.771)	4.80 (0.219)
2 h	5.03 (0.250)	5.72 (1.543)	5.57 (0.761)	4.74 (0.329)
4 h	4.60 (0.363)	4.62 (0.377)	5.08 (0.662)	4.70 (0.374)
12 h	5.58 (0.319)	6.00 (0.745)	7.03 (1.111)	6.02 (0.615)
24 h	4.92 (0.264)	5.10 (0.490)	5.17 (0.273)	4.82 (0.160)
48 h	5.02 (0.194)	5.07 (0.532)	5.10 (0.390)	4.90 (0.379)
72 h	4.87 (0.350)	5.13 (0.589)	5.03 (0.308)	5.03 (0.280)
96 h	4.80 (0.276)	5.10 (0.540)	4.85 (0.315)	4.87 (0.320)
120 h	5.00 (0.352)	4.98 (0.458)	5.05 (0.288)	4.90 (0.352)

36. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: 5mg EMODEPSIDE OD	Cohort 2: 10mg EMODEPSIDE OD	Cohort 3: 10mg EMODEPSIDE BID	Placebo Group
Arm/Group Description	6 subjects with LSF emodepside 5mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, BID LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with matching placebo (2 subjects per dose group)
Measure Participants	6	6	6	6
Mean (Standard Deviation) [mmol/L]	4.83 (0.288)	5.23 (0.993)	4.97 (0.234)	4.53 (0.350)

37. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: 5mg EMODEPSIDE OD	Cohort 2: 10mg EMODEPSIDE OD	Cohort 3: 10mg EMODEPSIDE BID	Placebo Group
Arm/Group Description	6 subjects with LSF emodepside 5mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, BID LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with matching placebo (2 subjects per dose group)
Measure Participants	6	6	6	6
-24 h	29.0 (8.60)	25.8 (8.11)	33.2 (17.90)	32.3 (12.31)
-23 h	25.8 (3.87)	26.2 (7.73)	28.0 (11.33)	26.5 (8.92)
-22 h	24.0 (6.69)	25.7 (8.91)	28.3 (14.50)	33.0 (5.73)
-20 h	22.7 (6.02)	22.7 (7.97)	24.3 (9.18)	24.5 (12.76)
-12 h	129.5 (54.14)	157.0 (81.51)	204.7 (78.37)	136.5 (64.30)

38. Secondary Outcome

Title	Mean Insulin Concentration at Day 0
Description	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.
Time Frame	Mean insulin concentration at Day 0 after repeated once or twice daily dosing

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: 5mg EMODEPSIDE OD	Cohort 2: 10mg EMODEPSIDE OD	Cohort 3: 10mg EMODEPSIDE BID	Placebo Group
Arm/Group Description	6 subjects with LSF emodepside 5mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, BID LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with matching placebo (2 subjects per dose group)
Measure Participants	6	6	6	6
Predose (Baseline)	27.8 (15.41)	29.3 (5.09)	32.2 (14.34)	30.5 (12.55)
1 h	25.0 (3.79)	23.2 (10.85)	29.2 (14.86)	33.0 (9.10)
2 h	24.3 (5.20)	25.3 (9.99)	36.3 (20.39)	31.2 (12.89)
4 h	21.7 (5.01)	21.7 (5.39)	27.7 (11.69)	20.2 (6.85)
12 h	127.2 (67.59)	203.2 (83.22)	175.3 (64.59)	195.0 (88.03)
24 h	36.7 (15.49)	41.2 (14.51)	30.3 (11.43)	35.2 (16.59)

39. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: 5mg EMODEPSIDE OD	Cohort 2: 10mg EMODEPSIDE OD	Cohort 3: 10mg EMODEPSIDE BID	Placebo Group
Arm/Group Description	6 subjects with LSF emodepside 5mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, BID LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with matching placebo (2 subjects per dose group)
Measure Participants	6	6	6	6
Predose	31.5 (8.62)	32.7 (15.02)	29.2 (10.19)	31.3 (9.83)
1 h	29.2 (9.66)	24.4 (15.39)	22.2 (8.89)	27.8 (9.77)
2 h	27.7 (4.84)	31.2 (10.53)	30.2 (13.91)	29.8 (10.26)
4 h	23.0 (7.35)	28.4 (13.24)	19.5 (9.12)	21.8 (6.37)
12 h	147.2 (77.58)	143.0 (113.7)	215.8 (128.1)	215.7 (151.8)
24 h	34.5 (11.88)	36.5 (12.24)	32.7 (17.44)	36.3 (13.03)
48 h	36.2 (5.60)	44.8 (17.89)	36.3 (13.59)	38.2 (19.17)
72 h	48.3 (23.53)	40.7 (13.88)	39.8 (15.61)	38.7 (14.42)
96 h	37.8 (10.42)	39.3 (12.31)	37.2 (17.66)	30.0 (11.63)
120 h	39.0 (8.63)	42.3 (17.92)	36.0 (15.24)	33.2 (21.68)

40. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: 5mg EMODEPSIDE OD	Cohort 2: 10mg EMODEPSIDE OD	Cohort 3: 10mg EMODEPSIDE BID	Placebo Group
Arm/Group Description	6 subjects with LSF emodepside 5mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, BID LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with matching placebo (2 subjects per dose group)
Measure Participants	6	6	6	6
Mean (Standard Deviation) [pmol/L]	29.2 (12.50)	60.3 (90.19)	24.3 (9.79)	29.2 (20.21)

41. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: 5mg EMODEPSIDE OD	Cohort 2: 10mg EMODEPSIDE OD	Cohort 3: 10mg EMODEPSIDE BID	Placebo Group
Arm/Group Description	6 subjects with LSF emodepside 5mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, BID LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with matching placebo (2 subjects per dose group)
Measure Participants	6	6	6	6
0 h (Baseline)	4.72 (0.319)	4.92 (0.256)	4.97 (0.294)	4.78 (0.133)
1 h	8.78 (1.659)	7.03 (0.301)	7.00 (0.867)	6.48 (1.450)
2 h	5.98 (1.512)	5.05 (0.589)	5.48 (0.608)	4.95 (0.965)
4 h	4.57 (0.979)	3.95 (0.622)	4.22 (0.371)	4.53 (0.294)

42. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: 5mg EMODEPSIDE OD	Cohort 2: 10mg EMODEPSIDE OD	Cohort 3: 10mg EMODEPSIDE BID	Placebo Group
Arm/Group Description	6 subjects with LSF emodepside 5mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, BID LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with matching placebo (2 subjects per dose group)
Measure Participants	6	6	6	6
Predose (Baseline)	5.07 (0.314)	4.88 (0.264)	4.87 (0.273)	4.97 (0.228)
1 h	10.10 (1.170)	12.37 (2.826)	12.03 (0.989)	7.58 (2.242)
2 h	6.17 (1.600)	7.95 (1.653)	9.25 (2.740)	5.88 (1.174)
4 h	3.95 (0.339)	3.65 (0.362)	4.02 (0.204)	4.15 (0.575)

43. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: 5mg EMODEPSIDE OD	Cohort 2: 10mg EMODEPSIDE OD	Cohort 3: 10mg EMODEPSIDE BID	Placebo Group
Arm/Group Description	6 subjects with LSF emodepside 5mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, BID LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with matching placebo (2 subjects per dose group)
Measure Participants	6	6	6	6
Predose (Baseline)	4.87 (0.314)	5.10 (0.533)	4.90 (0.303)	4.83 (0.258)
1 h	10.02 (1.857)	11.75 (4.574)	11.27 (2.738)	7.77 (1.679)
2 h	7.05 (1.533)	8.98 (4.311)	8.97 (2.837)	5.52 (0.783)
4 h	3.93 (0.965)	4.12 (0.933)	4.52 (0.806)	4.13 (0.197)

44. Secondary Outcome

Title	Mean Serum Glucose Concentration at Day 120
Description	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)
Time Frame	Mean serum glucose concentration at Day 120, before and up to 4 hours after intake of a high-glucose solution

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 3: 10mg EMODEPSIDE BID
Arm/Group Description	6 subjects with LSF emodepside 10mg, BID LSF emodepside (BAY 44-4400) oral solution (1mg/mL)
Measure Participants	6
0 h (Baseline)	4.93 (0.294)
1 h	8.12 (2.542)
2 h	6.08 (0.540)
4 h	4.26 (0.305)

45. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: 5mg EMODEPSIDE OD	Cohort 2: 10mg EMODEPSIDE OD	Cohort 3: 10mg EMODEPSIDE BID	Placebo Group
Arm/Group Description	6 subjects with LSF emodepside 5mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, BID LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with matching placebo (2 subjects per dose group)
Measure Participants	6	6	6	6
0 h (Baseline)	24.5 (13.81)	25.7 (8.55)	27.0 (14.00)	29.0 (14.68)
1 h	334.8 (207.66)	305.3 (65.59)	306.7 (180.00)	338.3 (189.61)
2 h	174.7 (206.08)	103.7 (32.38)	136.0 (70.52)	186.8 (83.55)
4 h	44.3 (72.56)	17.2 (6.11)	20.8 (7.44)	21.8 (9.33)

46. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: 5mg EMODEPSIDE OD	Cohort 2: 10mg EMODEPSIDE OD	Cohort 3: 10mg EMODEPSIDE BID	Placebo Group
Arm/Group Description	6 subjects with LSF emodepside 5mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, BID LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with matching placebo (2 subjects per dose group)
Measure Participants	6	6	6	6
Predose (Baseline)	36.7 (15.49)	41.2 (14.51)	30.3 (11.43)	35.2 (16.59)
1 h	312.2 (153.67)	288.8 (171.44)	332.2 (228.84)	606.7 (157.35)
2 h	268.5 (107.14)	377.3 (224.73)	336.2 (165.71)	238.0 (165.06)
4 h	28.8 (22.35)	30.8 (12.35)	35.7 (4.59)	33.8 (19.56)

47. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: 5mg EMODEPSIDE OD	Cohort 2: 10mg EMODEPSIDE OD	Cohort 3: 10mg EMODEPSIDE BID	Placebo Group
Arm/Group Description	6 subjects with LSF emodepside 5mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, BID LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with matching placebo (2 subjects per dose group)
Measure Participants	6	6	6	6
Predose (Baseline)	32.5 (9.85)	39.3 (22.59)	34.5 (15.83)	33.8 (12.94)
1 h	302.5 (145.61)	286.8 (179.53)	225.3 (148.93)	690.5 (342.10)
2 h	337.0 (110.23)	225.7 (101.02)	229.8 (79.00)	238.3 (92.34)
4 h	63.0 (86.69)	63.3 (83.32)	36.8 (21.17)	21.7 (19.97)

48. Secondary Outcome

Title	Mean Serum Insulin Concentration at Day 120
Description	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)
Time Frame	Mean serum insulin concentration at Day 120, before and up to 4 hours after intake of a high-glucose solution

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 3: 10mg EMODEPSIDE BID
Arm/Group Description	6 subjects with LSF emodepside 10mg, BID LSF emodepside (BAY 44-4400) oral solution (1mg/mL)
Measure Participants	6
0 h (Baseline)	28.0 (13.74)
1 h	417.8 (379.72)
2 h	152.8 (114.92)
4 h	18.8 (11.39)

49. Other Pre-specified Outcome

Title	Drug-related Adverse Events
Description	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.
Time Frame	Drug-related AEs were reported throughout the study

Outcome Measure Data

Analysis Population Description

OD=once daily; BID=twice daily.

Arm/Group Title	Cohort 1: 5mg EMODEPSIDE OD	Cohort 2: 10mg EMODEPSIDE OD	Cohort 3: 10mg EMODEPSIDE BID	Placebo Group
Arm/Group Description	6 subjects with LSF emodepside 5mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with LSF emodepside 10mg, BID LSF emodepside (BAY 44-4400) oral solution (1mg/mL)	6 subjects with matching placebo (2 subjects per dose group)
Measure Participants	6	6	6	6
Visual impairment	2 33.3%	1 16.7%	3 50%	1 16.7%
Euphoric mood	1 16.7%	1 16.7%	0 0%	0 0%
Nervousness	1 16.7%	0 0%	0 0%	0 0%
Dizziness	1 16.7%	0 0%	0 0%	0 0%

Adverse Events

Time Frame	Adverse events were monitored from Screening (Day -28 and until Day -3) to Follow-up (up to Day 120 ±2 days).
Arm/Group Title	Cohort 1: 5mg EMODEPSIDE OD		Cohort 2: 10mg EMODEPSIDE OD		Cohort 3: 10mg EMODEPSIDE BID		Placebo Group
Arm/Group Description	6 subjects with LSF emodepside 5mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)		6 subjects with LSF emodepside 10mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)		6 subjects with LSF emodepside 10mg, BID LSF emodepside (BAY 44-4400) oral solution (1mg/mL)		6 subjects with matching placebo (2 subjects per dose group)
All Cause Mortality
	Cohort 1: 5mg EMODEPSIDE OD		Cohort 2: 10mg EMODEPSIDE OD		Cohort 3: 10mg EMODEPSIDE BID		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Serious Adverse Events
	Cohort 1: 5mg EMODEPSIDE OD		Cohort 2: 10mg EMODEPSIDE OD		Cohort 3: 10mg EMODEPSIDE BID		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Gastrointestinal disorders
Anal fistula	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Infections and infestations
Anal abscess	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Other (Not Including Serious) Adverse Events
	Cohort 1: 5mg EMODEPSIDE OD		Cohort 2: 10mg EMODEPSIDE OD		Cohort 3: 10mg EMODEPSIDE BID		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/6 (83.3%)		6/6 (100%)		6/6 (100%)		4/6 (66.7%)
Eye disorders
Visual impairment	2/6 (33.3%)	3	1/6 (16.7%)	2	3/6 (50%)	3	1/6 (16.7%)	1
Vision blurred	1/6 (16.7%)	2	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Gastrointestinal disorders
Nausea	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	2/6 (33.3%)	2
Abdominal pain	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
General disorders
Fatigue	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1
Influenza like illness	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Malaise	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Medical device site erythema	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0
Immune system disorders
Allergy to animal	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Infections and infestations
Nasopharyngitis	3/6 (50%)	3	3/6 (50%)	3	0/6 (0%)	0	0/6 (0%)	0
Ear infection	0/6 (0%)	0	1/6 (16.7%)	2	0/6 (0%)	0	0/6 (0%)	0
Tonsilitis	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Urethritis	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Injury, poisoning and procedural complications
Skin laceration	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Investigations
Hepatic enzyme increased	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Hepatitis E antibody positive	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	1/6 (16.7%)	1	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0
Musculoskeletal chest pain	1/6 (16.7%)	1	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Arthralgia	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0
Nervous system disorders
Headache	1/6 (16.7%)	3	0/6 (0%)	0	0/6 (0%)	0	2/6 (33.3%)	4
Dizziness	2/6 (33.3%)	2	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Psychiatric disorders
Euphoric mood	1/6 (16.7%)	1	1/6 (16.7%)	2	0/6 (0%)	0	0/6 (0%)	0
Nervousness	1/6 (16.7%)	2	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Skin and subcutaneous tissue disorders
Acne	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Dry skin	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0
Rash	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0
Surgical and medical procedures
Sebaceous cyst excision	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.