Healthy Volunteers
Conditions
Keywords
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
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.
Interventions
DRUGplacebo
Sponsors
Bayer
Bill and Melinda Gates Foundation
Drugs for Neglected Diseases
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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 |
| 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, |
| 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. |
| 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 |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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∞ |
| 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 |
| 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 |
| 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) |
| 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∞) |
| 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 |
| 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 |
| 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)) |
| 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. |
| 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. |
| 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 |
| 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. |
| 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 |
| 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 |
| 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) |
| 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 |
Countries
United Kingdom
Participant flow
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| Emodepside 0.1mg Solution, Fasted (Part 1) 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) | 1 |
| Emodepside 1mg Solution, Fasted (Part 1) Emodepside (BAY 44-4400) 1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) | 5 |
| Emodepside 2.5mg Solution, Fasted (Part 1) 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) | 6 |
| Emodepside 5mg Solution, Fasted (Part 1) Emodepside (BAY 44-4400) 5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) | 6 |
| Emodepside 5mg Tablet, Fasted (Part 1) Emodepside (BAY 44-4400) 5mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase) | 5 |
| Emodepside 10mg Solution, Fasted (Part 1) Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) | 6 |
| Emodepside 20mg Solution, Fasted (Part 1) Emodepside (BAY 44-4400) 20mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) | 6 |
| Emodepside 20mg Tablet, Fasted (Part 1) Emodepside (BAY 44-4400) 20mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase) | 6 |
| Emodepside 40mg Solution, Fasted (Part 1) Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) | 6 |
| Placebo Solution, Fasted (Part 1) Matching placebo of emodepside (BAY 44-4400), solution, administered in fasted state Part one of study (FIH, single ascending dose phase) | 12 |
| Placebo Tablet, Fasted (Part 1) Matching placebo of emodepside (BAY 44-4400), tablet, administered in fasted state Part one of study (FIH, single ascending dose phase) | 4 |
| Emodepside 10mg Solution, Fed (Part 2) 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) | 6 |
| Emodepside 40mg Solution, Fasted, AE Follow-up Arm (Part 2) 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) | 6 |
| Placebo Solution, Fed (Part 2) 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) | 2 |
| Placebo Solution, Fasted (Part 2) 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) | 2 |
| Total | 79 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1 | Protocol Violation | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | 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) | Total | 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) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous Part 1 | 23 years STANDARD_DEVIATION 0 | 38.6 years STANDARD_DEVIATION 10.06 | 34.8 years STANDARD_DEVIATION 9.2 | 29.3 years STANDARD_DEVIATION 8.12 | 36.8 years STANDARD_DEVIATION 10.69 | 34.2 years STANDARD_DEVIATION 10.55 | 32.8 years STANDARD_DEVIATION 9.75 | 31.3 years STANDARD_DEVIATION 8.91 | 30.8 years STANDARD_DEVIATION 10.83 | 30.7 years STANDARD_DEVIATION 7.46 | 28.0 years STANDARD_DEVIATION 3.56 | 32.4 years STANDARD_DEVIATION 8.89 | — | — | — | — |
| Age, Continuous Part 2 | — | — | — | — | — | — | — | — | — | — | — | 38.3 years STANDARD_DEVIATION 13.67 | 27.7 years STANDARD_DEVIATION 7.34 | 38.5 years STANDARD_DEVIATION 10.67 | 51.5 years STANDARD_DEVIATION 0.71 | 40 years STANDARD_DEVIATION 11.31 |
| BMI Part 1 | 24.10 kg/m^2 STANDARD_DEVIATION 0 | 22.60 kg/m^2 STANDARD_DEVIATION 2.117 | 23.30 kg/m^2 STANDARD_DEVIATION 2.683 | 24.65 kg/m^2 STANDARD_DEVIATION 1.162 | 24.20 kg/m^2 STANDARD_DEVIATION 1.707 | 23.75 kg/m^2 STANDARD_DEVIATION 2.868 | 25.55 kg/m^2 STANDARD_DEVIATION 2.651 | 25.43 kg/m^2 STANDARD_DEVIATION 3.169 | 24.72 kg/m^2 STANDARD_DEVIATION 2.613 | 24.49 kg/m^2 STANDARD_DEVIATION 2.131 | 25.38 kg/m^2 STANDARD_DEVIATION 2.291 | 24.41 kg/m^2 STANDARD_DEVIATION 2.356 | — | — | — | — |
| BMI Part 2 | — | — | — | — | — | — | — | — | — | — | — | 25.21 kg/m^2 STANDARD_DEVIATION 3.117 | 24.5 kg/m^2 STANDARD_DEVIATION 2.137 | 26.55 kg/m^2 STANDARD_DEVIATION 3.213 | 23.1 kg/m^2 STANDARD_DEVIATION 2.83 | 25.4 kg/m^2 STANDARD_DEVIATION 6.36 |
| Ethnicity (NIH/OMB) Part 1 Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants | — | — | — | — |
| Ethnicity (NIH/OMB) Part 1 Not Hispanic or Latino | 1 Participants | 5 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 5 Participants | 6 Participants | 6 Participants | 11 Participants | 3 Participants | 60 Participants | — | — | — | — |
| Ethnicity (NIH/OMB) Part 1 Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — | — | — |
| Ethnicity (NIH/OMB) Part 2 Hispanic or Latino | — | — | — | — | — | — | — | — | — | — | — | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Part 2 Not Hispanic or Latino | — | — | — | — | — | — | — | — | — | — | — | 15 Participants | 5 Participants | 6 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Part 2 Unknown or Not Reported | — | — | — | — | — | — | — | — | — | — | — | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height Part 1 | 173 cm STANDARD_DEVIATION 0 | 176.8 cm STANDARD_DEVIATION 4.87 | 179.8 cm STANDARD_DEVIATION 6.24 | 175.5 cm STANDARD_DEVIATION 5.82 | 177.2 cm STANDARD_DEVIATION 10.87 | 177.2 cm STANDARD_DEVIATION 3.54 | 179.0 cm STANDARD_DEVIATION 7.51 | 179.5 cm STANDARD_DEVIATION 7.45 | 183.3 cm STANDARD_DEVIATION 7.63 | 180.0 cm STANDARD_DEVIATION 7.98 | 183.3 cm STANDARD_DEVIATION 2.99 | 179.1 cm STANDARD_DEVIATION 6.89 | — | — | — | — |
| Height Part 2 | — | — | — | — | — | — | — | — | — | — | — | 179.6 cm STANDARD_DEVIATION 6.28 | 183.2 cm STANDARD_DEVIATION 6.37 | 176.0 cm STANDARD_DEVIATION 5.22 | 178 cm STANDARD_DEVIATION 8.49 | 181 cm STANDARD_DEVIATION 4.24 |
| Race (NIH/OMB) Part 1 American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — | — | — |
| Race (NIH/OMB) Part 1 Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — | — | — |
| Race (NIH/OMB) Part 1 Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — | — | — |
| Race (NIH/OMB) Part 1 More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — | — | — |
| Race (NIH/OMB) Part 1 Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — | — | — |
| Race (NIH/OMB) Part 1 Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — | — | — |
| Race (NIH/OMB) Part 1 White | 1 Participants | 5 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 12 Participants | 4 Participants | 63 Participants | — | — | — | — |
| Race (NIH/OMB) Part 2 American Indian or Alaska Native | — | — | — | — | — | — | — | — | — | — | — | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Part 2 Asian | — | — | — | — | — | — | — | — | — | — | — | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Part 2 Black or African American | — | — | — | — | — | — | — | — | — | — | — | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Part 2 More than one race | — | — | — | — | — | — | — | — | — | — | — | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Part 2 Native Hawaiian or Other Pacific Islander | — | — | — | — | — | — | — | — | — | — | — | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Part 2 Unknown or Not Reported | — | — | — | — | — | — | — | — | — | — | — | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Part 2 White | — | — | — | — | — | — | — | — | — | — | — | 16 Participants | 6 Participants | 6 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Part 1 Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — | — | — |
| Sex: Female, Male Part 1 Male | 1 Participants | 5 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 12 Participants | 4 Participants | 63 Participants | — | — | — | — |
| Sex: Female, Male Part 2 Female | — | — | — | — | — | — | — | — | — | — | — | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Part 2 Male | — | — | — | — | — | — | — | — | — | — | — | 16 Participants | 6 Participants | 6 Participants | 2 Participants | 2 Participants |
| Weight Part 1 | 72.00 kg STANDARD_DEVIATION 0 | 70.64 kg STANDARD_DEVIATION 6.815 | 75.47 kg STANDARD_DEVIATION 11.331 | 75.83 kg STANDARD_DEVIATION 3.506 | 76.56 kg STANDARD_DEVIATION 13.197 | 74.80 kg STANDARD_DEVIATION 11.383 | 81.93 kg STANDARD_DEVIATION 10.397 | 81.73 kg STANDARD_DEVIATION 9.075 | 83.27 kg STANDARD_DEVIATION 11.267 | 79.52 kg STANDARD_DEVIATION 10.13 | 85.15 kg STANDARD_DEVIATION 7.217 | 78.43 kg STANDARD_DEVIATION 9.931 | — | — | — | — |
| Weight Part 2 | — | — | — | — | — | — | — | — | — | — | — | 81.38 kg STANDARD_DEVIATION 11.636 | 82.20 kg STANDARD_DEVIATION 7.979 | 82.65 kg STANDARD_DEVIATION 13.598 | 72.8 kg STANDARD_DEVIATION 1.98 | 83.7 kg STANDARD_DEVIATION 24.75 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 12 | 0 / 4 | 0 / 2 | 0 / 2 |
| other Total, other adverse events | 1 / 1 | 3 / 5 | 0 / 6 | 3 / 6 | 3 / 5 | 5 / 6 | 3 / 6 | 2 / 6 | 5 / 6 | 3 / 6 | 5 / 6 | 5 / 12 | 1 / 4 | 0 / 2 | 0 / 2 |
| serious Total, serious adverse events | 0 / 1 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 12 | 0 / 4 | 0 / 2 | 0 / 2 |
Outcome results
Primary
Safety and Tolerability as Measured by 12-lead ECG
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)
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Emodepside 0.1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in PR interval | 0 participants |
| Emodepside 0.1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in ventricular rate | 0 participants |
| Emodepside 0.1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QTcF interval | 0 participants |
| Emodepside 0.1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QTcB | 0 participants |
| Emodepside 0.1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QRS interval | 0 participants |
| Emodepside 1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in ventricular rate | 0 participants |
| Emodepside 1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QRS interval | 0 participants |
| Emodepside 1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QTcF interval | 0 participants |
| Emodepside 1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in PR interval | 0 participants |
| Emodepside 1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QTcB | 0 participants |
| Emodepside 2.5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in ventricular rate | 0 participants |
| Emodepside 2.5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in PR interval | 0 participants |
| Emodepside 2.5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QRS interval | 0 participants |
| Emodepside 2.5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QTcF interval | 0 participants |
| Emodepside 2.5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QTcB | 0 participants |
| Emodepside 5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QRS interval | 0 participants |
| Emodepside 5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in ventricular rate | 0 participants |
| Emodepside 5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QTcB | 0 participants |
| Emodepside 5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QTcF interval | 0 participants |
| Emodepside 5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in PR interval | 0 participants |
| Emodepside 5mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in ventricular rate | 0 participants |
| Emodepside 5mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QTcF interval | 0 participants |
| Emodepside 5mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in PR interval | 0 participants |
| Emodepside 5mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QRS interval | 0 participants |
| Emodepside 5mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QTcB | 0 participants |
| Emodepside 10mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QTcB | 0 participants |
| Emodepside 10mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in PR interval | 0 participants |
| Emodepside 10mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QTcF interval | 0 participants |
| Emodepside 10mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in ventricular rate | 0 participants |
| Emodepside 10mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QRS interval | 0 participants |
| Emodepside 20mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QRS interval | 0 participants |
| Emodepside 20mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in ventricular rate | 0 participants |
| Emodepside 20mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QTcB | 0 participants |
| Emodepside 20mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in PR interval | 0 participants |
| Emodepside 20mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QTcF interval | 0 participants |
| Emodepside 20mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QRS interval | 0 participants |
| Emodepside 20mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QTcF interval | 0 participants |
| Emodepside 20mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in PR interval | 0 participants |
| Emodepside 20mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QTcB | 0 participants |
| Emodepside 20mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in ventricular rate | 0 participants |
| Emodepside 40mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QTcF interval | 0 participants |
| Emodepside 40mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in ventricular rate | 0 participants |
| Emodepside 40mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in PR interval | 0 participants |
| Emodepside 40mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QRS interval | 0 participants |
| Emodepside 40mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QTcB | 0 participants |
| Emodepside 10mg Solution, Fed (Part 2) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in PR interval | 0 participants |
| Emodepside 10mg Solution, Fed (Part 2) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QRS interval | 0 participants |
| Emodepside 10mg Solution, Fed (Part 2) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in ventricular rate | 0 participants |
| Emodepside 10mg Solution, Fed (Part 2) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QTcF interval | 0 participants |
| Emodepside 10mg Solution, Fed (Part 2) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QTcB | 0 participants |
| Emodepside 40mg Solution, Fasted, (Part 2) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QTcB | 0 participants |
| Emodepside 40mg Solution, Fasted, (Part 2) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in PR interval | 0 participants |
| Emodepside 40mg Solution, Fasted, (Part 2) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in ventricular rate | 0 participants |
| Emodepside 40mg Solution, Fasted, (Part 2) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QTcF interval | 0 participants |
| Emodepside 40mg Solution, Fasted, (Part 2) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QRS interval | 0 participants |
| Placebo Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QTcB | 0 participants |
| Placebo Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in ventricular rate | 0 participants |
| Placebo Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in PR interval | 0 participants |
| Placebo Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QRS interval | 0 participants |
| Placebo Solution, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QTcF interval | 0 participants |
| Placebo Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in ventricular rate | 0 participants |
| Placebo Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QTcF interval | 0 participants |
| Placebo Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in PR interval | 0 participants |
| Placebo Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QTcB | 0 participants |
| Placebo Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QRS interval | 0 participants |
| Placebo Solution, Fed (Part 2) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QTcB | 0 participants |
| Placebo Solution, Fed (Part 2) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QRS interval | 0 participants |
| Placebo Solution, Fed (Part 2) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in PR interval | 0 participants |
| Placebo Solution, Fed (Part 2) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in ventricular rate | 0 participants |
| Placebo Solution, Fed (Part 2) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QTcF interval | 0 participants |
| Placebo Solution, Fasted (Part 2) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in PR interval | 0 participants |
| Placebo Solution, Fasted (Part 2) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QTcF interval | 0 participants |
| Placebo Solution, Fasted (Part 2) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QRS interval | 0 participants |
| Placebo Solution, Fasted (Part 2) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in ventricular rate | 0 participants |
| Placebo Solution, Fasted (Part 2) | Safety and Tolerability as Measured by 12-lead ECG | Notable changes in QTcB | 0 participants |
Primary
Safety and Tolerability as Measured by Adverse Events
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)
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Emodepside 0.1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Subjects with SAE | 0 participants |
| Emodepside 0.1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Deaths | 0 participants |
| Emodepside 0.1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Subjects with TEAE | 1 participants |
| Emodepside 1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Subjects with TEAE | 3 participants |
| Emodepside 1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Deaths | 0 participants |
| Emodepside 1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Subjects with SAE | 0 participants |
| Emodepside 2.5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Subjects with TEAE | 0 participants |
| Emodepside 2.5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Deaths | 0 participants |
| Emodepside 2.5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Subjects with SAE | 0 participants |
| Emodepside 5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Subjects with TEAE | 3 participants |
| Emodepside 5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Deaths | 0 participants |
| Emodepside 5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Subjects with SAE | 0 participants |
| Emodepside 5mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Subjects with SAE | 0 participants |
| Emodepside 5mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Deaths | 0 participants |
| Emodepside 5mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Subjects with TEAE | 3 participants |
| Emodepside 10mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Subjects with SAE | 0 participants |
| Emodepside 10mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Deaths | 0 participants |
| Emodepside 10mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Subjects with TEAE | 5 participants |
| Emodepside 20mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Subjects with TEAE | 3 participants |
| Emodepside 20mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Deaths | 0 participants |
| Emodepside 20mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Subjects with SAE | 0 participants |
| Emodepside 20mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Subjects with SAE | 0 participants |
| Emodepside 20mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Deaths | 0 participants |
| Emodepside 20mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Subjects with TEAE | 2 participants |
| Emodepside 40mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Deaths | 0 participants |
| Emodepside 40mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Subjects with SAE | 0 participants |
| Emodepside 40mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Subjects with TEAE | 5 participants |
| Emodepside 10mg Solution, Fed (Part 2) | Safety and Tolerability as Measured by Adverse Events | Subjects with SAE | 0 participants |
| Emodepside 10mg Solution, Fed (Part 2) | Safety and Tolerability as Measured by Adverse Events | Deaths | 0 participants |
| Emodepside 10mg Solution, Fed (Part 2) | Safety and Tolerability as Measured by Adverse Events | Subjects with TEAE | 3 participants |
| Emodepside 40mg Solution, Fasted, (Part 2) | Safety and Tolerability as Measured by Adverse Events | Subjects with SAE | 0 participants |
| Emodepside 40mg Solution, Fasted, (Part 2) | Safety and Tolerability as Measured by Adverse Events | Deaths | 0 participants |
| Emodepside 40mg Solution, Fasted, (Part 2) | Safety and Tolerability as Measured by Adverse Events | Subjects with TEAE | 5 participants |
| Placebo Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Subjects with TEAE | 5 participants |
| Placebo Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Subjects with SAE | 0 participants |
| Placebo Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Deaths | 0 participants |
| Placebo Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Subjects with SAE | 0 participants |
| Placebo Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Deaths | 0 participants |
| Placebo Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Adverse Events | Subjects with TEAE | 1 participants |
| Placebo Solution, Fed (Part 2) | Safety and Tolerability as Measured by Adverse Events | Deaths | 0 participants |
| Placebo Solution, Fed (Part 2) | Safety and Tolerability as Measured by Adverse Events | Subjects with TEAE | 0 participants |
| Placebo Solution, Fed (Part 2) | Safety and Tolerability as Measured by Adverse Events | Subjects with SAE | 0 participants |
| Placebo Solution, Fasted (Part 2) | Safety and Tolerability as Measured by Adverse Events | Subjects with SAE | 0 participants |
| Placebo Solution, Fasted (Part 2) | Safety and Tolerability as Measured by Adverse Events | Subjects with TEAE | 0 participants |
| Placebo Solution, Fasted (Part 2) | Safety and Tolerability as Measured by Adverse Events | Deaths | 0 participants |
Primary
Safety and Tolerability as Measured by Clinical Laboratory Parameters
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)
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Emodepside 0.1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant coagulation changes | 0 participants |
| Emodepside 0.1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant serological changes | 0 participants |
| Emodepside 0.1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant urinalysis changes | 0 participants |
| Emodepside 0.1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant hematological changes | 0 participants |
| Emodepside 0.1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant biochemical changes | 0 participants |
| Emodepside 1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant biochemical changes | 0 participants |
| Emodepside 1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant urinalysis changes | 0 participants |
| Emodepside 1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant coagulation changes | 0 participants |
| Emodepside 1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant hematological changes | 0 participants |
| Emodepside 1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant serological changes | 0 participants |
| Emodepside 2.5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant coagulation changes | 0 participants |
| Emodepside 2.5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant hematological changes | 0 participants |
| Emodepside 2.5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant urinalysis changes | 0 participants |
| Emodepside 2.5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant biochemical changes | 0 participants |
| Emodepside 2.5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant serological changes | 0 participants |
| Emodepside 5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant coagulation changes | 0 participants |
| Emodepside 5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant biochemical changes | 0 participants |
| Emodepside 5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant urinalysis changes | 0 participants |
| Emodepside 5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant hematological changes | 0 participants |
| Emodepside 5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant serological changes | 0 participants |
| Emodepside 5mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant coagulation changes | 0 participants |
| Emodepside 5mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant hematological changes | 0 participants |
| Emodepside 5mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant biochemical changes | 0 participants |
| Emodepside 5mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant urinalysis changes | 0 participants |
| Emodepside 5mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant serological changes | 0 participants |
| Emodepside 10mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant urinalysis changes | 0 participants |
| Emodepside 10mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant hematological changes | 0 participants |
| Emodepside 10mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant biochemical changes | 0 participants |
| Emodepside 10mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant coagulation changes | 0 participants |
| Emodepside 10mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant serological changes | 0 participants |
| Emodepside 20mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant serological changes | 0 participants |
| Emodepside 20mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant urinalysis changes | 0 participants |
| Emodepside 20mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant biochemical changes | 0 participants |
| Emodepside 20mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant hematological changes | 0 participants |
| Emodepside 20mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant coagulation changes | 0 participants |
| Emodepside 20mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant coagulation changes | 0 participants |
| Emodepside 20mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant hematological changes | 0 participants |
| Emodepside 20mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant biochemical changes | 0 participants |
| Emodepside 20mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant serological changes | 0 participants |
| Emodepside 20mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant urinalysis changes | 0 participants |
| Emodepside 40mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant hematological changes | 0 participants |
| Emodepside 40mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant biochemical changes | 0 participants |
| Emodepside 40mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant serological changes | 0 participants |
| Emodepside 40mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant coagulation changes | 0 participants |
| Emodepside 40mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant urinalysis changes | 0 participants |
| Emodepside 10mg Solution, Fed (Part 2) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant coagulation changes | 0 participants |
| Emodepside 10mg Solution, Fed (Part 2) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant hematological changes | 0 participants |
| Emodepside 10mg Solution, Fed (Part 2) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant serological changes | 0 participants |
| Emodepside 10mg Solution, Fed (Part 2) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant urinalysis changes | 0 participants |
| Emodepside 10mg Solution, Fed (Part 2) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant biochemical changes | 0 participants |
| Emodepside 40mg Solution, Fasted, (Part 2) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant hematological changes | 0 participants |
| Emodepside 40mg Solution, Fasted, (Part 2) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant coagulation changes | 0 participants |
| Emodepside 40mg Solution, Fasted, (Part 2) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant urinalysis changes | 0 participants |
| Emodepside 40mg Solution, Fasted, (Part 2) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant serological changes | 0 participants |
| Emodepside 40mg Solution, Fasted, (Part 2) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant biochemical changes | 0 participants |
| Placebo Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant serological changes | 0 participants |
| Placebo Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant urinalysis changes | 0 participants |
| Placebo Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant biochemical changes | 0 participants |
| Placebo Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant coagulation changes | 0 participants |
| Placebo Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant hematological changes | 0 participants |
| Placebo Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant coagulation changes | 0 participants |
| Placebo Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant biochemical changes | 0 participants |
| Placebo Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant hematological changes | 0 participants |
| Placebo Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant urinalysis changes | 0 participants |
| Placebo Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant serological changes | 0 participants |
| Placebo Solution, Fed (Part 2) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant coagulation changes | 0 participants |
| Placebo Solution, Fed (Part 2) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant urinalysis changes | 0 participants |
| Placebo Solution, Fed (Part 2) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant biochemical changes | 0 participants |
| Placebo Solution, Fed (Part 2) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant hematological changes | 0 participants |
| Placebo Solution, Fed (Part 2) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant serological changes | 0 participants |
| Placebo Solution, Fasted (Part 2) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant coagulation changes | 0 participants |
| Placebo Solution, Fasted (Part 2) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant biochemical changes | 0 participants |
| Placebo Solution, Fasted (Part 2) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant serological changes | 0 participants |
| Placebo Solution, Fasted (Part 2) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant hematological changes | 0 participants |
| Placebo Solution, Fasted (Part 2) | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinically significant urinalysis changes | 0 participants |
Primary
Safety and Tolerability as Measured by Ophthalmological Examination Findings in One Study Arm Only
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)
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Emodepside 0.1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Ophthalmological Examination Findings in One Study Arm Only | Clinically significant occular symptoms | 4 participants |
| Emodepside 0.1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Ophthalmological Examination Findings in One Study Arm Only | Clinically significant best corrected vis acuity | 1 participants |
| Emodepside 0.1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Ophthalmological Examination Findings in One Study Arm Only | Clinically significant changes in remaining exams | 0 participants |
| Emodepside 1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Ophthalmological Examination Findings in One Study Arm Only | Clinically significant occular symptoms | 0 participants |
| Emodepside 1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Ophthalmological Examination Findings in One Study Arm Only | Clinically significant best corrected vis acuity | 0 participants |
| Emodepside 1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Ophthalmological Examination Findings in One Study Arm Only | Clinically significant changes in remaining exams | 0 participants |
Primary
Safety and Tolerability as Measured by Physical and Neurological Examination Findings
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)
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Emodepside 0.1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal physcial examination | 0 participants |
| Emodepside 0.1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Neurological examination reported as AE | 0 participants |
| Emodepside 0.1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Physical examination reported as AE | 0 participants |
| Emodepside 0.1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal neurological examination | 0 participants |
| Emodepside 1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal neurological examination | 0 participants |
| Emodepside 1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal physcial examination | 0 participants |
| Emodepside 1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Neurological examination reported as AE | 0 participants |
| Emodepside 1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Physical examination reported as AE | 0 participants |
| Emodepside 2.5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal physcial examination | 0 participants |
| Emodepside 2.5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Physical examination reported as AE | 0 participants |
| Emodepside 2.5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Neurological examination reported as AE | 0 participants |
| Emodepside 2.5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal neurological examination | 0 participants |
| Emodepside 5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Physical examination reported as AE | 0 participants |
| Emodepside 5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal neurological examination | 0 participants |
| Emodepside 5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Neurological examination reported as AE | 0 participants |
| Emodepside 5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal physcial examination | 0 participants |
| Emodepside 5mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Physical examination reported as AE | 0 participants |
| Emodepside 5mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal neurological examination | 0 participants |
| Emodepside 5mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal physcial examination | 0 participants |
| Emodepside 5mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Neurological examination reported as AE | 0 participants |
| Emodepside 10mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Neurological examination reported as AE | 0 participants |
| Emodepside 10mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal neurological examination | 0 participants |
| Emodepside 10mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Physical examination reported as AE | 0 participants |
| Emodepside 10mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal physcial examination | 0 participants |
| Emodepside 20mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal physcial examination | 0 participants |
| Emodepside 20mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Neurological examination reported as AE | 0 participants |
| Emodepside 20mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Physical examination reported as AE | 0 participants |
| Emodepside 20mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal neurological examination | 0 participants |
| Emodepside 20mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Physical examination reported as AE | 0 participants |
| Emodepside 20mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal neurological examination | 0 participants |
| Emodepside 20mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Neurological examination reported as AE | 0 participants |
| Emodepside 20mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal physcial examination | 0 participants |
| Emodepside 40mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Neurological examination reported as AE | 0 participants |
| Emodepside 40mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal neurological examination | 0 participants |
| Emodepside 40mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal physcial examination | 0 participants |
| Emodepside 40mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Physical examination reported as AE | 0 participants |
| Emodepside 10mg Solution, Fed (Part 2) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Physical examination reported as AE | 0 participants |
| Emodepside 10mg Solution, Fed (Part 2) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Neurological examination reported as AE | 0 participants |
| Emodepside 10mg Solution, Fed (Part 2) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal physcial examination | 0 participants |
| Emodepside 10mg Solution, Fed (Part 2) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal neurological examination | 0 participants |
| Emodepside 40mg Solution, Fasted, (Part 2) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal physcial examination | 0 participants |
| Emodepside 40mg Solution, Fasted, (Part 2) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Physical examination reported as AE | 0 participants |
| Emodepside 40mg Solution, Fasted, (Part 2) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Neurological examination reported as AE | 0 participants |
| Emodepside 40mg Solution, Fasted, (Part 2) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal neurological examination | 0 participants |
| Placebo Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Neurological examination reported as AE | 0 participants |
| Placebo Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal physcial examination | 0 participants |
| Placebo Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Physical examination reported as AE | 0 participants |
| Placebo Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal neurological examination | 0 participants |
| Placebo Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal neurological examination | 0 participants |
| Placebo Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Physical examination reported as AE | 0 participants |
| Placebo Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal physcial examination | 0 participants |
| Placebo Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Neurological examination reported as AE | 0 participants |
| Placebo Solution, Fed (Part 2) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal neurological examination | 0 participants |
| Placebo Solution, Fed (Part 2) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Neurological examination reported as AE | 0 participants |
| Placebo Solution, Fed (Part 2) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal physcial examination | 0 participants |
| Placebo Solution, Fed (Part 2) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Physical examination reported as AE | 0 participants |
| Placebo Solution, Fasted (Part 2) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Neurological examination reported as AE | 0 participants |
| Placebo Solution, Fasted (Part 2) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Physical examination reported as AE | 0 participants |
| Placebo Solution, Fasted (Part 2) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal physcial examination | 0 participants |
| Placebo Solution, Fasted (Part 2) | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal neurological examination | 0 participants |
Primary
Safety and Tolerability as Measured by Vital Signs
Vital signs included heart rate, systolic and diastolic blood pressure,
Time frame: Up to 14 days post dose (may be extended to 21 days)
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Emodepside 0.1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in systolic BP | 0 participants |
| Emodepside 0.1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in heart rate | 0 participants |
| Emodepside 0.1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in diastolic BP | 0 participants |
| Emodepside 1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in heart rate | 0 participants |
| Emodepside 1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in systolic BP | 0 participants |
| Emodepside 1mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in diastolic BP | 0 participants |
| Emodepside 2.5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in systolic BP | 0 participants |
| Emodepside 2.5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in heart rate | 0 participants |
| Emodepside 2.5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in diastolic BP | 0 participants |
| Emodepside 5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in diastolic BP | 0 participants |
| Emodepside 5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in heart rate | 0 participants |
| Emodepside 5mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in systolic BP | 0 participants |
| Emodepside 5mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in heart rate | 0 participants |
| Emodepside 5mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in diastolic BP | 0 participants |
| Emodepside 5mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in systolic BP | 0 participants |
| Emodepside 10mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in systolic BP | 0 participants |
| Emodepside 10mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in heart rate | 0 participants |
| Emodepside 10mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in diastolic BP | 0 participants |
| Emodepside 20mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in diastolic BP | 0 participants |
| Emodepside 20mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in heart rate | 0 participants |
| Emodepside 20mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in systolic BP | 0 participants |
| Emodepside 20mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in systolic BP | 0 participants |
| Emodepside 20mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in heart rate | 0 participants |
| Emodepside 20mg Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in diastolic BP | 0 participants |
| Emodepside 40mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in heart rate | 0 participants |
| Emodepside 40mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in systolic BP | 0 participants |
| Emodepside 40mg Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in diastolic BP | 0 participants |
| Emodepside 10mg Solution, Fed (Part 2) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in systolic BP | 0 participants |
| Emodepside 10mg Solution, Fed (Part 2) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in heart rate | 0 participants |
| Emodepside 10mg Solution, Fed (Part 2) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in diastolic BP | 0 participants |
| Emodepside 40mg Solution, Fasted, (Part 2) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in systolic BP | 0 participants |
| Emodepside 40mg Solution, Fasted, (Part 2) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in heart rate | 0 participants |
| Emodepside 40mg Solution, Fasted, (Part 2) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in diastolic BP | 0 participants |
| Placebo Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in diastolic BP | 0 participants |
| Placebo Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in systolic BP | 0 participants |
| Placebo Solution, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in heart rate | 0 participants |
| Placebo Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in systolic BP | 0 participants |
| Placebo Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in heart rate | 0 participants |
| Placebo Tablet, Fasted (Part 1) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in diastolic BP | 0 participants |
| Placebo Solution, Fed (Part 2) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in heart rate | 0 participants |
| Placebo Solution, Fed (Part 2) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in diastolic BP | 0 participants |
| Placebo Solution, Fed (Part 2) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in systolic BP | 0 participants |
| Placebo Solution, Fasted (Part 2) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in systolic BP | 0 participants |
| Placebo Solution, Fasted (Part 2) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in diastolic BP | 0 participants |
| Placebo Solution, Fasted (Part 2) | Safety and Tolerability as Measured by Vital Signs | Clinically significant change in heart rate | 0 participants |
Secondary
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
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)
Population: emodepside assessed in fasted condition: only one cohort (10mg solution) assessed with high fat high calories meal.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Emodepside 0.1mg Solution, Fasted (Part 1) | 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 | 996 ng*h/mL |
| Emodepside 1mg Solution, Fasted (Part 1) | 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 | 673 ng*h/mL |
Secondary
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
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)
Population: emodepside assessed in fasted condition: only one cohort (10mg solution) assessed with high fat high calories meal.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Emodepside 0.1mg Solution, Fasted (Part 1) | 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 | 172 ng/ml |
| Emodepside 1mg Solution, Fasted (Part 1) | 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 | 71.9 ng/ml |
Secondary
Frel of the IR (Immediate Release) Tablet of Emodepside
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)
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Emodepside 0.1mg Solution, Fasted (Part 1) | Frel of the IR (Immediate Release) Tablet of Emodepside | 35.0 Frel percentage |
| Emodepside 1mg Solution, Fasted (Part 1) | Frel of the IR (Immediate Release) Tablet of Emodepside | 11.7 Frel percentage |
Secondary
The AUC 0-24/D of Emodepside in Plasma
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)
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Emodepside 0.1mg Solution, Fasted (Part 1) | The AUC 0-24/D of Emodepside in Plasma | 100 (h.ng/mL)/mg) | Geometric Coefficient of Variation 50.4 |
| Emodepside 1mg Solution, Fasted (Part 1) | The AUC 0-24/D of Emodepside in Plasma | 100 (h.ng/mL)/mg) | Geometric Coefficient of Variation 6.5 |
| Emodepside 2.5mg Solution, Fasted (Part 1) | The AUC 0-24/D of Emodepside in Plasma | 104 (h.ng/mL)/mg) | Geometric Coefficient of Variation 25.8 |
| Emodepside 5mg Solution, Fasted (Part 1) | The AUC 0-24/D of Emodepside in Plasma | 36.5 (h.ng/mL)/mg) | Geometric Coefficient of Variation 24.3 |
| Emodepside 5mg Tablet, Fasted (Part 1) | The AUC 0-24/D of Emodepside in Plasma | 99.6 (h.ng/mL)/mg) | Geometric Coefficient of Variation 21.2 |
| Emodepside 10mg Solution, Fasted (Part 1) | The AUC 0-24/D of Emodepside in Plasma | 95.3 (h.ng/mL)/mg) | Geometric Coefficient of Variation 16.3 |
| Emodepside 20mg Solution, Fasted (Part 1) | The AUC 0-24/D of Emodepside in Plasma | 11.2 (h.ng/mL)/mg) | Geometric Coefficient of Variation 58 |
| Emodepside 20mg Tablet, Fasted (Part 1) | The AUC 0-24/D of Emodepside in Plasma | 103 (h.ng/mL)/mg) | Geometric Coefficient of Variation 33.6 |
| Emodepside 40mg Solution, Fasted (Part 1) | The AUC 0-24/D of Emodepside in Plasma | 67.3 (h.ng/mL)/mg) | Geometric Coefficient of Variation 26.4 |
| Emodepside 10mg Solution, Fed (Part 2) | The AUC 0-24/D of Emodepside in Plasma | 82.9 (h.ng/mL)/mg) | Geometric Coefficient of Variation 26 |
Secondary
The AUC 0-24 of Emodepside in Plasma
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)
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Emodepside 0.1mg Solution, Fasted (Part 1) | The AUC 0-24 of Emodepside in Plasma | 100 h*ng/mL | Geometric Coefficient of Variation 50.4 |
| Emodepside 1mg Solution, Fasted (Part 1) | The AUC 0-24 of Emodepside in Plasma | 250 h*ng/mL | Geometric Coefficient of Variation 6.5 |
| Emodepside 2.5mg Solution, Fasted (Part 1) | The AUC 0-24 of Emodepside in Plasma | 522 h*ng/mL | Geometric Coefficient of Variation 25.8 |
| Emodepside 5mg Solution, Fasted (Part 1) | The AUC 0-24 of Emodepside in Plasma | 183 h*ng/mL | Geometric Coefficient of Variation 24.3 |
| Emodepside 5mg Tablet, Fasted (Part 1) | The AUC 0-24 of Emodepside in Plasma | 996 h*ng/mL | Geometric Coefficient of Variation 21.2 |
| Emodepside 10mg Solution, Fasted (Part 1) | The AUC 0-24 of Emodepside in Plasma | 1910 h*ng/mL | Geometric Coefficient of Variation 16.3 |
| Emodepside 20mg Solution, Fasted (Part 1) | The AUC 0-24 of Emodepside in Plasma | 223 h*ng/mL | Geometric Coefficient of Variation 58 |
| Emodepside 20mg Tablet, Fasted (Part 1) | The AUC 0-24 of Emodepside in Plasma | 4110 h*ng/mL | Geometric Coefficient of Variation 33.6 |
| Emodepside 40mg Solution, Fasted (Part 1) | The AUC 0-24 of Emodepside in Plasma | 673 h*ng/mL | Geometric Coefficient of Variation 26.4 |
| Emodepside 10mg Solution, Fed (Part 2) | The AUC 0-24 of Emodepside in Plasma | 3320 h*ng/mL | Geometric Coefficient of Variation 26 |
Secondary
The AUC 24, Norm of Emodepside in Plasma
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)
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Emodepside 0.1mg Solution, Fasted (Part 1) | The AUC 24, Norm of Emodepside in Plasma | 1.43 (h*ng/mL)/(mg*kg) | Geometric Coefficient of Variation 58.7 |
| Emodepside 1mg Solution, Fasted (Part 1) | The AUC 24, Norm of Emodepside in Plasma | 1.35 (h*ng/mL)/(mg*kg) | Geometric Coefficient of Variation 17.5 |
| Emodepside 2.5mg Solution, Fasted (Part 1) | The AUC 24, Norm of Emodepside in Plasma | 1.38 (h*ng/mL)/(mg*kg) | Geometric Coefficient of Variation 27.8 |
| Emodepside 5mg Solution, Fasted (Part 1) | The AUC 24, Norm of Emodepside in Plasma | 0.483 (h*ng/mL)/(mg*kg) | Geometric Coefficient of Variation 28.9 |
| Emodepside 5mg Tablet, Fasted (Part 1) | The AUC 24, Norm of Emodepside in Plasma | 1.35 (h*ng/mL)/(mg*kg) | Geometric Coefficient of Variation 33.8 |
| Emodepside 10mg Solution, Fasted (Part 1) | The AUC 24, Norm of Emodepside in Plasma | 1.18 (h*ng/mL)/(mg*kg) | Geometric Coefficient of Variation 27.8 |
| Emodepside 20mg Solution, Fasted (Part 1) | The AUC 24, Norm of Emodepside in Plasma | 0.138 (h*ng/mL)/(mg*kg) | Geometric Coefficient of Variation 66 |
| Emodepside 20mg Tablet, Fasted (Part 1) | The AUC 24, Norm of Emodepside in Plasma | 1.23 (h*ng/mL)/(mg*kg) | Geometric Coefficient of Variation 42.9 |
| Emodepside 40mg Solution, Fasted (Part 1) | The AUC 24, Norm of Emodepside in Plasma | 0.825 (h*ng/mL)/(mg*kg) | Geometric Coefficient of Variation 30.8 |
| Emodepside 10mg Solution, Fed (Part 2) | The AUC 24, Norm of Emodepside in Plasma | 1.01 (h*ng/mL)/(mg*kg) | Geometric Coefficient of Variation 45.8 |
Secondary
The AUC∞/D of Emodepside in Plasma
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)
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Emodepside 0.1mg Solution, Fasted (Part 1) | The AUC∞/D of Emodepside in Plasma | NA No values calculated |
| Emodepside 1mg Solution, Fasted (Part 1) | The AUC∞/D of Emodepside in Plasma | NA No values calculated |
| Emodepside 2.5mg Solution, Fasted (Part 1) | The AUC∞/D of Emodepside in Plasma | NA No values calculated |
| Emodepside 5mg Solution, Fasted (Part 1) | The AUC∞/D of Emodepside in Plasma | NA No values calculated |
| Emodepside 5mg Tablet, Fasted (Part 1) | The AUC∞/D of Emodepside in Plasma | NA No values calculated |
| Emodepside 10mg Solution, Fasted (Part 1) | The AUC∞/D of Emodepside in Plasma | NA No values calculated |
| Emodepside 20mg Solution, Fasted (Part 1) | The AUC∞/D of Emodepside in Plasma | NA No values calculated |
| Emodepside 20mg Tablet, Fasted (Part 1) | The AUC∞/D of Emodepside in Plasma | NA No values calculated |
| Emodepside 40mg Solution, Fasted (Part 1) | The AUC∞/D of Emodepside in Plasma | NA No values calculated |
| Emodepside 10mg Solution, Fed (Part 2) | The AUC∞/D of Emodepside in Plasma | NA No values calculated |
| Emodepside 40mg Solution, Fasted, (Part 2) | The AUC∞/D of Emodepside in Plasma | NA No values calculated |
Secondary
The AUC Last, Norm of Emodepside in Plasma
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)
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Emodepside 0.1mg Solution, Fasted (Part 1) | The AUC Last, Norm of Emodepside in Plasma | 2.60 (h*ng/mL)/(mg*kg) | Geometric Coefficient of Variation 127 |
| Emodepside 1mg Solution, Fasted (Part 1) | The AUC Last, Norm of Emodepside in Plasma | 4.56 (h*ng/mL)/(mg*kg) | Geometric Coefficient of Variation 19.5 |
| Emodepside 2.5mg Solution, Fasted (Part 1) | The AUC Last, Norm of Emodepside in Plasma | 4.50 (h*ng/mL)/(mg*kg) | Geometric Coefficient of Variation 27.1 |
| Emodepside 5mg Solution, Fasted (Part 1) | The AUC Last, Norm of Emodepside in Plasma | 1.33 (h*ng/mL)/(mg*kg) | Geometric Coefficient of Variation 78.4 |
| Emodepside 5mg Tablet, Fasted (Part 1) | The AUC Last, Norm of Emodepside in Plasma | 4.17 (h*ng/mL)/(mg*kg) | Geometric Coefficient of Variation 42.6 |
| Emodepside 10mg Solution, Fasted (Part 1) | The AUC Last, Norm of Emodepside in Plasma | 4.62 (h*ng/mL)/(mg*kg) | Geometric Coefficient of Variation 30.8 |
| Emodepside 20mg Solution, Fasted (Part 1) | The AUC Last, Norm of Emodepside in Plasma | 0.414 (h*ng/mL)/(mg*kg) | Geometric Coefficient of Variation 138 |
| Emodepside 20mg Tablet, Fasted (Part 1) | The AUC Last, Norm of Emodepside in Plasma | 4.91 (h*ng/mL)/(mg*kg) | Geometric Coefficient of Variation 36.5 |
| Emodepside 40mg Solution, Fasted (Part 1) | The AUC Last, Norm of Emodepside in Plasma | 4.16 (h*ng/mL)/(mg*kg) | Geometric Coefficient of Variation 25.5 |
| Emodepside 10mg Solution, Fed (Part 2) | The AUC Last, Norm of Emodepside in Plasma | 4.21 (h*ng/mL)/(mg*kg) | Geometric Coefficient of Variation 42.6 |
Secondary
The AUC Last of Emodepside in Plasma
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)
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Emodepside 0.1mg Solution, Fasted (Part 1) | The AUC Last of Emodepside in Plasma | 182 h*ng/mL | Geometric Coefficient of Variation 111 |
| Emodepside 1mg Solution, Fasted (Part 1) | The AUC Last of Emodepside in Plasma | 845 h*ng/mL | Geometric Coefficient of Variation 10.4 |
| Emodepside 2.5mg Solution, Fasted (Part 1) | The AUC Last of Emodepside in Plasma | 1700 h*ng/mL | Geometric Coefficient of Variation 24.2 |
| Emodepside 5mg Solution, Fasted (Part 1) | The AUC Last of Emodepside in Plasma | 501 h*ng/mL | Geometric Coefficient of Variation 76.8 |
| Emodepside 5mg Tablet, Fasted (Part 1) | The AUC Last of Emodepside in Plasma | 3070 h*ng/mL | Geometric Coefficient of Variation 27.7 |
| Emodepside 10mg Solution, Fasted (Part 1) | The AUC Last of Emodepside in Plasma | 7480 h*ng/mL | Geometric Coefficient of Variation 22.1 |
| Emodepside 20mg Solution, Fasted (Part 1) | The AUC Last of Emodepside in Plasma | 667 h*ng/mL | Geometric Coefficient of Variation 125 |
| Emodepside 20mg Tablet, Fasted (Part 1) | The AUC Last of Emodepside in Plasma | 16400 h*ng/mL | Geometric Coefficient of Variation 23.6 |
| Emodepside 40mg Solution, Fasted (Part 1) | The AUC Last of Emodepside in Plasma | 3390 h*ng/mL | Geometric Coefficient of Variation 20.4 |
| Emodepside 10mg Solution, Fed (Part 2) | The AUC Last of Emodepside in Plasma | 13800 h*ng/mL | Geometric Coefficient of Variation 23.4 |
Secondary
The AUC∞ of Emodepside in Plasma
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)
Population: 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 | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Emodepside 0.1mg Solution, Fasted (Part 1) | The AUC∞ of Emodepside in Plasma | NA h*ng/ml |
| Emodepside 1mg Solution, Fasted (Part 1) | The AUC∞ of Emodepside in Plasma | NA h*ng/ml |
| Emodepside 2.5mg Solution, Fasted (Part 1) | The AUC∞ of Emodepside in Plasma | NA h*ng/ml |
| Emodepside 5mg Solution, Fasted (Part 1) | The AUC∞ of Emodepside in Plasma | NA h*ng/ml |
| Emodepside 5mg Tablet, Fasted (Part 1) | The AUC∞ of Emodepside in Plasma | NA h*ng/ml |
| Emodepside 10mg Solution, Fasted (Part 1) | The AUC∞ of Emodepside in Plasma | NA h*ng/ml |
| Emodepside 20mg Solution, Fasted (Part 1) | The AUC∞ of Emodepside in Plasma | NA h*ng/ml |
| Emodepside 20mg Tablet, Fasted (Part 1) | The AUC∞ of Emodepside in Plasma | NA h*ng/ml |
| Emodepside 40mg Solution, Fasted (Part 1) | The AUC∞ of Emodepside in Plasma | NA h*ng/ml |
| Emodepside 10mg Solution, Fed (Part 2) | The AUC∞ of Emodepside in Plasma | NA h*ng/ml |
| Emodepside 40mg Solution, Fasted, (Part 2) | The AUC∞ of Emodepside in Plasma | NA h*ng/ml |
Secondary
The CL/F of Emodepside in Plasma
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)
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Emodepside 0.1mg Solution, Fasted (Part 1) | The CL/F of Emodepside in Plasma | 3.88 L/hour | Geometric Coefficient of Variation 151 |
| Emodepside 1mg Solution, Fasted (Part 1) | The CL/F of Emodepside in Plasma | 1.37 L/hour | Geometric Coefficient of Variation 44.1 |
| Emodepside 2.5mg Solution, Fasted (Part 1) | The CL/F of Emodepside in Plasma | 1.34 L/hour | Geometric Coefficient of Variation 57.8 |
| Emodepside 5mg Solution, Fasted (Part 1) | The CL/F of Emodepside in Plasma | 4.79 L/hour | Geometric Coefficient of Variation 179 |
| Emodepside 5mg Tablet, Fasted (Part 1) | The CL/F of Emodepside in Plasma | 1.42 L/hour | Geometric Coefficient of Variation 115 |
| Emodepside 10mg Solution, Fasted (Part 1) | The CL/F of Emodepside in Plasma | 1.34 L/hour | Geometric Coefficient of Variation 24.8 |
| Emodepside 20mg Solution, Fasted (Part 1) | The CL/F of Emodepside in Plasma | 13.3 L/hour | Geometric Coefficient of Variation 150 |
| Emodepside 20mg Tablet, Fasted (Part 1) | The CL/F of Emodepside in Plasma | 1.57 L/hour | Geometric Coefficient of Variation 32.6 |
| Emodepside 40mg Solution, Fasted (Part 1) | The CL/F of Emodepside in Plasma | 1.42 L/hour | Geometric Coefficient of Variation 57.3 |
| Emodepside 10mg Solution, Fed (Part 2) | The CL/F of Emodepside in Plasma | 1.69 L/hour | Geometric Coefficient of Variation 22.1 |
Secondary
The Cmax/D of Emodepside in Plasma
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)
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Emodepside 0.1mg Solution, Fasted (Part 1) | The Cmax/D of Emodepside in Plasma | 18.6 (ng/mL)/mg | Geometric Coefficient of Variation 20.8 |
| Emodepside 1mg Solution, Fasted (Part 1) | The Cmax/D of Emodepside in Plasma | 15.0 (ng/mL)/mg | Geometric Coefficient of Variation 15.5 |
| Emodepside 2.5mg Solution, Fasted (Part 1) | The Cmax/D of Emodepside in Plasma | 18.4 (ng/mL)/mg | Geometric Coefficient of Variation 16.2 |
| Emodepside 5mg Solution, Fasted (Part 1) | The Cmax/D of Emodepside in Plasma | 5.15 (ng/mL)/mg | Geometric Coefficient of Variation 23.9 |
| Emodepside 5mg Tablet, Fasted (Part 1) | The Cmax/D of Emodepside in Plasma | 17.2 (ng/mL)/mg | Geometric Coefficient of Variation 32.3 |
| Emodepside 10mg Solution, Fasted (Part 1) | The Cmax/D of Emodepside in Plasma | 15.3 (ng/mL)/mg | Geometric Coefficient of Variation 28.7 |
| Emodepside 20mg Solution, Fasted (Part 1) | The Cmax/D of Emodepside in Plasma | 1.51 (ng/mL)/mg | Geometric Coefficient of Variation 62.5 |
| Emodepside 20mg Tablet, Fasted (Part 1) | The Cmax/D of Emodepside in Plasma | 14.9 (ng/mL)/mg | Geometric Coefficient of Variation 27.9 |
| Emodepside 40mg Solution, Fasted (Part 1) | The Cmax/D of Emodepside in Plasma | 71.9 (ng/mL)/mg | Geometric Coefficient of Variation 29.6 |
| Emodepside 10mg Solution, Fed (Part 2) | The Cmax/D of Emodepside in Plasma | 10.9 (ng/mL)/mg | Geometric Coefficient of Variation 32.7 |
Secondary
The Cmax, Norm of Emodepside in Plasma
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)
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Emodepside 0.1mg Solution, Fasted (Part 1) | The Cmax, Norm of Emodepside in Plasma | 0.265 (ng/mL)/(mg*kg) | Geometric Coefficient of Variation 25.1 |
| Emodepside 1mg Solution, Fasted (Part 1) | The Cmax, Norm of Emodepside in Plasma | 0.203 (ng/mL)/(mg*kg) | Geometric Coefficient of Variation 25.2 |
| Emodepside 2.5mg Solution, Fasted (Part 1) | The Cmax, Norm of Emodepside in Plasma | 0.244 (ng/mL)/(mg*kg) | Geometric Coefficient of Variation 18.4 |
| Emodepside 5mg Solution, Fasted (Part 1) | The Cmax, Norm of Emodepside in Plasma | 0.0680 (ng/mL)/(mg*kg) | Geometric Coefficient of Variation 27.7 |
| Emodepside 5mg Tablet, Fasted (Part 1) | The Cmax, Norm of Emodepside in Plasma | 0.233 (ng/mL)/(mg*kg) | Geometric Coefficient of Variation 46.7 |
| Emodepside 10mg Solution, Fasted (Part 1) | The Cmax, Norm of Emodepside in Plasma | 0.189 (ng/mL)/(mg*kg) | Geometric Coefficient of Variation 35.7 |
| Emodepside 20mg Solution, Fasted (Part 1) | The Cmax, Norm of Emodepside in Plasma | 0.0187 (ng/mL)/(mg*kg) | Geometric Coefficient of Variation 69.1 |
| Emodepside 20mg Tablet, Fasted (Part 1) | The Cmax, Norm of Emodepside in Plasma | 0.178 (ng/mL)/(mg*kg) | Geometric Coefficient of Variation 36.3 |
| Emodepside 40mg Solution, Fasted (Part 1) | The Cmax, Norm of Emodepside in Plasma | 0.0882 (ng/mL)/(mg*kg) | Geometric Coefficient of Variation 28.9 |
| Emodepside 10mg Solution, Fed (Part 2) | The Cmax, Norm of Emodepside in Plasma | 0.133 (ng/mL)/(mg*kg) | Geometric Coefficient of Variation 49.7 |
Secondary
The Cmax of Emodepside in Plasma
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)
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Emodepside 0.1mg Solution, Fasted (Part 1) | The Cmax of Emodepside in Plasma | 18.6 ng/mL | Geometric Coefficient of Variation 20.8 |
| Emodepside 1mg Solution, Fasted (Part 1) | The Cmax of Emodepside in Plasma | 37.6 ng/mL | Geometric Coefficient of Variation 15.5 |
| Emodepside 2.5mg Solution, Fasted (Part 1) | The Cmax of Emodepside in Plasma | 92.1 ng/mL | Geometric Coefficient of Variation 16.2 |
| Emodepside 5mg Solution, Fasted (Part 1) | The Cmax of Emodepside in Plasma | 25.7 ng/mL | Geometric Coefficient of Variation 23.9 |
| Emodepside 5mg Tablet, Fasted (Part 1) | The Cmax of Emodepside in Plasma | 172 ng/mL | Geometric Coefficient of Variation 32.3 |
| Emodepside 10mg Solution, Fasted (Part 1) | The Cmax of Emodepside in Plasma | 306 ng/mL | Geometric Coefficient of Variation 28.7 |
| Emodepside 20mg Solution, Fasted (Part 1) | The Cmax of Emodepside in Plasma | 30.2 ng/mL | Geometric Coefficient of Variation 62.5 |
| Emodepside 20mg Tablet, Fasted (Part 1) | The Cmax of Emodepside in Plasma | 595 ng/mL | Geometric Coefficient of Variation 27.9 |
| Emodepside 40mg Solution, Fasted (Part 1) | The Cmax of Emodepside in Plasma | 71.9 ng/mL | Geometric Coefficient of Variation 29.6 |
| Emodepside 10mg Solution, Fed (Part 2) | The Cmax of Emodepside in Plasma | 434 ng/mL | Geometric Coefficient of Variation 32.7 |
Secondary
The MRT of Emodepside in Plasma
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)
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Emodepside 0.1mg Solution, Fasted (Part 1) | The MRT of Emodepside in Plasma | 52.7 Hours | Geometric Coefficient of Variation 528 |
| Emodepside 1mg Solution, Fasted (Part 1) | The MRT of Emodepside in Plasma | 572 Hours | Geometric Coefficient of Variation 78.8 |
| Emodepside 2.5mg Solution, Fasted (Part 1) | The MRT of Emodepside in Plasma | 570 Hours | Geometric Coefficient of Variation 92.1 |
| Emodepside 5mg Solution, Fasted (Part 1) | The MRT of Emodepside in Plasma | 337 Hours | Geometric Coefficient of Variation 430 |
| Emodepside 5mg Tablet, Fasted (Part 1) | The MRT of Emodepside in Plasma | 533 Hours | Geometric Coefficient of Variation 232 |
| Emodepside 10mg Solution, Fasted (Part 1) | The MRT of Emodepside in Plasma | 757 Hours | Geometric Coefficient of Variation 69.9 |
| Emodepside 20mg Solution, Fasted (Part 1) | The MRT of Emodepside in Plasma | 443 Hours | Geometric Coefficient of Variation 182 |
| Emodepside 20mg Tablet, Fasted (Part 1) | The MRT of Emodepside in Plasma | 489 Hours | Geometric Coefficient of Variation 31.4 |
| Emodepside 40mg Solution, Fasted (Part 1) | The MRT of Emodepside in Plasma | 752 Hours | Geometric Coefficient of Variation 91.7 |
| Emodepside 10mg Solution, Fed (Part 2) | The MRT of Emodepside in Plasma | 569 Hours | Geometric Coefficient of Variation 52.5 |
Secondary
The t½ of Emodepside in Plasma
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)
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Emodepside 0.1mg Solution, Fasted (Part 1) | The t½ of Emodepside in Plasma | 42.7 Hours | Geometric Coefficient of Variation 531 |
| Emodepside 1mg Solution, Fasted (Part 1) | The t½ of Emodepside in Plasma | 449 Hours | Geometric Coefficient of Variation 74 |
| Emodepside 2.5mg Solution, Fasted (Part 1) | The t½ of Emodepside in Plasma | 415 Hours | Geometric Coefficient of Variation 117 |
| Emodepside 5mg Solution, Fasted (Part 1) | The t½ of Emodepside in Plasma | 267 Hours | Geometric Coefficient of Variation 392 |
| Emodepside 5mg Tablet, Fasted (Part 1) | The t½ of Emodepside in Plasma | 365 Hours | Geometric Coefficient of Variation 286 |
| Emodepside 10mg Solution, Fasted (Part 1) | The t½ of Emodepside in Plasma | 590 Hours | Geometric Coefficient of Variation 68.1 |
| Emodepside 20mg Solution, Fasted (Part 1) | The t½ of Emodepside in Plasma | 348 Hours | Geometric Coefficient of Variation 171 |
| Emodepside 20mg Tablet, Fasted (Part 1) | The t½ of Emodepside in Plasma | 392 Hours | Geometric Coefficient of Variation 31.7 |
| Emodepside 40mg Solution, Fasted (Part 1) | The t½ of Emodepside in Plasma | 531 Hours | Geometric Coefficient of Variation 99.3 |
| Emodepside 10mg Solution, Fed (Part 2) | The t½ of Emodepside in Plasma | 440 Hours | Geometric Coefficient of Variation 49.9 |
Secondary
The Tmax of Emodepside in Plasma
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)
Population: 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 | Measure | Value (MEAN) |
|---|---|---|
| Emodepside 0.1mg Solution, Fasted (Part 1) | The Tmax of Emodepside in Plasma | 1.00 Hours |
| Emodepside 1mg Solution, Fasted (Part 1) | The Tmax of Emodepside in Plasma | 1.00 Hours |
| Emodepside 2.5mg Solution, Fasted (Part 1) | The Tmax of Emodepside in Plasma | 1.00 Hours |
| Emodepside 5mg Solution, Fasted (Part 1) | The Tmax of Emodepside in Plasma | 2.00 Hours |
| Emodepside 5mg Tablet, Fasted (Part 1) | The Tmax of Emodepside in Plasma | 1.00 Hours |
| Emodepside 10mg Solution, Fasted (Part 1) | The Tmax of Emodepside in Plasma | 1.50 Hours |
| Emodepside 20mg Solution, Fasted (Part 1) | The Tmax of Emodepside in Plasma | 2.00 Hours |
| Emodepside 20mg Tablet, Fasted (Part 1) | The Tmax of Emodepside in Plasma | 1.05 Hours |
| Emodepside 40mg Solution, Fasted (Part 1) | The Tmax of Emodepside in Plasma | 2.50 Hours |
| Emodepside 10mg Solution, Fed (Part 2) | The Tmax of Emodepside in Plasma | 0.967 Hours |
Secondary
The Vz/F of Emodepside in Plasma
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)
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Emodepside 0.1mg Solution, Fasted (Part 1) | The Vz/F of Emodepside in Plasma | 239 Litres | Geometric Coefficient of Variation 88 |
| Emodepside 1mg Solution, Fasted (Part 1) | The Vz/F of Emodepside in Plasma | 885 Litres | Geometric Coefficient of Variation 27.4 |
| Emodepside 2.5mg Solution, Fasted (Part 1) | The Vz/F of Emodepside in Plasma | 802 Litres | Geometric Coefficient of Variation 49.1 |
| Emodepside 5mg Solution, Fasted (Part 1) | The Vz/F of Emodepside in Plasma | 1850 Litres | Geometric Coefficient of Variation 56.1 |
| Emodepside 5mg Tablet, Fasted (Part 1) | The Vz/F of Emodepside in Plasma | 748 Litres | Geometric Coefficient of Variation 68.7 |
| Emodepside 10mg Solution, Fasted (Part 1) | The Vz/F of Emodepside in Plasma | 1140 Litres | Geometric Coefficient of Variation 47.1 |
| Emodepside 20mg Solution, Fasted (Part 1) | The Vz/F of Emodepside in Plasma | 6700 Litres | Geometric Coefficient of Variation 40.1 |
| Emodepside 20mg Tablet, Fasted (Part 1) | The Vz/F of Emodepside in Plasma | 888 Litres | Geometric Coefficient of Variation 21.3 |
| Emodepside 40mg Solution, Fasted (Part 1) | The Vz/F of Emodepside in Plasma | 1090 Litres | Geometric Coefficient of Variation 36.2 |
| Emodepside 10mg Solution, Fed (Part 2) | The Vz/F of Emodepside in Plasma | 1070 Litres | Geometric Coefficient of Variation 41.8 |