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

• Sponsor: Drugs for Neglected Diseases (Other)
• Overall Status: Completed
• CT.gov ID: NCT02661178
• Collaborator: Bayer (Industry), Bill and Melinda Gates Foundation (Other)
• Enrollment: 79
• Location: 1
• Arms: 2
• Actual Duration (Months): 15.8
• Patients Per Site Per Month: 5

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: emodepside (BAY 44-4400); Drug: placebo	Phase 1

Study Design

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

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Safety and Tolerability as Measured by Adverse Events [Up to 14 days post dose (may be extended to 21 days)]

   Deaths, serious adverse events (SAEs) and treatment-emergent adverse events (TEAEs)

2. Safety and Tolerability as Measured by Physical and Neurological Examination Findings [Up to 14 days post dose (may be extended to 21 days)]

   Abnormal or clinically significant neurological examination findings during the study or reported as an AE

3. Safety and Tolerability as Measured by Vital Signs [Up to 14 days post dose (may be extended to 21 days)]

   Vital signs included heart rate, systolic and diastolic blood pressure,

4. Safety and Tolerability as Measured by 12-lead ECG [Up to 14 days post dose (may be extended to 21 days)]

   The following variables were recorded in 12-lead ECGs and extracted from continuous 12-lead ECG recordings: ventricular rate, PR interval, QRS interval, QTcB and QTcF interval.

5. Safety and Tolerability as Measured by Clinical Laboratory Parameters [Up to 14 days post dose (may be extended to 21 days)]

   Clinical laboratory parameters included hematology, biochemistry, serology and coagulation in blood samples and urinalysis in urine samples

6. Safety and Tolerability as Measured by Ophthalmological Examination Findings in One Study Arm Only [Up to 14 days post dose (may be extended to 21 days)]

   Subjects attended a specialist eye hospital for ophthalmology assessments by a Consultant Ophthalmologist. Opthalmology assessments included:ocular symptoms, past ocular history, auto-refraction, best corrected distance visual acuity, color vision assessment, amsler grid assessment, ocular alignment and ocular motility assessment, confrontation visual field assessment, slit lamp examination (anterior segment), intraocular pressure (Goldmann Tonometry), optical coherence scanning of tomography, post mydriatic ocular media (at Screening visit 2 only) and retinal examination with slit lamp and lens.

Secondary Outcome Measures

1. The AUC∞ of Emodepside in Plasma [From pre-dose until 336h post-dose (may be extended to 504h post-dose)]

   The area under the plasma drug concentration versus time curve from time zero to infinity (AUC∞)

2. The AUC∞/D of Emodepside in Plasma [From pre-dose until 336h post-dose (may be extended to 504h post-dose)]

   Dose-normalized area under the plasma drug concentration versus time curve from time zero to infinity (AUC∞/D), calculated as AUC∞/Dose administered.

3. The Cmax of Emodepside in Plasma [From pre-dose until 336h post-dose (may be extended to 504h post-dose)]

   Maximum observed plasma concentration (Cmax) was obtained directly from the concentration-time data

4. The Cmax/D of Emodepside in Plasma [From pre-dose until 336h post-dose (may be extended to 504h post-dose)]

   Dose-normalized observed maximum plasma concentration (Cmax/D) was calculated as Cmax/Dose administered

5. The Cmax, Norm of Emodepside in Plasma [From pre-dose until 336h post-dose (may be extended to 504h post-dose)]

   The observed maximum plasma concentration (Cmax) normalized by dose and body weight was calculated as Cmax/(Dose administered*body weight)

6. The Tmax of Emodepside in Plasma [From pre-dose until 336h post-dose (may be extended to 504h post-dose)]

   Time to reach maximum plasma concentration (Tmax) was obtained directly from the concentration-time data

7. The t½ of Emodepside in Plasma [From pre-dose until 336h post-dose (may be extended to 504h post-dose)]

   Terminal half-life (t½), calculated according to the equation t½ = ln2/λz, where λz is the apparent terminal elimination rate constant, estimated by linear regression of log-transformed concentration versus time data

8. The MRT of Emodepside in Plasma [From pre-dose until 336h post-dose (may be extended to 504h post-dose)]

   The mean residence time (MRT) was calculated as MRT = AUMC/AUC∞, where AUMC is the area under the first moment of the concentration-time curve from zero time (pre-dose) extrapolated to infinite time

9. The CL/F of Emodepside in Plasma [From pre-dose until 336h post-dose (may be extended to 504h post-dose)]

   Apparent total clearance from plasma (CL/F) was calculated as CL/F = Dose/AUC∞

10. The AUC 0-24 of Emodepside in Plasma [From pre-dose until 336h post-dose (may be extended to 504h post-dose)]

    Area under the plasma concentration-time curve from time zero (pre-dose) to 24 h was calculated using the trapezoidal method

11. The AUC 0-24/D of Emodepside in Plasma [From pre-dose until 336h post-dose (may be extended to 504h post-dose)]

    Dose-normalized area under the concentration-time curve (AUC) from time zero (pre-dose) to 24 h was calculated as AUC0-24/Dose administered

12. The AUC 24, Norm of Emodepside in Plasma [From pre-dose until 336h post-dose (may be extended to 504h post-dose)]

    Area under the concentration-time curve from time zero (pre-dose) to 24 h, normalized by dose and body weight (AUC 24, norm) was calculated as AUC0-24/(Dose administered*body weight)

13. The Vz/F of Emodepside in Plasma [From pre-dose until 336h post-dose (may be extended to 504h post-dose)]

    Apparent volume of distribution (Vz/F) was calculated as Vz/F = Dose/(λz × AUC∞), where λz is the apparent terminal elimination rate constant, estimated by linear regression of log-transformed concentration versus time data

14. The AUC Last of Emodepside in Plasma [From pre-dose until 336h post-dose (may be extended to 504h post-dose)]

    The area under the concentration-time curve from time zero (pre-dose) to the time of last quantifiable concentration (t), calculated using the linear trapezoidal method for increasing concentrations and the log trapezoidal method for decreasing concentrations

15. Frel of the IR (Immediate Release) Tablet of Emodepside [From pre-dose until 336h post-dose (may be extended to 504h post-dose)]

    The average relative bioavailability (Frel) of the IR tablet was calculated

16. The AUC Last, Norm of Emodepside in Plasma [From pre-dose until 336h post-dose (may be extended to 504h post-dose)]

    The area under the concentration-time curve from time zero (pre-dose) to the time of last quantifiable concentration normalized by dose and body weight (AUClast/(Dose administered*body weight))

17. Effect of Food on the Bioavailability (Cmax) of Emodepside (BAY 44-4400) After Single Oral Dose Administered as Solution or IR Tablets in One Arm Only [From pre-dose until 336h post-dose (may be extended to 504h post-dose)]

    Results of the statistical analysis of the effect of food on Emodepside exposure, after a single dose of 10 mg Emodepside LSF solution.

18. Effect of Food on the Bioavailability (AUC24) of Emodepside (BAY 44-4400) After Single Oral Dose Administered as Solution or IR Tablets in One Arm Only [From pre-dose until 336h post-dose (may be extended to 504h post-dose)]

    Results of the statistical analysis of the effect of food on Emodepside exposure, after a single dose of 10 mg Emodepside LSF solution.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Male, Caucasian volunteers, deemed healthy on the basis of a clinical history, physical examination, ECG, vital signs, and laboratory tests of blood and urine. Optionally, after further evaluation during the study, at the sponsor's discretion other ethnic groups may be recruited.

• Aged 18 to 55 years.

• With a body mass index (BMI; Quetelet index) in the range of 18 to 30.1 kg/m2 at screening.

• Sufficient intelligence to understand the nature of the trial and any hazards of participating in it. Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of, the entire trial.

• Willingness to give written consent to participate, after reading the information and consent form, and after having the opportunity to discuss the trial with the investigator or his delegate

Exclusion Criteria:

• Participation in another clinical trial within 3 months prior and during the study, or 5-times the half-life of the drug tested in the previous clinical trial, whichever is longer (time calculated relative to the last dose in the previous clinical trial)

• Clinically relevant abnormal medical history, concurrent medical condition, acute or chronic illness or history of chronic illness sufficient to invalidate the subject's participation in the trial or make it unnecessarily hazardous.

• Surgery (eg stomach bypass) or medical condition that might affect absorption of study drug taken orally.

• Presence of abnormal physical findings, ECG, or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the subject.

• Positive tests for hepatitis B & C, HIV

• Presence or history of drug or alcohol abuse during the last 10 years, or intake of more than 21 units of alcohol weekly.

• Regular daily consumption of more than one liter of xanthine-containing beverages

• Regular daily consumption of more than 5 cigarettes daily, or use more than 3 grams (1/8 ounce) of tobacco

• Use of a prescription medicine during the 28 days before the first dose of trial medication or use of an over-the-counter medicine, with the exception of acetaminophen (paracetamol), during the 7 days before the first dose of trial medication

• Use of dietary supplements or herbal remedies (such as St John's Wort) known to interfere with the CYP3A4 and/or P-gp metabolic pathways during the 28 days before the first dose of trial medication (see list in Study Procedures Manual)

Additional exclusion criteria for cohort with ophthalmological assessments:

• No contact lenses wear within 1 month prior to first dose of IMP. Contact lenses wear is not permitted during the study

• Any ocular disorder for which topical ocular therapy is currently or chronically prescribed, including inflammatory eye disease (dry eye allergic conjunctivitis [seasonal allergic conjunctivitis, vernal keratoconjunctivitis, atopic keratoconjunctivitis], uveitis and glaucoma)

• Past history of ocular disease requiring ongoing treatment

• Past ocular surgery including laser or other refractive corneal surgery

• Evidence of eye irritation, visual difficulties, corneal opacity, ocular surface (corneal or conjunctival damage, with or without ocular symptoms)

• Evidence of narrow anterior chamber angles causing increased risk of acute glaucoma

• Evidence of ocular media opacity including lens opacity/vitreous opacities

• Evidence of retinal or optic nerve pathology

• Evidence of pronounced colour blindness, as indicated by an Ishihara score of 9/13 or below

Contacts and Locations

Locations

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

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Malcolm Boyce, MD, BSc, Hammersmith Medicines Research
• Study Director: Frederic Monnot, Drugs for Neglected Diseases initiative

Study Documents (Full-Text)

• Study Protocol - Jan 18, 2017
• Statistical Analysis Plan - Mar 10, 2017

More Information

Publications

None provided.

• Responsible Party: Drugs for Neglected Diseases
• ClinicalTrials.gov Identifier: NCT02661178
• Other Study ID Numbers: DNDI-EMO-001; 2015-003592-29
• First Posted: Jan 22, 2016
• Last Update Posted: Apr 13, 2020
• Last Verified: Oct 1, 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Drugs for Neglected Diseases: Parasitic Diseases; Helminthiasis; Nematode Infections; Secernentea Infections; Spirurida Infections; Filariasis; Skin Diseases, Parasitic; Skin and Connective Tissue Diseases; Skin Diseases; Skin Diseases, Infectious; Depsipeptides; Emodepside; Neglected disease; Africa; New drug; Oral drug; Parasite; Anthelmintic drug; Cyclooctadepsipeptide; Single ascending dose; Volunteers; Phase 1; Safety; Tolerability; Pharmacokinetics; Relative bioavailability; Onchocerciasis
• Additional relevant MeSH terms: Emodepside

Study Results

Participant Flow

Pre-assignment Detail	79 healthy subjects were randomized and received study drug. Protocol Enrollment reflects the total number of participants enrolled in both Part 1 (63 participants) and Part 2 (16 participants).

Arm/Group Title	Emodepside 0.1mg Solution, Fasted (Part 1)	Emodepside 1mg Solution, Fasted (Part 1)	Emodepside 2.5mg Solution, Fasted (Part 1)	Emodepside 5mg Solution, Fasted (Part 1)	Emodepside 5mg Tablet, Fasted (Part 1)	Emodepside 10mg Solution, Fasted (Part 1)	Emodepside 20mg Solution, Fasted (Part 1)	Emodepside 20mg Tablet, Fasted (Part 1)	Emodepside 40mg Solution, Fasted (Part 1)	Placebo Solution, Fasted (Part 1)	Placebo Tablet, Fasted (Part 1)	Emodepside 10mg Solution, Fed (Part 2)	Emodepside 40mg Solution, Fasted, (Part 2)	Placebo Solution, Fed (Part 2)	Placebo Solution, Fasted (Part 2)
Arm/Group Description	Emodepside (BAY 44-4400) 0.1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 2.5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Matching placebo of emodepside (BAY 44-4400), solution, administered in fasted state Part one of study (FIH, single ascending dose phase)	Matching placebo of emodepside (BAY 44-4400), tablet, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fed state This cohort was not classed as first in human Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Matching placebo of emodepside (BAY 44-4400), solution, administered in fed state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Matching placebo of emodepside (BAY 44-4400), solution, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)
Period Title: Part 1
STARTED	1	5	6	6	5	6	6	6	6	12	4	0	0	0	0
COMPLETED	0	5	6	6	5	6	6	6	6	12	4	0	0	0	0
NOT COMPLETED	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1
STARTED	0	0	0	0	0	0	0	0	0	0	0	6	6	2	2
COMPLETED	0	0	0	0	0	0	0	0	0	0	0	6	6	2	2
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Emodepside 0.1mg Solution, Fasted (Part 1)	Emodepside 1mg Solution, Fasted (Part 1)	Emodepside 2.5mg Solution, Fasted (Part 1)	Emodepside 5mg Solution, Fasted (Part 1)	Emodepside 5mg Tablet, Fasted (Part 1)	Emodepside 10mg Solution, Fasted (Part 1)	Emodepside 20mg Solution, Fasted (Part 1)	Emodepside 20mg Tablet, Fasted (Part 1)	Emodepside 40mg Solution, Fasted (Part 1)	Placebo Solution, Fasted (Part 1)	Placebo Tablet, Fasted (Part 1)	Emodepside 10mg Solution, Fed (Part 2)	Emodepside 40mg Solution, Fasted, AE Follow-up Arm (Part 2)	Placebo Solution, Fed (Part 2)	Placebo Solution, Fasted (Part 2)	Total
Arm/Group Description	Emodepside (BAY 44-4400) 0.1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 2.5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Matching placebo of emodepside (BAY 44-4400), solution, administered in fasted state Part one of study (FIH, single ascending dose phase)	Matching placebo of emodepside (BAY 44-4400), tablet, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fed state This cohort was not classed as first in human Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Matching placebo of emodepside (BAY 44-4400), solution, administered in fed state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Matching placebo of emodepside (BAY 44-4400), solution, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Total of all reporting groups
Overall Participants	1	5	6	6	5	6	6	6	6	12	4	6	6	2	2	79
Age (years) [Mean (Standard Deviation) ]
Part 1	23 (0)	38.6 (10.06)	34.8 (9.20)	29.3 (8.12)	36.8 (10.69)	34.2 (10.55)	32.8 (9.75)	31.3 (8.91)	30.8 (10.83)	30.7 (7.46)	28.0 (3.56)	32.4 (8.89)
Part 2	27.7 (7.34)	38.5 (10.67)	51.5 (0.71)	40 (11.31)	38.3 (13.67)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Male	1 100%	5 100%	6 100%	6 100%	5 100%	6 100%	6 100%	6 100%	6 100%	12 100%	4 100%	63 1050%
Female	0 0%	0 0%	0 0%	0 0%	0 0%
Male	6 600%	6 120%	2 33.3%	2 33.3%	16 320%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 16.7%	0 0%	0 0%	1 8.3%	1 25%	3 50%
Not Hispanic or Latino	1 100%	5 100%	6 100%	6 100%	5 100%	6 100%	5 83.3%	6 100%	6 100%	11 91.7%	3 75%	60 1000%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Hispanic or Latino	1 100%	0 0%	0 0%	0 0%	1 20%
Not Hispanic or Latino	5 500%	6 120%	2 33.3%	2 33.3%	15 300%
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%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	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%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
White	1 100%	5 100%	6 100%	6 100%	5 100%	6 100%	6 100%	6 100%	6 100%	12 100%	4 100%	63 1050%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
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	6 600%	6 120%	2 33.3%	2 33.3%	16 320%
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%
Height (cm) [Mean (Standard Deviation) ]
Part 1	173 (0)	176.8 (4.87)	179.8 (6.24)	175.5 (5.82)	177.2 (10.87)	177.2 (3.54)	179.0 (7.51)	179.5 (7.45)	183.3 (7.63)	180.0 (7.98)	183.3 (2.99)	179.1 (6.89)
Part 2	183.2 (6.37)	176.0 (5.22)	178 (8.49)	181 (4.24)	179.6 (6.28)
Weight (kg) [Mean (Standard Deviation) ]
Part 1	72.00 (0)	70.64 (6.815)	75.47 (11.331)	75.83 (3.506)	76.56 (13.197)	74.80 (11.383)	81.93 (10.397)	81.73 (9.075)	83.27 (11.267)	79.52 (10.130)	85.15 (7.217)	78.43 (9.931)
Part 2	82.20 (7.979)	82.65 (13.598)	72.8 (1.98)	83.7 (24.75)	81.38 (11.636)
BMI (kg/m^2) [Mean (Standard Deviation) ]
Part 1	24.10 (0)	22.60 (2.117)	23.30 (2.683)	24.65 (1.162)	24.20 (1.707)	23.75 (2.868)	25.55 (2.651)	25.43 (3.169)	24.72 (2.613)	24.49 (2.131)	25.38 (2.291)	24.41 (2.356)
Part 2	24.5 (2.137)	26.55 (3.213)	23.1 (2.83)	25.4 (6.36)	25.21 (3.117)

Outcome Measures

1. Primary Outcome

Title	Safety and Tolerability as Measured by Adverse Events
Description	Deaths, serious adverse events (SAEs) and treatment-emergent adverse events (TEAEs)
Time Frame	Up to 14 days post dose (may be extended to 21 days)

Outcome Measure Data

Analysis Population Description

AEs were determined in the Safety Population. In Part 1 n=63 (n=62 subjects completed). One subject in the 1mg emodepside group was withdrawn after receiving 0.1mg emodepside LSF, owing to an AE. He consented to follow-up safety assessment until Day 7 as a 0.1mg emodepside group. In Part 2, n=16 (n=16 subjects completed)

Arm/Group Title	Emodepside 0.1mg Solution, Fasted (Part 1)	Emodepside 1mg Solution, Fasted (Part 1)	Emodepside 2.5mg Solution, Fasted (Part 1)	Emodepside 5mg Solution, Fasted (Part 1)	Emodepside 5mg Tablet, Fasted (Part 1)	Emodepside 10mg Solution, Fasted (Part 1)	Emodepside 20mg Solution, Fasted (Part 1)	Emodepside 20mg Tablet, Fasted (Part 1)	Emodepside 40mg Solution, Fasted (Part 1)	Emodepside 10mg Solution, Fed (Part 2)	Emodepside 40mg Solution, Fasted, (Part 2)	Placebo Solution, Fasted (Part 1)	Placebo Tablet, Fasted (Part 1)	Placebo Solution, Fed (Part 2)	Placebo Solution, Fasted (Part 2)
Arm/Group Description	No AEs were reported for Emodepside (BAY 44-4400) 0.1mg solution, as oral liquid service formulation, administered in fasted state	Emodepside (BAY 44-4400) 1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 2.5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fed state This cohort was not classed as first in human Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Matching placebo of emodepside (BAY 44-4400), solution, administered in fasted state Part one of study (FIH, single ascending dose phase)	Matching placebo of emodepside (BAY 44-4400), tablet, administered in fasted state Part one of study (FIH, single ascending dose phase)	Matching placebo of emodepside (BAY 44-4400), solution, administered in fed state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Matching placebo of emodepside (BAY 44-4400), solution, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)
Measure Participants	1	5	6	6	5	6	6	6	6	6	6	12	4	2	2
Deaths	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Subjects with SAE	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Subjects with TEAE	1 100%	3 60%	0 0%	3 50%	3 60%	5 83.3%	3 50%	2 33.3%	5 83.3%	3 25%	5 125%	5 83.3%	1 16.7%	0 0%	0 0%

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

AEs were determined in the Safety Population. In Part 1 n=63 (n=62 subjects completed). One subject in the 1mg emodepside group was withdrawn after receiving 0.1mg emodepside LSF, owing to an AE. He consented to follow-up safety assessment until Day 7 as a 0.1mg emodepside group.

Arm/Group Title	Emodepside 0.1mg Solution, Fasted (Part 1)	Emodepside 1mg Solution, Fasted (Part 1)	Emodepside 2.5mg Solution, Fasted (Part 1)	Emodepside 5mg Solution, Fasted (Part 1)	Emodepside 5mg Tablet, Fasted (Part 1)	Emodepside 10mg Solution, Fasted (Part 1)	Emodepside 20mg Solution, Fasted (Part 1)	Emodepside 20mg Tablet, Fasted (Part 1)	Emodepside 40mg Solution, Fasted (Part 1)	Emodepside 10mg Solution, Fed (Part 2)	Emodepside 40mg Solution, Fasted, (Part 2)	Placebo Solution, Fasted (Part 1)	Placebo Tablet, Fasted (Part 1)	Placebo Solution, Fed (Part 2)	Placebo Solution, Fasted (Part 2)
Arm/Group Description	No AEs were reported for Emodepside (BAY 44-4400) 0.1mg solution, as oral liquid service formulation, administered in fasted state	Emodepside (BAY 44-4400) 1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 2.5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fed state This cohort was not classed as first in human Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Matching placebo of emodepside (BAY 44-4400), solution, administered in fasted state Part one of study (FIH, single ascending dose phase)	Matching placebo of emodepside (BAY 44-4400), tablet, administered in fasted state Part one of study (FIH, single ascending dose phase)	Matching placebo of emodepside (BAY 44-4400), solution, administered in fed state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Matching placebo of emodepside (BAY 44-4400), solution, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)
Measure Participants	1	5	6	6	5	6	6	6	6	6	6	12	4	2	2
Abnormal neurological examination	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Neurological examination reported as AE	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Abnormal physcial examination	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Physical examination reported as AE	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

3. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

AEs were determined in the Safety Population. In Part 1 n=63 (n=62 subjects completed). One subject in the 1mg emodepside group was withdrawn after receiving 0.1mg emodepside LSF, owing to an AE. He consented to follow-up safety assessment until Day 7 as a 0.1mg emodepside group.

Arm/Group Title	Emodepside 0.1mg Solution, Fasted (Part 1)	Emodepside 1mg Solution, Fasted (Part 1)	Emodepside 2.5mg Solution, Fasted (Part 1)	Emodepside 5mg Solution, Fasted (Part 1)	Emodepside 5mg Tablet, Fasted (Part 1)	Emodepside 10mg Solution, Fasted (Part 1)	Emodepside 20mg Solution, Fasted (Part 1)	Emodepside 20mg Tablet, Fasted (Part 1)	Emodepside 40mg Solution, Fasted (Part 1)	Emodepside 10mg Solution, Fed (Part 2)	Emodepside 40mg Solution, Fasted, (Part 2)	Placebo Solution, Fasted (Part 1)	Placebo Tablet, Fasted (Part 1)	Placebo Solution, Fed (Part 2)	Placebo Solution, Fasted (Part 2)
Arm/Group Description	Emodepside (BAY 44-4400) 0.1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 2.5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fed state This cohort was not classed as first in human Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Matching placebo of emodepside (BAY 44-4400), solution, administered in fasted state Part one of study (FIH, single ascending dose phase)	Matching placebo of emodepside (BAY 44-4400), tablet, administered in fasted state Part one of study (FIH, single ascending dose phase)	Matching placebo of emodepside (BAY 44-4400), solution, administered in fed state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Matching placebo of emodepside (BAY 44-4400), solution, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)
Measure Participants	1	5	6	6	5	6	6	6	6	6	6	12	4	2	2
Clinically significant change in heart rate	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Clinically significant change in systolic BP	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Clinically significant change in diastolic BP	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

4. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

AEs were determined in the Safety Population. In Part 1 n=63 (n=62 subjects completed). One subject in the 1mg emodepside group was withdrawn after receiving 0.1mg emodepside LSF, owing to an AE. He consented to follow-up safety assessment until Day 7 as a 0.1mg emodepside group.

Arm/Group Title	Emodepside 0.1mg Solution, Fasted (Part 1)	Emodepside 1mg Solution, Fasted (Part 1)	Emodepside 2.5mg Solution, Fasted (Part 1)	Emodepside 5mg Solution, Fasted (Part 1)	Emodepside 5mg Tablet, Fasted (Part 1)	Emodepside 10mg Solution, Fasted (Part 1)	Emodepside 20mg Solution, Fasted (Part 1)	Emodepside 20mg Tablet, Fasted (Part 1)	Emodepside 40mg Solution, Fasted (Part 1)	Emodepside 10mg Solution, Fed (Part 2)	Emodepside 40mg Solution, Fasted, (Part 2)	Placebo Solution, Fasted (Part 1)	Placebo Tablet, Fasted (Part 1)	Placebo Solution, Fed (Part 2)	Placebo Solution, Fasted (Part 2)
Arm/Group Description	Emodepside (BAY 44-4400) 0.1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 2.5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fed state This cohort was not classed as first in human Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Matching placebo of emodepside (BAY 44-4400), solution, administered in fasted state Part one of study (FIH, single ascending dose phase)	Matching placebo of emodepside (BAY 44-4400), tablet, administered in fasted state Part one of study (FIH, single ascending dose phase)	Matching placebo of emodepside (BAY 44-4400), solution, administered in fed state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Matching placebo of emodepside (BAY 44-4400), solution, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)
Measure Participants	1	5	6	6	5	6	6	6	6	6	6	12	4	2	2
Notable changes in ventricular rate	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Notable changes in PR interval	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Notable changes in QRS interval	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Notable changes in QTcB	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Notable changes in QTcF interval	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

5. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

AEs were determined in the Safety Population. In Part 1 n=63 (n=62 subjects completed). One subject in the 1mg emodepside group was withdrawn after receiving 0.1mg emodepside LSF, owing to an AE. He consented to follow-up safety assessment until Day 7 as a 0.1mg emodepside group.

Arm/Group Title	Emodepside 0.1mg Solution, Fasted (Part 1)	Emodepside 1mg Solution, Fasted (Part 1)	Emodepside 2.5mg Solution, Fasted (Part 1)	Emodepside 5mg Solution, Fasted (Part 1)	Emodepside 5mg Tablet, Fasted (Part 1)	Emodepside 10mg Solution, Fasted (Part 1)	Emodepside 20mg Solution, Fasted (Part 1)	Emodepside 20mg Tablet, Fasted (Part 1)	Emodepside 40mg Solution, Fasted (Part 1)	Emodepside 10mg Solution, Fed (Part 2)	Emodepside 40mg Solution, Fasted, (Part 2)	Placebo Solution, Fasted (Part 1)	Placebo Tablet, Fasted (Part 1)	Placebo Solution, Fed (Part 2)	Placebo Solution, Fasted (Part 2)
Arm/Group Description	Emodepside (BAY 44-4400) 0.1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 2.5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fed state This cohort was not classed as first in human Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Matching placebo of emodepside (BAY 44-4400), solution, administered in fasted state Part one of study (FIH, single ascending dose phase)	Matching placebo of emodepside (BAY 44-4400), tablet, administered in fasted state Part one of study (FIH, single ascending dose phase)	Matching placebo of emodepside (BAY 44-4400), solution, administered in fed state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Matching placebo of emodepside (BAY 44-4400), solution, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)
Measure Participants	1	5	6	6	5	6	6	6	6	6	6	12	4	2	2
Clinically significant hematological changes	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Clinically significant biochemical changes	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Clinically significant serological changes	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Clinically significant coagulation changes	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Clinically significant urinalysis changes	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

6. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

AEs were determined in the Safety Population. Opthalmology examinations were only performed for the Emodepside 40mg group (n=6) and the corresponding placebo group (n=2)

Arm/Group Title	Emodepside 40mg Solution, Fasted, (Part 2)	Placebo Solution, Fasted (Part 2)
Arm/Group Description	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Matching placebo of emodepside (BAY 44-4400), solution, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)
Measure Participants	6	2
Clinically significant occular symptoms	4 400%	0 0%
Clinically significant best corrected vis acuity	1 100%	0 0%
Clinically significant changes in remaining exams	0 0%	0 0%

7. Secondary Outcome

Title	The AUC∞ of Emodepside in Plasma
Description	The area under the plasma drug concentration versus time curve from time zero to infinity (AUC∞)
Time Frame	From pre-dose until 336h post-dose (may be extended to 504h post-dose)

Outcome Measure Data

Analysis Population Description

It is unacceptable to use AUCinf data if>40% of the AUC has been extrapolated.This is in line with literature(Gabrielson&Weiner, 2000).The AUCinf values with<20% of the area extrapolated (reliable results) have not been summarised in the tables because n is either 1 or 2 per treatment (n=2 only for 1m solution).

Arm/Group Title	Emodepside 1mg Solution, Fasted (Part 1)	Emodepside 2.5mg Solution, Fasted (Part 1)	Emodepside 5mg Solution, Fasted (Part 1)	Emodepside 5mg Tablet, Fasted (Part 1)	Emodepside 10mg Solution, Fasted (Part 1)	Emodepside 20mg Solution, Fasted (Part 1)	Emodepside 20mg Tablet, Fasted (Part 1)	Emodepside 40mg Solution, Fasted (Part 1)	Emodepside 10mg Solution, Fed (Part 2)	Emodepside 40mg Solution, Fasted, (Part 2)	Emodepside 0.1mg Solution, Fasted (Part 1)
Arm/Group Description	Emodepside (BAY 44-4400) 1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 2.5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fed state This cohort was not classed as first in human Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 0.1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)
Measure Participants	5	6	6	5	6	6	6	6	6	6	1
Geometric Mean (Standard Deviation) [h*ng/ml]	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

It is unacceptable to use AUCinf data if>40% of the AUC has been extrapolated.This is in line with literature(Gabrielson&Weiner, 2000).The AUCinf values with<20% of the area extrapolated (reliable results) have not been summarised in the tables because n is either 1 or 2 per treatment (n=2 only for 1m solution).

Arm/Group Title	Emodepside 1mg Solution, Fasted (Part 1)	Emodepside 2.5mg Solution, Fasted (Part 1)	Emodepside 5mg Solution, Fasted (Part 1)	Emodepside 5mg Tablet, Fasted (Part 1)	Emodepside 10mg Solution, Fasted (Part 1)	Emodepside 20mg Solution, Fasted (Part 1)	Emodepside 20mg Tablet, Fasted (Part 1)	Emodepside 40mg Solution, Fasted (Part 1)	Emodepside 10mg Solution, Fed (Part 2)	Emodepside 40mg Solution, Fasted, (Part 2)	Emodepside 0.1mg Solution, Fasted (Part 1)
Arm/Group Description	Emodepside (BAY 44-4400) 1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 2.5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fed state This cohort was not classed as first in human Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 0.1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)
Measure Participants	5	6	6	5	6	6	6	6	6	6	1
Number [No values calculated]	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

PK Concentration were summarized using PK concentration population (all subjects who received at least one dose of study drug and for whom a PK sample was analyzed). PK parameters were summarized using the PK Parameter population (all subjects in the PK Concentration Population for whom PK parameters could be derived).

Arm/Group Title	Emodepside 1mg Solution, Fasted (Part 1)	Emodepside 2.5mg Solution, Fasted (Part 1)	Emodepside 5mg Solution, Fasted (Part 1)	Emodepside 5mg Tablet, Fasted (Part 1)	Emodepside 10mg Solution, Fasted (Part 1)	Emodepside 20mg Solution, Fasted (Part 1)	Emodepside 20mg Tablet, Fasted (Part 1)	Emodepside 40mg Solution, Fasted (Part 1)	Emodepside 10mg Solution, Fed (Part 2)	Emodepside 40mg Solution, Fasted, (Part 2)	Emodepside 0.1mg Solution, Fasted (Part 1)
Arm/Group Description	Emodepside (BAY 44-4400) 1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 2.5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fed state This cohort was not classed as first in human Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 0.1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)
Measure Participants	5	6	6	5	6	6	6	6	6	6	0
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	18.6 (20.8)	37.6 (15.5)	92.1 (16.2)	25.7 (23.9)	172 (32.3)	306 (28.7)	30.2 (62.5)	595 (27.9)	71.9 (29.6)	434 (32.7)

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

PK Concentration data were summarized using the PK concentration population (all subjects who received at least one dose of study drug and for whom a PK sample was analyzed). PK parameters were summarized using the PK Parameter population (all subjects in the PK Concentration Population for whom PK parameters could be derived).

Arm/Group Title	Emodepside 1mg Solution, Fasted (Part 1)	Emodepside 2.5mg Solution, Fasted (Part 1)	Emodepside 5mg Solution, Fasted (Part 1)	Emodepside 5mg Tablet, Fasted (Part 1)	Emodepside 10mg Solution, Fasted (Part 1)	Emodepside 20mg Solution, Fasted (Part 1)	Emodepside 20mg Tablet, Fasted (Part 1)	Emodepside 40mg Solution, Fasted (Part 1)	Emodepside 10mg Solution, Fed (Part 2)	Emodepside 40mg Solution, Fasted, (Part 2)	Emodepside 0.1mg Solution, Fasted (Part 1)
Arm/Group Description	Emodepside (BAY 44-4400) 1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 2.5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fed state This cohort was not classed as first in human Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 0.1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)
Measure Participants	5	6	6	5	6	6	6	6	6	6	0
Geometric Mean (Geometric Coefficient of Variation) [(ng/mL)/mg]	18.6 (20.8)	15.0 (15.5)	18.4 (16.2)	5.15 (23.9)	17.2 (32.3)	15.3 (28.7)	1.51 (62.5)	14.9 (27.9)	71.9 (29.6)	10.9 (32.7)

11. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

PK Concentration data were summarized using the PK concentration population (all subjects who received at least one dose of study drug and for whom a PK sample was analyzed). PK parameters were summarized using the PK Parameter population (all subjects in the PK Concentration Population for whom PK parameters could be derived).

Arm/Group Title	Emodepside 1mg Solution, Fasted (Part 1)	Emodepside 2.5mg Solution, Fasted (Part 1)	Emodepside 5mg Solution, Fasted (Part 1)	Emodepside 5mg Tablet, Fasted (Part 1)	Emodepside 10mg Solution, Fasted (Part 1)	Emodepside 20mg Solution, Fasted (Part 1)	Emodepside 20mg Tablet, Fasted (Part 1)	Emodepside 40mg Solution, Fasted (Part 1)	Emodepside 10mg Solution, Fed (Part 2)	Emodepside 40mg Solution, Fasted, (Part 2)	Emodepside 0.1mg Solution, Fasted (Part 1)
Arm/Group Description	Emodepside (BAY 44-4400) 1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 2.5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fed state This cohort was not classed as first in human Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 0.1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)
Measure Participants	5	6	6	5	6	6	6	6	6	6	0
Geometric Mean (Geometric Coefficient of Variation) [(ng/mL)/(mg*kg)]	0.265 (25.1)	0.203 (25.2)	0.244 (18.4)	0.0680 (27.7)	0.233 (46.7)	0.189 (35.7)	0.0187 (69.1)	0.178 (36.3)	0.0882 (28.9)	0.133 (49.7)

12. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

PK Concentration data were summarized using the PK concentration population (all subjects who received at least one dose of study drug and for whom a PK sample was analyzed). PK parameters were summarized using the PK Parameter population (all subjects in the PK Concentration Population for whom PK parameters could be derived)

Arm/Group Title	Emodepside 1mg Solution, Fasted (Part 1)	Emodepside 2.5mg Solution, Fasted (Part 1)	Emodepside 5mg Solution, Fasted (Part 1)	Emodepside 5mg Tablet, Fasted (Part 1)	Emodepside 10mg Solution, Fasted (Part 1)	Emodepside 20mg Solution, Fasted (Part 1)	Emodepside 20mg Tablet, Fasted (Part 1)	Emodepside 40mg Solution, Fasted (Part 1)	Emodepside 10mg Solution, Fed (Part 2)	Emodepside 40mg Solution, Fasted, (Part 2)	Emodepside 0.1mg Solution, Fasted (Part 1)
Arm/Group Description	Emodepside (BAY 44-4400) 1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 2.5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fed state This cohort was not classed as first in human Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 0.1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)
Measure Participants	5	6	6	5	6	6	6	6	6	6	0
Mean (Full Range) [Hours]	1.00	1.00	1.00	2.00	1.00	1.50	2.00	1.05	2.50	0.967

13. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

PK Concentration data were summarized using the PK concentration population (all subjects who received at least one dose of study drug and for whom a PK sample was analyzed). PK parameters were summarized using the PK Parameter population (all subjects in the PK Concentration Population for whom PK parameters could be derived)

Arm/Group Title	Emodepside 1mg Solution, Fasted (Part 1)	Emodepside 2.5mg Solution, Fasted (Part 1)	Emodepside 5mg Solution, Fasted (Part 1)	Emodepside 5mg Tablet, Fasted (Part 1)	Emodepside 10mg Solution, Fasted (Part 1)	Emodepside 20mg Solution, Fasted (Part 1)	Emodepside 20mg Tablet, Fasted (Part 1)	Emodepside 40mg Solution, Fasted (Part 1)	Emodepside 10mg Solution, Fed (Part 2)	Emodepside 40mg Solution, Fasted, (Part 2)	Emodepside 0.1mg Solution, Fasted (Part 1)
Arm/Group Description	Emodepside (BAY 44-4400) 1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 2.5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fed state This cohort was not classed as first in human Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 0.1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)
Measure Participants	5	6	6	5	6	6	6	6	6	6	0
Geometric Mean (Geometric Coefficient of Variation) [Hours]	42.7 (531)	449 (74.0)	415 (117)	267 (392)	365 (286)	590 (68.1)	348 (171)	392 (31.7)	531 (99.3)	440 (49.9)

14. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

PK Concentration data were summarized using the PK concentration population (all subjects who received at least one dose of study drug and for whom a PK sample was analyzed). PK parameters were summarized using the PK Parameter population (all subjects in the PK Concentration Population for whom PK parameters could be derived).

Arm/Group Title	Emodepside 1mg Solution, Fasted (Part 1)	Emodepside 2.5mg Solution, Fasted (Part 1)	Emodepside 5mg Solution, Fasted (Part 1)	Emodepside 5mg Tablet, Fasted (Part 1)	Emodepside 10mg Solution, Fasted (Part 1)	Emodepside 20mg Solution, Fasted (Part 1)	Emodepside 20mg Tablet, Fasted (Part 1)	Emodepside 40mg Solution, Fasted (Part 1)	Emodepside 10mg Solution, Fed (Part 2)	Emodepside 40mg Solution, Fasted, (Part 2)	Emodepside 0.1mg Solution, Fasted (Part 1)
Arm/Group Description	Emodepside (BAY 44-4400) 1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 2.5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fed state This cohort was not classed as first in human Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 0.1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)
Measure Participants	5	6	6	5	6	6	6	6	6	6	0
Geometric Mean (Geometric Coefficient of Variation) [Hours]	52.7 (528)	572 (78.8)	570 (92.1)	337 (430)	533 (232)	757 (69.9)	443 (182)	489 (31.4)	752 (91.7)	569 (52.5)

15. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

PK Concentration data were summarized using the PK concentration population (all subjects who received at least one dose of study drug and for whom a PK sample was analyzed). PK parameters were summarized using the PK Parameter population (all subjects in the PK Concentration Population for whom PK parameters could be derived).

Arm/Group Title	Emodepside 1mg Solution, Fasted (Part 1)	Emodepside 2.5mg Solution, Fasted (Part 1)	Emodepside 5mg Solution, Fasted (Part 1)	Emodepside 5mg Tablet, Fasted (Part 1)	Emodepside 10mg Solution, Fasted (Part 1)	Emodepside 20mg Solution, Fasted (Part 1)	Emodepside 20mg Tablet, Fasted (Part 1)	Emodepside 40mg Solution, Fasted (Part 1)	Emodepside 10mg Solution, Fed (Part 2)	Emodepside 40mg Solution, Fasted, (Part 2)	Emodepside 0.1mg Solution, Fasted (Part 1)
Arm/Group Description	Emodepside (BAY 44-4400) 1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 2.5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fed state This cohort was not classed as first in human Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 0.1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)
Measure Participants	5	6	6	5	6	6	6	6	6	6	0
Geometric Mean (Geometric Coefficient of Variation) [L/hour]	3.88 (151)	1.37 (44.1)	1.34 (57.8)	4.79 (179)	1.42 (115)	1.34 (24.8)	13.3 (150)	1.57 (32.6)	1.42 (57.3)	1.69 (22.1)

16. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

PK Concentration data were summarized using the PK concentration population (all subjects who received at least one dose of study drug and for whom a PK sample was analyzed). PK parameters were summarized using the PK Parameter population (all subjects in the PK Concentration Population for whom PK parameters could be derived).

Arm/Group Title	Emodepside 1mg Solution, Fasted (Part 1)	Emodepside 2.5mg Solution, Fasted (Part 1)	Emodepside 5mg Solution, Fasted (Part 1)	Emodepside 5mg Tablet, Fasted (Part 1)	Emodepside 10mg Solution, Fasted (Part 1)	Emodepside 20mg Solution, Fasted (Part 1)	Emodepside 20mg Tablet, Fasted (Part 1)	Emodepside 40mg Solution, Fasted (Part 1)	Emodepside 10mg Solution, Fed (Part 2)	Emodepside 40mg Solution, Fasted, (Part 2)	Emodepside 0.1mg Solution, Fasted (Part 1)
Arm/Group Description	Emodepside (BAY 44-4400) 1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 2.5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fed state This cohort was not classed as first in human Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 0.1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)
Measure Participants	5	6	6	5	6	6	6	6	6	6	0
Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]	100 (50.4)	250 (6.50)	522 (25.8)	183 (24.3)	996 (21.2)	1910 (16.3)	223 (58.0)	4110 (33.6)	673 (26.4)	3320 (26.0)

17. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

PK Concentration data were summarized using the PK concentration population (all subjects who received at least one dose of study drug and for whom a PK sample was analyzed). PK parameters were summarized using the PK Parameter population (all subjects in the PK Concentration Population for whom PK parameters could be derived).

Arm/Group Title	Emodepside 1mg Solution, Fasted (Part 1)	Emodepside 2.5mg Solution, Fasted (Part 1)	Emodepside 5mg Solution, Fasted (Part 1)	Emodepside 5mg Tablet, Fasted (Part 1)	Emodepside 10mg Solution, Fasted (Part 1)	Emodepside 20mg Solution, Fasted (Part 1)	Emodepside 20mg Tablet, Fasted (Part 1)	Emodepside 40mg Solution, Fasted (Part 1)	Emodepside 10mg Solution, Fed (Part 2)	Emodepside 40mg Solution, Fasted, (Part 2)	Emodepside 0.1mg Solution, Fasted (Part 1)
Arm/Group Description	Emodepside (BAY 44-4400) 1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 2.5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fed state This cohort was not classed as first in human Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 0.1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)
Measure Participants	5	6	6	5	6	6	6	6	6	6	0
Geometric Mean (Geometric Coefficient of Variation) [(h.ng/mL)/mg)]	100 (50.4)	100 (6.50)	104 (25.8)	36.5 (24.3)	99.6 (21.2)	95.3 (16.3)	11.2 (58.0)	103 (33.6)	67.3 (26.4)	82.9 (26.0)

18. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

PK Concentration data were summarized using the PK concentration population (all subjects who received at least one dose of study drug and for whom a PK sample was analyzed). PK parameters were summarized using the PK Parameter population (all subjects in the PK Concentration Population for whom PK parameters could be derived).

Arm/Group Title	Emodepside 1mg Solution, Fasted (Part 1)	Emodepside 2.5mg Solution, Fasted (Part 1)	Emodepside 5mg Solution, Fasted (Part 1)	Emodepside 5mg Tablet, Fasted (Part 1)	Emodepside 10mg Solution, Fasted (Part 1)	Emodepside 20mg Solution, Fasted (Part 1)	Emodepside 20mg Tablet, Fasted (Part 1)	Emodepside 40mg Solution, Fasted (Part 1)	Emodepside 10mg Solution, Fed (Part 2)	Emodepside 40mg Solution, Fasted, (Part 2)	Emodepside 0.1mg Solution, Fasted (Part 1)
Arm/Group Description	Emodepside (BAY 44-4400) 1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 2.5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fed state This cohort was not classed as first in human Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 0.1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)
Measure Participants	5	6	6	5	6	6	6	6	6	6	0
Geometric Mean (Geometric Coefficient of Variation) [(h*ng/mL)/(mg*kg)]	1.43 (58.7)	1.35 (17.5)	1.38 (27.8)	0.483 (28.9)	1.35 (33.8)	1.18 (27.8)	0.138 (66.0)	1.23 (42.9)	0.825 (30.8)	1.01 (45.8)

19. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

PK Concentration data were summarized using the PK concentration population (all subjects who received at least one dose of study drug and for whom a PK sample was analyzed). PK parameters were summarized using the PK Parameter population (all subjects in the PK Concentration Population for whom PK parameters could be derived).

Arm/Group Title	Emodepside 1mg Solution, Fasted (Part 1)	Emodepside 2.5mg Solution, Fasted (Part 1)	Emodepside 5mg Solution, Fasted (Part 1)	Emodepside 5mg Tablet, Fasted (Part 1)	Emodepside 10mg Solution, Fasted (Part 1)	Emodepside 20mg Solution, Fasted (Part 1)	Emodepside 20mg Tablet, Fasted (Part 1)	Emodepside 40mg Solution, Fasted (Part 1)	Emodepside 10mg Solution, Fed (Part 2)	Emodepside 40mg Solution, Fasted, (Part 2)	Emodepside 0.1mg Solution, Fasted (Part 1)
Arm/Group Description	Emodepside (BAY 44-4400) 1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 2.5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fed state This cohort was not classed as first in human Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 0.1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)
Measure Participants	5	6	6	5	6	6	6	6	6	6	0
Geometric Mean (Geometric Coefficient of Variation) [Litres]	239 (88.0)	885 (27.4)	802 (49.1)	1850 (56.1)	748 (68.7)	1140 (47.1)	6700 (40.1)	888 (21.3)	1090 (36.2)	1070 (41.8)

20. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

PK Concentration data were summarized using the PK concentration population (all subjects who received at least one dose of study drug and for whom a PK sample was analyzed). PK parameters were summarized using the PK Parameter population (all subjects in the PK Concentration Population for whom PK parameters could be derived).

Arm/Group Title	Emodepside 1mg Solution, Fasted (Part 1)	Emodepside 2.5mg Solution, Fasted (Part 1)	Emodepside 5mg Solution, Fasted (Part 1)	Emodepside 5mg Tablet, Fasted (Part 1)	Emodepside 10mg Solution, Fasted (Part 1)	Emodepside 20mg Solution, Fasted (Part 1)	Emodepside 20mg Tablet, Fasted (Part 1)	Emodepside 40mg Solution, Fasted (Part 1)	Emodepside 10mg Solution, Fed (Part 2)	Emodepside 40mg Solution, Fasted, (Part 2)	Emodepside 0.1mg Solution, Fasted (Part 1)
Arm/Group Description	Emodepside (BAY 44-4400) 1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 2.5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fed state This cohort was not classed as first in human Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 0.1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)
Measure Participants	5	6	6	5	6	6	6	6	6	6	0
Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]	182 (111)	845 (10.4)	1700 (24.2)	501 (76.8)	3070 (27.7)	7480 (22.1)	667 (125)	16400 (23.6)	3390 (20.4)	13800 (23.4)

21. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

PK Concentration data were summarized using the PK concentration population (all subjects who received at least one dose of study drug and for whom a PK sample was analyzed). PK parameters were summarized using the PK Parameter population (all subjects in the PK Concentration Population for whom PK parameters could be derived).

Arm/Group Title	Emodepside 5mg Solution Versus Tablet, Fasted (Part 1)	Emodepside 20mg Solution Versus Tablet, Fasted (Part 1)
Arm/Group Description	Emodepside (BAY 44-4400) 5mg solution versus tablet, administered in fasted state Part one of study	Emodepside (BAY 44-4400) 20mg solution versus tablet, administered in fasted state Part one of study
Measure Participants	5	6
Number (90% Confidence Interval) [Frel percentage]	35.0	11.7

22. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

PK Concentration data were summarized using the PK concentration population (all subjects who received at least one dose of study drug and for whom a PK sample was analyzed). PK parameters were summarized using the PK Parameter population (all subjects in the PK Concentration Population for whom PK parameters could be derived).

Arm/Group Title	Emodepside 1mg Solution, Fasted (Part 1)	Emodepside 2.5mg Solution, Fasted (Part 1)	Emodepside 5mg Solution, Fasted (Part 1)	Emodepside 5mg Tablet, Fasted (Part 1)	Emodepside 10mg Solution, Fasted (Part 1)	Emodepside 20mg Solution, Fasted (Part 1)	Emodepside 20mg Tablet, Fasted (Part 1)	Emodepside 40mg Solution, Fasted (Part 1)	Emodepside 10mg Solution, Fed (Part 2)	Emodepside 40mg Solution, Fasted, (Part 2)	Emodepside 0.1mg Solution, Fasted (Part 1)
Arm/Group Description	Emodepside (BAY 44-4400) 1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 2.5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 5mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 20mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fed state This cohort was not classed as first in human Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)	Emodepside (BAY 44-4400) 0.1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)
Measure Participants	5	6	6	5	6	6	6	6	6	6	0
Geometric Mean (Geometric Coefficient of Variation) [(h*ng/mL)/(mg*kg)]	2.60 (127)	4.56 (19.5)	4.50 (27.1)	1.33 (78.4)	4.17 (42.6)	4.62 (30.8)	0.414 (138)	4.91 (36.5)	4.16 (25.5)	4.21 (42.6)

23. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

emodepside assessed in fasted condition: only one cohort (10mg solution) assessed with high fat high calories meal.

Arm/Group Title	Emodepside 10mg Solution Fasted	Emodepside 10mg Solution Fed
Arm/Group Description	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fasted state	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fed state
Measure Participants	6	6
Least Squares Mean (Full Range) [ng/ml]	172	71.9

24. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

emodepside assessed in fasted condition: only one cohort (10mg solution) assessed with high fat high calories meal.

Arm/Group Title	Emodepside 10mg Solution Fasted	Emodepside 10mg Solution Fed
Arm/Group Description	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fasted state	Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fed state
Measure Participants	6	6
Least Squares Mean (Full Range) [ng*h/mL]	996	673

Adverse Events

Time Frame	The AE reporting period for this trial began after subject enrolment in the trial (after signature of informed consent) and ended at the follow-up visit (3 weeks after their dose of study medicine) .
Arm/Group Title	Emodepside 0.1mg Solution, Fasted (Part 1)		Emodepside 1mg Solution, Fasted (Part 1)		Emodepside 2.5mg Solution, Fasted (Part 1)		Emodepside 5mg Solution, Fasted (Part 1)		Emodepside 5mg Tablet, Fasted (Part 1)		Emodepside 10mg Solution, Fasted (Part 1)		Emodepside 20mg Solution, Fasted (Part 1)		Emodepside 20mg Tablet, Fasted (Part 1)		Emodepside 40mg Solution, Fasted (Part 1)		Emodepside 10mg Solution, Fed (Part 2)		Emodepside 40mg Solution, Fasted, (Part 2)		Placebo Solution, Fasted (Part 1)		Placebo Tablet, Fasted (Part 1)		Placebo Solution, Fed (Part 2)		Placebo Solution, Fasted (Part 2)
Arm/Group Description	Emodepside (BAY 44-4400) 0.1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)		Emodepside (BAY 44-4400) 1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)		Emodepside (BAY 44-4400) 2.5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)		Emodepside (BAY 44-4400) 5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)		Emodepside (BAY 44-4400) 5mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)		Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)		Emodepside (BAY 44-4400) 20mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)		Emodepside (BAY 44-4400) 20mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase)		Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase)		Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fed state This cohort was not classed as first in human Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)		Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)		Matching placebo of emodepside (BAY 44-4400), solution, administered in fasted state Part one of study (FIH, single ascending dose phase)		Matching placebo of emodepside (BAY 44-4400), tablet, administered in fasted state Part one of study (FIH, single ascending dose phase)		Matching placebo of emodepside (BAY 44-4400), solution, administered in fed state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)		Matching placebo of emodepside (BAY 44-4400), solution, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events)
All Cause Mortality
	Emodepside 0.1mg Solution, Fasted (Part 1)		Emodepside 1mg Solution, Fasted (Part 1)		Emodepside 2.5mg Solution, Fasted (Part 1)		Emodepside 5mg Solution, Fasted (Part 1)		Emodepside 5mg Tablet, Fasted (Part 1)		Emodepside 10mg Solution, Fasted (Part 1)		Emodepside 20mg Solution, Fasted (Part 1)		Emodepside 20mg Tablet, Fasted (Part 1)		Emodepside 40mg Solution, Fasted (Part 1)		Emodepside 10mg Solution, Fed (Part 2)		Emodepside 40mg Solution, Fasted, (Part 2)		Placebo Solution, Fasted (Part 1)		Placebo Tablet, Fasted (Part 1)		Placebo Solution, Fed (Part 2)		Placebo Solution, Fasted (Part 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/12 (0%)		0/4 (0%)		0/2 (0%)		0/2 (0%)
Serious Adverse Events
	Emodepside 0.1mg Solution, Fasted (Part 1)		Emodepside 1mg Solution, Fasted (Part 1)		Emodepside 2.5mg Solution, Fasted (Part 1)		Emodepside 5mg Solution, Fasted (Part 1)		Emodepside 5mg Tablet, Fasted (Part 1)		Emodepside 10mg Solution, Fasted (Part 1)		Emodepside 20mg Solution, Fasted (Part 1)		Emodepside 20mg Tablet, Fasted (Part 1)		Emodepside 40mg Solution, Fasted (Part 1)		Emodepside 10mg Solution, Fed (Part 2)		Emodepside 40mg Solution, Fasted, (Part 2)		Placebo Solution, Fasted (Part 1)		Placebo Tablet, Fasted (Part 1)		Placebo Solution, Fed (Part 2)		Placebo Solution, Fasted (Part 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/12 (0%)		0/4 (0%)		0/2 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Emodepside 0.1mg Solution, Fasted (Part 1)		Emodepside 1mg Solution, Fasted (Part 1)		Emodepside 2.5mg Solution, Fasted (Part 1)		Emodepside 5mg Solution, Fasted (Part 1)		Emodepside 5mg Tablet, Fasted (Part 1)		Emodepside 10mg Solution, Fasted (Part 1)		Emodepside 20mg Solution, Fasted (Part 1)		Emodepside 20mg Tablet, Fasted (Part 1)		Emodepside 40mg Solution, Fasted (Part 1)		Emodepside 10mg Solution, Fed (Part 2)		Emodepside 40mg Solution, Fasted, (Part 2)		Placebo Solution, Fasted (Part 1)		Placebo Tablet, Fasted (Part 1)		Placebo Solution, Fed (Part 2)		Placebo Solution, Fasted (Part 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		3/5 (60%)		0/6 (0%)		3/6 (50%)		3/5 (60%)		5/6 (83.3%)		3/6 (50%)		2/6 (33.3%)		5/6 (83.3%)		3/6 (50%)		5/6 (83.3%)		5/12 (41.7%)		1/4 (25%)		0/2 (0%)		0/2 (0%)
Eye disorders
TEAEs by primary system organ classes (SOCs)	0/1 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		1/5 (20%)		2/6 (33.3%)		1/6 (16.7%)		0/6 (0%)		5/6 (83.3%)		0/6 (0%)		5/6 (83.3%)		0/12 (0%)		1/4 (25%)		0/2 (0%)		0/2 (0%)
Gastrointestinal disorders
TEAEs by primary system organ classes (SOCs)	0/1 (0%)		0/5 (0%)		0/6 (0%)		1/6 (16.7%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		3/6 (50%)		1/12 (8.3%)		1/4 (25%)		0/2 (0%)		0/2 (0%)
General disorders
TEAEs by primary system organ classes (SOCs)	0/1 (0%)		0/5 (0%)		0/6 (0%)		2/6 (33.3%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		3/6 (50%)		0/12 (0%)		0/4 (0%)		0/2 (0%)		0/2 (0%)
Infections and infestations
TEAEs by primary system organ classes (SOCs)	1/1 (100%)		0/5 (0%)		0/6 (0%)		1/6 (16.7%)		0/5 (0%)		1/6 (16.7%)		1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		5/6 (83.3%)		0/12 (0%)		0/4 (0%)		0/2 (0%)		0/2 (0%)
Injury, poisoning and procedural complications
TEAEs by primary system organ classes (SOCs)	0/1 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/12 (8.3%)		0/4 (0%)		0/2 (0%)		0/2 (0%)
Musculoskeletal and connective tissue disorders
TEAEs by primary system organ classes (SOCs)	0/1 (0%)		1/5 (20%)		0/6 (0%)		1/6 (16.7%)		1/5 (20%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)		0/12 (0%)		0/4 (0%)		0/2 (0%)		0/2 (0%)
Nervous system disorders
TEAEs by primary system organ classes (SOCs)	0/1 (0%)		2/5 (40%)		0/6 (0%)		1/6 (16.7%)		1/5 (20%)		1/6 (16.7%)		1/6 (16.7%)		1/6 (16.7%)		3/6 (50%)		2/6 (33.3%)		4/6 (66.7%)		2/12 (16.7%)		0/4 (0%)		0/2 (0%)		0/2 (0%)
Psychiatric disorders
TEAEs by primary system organ classes (SOCs)	0/1 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		1/5 (20%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/12 (0%)		0/4 (0%)		0/2 (0%)		0/2 (0%)
Respiratory, thoracic and mediastinal disorders
TEAEs by primary system organ classes (SOCs)	0/1 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/5 (0%)		1/6 (16.7%)		1/6 (16.7%)		1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)		1/12 (8.3%)		0/4 (0%)		0/2 (0%)		0/2 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Institution (HMR) could not make any public communication related to the Results or Trial Subjects, notably, without DNDi's prior written approval. The Institution shall inform DNDi in advance of any media visits to the Clinical Trial site and comply with the guidance provided by DNDi.