Filariasis
Conditions
Brief summary
The study evaluates safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of emodepside, after administration as a Liquid Service Formulation (LSF), over 10 days, in healthy male caucasian subjects.
Detailed description
There is an urgent need for a macrofilaricidal drug, killing or sterilizing permanently O. volvulus adult worms, which could be used in individual case management and, after appropriate testing, as an alternative drug to ivermectin in Mass Drug Administration (MDA) programs. Emodepside is a promising candidate to kill the adult and sexually mature O. volvulus as explained below. Emodepside was shown to be macrofilaricidal against a variety of filarial nematodes and is a registered drug for animal health, commercialized by Bayer AG under the name of Profender® (in combination with praziquantel) or Procox® (in combination with toltrazuril). A first-in-human (FIH) double-blind, placebo-controlled study of single ascending doses of emodepside in healthy Caucasian men has been conducted and the preliminary results are favourable, supporting continuation of the Phase I development program. In the present repeat dose study, PK as well as safety and tolerability of the liquid service formulation of emodepside, given over 10 days, will be tested.
Interventions
DRUGLSF emodepside (BAY 44-4400) or matching placebo
Emodepside administered as an LSF oral solution (1mg/mL)
Sponsors
Bayer
Bill and Melinda Gates Foundation
Drugs for Neglected Diseases
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male, Caucasian volunteers, deemed healthy based on a clinical history, physical examination, ECG, vital signs, and laboratory tests of blood and urine. 2. 18 to 45 years of age. 3. Normal body weight (BMI; Quetelet index) in the range 18 to 30.1 kg/m2 at screening. 4. Blood pressure and heart rate in the supine position prior to randomisation must be within the ranges 90-140 mm Hg systolic, 60-90 mm Hg diastolic; heart rate 45-100 beats/min. 5. Sufficient intelligence to understand the nature of the trial and any hazards of participating in it. Ability to communicate satisfactorily with the Investigator and to participate in, and comply with the requirements of, the entire trial. 6. Willingness to give written consent to participate, after reading the information and consent form, and after having the opportunity to discuss the trial with the Investigator or his delegate. 7. Willingness to give written consent to have data entered into the Overvolunteering Prevention System. 8. Willingness to agree to the contraceptive requirements of the study from the first dose until 120 days after the last dose of study medication.
Exclusion criteria
1. Administration of a licensed or unlicensed medicinal product as part of another clinical trial within the 3 months before, or within 5 half-lives of, their first dose of study medication, whichever is longer, or is currently in the follow-up period for any clinical trial. 2. Clinically relevant abnormal medical history, concurrent medical condition, acute or chronic illness or history of chronic illness (such as diabetes mellitus or other abnormalities of glucose homeostasis) sufficient to invalidate the subject's participation in the trial or make it unnecessarily hazardous. 3. Past surgery (e.g., stomach bypass) or medical condition that might affect absorption of study drug taken orally. 4. Presence of abnormal physical findings, ECG, or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the subject. 5. Loss of more than 400 mL of blood within 3 months before admission. 6. Clinically relevant history of vital organ disease or other disease of an organ or the central nervous system. 7. Current or previous medical or psychiatric disorder, condition or history of such (e.g., seizures) that, in the opinion of the Investigator or the Sponsor, would increase the risk associated with study participation, or impair the subject's ability to participate or complete this study. 8. Positive test for hepatitis B, hepatitis C or HIV. 9. Febrile illness within 1 week before the first dose of study medication. 10. History of severe allergy, non-allergic drug reactions, severe adverse reaction to any drug, or multiple drug allergies. 11. Subjects with hypersensitivity to any ingredient of the study medication, including the active ingredient, emodepside. 12. Presence or history of drug or alcohol abuse in the last 10 years, or intake of more than 21 units of alcohol weekly. 13. Regular daily consumption of more than one liter of xanthine-containing beverages. 14. Regular daily consumption of more than 5 cigarettes daily, or use more than 3 grams (1/8 ounce) of tobacco. 15. Use of a prescription medicine during the 28 days before the first dose of study medication or use of an over-the-counter medicine (with exception of acetaminophen \[paracetamol\]), during the 7 days before the first dose of study medication. 16. Use of dietary supplements or herbal remedies (such as St John's Wort) that are known to be inducers or inhibitors of CYP3A4, or other co-medications known to be relevant substrates of CYP3A4, during the 28 days before the first dose of study medication (see list in the Study Procedures Manual). 17. Use of dietary supplements or herbal remedies (such as St John's Wort) that are known to be strong inhibitors of P-gp, or other co-medications known to be relevant substrates of P-gp, during the 28 days before the first dose of study medication (see list in the Study Procedures Manual). 18. Relevant pathological abnormalities in the ECG at screening, such as a second or third-degree atrioventricular (AV) block or prolongation of the QRS complex over 120 msec or QTc-interval over 450 msec (corrected using Bazett's \[QTcB\] or Fridericia's \[QTcF\] formulae). 19. Evidence of drug abuse (via urine testing) at the screening assessment or admission to the ward. 20. Use of excluded therapies that may impact on the interpretation of study results in the opinion of the Investigator or Sponsor. 21. Objection by General Practitioner (GP) to subject entering trial. 22. History of residing for 6 or more continuous months, within the last 3 years, in regions with endemic parasitic infections as determined by the Investigator. 23. Possibility that subject will not cooperate with the requirements of the protocol. 24. No contact lenses wear within 1 month before dosing. Wearing contact lenses is not permitted during the study. 25. Any ocular disorder for which topical ocular therapy is currently or chronically prescribed, including inflammatory eye disease (dry eye allergic conjunctivitis \[seasonal allergic conjunctivitis, vernal keratoconjunctivitis, atopic keratoconjunctivitis\], uveitis and glaucoma). 26. Past history of ocular disease requiring ongoing treatment. 27. Past ocular surgery including laser or other refractive corneal surgery. 28. Evidence of eye irritation, visual difficulties, corneal opacity, ocular surface (corneal or conjunctival damage, with or without ocular symptoms). 29. Evidence of narrow anterior chamber angles causing increased risk of acute glaucoma. 30. Evidence of ocular media opacity including lens opacity/vitreous opacities. 31. Evidence of retinal or optic nerve pathology. 32. Evidence of pronounced colour blindness, as indicated by an Ishihara score of 9/13 or below.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Neurological Examination Findings | up to 120 days | Abnormal or clinically significant neurological examination findings during the study or reported as an adverse event. |
| Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Adverse Events | up to 120 days | Death, serious adverse events (SAEs) and treatment-emergent adverse events (TEAEs). |
| Safety and Tolerability of Emodepside After Multiple Doses as Measured by Adverse Event Severity | Up to 120 days | Number of subjects with a TEAE, by highest level of severity. |
| Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Vital Signs Findings | up to 120 days | Vital signs included heart rate, systolic and diastolic blood pressure and temperature. |
| Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With 12-lead Electrocardiogram Findings | up to 30 days | The following variables were recorded in 12-lead ECGs: ventricular rate, PR interval, QRS interval, QTcB and QTcF interval. |
| Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Clinical Laboratory Tests Findings | up to 120 days | Clinical laboratory parameters included clinical chemistry, hematology, coagulation and urinalysis. |
| Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Ophthalmology Assessment Findings | up to 10 days | Ophthalmological examinations at Screening Visit 2 and Day 10 were done at a specialist eye hospital by a Consultant Ophthalmologist, or their assistant. Examinations included: ocular symptoms and history, autorefraction, best correct visual acuity, colour vision, Amsler grid, ocular alignment and motility, confrontation visual field, slit-lamp, measurement of intraocular pressure and an optical coherence tomography test. |
| Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Physical Examination Findings | up to 120 days | Abnormal or clinically significant physical examination findings during the study or reported as an adverse event. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The AUC24/D of Emodepside in Plasma | AUC24/D in plasma after the first (Day 0) and last (Day 9) dose | Summary of AUC24/D of emodepside after the first (Day 0) and last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15 h after the morning dose. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose. AUC24/D: the area under the concentration-time curve from time zero (pre-dose) to 24h corrected for dose. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb). |
| The AUC24,Norm of Emodepside in Plasma | AUC24,norm in plasma at Day 0 and Day 9 | Summary of AUC24,norm of emodepside after the first (Day 0) and last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15h after the morning dose. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120h (Day 14) after the morning dose. AUC24,norm: the area under the concentration-time curve from time zero (pre-dose) to 24h corrected by dose and body weight. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb). |
| The Cmax of Emodepside in Plasma | Cmax in plasma after the first (Day 0) and last (Day 9) dose | Summary of Cmax of emodepside after the first (Day 0) and last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15 h after the morning dose. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose. Cmax: the observed maximum plasma concentration measured in a subject after dosing identified by inspection of the drug concentration vs. time data. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb). |
| The Cmax/D of Emodepside in Plasma | Cmax/D in plasma after the first (Day 0) and last (Day 9) dose | Summary of Cmax/D of emodepside after the first (Day 0) and last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15 h after the morning dose. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose. Cmax/D: the observed maximum plasma concentration measured in a subject after dosing identified by inspection of the drug concentration vs. time data, corrected for dose. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb). |
| The Cmax,Norm of Emodepside in Plasma | Cmax,norm in plasma after the first (Day 0) and last (Day 9) dose | Summary of Cmax,norm of emodepside after the first (Day 0) and last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15 h after the morning dose. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose. Cmax,norm: the observed maximum plasma concentration measured in a subject after dosing identified by inspection of the drug concentration vs. time data, corrected for dose and body weight. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb). |
| The Ctrough of Emodepside in Plasma | Ctrough in plasma after the last (Day 9) dose | Summary of Ctrough (log-transformed) of emodepside after last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose. Ctrough: trough plasma concentration (measured concentration at the end of a dosing interval on Day 9 \[taken directly before next administration\]) obtained directly from the concentration-time data. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb). |
| The Tmax of Emodepside in Plasma | tmax in plasma after the first (Day 0) and last (Day 9) dose | Summary of tmax of emodepside after the first (Day 0) and last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15 h after the morning dose. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose. tmax: the time at which Cmax was apparent, identified by inspection of the drug concentration vs. time data. |
| The t1/2 of Emodepside in Plasma | t1/2 in plasma after the last (Day 9) dose | Summary of t1/2 of emodepside after the last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose. t1/2: terminal half-life. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb). |
| The t1/2,(0-24) of Emodepside in Plasma | t1/2,(0-24) in plasma after the last (Day 9) dose | Summary of t1/2,(0-24) of emodepside after the last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose. t1/2,(0-24): half-life calculated from the terminal slope of the log concentration-time (0-24h) curve. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb). |
| The λz of Emodepside in Plasma | λz in plasma after the last (Day 9) dose | Summary of λz of emodepside after the last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose. λz: terminal rate constant. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb). |
| The CLss/F of Emodepside in Plasma | CLss/F in plasma after the last (Day 9) dose | Summary of CLss/F of emodepside after the last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose. CLss/F: apparent total clearance from plasma on Day 9. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb). |
| The Vz/F of Emodepside in Plasma | Vz/F in plasma after the last (Day 9) dose | Summary of Vz/F of emodepside after the last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose. Vz/F: apparent volume of distribution on Day 9. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb). |
| The MRTlast of Emodepside in Plasma | MRTlast in plasma after the first (Day 0) dose | Summary of MRTlast of emodepside after the first (Day 0) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15 h after the morning dose. MRTlast: mean residence time from time zero (pre-dose) to the time of last quantifiable concentration (measurable up to 24h after dosing on Day 0). The geometric coefficient of variation is the between-subject coefficient of variation (%CVb). |
| The Rac(AUC12) of Emodepside in Plasma | Rac(AUC12) after 10 days' repeated doses of 10 mg emodepside (Day 9) | Summary of emodepside plasma Rac(AUC12) after 10 days' repeated doses of 10 mg emodepside (Day 9): PK parameter population. Rac(AUC12): accumulation ratio calculated from AUC12, where AUC12 is the area under the concentration-time curve from time zero (pre-dose) to 12h. Note: measure of dispersion is 'percentage coefficient of variation' (the between-subject coefficient of variation \[%CVb\]). Note: Rac(AUC12) was calculated only in Cohort 3. |
| The Rac(AUC24) of Emodepside in Plasma | Rac(AUC24) after 10 days' repeated doses of 10 mg emodepside (Day 9) | Summary of emodepside plasma Rac(AUC24) after 10 days' repeated doses of 10 mg emodepside (Day 9): PK parameter population. Rac(AUC24): accumulation ratio calculated from AUC24, where AUC24 is the area under the concentration-time curve from time zero (pre-dose) to 24h. Note: measure of dispersion is 'percentage coefficient of variation' (the between-subject coefficient of variation \[%CVb\]). |
| The Rac(Cmax) of Emodepside in Plasma | Rac(Cmax) after 10 days' repeated doses of 10 mg emodepside (Day 9) | Summary of emodepside plasma Rac(Cmax) after 10 days' repeated doses of 10 mg emodepside (Day 9): PK parameter population. Rac(Cmax): accumulation ratio calculated from Cmax, where Cmax is the observed maximum plasma concentration measured in a subject after dosing identified by inspection of the drug concentration vs. time data. Note: measure of dispersion is 'percentage coefficient of variation' (the between-subject coefficient of variation \[%CVb\]). |
| Mean Glucose Concentration at Day -1 | Mean glucose at Day -1 after repeated once or twice daily dosing | Mean glucose concentrations (mmol/L) after repeated once or twice daily dosing with up to 10 mg emodepside or placebo at Day -1. |
| Mean Glucose Concentration at Day 0 | Mean glucose after repeated once or twice daily dosing for up to 10 days | Mean glucose concentrations (mmol/L) after repeated once or twice daily dosing with up to 10 mg emodepside or placebo at Day 0. Baseline=predose on Day 0. |
| Mean Glucose Concentration at Day 9 | Mean glucose at Day 9 after repeated once or twice daily dosing | Mean glucose concentrations (mmol/L) after repeated once or twice daily dosing with up to 10 mg emodepside or placebo at Day 9. |
| Mean Glucose Concentration at Day 30 | Mean glucose at Day 30 after repeated once or twice daily dosing | Mean glucose concentrations (mmol/L) after repeated once or twice daily dosing with up to 10 mg emodepside or placebo at Day 30. |
| Mean Insulin Concentration at Day -1 | Mean insulin concentration at Day-1 after repeated once or twice daily dosing | Mean insulin concentration (pmol/L) after repeated once or twice daily dosing with up to 10 mg emodepside or placebo at Day -1. |
| Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period | From Day 1, pre-dose to Day 9, 24 hours post-dose | Summary of geometric mean emodepside plasma pharmacokinetic concentration-time data (ng/mL) during the repeated dosing period (Days 0-9) in healthy men. Subjects in the 10 mg emodepside BID dosing group had twice-daily doses on Days 0-8 and a single dose on the morning of Day 9. Therefore, the Day 9, 24 h post-dose value was not comparable to the previous value in that dosing group. |
| Mean Insulin Concentration at Day 9 | Mean insulin concentration at Day 9 after repeated once or twice daily dosing | Mean insulin concentration (pmol/L) after repeated once or twice daily dosing with up to 10 mg emodepside or placebo at Day 9. |
| Mean Insulin Concentration at Day 30 | Mean insulin concentration at Day 30 after repeated once or twice daily dosing | Mean insulin concentration (pmol/L) after repeated once or twice daily dosing with up to 10 mg emodepside or placebo at Day 30. |
| Mean Serum Glucose Concentration at Day -2 | Mean serum glucose concentration at Day -2, before and up to 4 hours after intake of a high-glucose solution | Oral glucose tolerance test: mean serum glucose concentration at Day -2, before and up to 4 hours after intake of a high-glucose solution, in subjects receiving repeated doses of emodepside or placebo for 10 days (Days 0-9). Baseline=pre-glucose intake on each respective day. |
| Mean Serum Glucose Concentration at Day 1 | Mean serum glucose concentration at Day 1, before and up to 4 hours after intake of a high-glucose solution | Oral glucose tolerance test: mean serum glucose concentration at Day 1, before and up to 4 hours after intake of a high-glucose solution, in subjects receiving repeated doses of emodepside or placebo for 10 days (Days 0-9). Baseline=pre-glucose intake on each respective day. |
| Mean Serum Glucose Concentration at Day 8 | Mean serum glucose concentration at Day 8, before and up to 4 hours after intake of a high-glucose solution | Oral glucose tolerance test: mean serum glucose concentration at Day 8, before and up to 4 hours after intake of a high-glucose solution, in subjects receiving repeated doses of emodepside or placebo for 10 days (Days 0-9). Baseline=pre-glucose intake on each respective day. |
| Mean Serum Glucose Concentration at Day 120 | Mean serum glucose concentration at Day 120, before and up to 4 hours after intake of a high-glucose solution | Oral glucose tolerance test: mean serum glucose concentration at Day 120, before and up to 4 hours after intake of a high-glucose solution, in subjects receiving repeated doses of emodepside or placebo for 10 days (Days 0-9). Baseline=pre-glucose intake on each respective day. Note: At Day 120, serum glucose concentration was only measured in Cohort 3 (10 mg BID) |
| Mean Serum Insulin Concentration at Day -2 | Mean serum insulin concentration at Day -2, before and up to 4 hours after intake of a high-glucose solution | Oral glucose tolerance test: mean serum insulin concentration at Day -2, before and up to 4 hours after intake of a high-glucose solution, in subjects receiving repeated doses of emodepside or placebo for 10 days (Days 0-9). Baseline=pre-glucose intake on each respective day. |
| Mean Serum Insulin Concentration at Day 1 | Mean serum insulin concentration at Day 1, before and up to 4 hours after intake of a high-glucose solution | Oral glucose tolerance test: mean serum insulin concentration at Day 1, before and up to 4 hours after intake of a high-glucose solution, in subjects receiving repeated doses of emodepside or placebo for 10 days (Days 0-9). Baseline=pre-glucose intake on each respective day. |
| Mean Serum Insulin Concentration at Day 8 | Mean serum insulin concentration at Day 8, before and up to 4 hours after intake of a high-glucose solution | Oral glucose tolerance test: mean serum insulin concentration at Day 8, before and up to 4 hours after intake of a high-glucose solution, in subjects receiving repeated doses of emodepside or placebo for 10 days (Days 0-9). Baseline=pre-glucose intake on each respective day. |
| Mean Serum Insulin Concentration at Day 120 | Mean serum insulin concentration at Day 120, before and up to 4 hours after intake of a high-glucose solution | Oral glucose tolerance test: mean serum insulin concentration at Day 120, before and up to 4 hours after intake of a high-glucose solution, in subjects receiving repeated doses of emodepside or placebo for 10 days (Days 0-9). Baseline=pre-glucose intake on each respective day. Note: At Day 120, serum glucose concentration was only measured in Cohort 3 (10 mg BID) |
| Mean Insulin Concentration at Day 0 | Mean insulin concentration at Day 0 after repeated once or twice daily dosing | Mean insulin concentration (pmol/L) after repeated once or twice daily dosing with up to 10 mg emodepside or placebo at Day 0. Baseline=predose on Day 0. |
| The AUClast of Emodepside in Plasma | AUClast in plasma after the last dose (Day 9) | Summary of AUClast of emodepside after the last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120h (Day 14) after the morning dose. AUClast: the area under the concentration-time curve from time zero (pre-dose) to the time of last quantifiable concentration. PK=pharmacokinetic. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb). |
| The AUClast/D of Emodepside in Plasma | AUClast /D in plasma after the last dose (Day 9) | Summary of AUClast/D of emodepside after the last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120h (Day 14) after the morning dose. AUClast/D: the area under the concentration-time curve from time zero (pre-dose) to the time of last quantifiable concentration corrected for dose. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb). |
| The AUClast,Norm of Emodepside in Plasma | AUClast,norm in plasma after the last (Day 9) dose | Summary of AUClast,norm of emodepside after the last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120h (Day 14) after the morning dose. AUClast,norm: the area under the concentration-time curve from time zero (pre-dose) to the time of last quantifiable concentration corrected by dose and body weight. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb). |
| The AUC12 of Emodepside in Plasma | AUC12 in plasma after the first (Day 0) and last (Day 9) dose | Summary of AUC12 of emodepside after the first (Day 0) and last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15h after the morning dose. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120h (Day 14) after the morning dose. AUC12: the area under the concentration-time curve from time zero (pre-dose) to 12h. Note: AUC12 was calculated only in Cohort 3. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb). |
| The AUC12/D of Emodepside in Plasma | AUC12/D in plasma after the first (Day 0) and last (Day 9) dose | Summary of AUC12/D of emodepside after the first (Day 0) and last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15h after the morning dose. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120h (Day 14) after the morning dose. AUC12/D: the area under the concentration-time curve from time zero (pre-dose) to 12h, corrected for dose. Note: AUC12/D was collected only in Cohort 3. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb). |
| The AUC12,Norm of Emodepside in Plasma | AUC12,norm in plasma after the first (Day 0) and last (Day 9) dose | Summary of AUC12,norm of emodepside after the first (Day 0) and last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15 h after the morning dose. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose. AUC12,norm: the area under the concentration-time curve from time zero (pre-dose) to 12 h corrected by dose and body weight. Note: AUC12,norm was calculated only in Cohort 3. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb). |
| The AUC24 of Emodepside in Plasma | AUC24 in plasma after the first (Day 0) and last (Day 9) dose | Summary of AUC24 of emodepside after the first (Day 0) and last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15 h after the morning dose. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose. AUC24: the area under the concentration-time curve from time zero (pre-dose) to 24 h. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Drug-related Adverse Events | Drug-related AEs were reported throughout the study | Subjects presenting drug-related treatment-emergent adverse events listed by preferred term. Note: subjects with ≥1 adverse event are counted only once per preferred term. |
Countries
United Kingdom
Participant flow
Pre-assignment details
24 healthy subjects were randomized and received study drug or matching placebo.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: 5mg EMODEPSIDE OD 6 subjects with LSF emodepside 5mg, OD
LSF emodepside (BAY 44-4400) oral solution (1mg/mL) | 6 |
| Cohort 2: 10mg EMODEPSIDE OD 6 subjects with LSF emodepside 10mg, OD
LSF emodepside (BAY 44-4400) oral solution (1mg/mL) | 6 |
| Cohort 3: 10mg EMODEPSIDE BID 6 subjects with LSF emodepside 10mg, BID
LSF emodepside (BAY 44-4400) oral solution (1mg/mL) | 6 |
| Placebo Group 6 subjects with matching placebo (2 subjects per dose group) | 6 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Cohort 1: 5mg EMODEPSIDE OD | Placebo Group |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants |
| Age, Continuous | 31.3 years | 33.3 years | 28.0 years | 31.0 years | 32.7 years |
| BMI | 22.85 kg/m^2 STANDARD_DEVIATION 2.664 | 23.88 kg/m^2 STANDARD_DEVIATION 4.392 | 22.72 kg/m^2 STANDARD_DEVIATION 2.111 | 22.48 kg/m^2 STANDARD_DEVIATION 2.52 | 22.33 kg/m^2 STANDARD_DEVIATION 0.882 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 180.9 cm STANDARD_DEVIATION 6.1 | 179.7 cm STANDARD_DEVIATION 4.59 | 181.8 cm STANDARD_DEVIATION 6.74 | 179.3 cm STANDARD_DEVIATION 4.18 | 182.7 cm STANDARD_DEVIATION 8.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 24 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants |
| Region of Enrollment United Kingdom | 24 participants | 6 participants | 6 participants | 6 participants | 6 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 24 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants |
| Smokers | 4 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants |
| Weekly alcohol consumption (units) | 6.1 units/week STANDARD_DEVIATION 3.11 | 3.3 units/week STANDARD_DEVIATION 2.31 | 7.0 units/week STANDARD_DEVIATION 3.46 | 8.3 units/week STANDARD_DEVIATION 3.79 | 5.8 units/week STANDARD_DEVIATION 2.17 |
| Weight | 74.96 kg STANDARD_DEVIATION 10.807 | 77.70 kg STANDARD_DEVIATION 17.57 | 75.23 kg STANDARD_DEVIATION 9.52 | 72.18 kg STANDARD_DEVIATION 6.204 | 74.73 kg STANDARD_DEVIATION 8.999 |
| Xanthine | 397.4 mL/day STANDARD_DEVIATION 209.15 | 562.5 mL/day STANDARD_DEVIATION 239.36 | 283.3 mL/day STANDARD_DEVIATION 104.08 | 441.7 mL/day STANDARD_DEVIATION 245.8 | 300.0 mL/day STANDARD_DEVIATION 122.47 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 5 / 6 | 6 / 6 | 6 / 6 | 4 / 6 |
| serious Total, serious adverse events | 1 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Safety and Tolerability of Emodepside After Multiple Doses as Measured by Adverse Event Severity
Number of subjects with a TEAE, by highest level of severity.
Time frame: Up to 120 days
Population: Adverse events were determined in the Safety population. Adverse events were monitored from Screening (Day -28 and until Day -3) to Follow-up (up to Day 120 ±2 days).~AE=adverse event; OD=once daily; BID=twice daily.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Adverse Event Severity | Moderate | 2 Participants |
| Cohort 1: 5mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Adverse Event Severity | Severe | 1 Participants |
| Cohort 1: 5mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Adverse Event Severity | Mild | 2 Participants |
| Cohort 2: 10mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Adverse Event Severity | Moderate | 3 Participants |
| Cohort 2: 10mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Adverse Event Severity | Mild | 3 Participants |
| Cohort 2: 10mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Adverse Event Severity | Severe | 0 Participants |
| Cohort 3: 10mg EMODEPSIDE BID | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Adverse Event Severity | Mild | 4 Participants |
| Cohort 3: 10mg EMODEPSIDE BID | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Adverse Event Severity | Severe | 0 Participants |
| Cohort 3: 10mg EMODEPSIDE BID | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Adverse Event Severity | Moderate | 2 Participants |
| Placebo Group | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Adverse Event Severity | Severe | 0 Participants |
| Placebo Group | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Adverse Event Severity | Moderate | 1 Participants |
| Placebo Group | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Adverse Event Severity | Mild | 3 Participants |
Primary
Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With 12-lead Electrocardiogram Findings
The following variables were recorded in 12-lead ECGs: ventricular rate, PR interval, QRS interval, QTcB and QTcF interval.
Time frame: up to 30 days
Population: Twelve-lead ECG assessments were made predose on Day -1 and at regular timepoints until Follow-up (Day 30).~ECG=electrocardiogram; OD=once daily; BID=twice daily; PR=PR interval.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With 12-lead Electrocardiogram Findings | Clinically significant changes in ventricular rate | 0 Participants |
| Cohort 1: 5mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With 12-lead Electrocardiogram Findings | Clinically significant changes in PR interval | 0 Participants |
| Cohort 1: 5mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With 12-lead Electrocardiogram Findings | Clinically significant changes in QRS interval | 0 Participants |
| Cohort 1: 5mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With 12-lead Electrocardiogram Findings | Clinically significant changes in QTcB interval | 0 Participants |
| Cohort 2: 10mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With 12-lead Electrocardiogram Findings | Clinically significant changes in PR interval | 0 Participants |
| Cohort 2: 10mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With 12-lead Electrocardiogram Findings | Clinically significant changes in QRS interval | 0 Participants |
| Cohort 2: 10mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With 12-lead Electrocardiogram Findings | Clinically significant changes in QTcB interval | 0 Participants |
| Cohort 2: 10mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With 12-lead Electrocardiogram Findings | Clinically significant changes in ventricular rate | 0 Participants |
| Cohort 3: 10mg EMODEPSIDE BID | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With 12-lead Electrocardiogram Findings | Clinically significant changes in QRS interval | 0 Participants |
| Cohort 3: 10mg EMODEPSIDE BID | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With 12-lead Electrocardiogram Findings | Clinically significant changes in PR interval | 0 Participants |
| Cohort 3: 10mg EMODEPSIDE BID | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With 12-lead Electrocardiogram Findings | Clinically significant changes in QTcB interval | 0 Participants |
| Cohort 3: 10mg EMODEPSIDE BID | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With 12-lead Electrocardiogram Findings | Clinically significant changes in ventricular rate | 0 Participants |
| Placebo Group | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With 12-lead Electrocardiogram Findings | Clinically significant changes in QTcB interval | 0 Participants |
| Placebo Group | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With 12-lead Electrocardiogram Findings | Clinically significant changes in PR interval | 0 Participants |
| Placebo Group | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With 12-lead Electrocardiogram Findings | Clinically significant changes in ventricular rate | 0 Participants |
| Placebo Group | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With 12-lead Electrocardiogram Findings | Clinically significant changes in QRS interval | 0 Participants |
Primary
Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Adverse Events
Death, serious adverse events (SAEs) and treatment-emergent adverse events (TEAEs).
Time frame: up to 120 days
Population: Adverse events were determined in the Safety population. Adverse events were monitored from Screening (Day -28 and until Day -3) to Follow-up (up to Day 120 ±2 days).~AE=adverse event; OD=once daily; BID=twice daily.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Adverse Events | Deaths | 0 Participants |
| Cohort 1: 5mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Adverse Events | TEAEs | 5 Participants |
| Cohort 1: 5mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Adverse Events | Withdrawals from the study owing to a TEAE | 0 Participants |
| Cohort 1: 5mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Adverse Events | Drug-related TEAEs | 2 Participants |
| Cohort 1: 5mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Adverse Events | SAEs | 1 Participants |
| Cohort 1: 5mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Adverse Events | AEs | 5 Participants |
| Cohort 2: 10mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Adverse Events | Drug-related TEAEs | 1 Participants |
| Cohort 2: 10mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Adverse Events | AEs | 6 Participants |
| Cohort 2: 10mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Adverse Events | Deaths | 0 Participants |
| Cohort 2: 10mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Adverse Events | SAEs | 0 Participants |
| Cohort 2: 10mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Adverse Events | Withdrawals from the study owing to a TEAE | 0 Participants |
| Cohort 2: 10mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Adverse Events | TEAEs | 6 Participants |
| Cohort 3: 10mg EMODEPSIDE BID | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Adverse Events | Withdrawals from the study owing to a TEAE | 0 Participants |
| Cohort 3: 10mg EMODEPSIDE BID | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Adverse Events | TEAEs | 6 Participants |
| Cohort 3: 10mg EMODEPSIDE BID | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Adverse Events | SAEs | 0 Participants |
| Cohort 3: 10mg EMODEPSIDE BID | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Adverse Events | Drug-related TEAEs | 3 Participants |
| Cohort 3: 10mg EMODEPSIDE BID | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Adverse Events | AEs | 6 Participants |
| Cohort 3: 10mg EMODEPSIDE BID | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Adverse Events | Deaths | 0 Participants |
| Placebo Group | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Adverse Events | Drug-related TEAEs | 1 Participants |
| Placebo Group | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Adverse Events | AEs | 4 Participants |
| Placebo Group | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Adverse Events | TEAEs | 4 Participants |
| Placebo Group | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Adverse Events | Withdrawals from the study owing to a TEAE | 0 Participants |
| Placebo Group | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Adverse Events | SAEs | 0 Participants |
| Placebo Group | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Adverse Events | Deaths | 0 Participants |
Primary
Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Clinical Laboratory Tests Findings
Clinical laboratory parameters included clinical chemistry, hematology, coagulation and urinalysis.
Time frame: up to 120 days
Population: Clinical laboratory parameters were measured pre-dose on Day -1, at regular time points until Follow-up (Day 30), and at each long-term follow-up visit.~OD=once daily; BID=twice daily.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Clinical Laboratory Tests Findings | Clinically significant clinical chemistry changes | 0 Participants |
| Cohort 1: 5mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Clinical Laboratory Tests Findings | Clinically significant hematology changes | 0 Participants |
| Cohort 1: 5mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Clinical Laboratory Tests Findings | Clinically significant coagulation changes | 0 Participants |
| Cohort 1: 5mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Clinical Laboratory Tests Findings | Clinically significant urinalysis changes | 0 Participants |
| Cohort 2: 10mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Clinical Laboratory Tests Findings | Clinically significant hematology changes | 0 Participants |
| Cohort 2: 10mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Clinical Laboratory Tests Findings | Clinically significant urinalysis changes | 0 Participants |
| Cohort 2: 10mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Clinical Laboratory Tests Findings | Clinically significant clinical chemistry changes | 0 Participants |
| Cohort 2: 10mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Clinical Laboratory Tests Findings | Clinically significant coagulation changes | 0 Participants |
| Cohort 3: 10mg EMODEPSIDE BID | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Clinical Laboratory Tests Findings | Clinically significant clinical chemistry changes | 1 Participants |
| Cohort 3: 10mg EMODEPSIDE BID | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Clinical Laboratory Tests Findings | Clinically significant urinalysis changes | 0 Participants |
| Cohort 3: 10mg EMODEPSIDE BID | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Clinical Laboratory Tests Findings | Clinically significant coagulation changes | 0 Participants |
| Cohort 3: 10mg EMODEPSIDE BID | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Clinical Laboratory Tests Findings | Clinically significant hematology changes | 0 Participants |
| Placebo Group | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Clinical Laboratory Tests Findings | Clinically significant urinalysis changes | 0 Participants |
| Placebo Group | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Clinical Laboratory Tests Findings | Clinically significant clinical chemistry changes | 0 Participants |
| Placebo Group | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Clinical Laboratory Tests Findings | Clinically significant hematology changes | 0 Participants |
| Placebo Group | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Clinical Laboratory Tests Findings | Clinically significant coagulation changes | 0 Participants |
Primary
Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Neurological Examination Findings
Abnormal or clinically significant neurological examination findings during the study or reported as an adverse event.
Time frame: up to 120 days
Population: Neurological examinations were measured pre-dose on Day -1, at regular time points until Follow-up (Day 30), and at each long-term follow-up visit.~OD=once daily; BID=twice daily.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Neurological Examination Findings | Abnormal neurological examination | 2 Participants |
| Cohort 1: 5mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Neurological Examination Findings | Neurological examination reported as an AE | 1 Participants |
| Cohort 2: 10mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Neurological Examination Findings | Abnormal neurological examination | 1 Participants |
| Cohort 2: 10mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Neurological Examination Findings | Neurological examination reported as an AE | 1 Participants |
| Cohort 3: 10mg EMODEPSIDE BID | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Neurological Examination Findings | Neurological examination reported as an AE | 1 Participants |
| Cohort 3: 10mg EMODEPSIDE BID | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Neurological Examination Findings | Abnormal neurological examination | 1 Participants |
| Placebo Group | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Neurological Examination Findings | Neurological examination reported as an AE | 1 Participants |
| Placebo Group | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Neurological Examination Findings | Abnormal neurological examination | 1 Participants |
Primary
Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Ophthalmology Assessment Findings
Ophthalmological examinations at Screening Visit 2 and Day 10 were done at a specialist eye hospital by a Consultant Ophthalmologist, or their assistant. Examinations included: ocular symptoms and history, autorefraction, best correct visual acuity, colour vision, Amsler grid, ocular alignment and motility, confrontation visual field, slit-lamp, measurement of intraocular pressure and an optical coherence tomography test.
Time frame: up to 10 days
Population: Ophthalmological assessments were performed at the second screening visit after all other eligibility criteria had been met and on Day 10.~OD=once daily; BID=twice daily.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Ophthalmology Assessment Findings | Clinically significant ocular symptoms | 3 Participants |
| Cohort 1: 5mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Ophthalmology Assessment Findings | Clinically significant Amsler grid assessment | 1 Participants |
| Cohort 2: 10mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Ophthalmology Assessment Findings | Clinically significant ocular symptoms | 0 Participants |
| Cohort 2: 10mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Ophthalmology Assessment Findings | Clinically significant Amsler grid assessment | 0 Participants |
| Cohort 3: 10mg EMODEPSIDE BID | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Ophthalmology Assessment Findings | Clinically significant Amsler grid assessment | 0 Participants |
| Cohort 3: 10mg EMODEPSIDE BID | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Ophthalmology Assessment Findings | Clinically significant ocular symptoms | 3 Participants |
| Placebo Group | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Ophthalmology Assessment Findings | Clinically significant Amsler grid assessment | 0 Participants |
| Placebo Group | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Ophthalmology Assessment Findings | Clinically significant ocular symptoms | 1 Participants |
Primary
Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Physical Examination Findings
Abnormal or clinically significant physical examination findings during the study or reported as an adverse event.
Time frame: up to 120 days
Population: Physical and neurological examinations were measured pre-dose on Day -1, at regular time points until Follow-up (Day 30), and at each long-term follow-up visit. Results are reported for subjects experiencing abnormal result/AE, as opposed to individual events.~OD=once daily; BID=twice daily.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Physical Examination Findings | Abnormal physical examination | 2 Participants |
| Cohort 1: 5mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Physical Examination Findings | Physical examination reported as an AE | 2 Participants |
| Cohort 2: 10mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Physical Examination Findings | Physical examination reported as an AE | 1 Participants |
| Cohort 2: 10mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Physical Examination Findings | Abnormal physical examination | 1 Participants |
| Cohort 3: 10mg EMODEPSIDE BID | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Physical Examination Findings | Abnormal physical examination | 2 Participants |
| Cohort 3: 10mg EMODEPSIDE BID | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Physical Examination Findings | Physical examination reported as an AE | 1 Participants |
| Placebo Group | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Physical Examination Findings | Abnormal physical examination | 0 Participants |
| Placebo Group | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Physical Examination Findings | Physical examination reported as an AE | 0 Participants |
Primary
Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Vital Signs Findings
Vital signs included heart rate, systolic and diastolic blood pressure and temperature.
Time frame: up to 120 days
Population: Vital signs were measured pre-dose on Day -1, at regular time points until Follow-up (Day 30), and at each long-term follow-up visit.~OD=once daily; BID=twice daily; HR=heart rate; BP=blood pressure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Vital Signs Findings | Clinically significant change in HR | 0 Participants |
| Cohort 1: 5mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Vital Signs Findings | Clinically significant change in systolic BP | 0 Participants |
| Cohort 1: 5mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Vital Signs Findings | Clinically significant change in diastolic BP | 0 Participants |
| Cohort 1: 5mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Vital Signs Findings | Clinically significant change in temperature | 0 Participants |
| Cohort 2: 10mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Vital Signs Findings | Clinically significant change in systolic BP | 0 Participants |
| Cohort 2: 10mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Vital Signs Findings | Clinically significant change in diastolic BP | 0 Participants |
| Cohort 2: 10mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Vital Signs Findings | Clinically significant change in temperature | 0 Participants |
| Cohort 2: 10mg EMODEPSIDE OD | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Vital Signs Findings | Clinically significant change in HR | 0 Participants |
| Cohort 3: 10mg EMODEPSIDE BID | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Vital Signs Findings | Clinically significant change in diastolic BP | 0 Participants |
| Cohort 3: 10mg EMODEPSIDE BID | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Vital Signs Findings | Clinically significant change in systolic BP | 0 Participants |
| Cohort 3: 10mg EMODEPSIDE BID | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Vital Signs Findings | Clinically significant change in temperature | 0 Participants |
| Cohort 3: 10mg EMODEPSIDE BID | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Vital Signs Findings | Clinically significant change in HR | 0 Participants |
| Placebo Group | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Vital Signs Findings | Clinically significant change in temperature | 0 Participants |
| Placebo Group | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Vital Signs Findings | Clinically significant change in systolic BP | 0 Participants |
| Placebo Group | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Vital Signs Findings | Clinically significant change in HR | 0 Participants |
| Placebo Group | Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Vital Signs Findings | Clinically significant change in diastolic BP | 0 Participants |
Secondary
Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period
Summary of geometric mean emodepside plasma pharmacokinetic concentration-time data (ng/mL) during the repeated dosing period (Days 0-9) in healthy men. Subjects in the 10 mg emodepside BID dosing group had twice-daily doses on Days 0-8 and a single dose on the morning of Day 9. Therefore, the Day 9, 24 h post-dose value was not comparable to the previous value in that dosing group.
Time frame: From Day 1, pre-dose to Day 9, 24 hours post-dose
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period | Day 4, pre-dose | 24.81 ng/mL | Geometric Coefficient of Variation 37.4 |
| Cohort 1: 5mg EMODEPSIDE OD | Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period | Day 1, pre-dose | 8.77 ng/mL | Geometric Coefficient of Variation 35.8 |
| Cohort 1: 5mg EMODEPSIDE OD | Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period | Day 2, pre-dose | 15.24 ng/mL | Geometric Coefficient of Variation 31.1 |
| Cohort 1: 5mg EMODEPSIDE OD | Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period | Day 3, pre-dose | 21.22 ng/mL | Geometric Coefficient of Variation 35 |
| Cohort 1: 5mg EMODEPSIDE OD | Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period | Day 5, pre-dose | 31.46 ng/mL | Geometric Coefficient of Variation 36.3 |
| Cohort 1: 5mg EMODEPSIDE OD | Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period | Day 6, pre-dose | 36.68 ng/mL | Geometric Coefficient of Variation 36.7 |
| Cohort 1: 5mg EMODEPSIDE OD | Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period | Day 7, pre-dose | 40.57 ng/mL | Geometric Coefficient of Variation 31.4 |
| Cohort 1: 5mg EMODEPSIDE OD | Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period | Day 8, pre-dose | 46.91 ng/mL | Geometric Coefficient of Variation 36.8 |
| Cohort 1: 5mg EMODEPSIDE OD | Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period | Day 9, pre-dose | 49.73 ng/mL | Geometric Coefficient of Variation 35.1 |
| Cohort 1: 5mg EMODEPSIDE OD | Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period | Day 9, 24 hour post-dose | 51.76 ng/mL | Geometric Coefficient of Variation 36.6 |
| Cohort 2: 10mg EMODEPSIDE OD | Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period | Day 9, pre-dose | 97.11 ng/mL | Geometric Coefficient of Variation 44 |
| Cohort 2: 10mg EMODEPSIDE OD | Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period | Day 4, pre-dose | 47.38 ng/mL | Geometric Coefficient of Variation 42.2 |
| Cohort 2: 10mg EMODEPSIDE OD | Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period | Day 6, pre-dose | 70.88 ng/mL | Geometric Coefficient of Variation 39.6 |
| Cohort 2: 10mg EMODEPSIDE OD | Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period | Day 1, pre-dose | 15.78 ng/mL | Geometric Coefficient of Variation 42.9 |
| Cohort 2: 10mg EMODEPSIDE OD | Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period | Day 5, pre-dose | 60.07 ng/mL | Geometric Coefficient of Variation 42.9 |
| Cohort 2: 10mg EMODEPSIDE OD | Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period | Day 8, pre-dose | 91.63 ng/mL | Geometric Coefficient of Variation 42.4 |
| Cohort 2: 10mg EMODEPSIDE OD | Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period | Day 2, pre-dose | 28.80 ng/mL | Geometric Coefficient of Variation 40 |
| Cohort 2: 10mg EMODEPSIDE OD | Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period | Day 9, 24 hour post-dose | 108.17 ng/mL | Geometric Coefficient of Variation 49.1 |
| Cohort 2: 10mg EMODEPSIDE OD | Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period | Day 7, pre-dose | 83.31 ng/mL | Geometric Coefficient of Variation 43 |
| Cohort 2: 10mg EMODEPSIDE OD | Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period | Day 3, pre-dose | 39.08 ng/mL | Geometric Coefficient of Variation 45.6 |
| Cohort 3: 10mg EMODEPSIDE BID | Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period | Day 7, pre-dose | 149.41 ng/mL | Geometric Coefficient of Variation 33.3 |
| Cohort 3: 10mg EMODEPSIDE BID | Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period | Day 4, pre-dose | 98.01 ng/mL | Geometric Coefficient of Variation 32 |
| Cohort 3: 10mg EMODEPSIDE BID | Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period | Day 5, pre-dose | 120.98 ng/mL | Geometric Coefficient of Variation 31.1 |
| Cohort 3: 10mg EMODEPSIDE BID | Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period | Day 6, pre-dose | 137.60 ng/mL | Geometric Coefficient of Variation 35.2 |
| Cohort 3: 10mg EMODEPSIDE BID | Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period | Day 9, pre-dose | 184.94 ng/mL | Geometric Coefficient of Variation 37.1 |
| Cohort 3: 10mg EMODEPSIDE BID | Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period | Day 3, pre-dose | 84.65 ng/mL | Geometric Coefficient of Variation 37.7 |
| Cohort 3: 10mg EMODEPSIDE BID | Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period | Day 9, 24 hour post-dose | 176.10 ng/mL | Geometric Coefficient of Variation 39.8 |
| Cohort 3: 10mg EMODEPSIDE BID | Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period | Day 1, pre-dose | 45.94 ng/mL | Geometric Coefficient of Variation 35.1 |
| Cohort 3: 10mg EMODEPSIDE BID | Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period | Day 2, pre-dose | 64.62 ng/mL | Geometric Coefficient of Variation 38.5 |
| Cohort 3: 10mg EMODEPSIDE BID | Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period | Day 8, pre-dose | 179.90 ng/mL | Geometric Coefficient of Variation 35.3 |
Secondary
Mean Glucose Concentration at Day 0
Mean glucose concentrations (mmol/L) after repeated once or twice daily dosing with up to 10 mg emodepside or placebo at Day 0. Baseline=predose on Day 0.
Time frame: Mean glucose after repeated once or twice daily dosing for up to 10 days
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | Mean Glucose Concentration at Day 0 | 4 h | 4.73 mmol/L | Standard Deviation 0.378 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Glucose Concentration at Day 0 | Predose (Baseline) | 4.96 mmol/L | Standard Deviation 0.321 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Glucose Concentration at Day 0 | 12 h | 5.68 mmol/L | Standard Deviation 0.268 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Glucose Concentration at Day 0 | 1 h | 5.07 mmol/L | Standard Deviation 0.367 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Glucose Concentration at Day 0 | 24 h | 5.07 mmol/L | Standard Deviation 0.314 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Glucose Concentration at Day 0 | 2 h | 5.05 mmol/L | Standard Deviation 0.327 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Glucose Concentration at Day 0 | 2 h | 5.28 mmol/L | Standard Deviation 0.508 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Glucose Concentration at Day 0 | 4 h | 4.75 mmol/L | Standard Deviation 0.274 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Glucose Concentration at Day 0 | 1 h | 5.57 mmol/L | Standard Deviation 0.816 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Glucose Concentration at Day 0 | 12 h | 6.22 mmol/L | Standard Deviation 0.343 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Glucose Concentration at Day 0 | Predose (Baseline) | 4.85 mmol/L | Standard Deviation 0.409 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Glucose Concentration at Day 0 | 24 h | 4.88 mmol/L | Standard Deviation 0.264 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Glucose Concentration at Day 0 | Predose (Baseline) | 4.85 mmol/L | Standard Deviation 0.351 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Glucose Concentration at Day 0 | 1 h | 5.42 mmol/L | Standard Deviation 0.445 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Glucose Concentration at Day 0 | 2 h | 5.27 mmol/L | Standard Deviation 0.472 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Glucose Concentration at Day 0 | 4 h | 4.82 mmol/L | Standard Deviation 0.279 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Glucose Concentration at Day 0 | 12 h | 5.57 mmol/L | Standard Deviation 0.554 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Glucose Concentration at Day 0 | 24 h | 4.87 mmol/L | Standard Deviation 0.273 |
| Placebo Group | Mean Glucose Concentration at Day 0 | 24 h | 4.97 mmol/L | Standard Deviation 0.288 |
| Placebo Group | Mean Glucose Concentration at Day 0 | 12 h | 6.27 mmol/L | Standard Deviation 0.761 |
| Placebo Group | Mean Glucose Concentration at Day 0 | 1 h | 4.78 mmol/L | Standard Deviation 0.214 |
| Placebo Group | Mean Glucose Concentration at Day 0 | Predose (Baseline) | 4.85 mmol/L | Standard Deviation 0.288 |
| Placebo Group | Mean Glucose Concentration at Day 0 | 4 h | 4.70 mmol/L | Standard Deviation 0.276 |
| Placebo Group | Mean Glucose Concentration at Day 0 | 2 h | 4.70 mmol/L | Standard Deviation 0.31 |
Secondary
Mean Glucose Concentration at Day -1
Mean glucose concentrations (mmol/L) after repeated once or twice daily dosing with up to 10 mg emodepside or placebo at Day -1.
Time frame: Mean glucose at Day -1 after repeated once or twice daily dosing
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | Mean Glucose Concentration at Day -1 | -12 h | 5.17 mmol/L | Standard Deviation 0.712 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Glucose Concentration at Day -1 | -24 h | 4.72 mmol/L | Standard Deviation 0.286 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Glucose Concentration at Day -1 | -23 h | 4.90 mmol/L | Standard Deviation 0.308 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Glucose Concentration at Day -1 | -22 h | 4.77 mmol/L | Standard Deviation 0.378 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Glucose Concentration at Day -1 | -20 h | 4.63 mmol/L | Standard Deviation 0.388 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Glucose Concentration at Day -1 | -23 h | 4.85 mmol/L | Standard Deviation 0.259 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Glucose Concentration at Day -1 | -22 h | 4.72 mmol/L | Standard Deviation 0.371 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Glucose Concentration at Day -1 | -24 h | 4.68 mmol/L | Standard Deviation 0.349 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Glucose Concentration at Day -1 | -20 h | 4.57 mmol/L | Standard Deviation 0.207 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Glucose Concentration at Day -1 | -12 h | 5.55 mmol/L | Standard Deviation 0.451 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Glucose Concentration at Day -1 | -24 h | 4.80 mmol/L | Standard Deviation 0.245 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Glucose Concentration at Day -1 | -23 h | 4.85 mmol/L | Standard Deviation 0.281 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Glucose Concentration at Day -1 | -12 h | 5.52 mmol/L | Standard Deviation 0.556 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Glucose Concentration at Day -1 | -22 h | 4.72 mmol/L | Standard Deviation 0.279 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Glucose Concentration at Day -1 | -20 h | 4.55 mmol/L | Standard Deviation 0.207 |
| Placebo Group | Mean Glucose Concentration at Day -1 | -22 h | 4.82 mmol/L | Standard Deviation 0.36 |
| Placebo Group | Mean Glucose Concentration at Day -1 | -23 h | 4.92 mmol/L | Standard Deviation 0.313 |
| Placebo Group | Mean Glucose Concentration at Day -1 | -24 h | 4.77 mmol/L | Standard Deviation 0.468 |
| Placebo Group | Mean Glucose Concentration at Day -1 | -20 h | 4.73 mmol/L | Standard Deviation 0.48 |
| Placebo Group | Mean Glucose Concentration at Day -1 | -12 h | 5.48 mmol/L | Standard Deviation 0.806 |
Secondary
Mean Glucose Concentration at Day 30
Mean glucose concentrations (mmol/L) after repeated once or twice daily dosing with up to 10 mg emodepside or placebo at Day 30.
Time frame: Mean glucose at Day 30 after repeated once or twice daily dosing
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | Mean Glucose Concentration at Day 30 | 4.83 mmol/L | Standard Deviation 0.288 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Glucose Concentration at Day 30 | 5.23 mmol/L | Standard Deviation 0.993 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Glucose Concentration at Day 30 | 4.97 mmol/L | Standard Deviation 0.234 |
| Placebo Group | Mean Glucose Concentration at Day 30 | 4.53 mmol/L | Standard Deviation 0.35 |
Secondary
Mean Glucose Concentration at Day 9
Mean glucose concentrations (mmol/L) after repeated once or twice daily dosing with up to 10 mg emodepside or placebo at Day 9.
Time frame: Mean glucose at Day 9 after repeated once or twice daily dosing
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | Mean Glucose Concentration at Day 9 | 4 h | 4.60 mmol/L | Standard Deviation 0.363 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Glucose Concentration at Day 9 | 1 h | 5.10 mmol/L | Standard Deviation 0.352 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Glucose Concentration at Day 9 | 48 h | 5.02 mmol/L | Standard Deviation 0.194 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Glucose Concentration at Day 9 | 2 h | 5.03 mmol/L | Standard Deviation 0.25 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Glucose Concentration at Day 9 | 72 h | 4.87 mmol/L | Standard Deviation 0.35 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Glucose Concentration at Day 9 | 120 h | 5.00 mmol/L | Standard Deviation 0.352 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Glucose Concentration at Day 9 | 24 h | 4.92 mmol/L | Standard Deviation 0.264 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Glucose Concentration at Day 9 | Predose | 4.52 mmol/L | Standard Deviation 0.306 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Glucose Concentration at Day 9 | 96 h | 4.80 mmol/L | Standard Deviation 0.276 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Glucose Concentration at Day 9 | 12 h | 5.58 mmol/L | Standard Deviation 0.319 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Glucose Concentration at Day 9 | 24 h | 5.10 mmol/L | Standard Deviation 0.49 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Glucose Concentration at Day 9 | 72 h | 5.13 mmol/L | Standard Deviation 0.589 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Glucose Concentration at Day 9 | Predose | 4.95 mmol/L | Standard Deviation 0.362 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Glucose Concentration at Day 9 | 1 h | 5.98 mmol/L | Standard Deviation 1.972 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Glucose Concentration at Day 9 | 2 h | 5.72 mmol/L | Standard Deviation 1.543 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Glucose Concentration at Day 9 | 4 h | 4.62 mmol/L | Standard Deviation 0.377 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Glucose Concentration at Day 9 | 12 h | 6.00 mmol/L | Standard Deviation 0.745 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Glucose Concentration at Day 9 | 48 h | 5.07 mmol/L | Standard Deviation 0.532 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Glucose Concentration at Day 9 | 96 h | 5.10 mmol/L | Standard Deviation 0.54 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Glucose Concentration at Day 9 | 120 h | 4.98 mmol/L | Standard Deviation 0.458 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Glucose Concentration at Day 9 | 24 h | 5.17 mmol/L | Standard Deviation 0.273 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Glucose Concentration at Day 9 | 12 h | 7.03 mmol/L | Standard Deviation 1.111 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Glucose Concentration at Day 9 | 4 h | 5.08 mmol/L | Standard Deviation 0.662 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Glucose Concentration at Day 9 | 120 h | 5.05 mmol/L | Standard Deviation 0.288 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Glucose Concentration at Day 9 | 72 h | 5.03 mmol/L | Standard Deviation 0.308 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Glucose Concentration at Day 9 | 1 h | 5.65 mmol/L | Standard Deviation 0.771 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Glucose Concentration at Day 9 | 96 h | 4.85 mmol/L | Standard Deviation 0.315 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Glucose Concentration at Day 9 | 2 h | 5.57 mmol/L | Standard Deviation 0.761 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Glucose Concentration at Day 9 | Predose | 4.97 mmol/L | Standard Deviation 0.314 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Glucose Concentration at Day 9 | 48 h | 5.10 mmol/L | Standard Deviation 0.39 |
| Placebo Group | Mean Glucose Concentration at Day 9 | Predose | 4.67 mmol/L | Standard Deviation 0.234 |
| Placebo Group | Mean Glucose Concentration at Day 9 | 4 h | 4.70 mmol/L | Standard Deviation 0.374 |
| Placebo Group | Mean Glucose Concentration at Day 9 | 12 h | 6.02 mmol/L | Standard Deviation 0.615 |
| Placebo Group | Mean Glucose Concentration at Day 9 | 120 h | 4.90 mmol/L | Standard Deviation 0.352 |
| Placebo Group | Mean Glucose Concentration at Day 9 | 48 h | 4.90 mmol/L | Standard Deviation 0.379 |
| Placebo Group | Mean Glucose Concentration at Day 9 | 72 h | 5.03 mmol/L | Standard Deviation 0.28 |
| Placebo Group | Mean Glucose Concentration at Day 9 | 24 h | 4.82 mmol/L | Standard Deviation 0.16 |
| Placebo Group | Mean Glucose Concentration at Day 9 | 1 h | 4.80 mmol/L | Standard Deviation 0.219 |
| Placebo Group | Mean Glucose Concentration at Day 9 | 2 h | 4.74 mmol/L | Standard Deviation 0.329 |
| Placebo Group | Mean Glucose Concentration at Day 9 | 96 h | 4.87 mmol/L | Standard Deviation 0.32 |
Secondary
Mean Insulin Concentration at Day 0
Mean insulin concentration (pmol/L) after repeated once or twice daily dosing with up to 10 mg emodepside or placebo at Day 0. Baseline=predose on Day 0.
Time frame: Mean insulin concentration at Day 0 after repeated once or twice daily dosing
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | Mean Insulin Concentration at Day 0 | 12 h | 127.2 pmol/L | Standard Deviation 67.59 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Insulin Concentration at Day 0 | 4 h | 21.7 pmol/L | Standard Deviation 5.01 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Insulin Concentration at Day 0 | 1 h | 25.0 pmol/L | Standard Deviation 3.79 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Insulin Concentration at Day 0 | Predose (Baseline) | 27.8 pmol/L | Standard Deviation 15.41 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Insulin Concentration at Day 0 | 24 h | 36.7 pmol/L | Standard Deviation 15.49 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Insulin Concentration at Day 0 | 2 h | 24.3 pmol/L | Standard Deviation 5.2 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Insulin Concentration at Day 0 | 2 h | 25.3 pmol/L | Standard Deviation 9.99 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Insulin Concentration at Day 0 | 4 h | 21.7 pmol/L | Standard Deviation 5.39 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Insulin Concentration at Day 0 | 1 h | 23.2 pmol/L | Standard Deviation 10.85 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Insulin Concentration at Day 0 | Predose (Baseline) | 29.3 pmol/L | Standard Deviation 5.09 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Insulin Concentration at Day 0 | 12 h | 203.2 pmol/L | Standard Deviation 83.22 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Insulin Concentration at Day 0 | 24 h | 41.2 pmol/L | Standard Deviation 14.51 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Insulin Concentration at Day 0 | 2 h | 36.3 pmol/L | Standard Deviation 20.39 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Insulin Concentration at Day 0 | Predose (Baseline) | 32.2 pmol/L | Standard Deviation 14.34 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Insulin Concentration at Day 0 | 1 h | 29.2 pmol/L | Standard Deviation 14.86 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Insulin Concentration at Day 0 | 4 h | 27.7 pmol/L | Standard Deviation 11.69 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Insulin Concentration at Day 0 | 12 h | 175.3 pmol/L | Standard Deviation 64.59 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Insulin Concentration at Day 0 | 24 h | 30.3 pmol/L | Standard Deviation 11.43 |
| Placebo Group | Mean Insulin Concentration at Day 0 | 24 h | 35.2 pmol/L | Standard Deviation 16.59 |
| Placebo Group | Mean Insulin Concentration at Day 0 | 12 h | 195.0 pmol/L | Standard Deviation 88.03 |
| Placebo Group | Mean Insulin Concentration at Day 0 | 1 h | 33.0 pmol/L | Standard Deviation 9.1 |
| Placebo Group | Mean Insulin Concentration at Day 0 | 2 h | 31.2 pmol/L | Standard Deviation 12.89 |
| Placebo Group | Mean Insulin Concentration at Day 0 | Predose (Baseline) | 30.5 pmol/L | Standard Deviation 12.55 |
| Placebo Group | Mean Insulin Concentration at Day 0 | 4 h | 20.2 pmol/L | Standard Deviation 6.85 |
Secondary
Mean Insulin Concentration at Day -1
Mean insulin concentration (pmol/L) after repeated once or twice daily dosing with up to 10 mg emodepside or placebo at Day -1.
Time frame: Mean insulin concentration at Day-1 after repeated once or twice daily dosing
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | Mean Insulin Concentration at Day -1 | -22 h | 24.0 pmol/L | Standard Deviation 6.69 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Insulin Concentration at Day -1 | -23 h | 25.8 pmol/L | Standard Deviation 3.87 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Insulin Concentration at Day -1 | -12 h | 129.5 pmol/L | Standard Deviation 54.14 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Insulin Concentration at Day -1 | -20 h | 22.7 pmol/L | Standard Deviation 6.02 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Insulin Concentration at Day -1 | -24 h | 29.0 pmol/L | Standard Deviation 8.6 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Insulin Concentration at Day -1 | -24 h | 25.8 pmol/L | Standard Deviation 8.11 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Insulin Concentration at Day -1 | -12 h | 157.0 pmol/L | Standard Deviation 81.51 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Insulin Concentration at Day -1 | -23 h | 26.2 pmol/L | Standard Deviation 7.73 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Insulin Concentration at Day -1 | -22 h | 25.7 pmol/L | Standard Deviation 8.91 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Insulin Concentration at Day -1 | -20 h | 22.7 pmol/L | Standard Deviation 7.97 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Insulin Concentration at Day -1 | -22 h | 28.3 pmol/L | Standard Deviation 14.5 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Insulin Concentration at Day -1 | -24 h | 33.2 pmol/L | Standard Deviation 17.9 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Insulin Concentration at Day -1 | -12 h | 204.7 pmol/L | Standard Deviation 78.37 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Insulin Concentration at Day -1 | -23 h | 28.0 pmol/L | Standard Deviation 11.33 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Insulin Concentration at Day -1 | -20 h | 24.3 pmol/L | Standard Deviation 9.18 |
| Placebo Group | Mean Insulin Concentration at Day -1 | -12 h | 136.5 pmol/L | Standard Deviation 64.3 |
| Placebo Group | Mean Insulin Concentration at Day -1 | -24 h | 32.3 pmol/L | Standard Deviation 12.31 |
| Placebo Group | Mean Insulin Concentration at Day -1 | -22 h | 33.0 pmol/L | Standard Deviation 5.73 |
| Placebo Group | Mean Insulin Concentration at Day -1 | -20 h | 24.5 pmol/L | Standard Deviation 12.76 |
| Placebo Group | Mean Insulin Concentration at Day -1 | -23 h | 26.5 pmol/L | Standard Deviation 8.92 |
Secondary
Mean Insulin Concentration at Day 30
Mean insulin concentration (pmol/L) after repeated once or twice daily dosing with up to 10 mg emodepside or placebo at Day 30.
Time frame: Mean insulin concentration at Day 30 after repeated once or twice daily dosing
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | Mean Insulin Concentration at Day 30 | 29.2 pmol/L | Standard Deviation 12.5 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Insulin Concentration at Day 30 | 60.3 pmol/L | Standard Deviation 90.19 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Insulin Concentration at Day 30 | 24.3 pmol/L | Standard Deviation 9.79 |
| Placebo Group | Mean Insulin Concentration at Day 30 | 29.2 pmol/L | Standard Deviation 20.21 |
Secondary
Mean Insulin Concentration at Day 9
Mean insulin concentration (pmol/L) after repeated once or twice daily dosing with up to 10 mg emodepside or placebo at Day 9.
Time frame: Mean insulin concentration at Day 9 after repeated once or twice daily dosing
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | Mean Insulin Concentration at Day 9 | 72 h | 48.3 pmol/L | Standard Deviation 23.53 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Insulin Concentration at Day 9 | 1 h | 29.2 pmol/L | Standard Deviation 9.66 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Insulin Concentration at Day 9 | 12 h | 147.2 pmol/L | Standard Deviation 77.58 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Insulin Concentration at Day 9 | 4 h | 23.0 pmol/L | Standard Deviation 7.35 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Insulin Concentration at Day 9 | 48 h | 36.2 pmol/L | Standard Deviation 5.6 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Insulin Concentration at Day 9 | Predose | 31.5 pmol/L | Standard Deviation 8.62 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Insulin Concentration at Day 9 | 2 h | 27.7 pmol/L | Standard Deviation 4.84 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Insulin Concentration at Day 9 | 120 h | 39.0 pmol/L | Standard Deviation 8.63 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Insulin Concentration at Day 9 | 96 h | 37.8 pmol/L | Standard Deviation 10.42 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Insulin Concentration at Day 9 | 24 h | 34.5 pmol/L | Standard Deviation 11.88 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Insulin Concentration at Day 9 | 72 h | 40.7 pmol/L | Standard Deviation 13.88 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Insulin Concentration at Day 9 | Predose | 32.7 pmol/L | Standard Deviation 15.02 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Insulin Concentration at Day 9 | 96 h | 39.3 pmol/L | Standard Deviation 12.31 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Insulin Concentration at Day 9 | 120 h | 42.3 pmol/L | Standard Deviation 17.92 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Insulin Concentration at Day 9 | 2 h | 31.2 pmol/L | Standard Deviation 10.53 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Insulin Concentration at Day 9 | 4 h | 28.4 pmol/L | Standard Deviation 13.24 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Insulin Concentration at Day 9 | 12 h | 143.0 pmol/L | Standard Deviation 113.7 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Insulin Concentration at Day 9 | 24 h | 36.5 pmol/L | Standard Deviation 12.24 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Insulin Concentration at Day 9 | 1 h | 24.4 pmol/L | Standard Deviation 15.39 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Insulin Concentration at Day 9 | 48 h | 44.8 pmol/L | Standard Deviation 17.89 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Insulin Concentration at Day 9 | 2 h | 30.2 pmol/L | Standard Deviation 13.91 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Insulin Concentration at Day 9 | 120 h | 36.0 pmol/L | Standard Deviation 15.24 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Insulin Concentration at Day 9 | 48 h | 36.3 pmol/L | Standard Deviation 13.59 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Insulin Concentration at Day 9 | 24 h | 32.7 pmol/L | Standard Deviation 17.44 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Insulin Concentration at Day 9 | 1 h | 22.2 pmol/L | Standard Deviation 8.89 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Insulin Concentration at Day 9 | 96 h | 37.2 pmol/L | Standard Deviation 17.66 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Insulin Concentration at Day 9 | 4 h | 19.5 pmol/L | Standard Deviation 9.12 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Insulin Concentration at Day 9 | Predose | 29.2 pmol/L | Standard Deviation 10.19 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Insulin Concentration at Day 9 | 72 h | 39.8 pmol/L | Standard Deviation 15.61 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Insulin Concentration at Day 9 | 12 h | 215.8 pmol/L | Standard Deviation 128.1 |
| Placebo Group | Mean Insulin Concentration at Day 9 | 120 h | 33.2 pmol/L | Standard Deviation 21.68 |
| Placebo Group | Mean Insulin Concentration at Day 9 | Predose | 31.3 pmol/L | Standard Deviation 9.83 |
| Placebo Group | Mean Insulin Concentration at Day 9 | 1 h | 27.8 pmol/L | Standard Deviation 9.77 |
| Placebo Group | Mean Insulin Concentration at Day 9 | 2 h | 29.8 pmol/L | Standard Deviation 10.26 |
| Placebo Group | Mean Insulin Concentration at Day 9 | 4 h | 21.8 pmol/L | Standard Deviation 6.37 |
| Placebo Group | Mean Insulin Concentration at Day 9 | 12 h | 215.7 pmol/L | Standard Deviation 151.8 |
| Placebo Group | Mean Insulin Concentration at Day 9 | 24 h | 36.3 pmol/L | Standard Deviation 13.03 |
| Placebo Group | Mean Insulin Concentration at Day 9 | 48 h | 38.2 pmol/L | Standard Deviation 19.17 |
| Placebo Group | Mean Insulin Concentration at Day 9 | 72 h | 38.7 pmol/L | Standard Deviation 14.42 |
| Placebo Group | Mean Insulin Concentration at Day 9 | 96 h | 30.0 pmol/L | Standard Deviation 11.63 |
Secondary
Mean Serum Glucose Concentration at Day 1
Oral glucose tolerance test: mean serum glucose concentration at Day 1, before and up to 4 hours after intake of a high-glucose solution, in subjects receiving repeated doses of emodepside or placebo for 10 days (Days 0-9). Baseline=pre-glucose intake on each respective day.
Time frame: Mean serum glucose concentration at Day 1, before and up to 4 hours after intake of a high-glucose solution
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Glucose Concentration at Day 1 | Predose (Baseline) | 5.07 mmol/L | Standard Deviation 0.314 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Glucose Concentration at Day 1 | 1 h | 10.10 mmol/L | Standard Deviation 1.17 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Glucose Concentration at Day 1 | 2 h | 6.17 mmol/L | Standard Deviation 1.6 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Glucose Concentration at Day 1 | 4 h | 3.95 mmol/L | Standard Deviation 0.339 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Serum Glucose Concentration at Day 1 | 1 h | 12.37 mmol/L | Standard Deviation 2.826 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Serum Glucose Concentration at Day 1 | 2 h | 7.95 mmol/L | Standard Deviation 1.653 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Serum Glucose Concentration at Day 1 | 4 h | 3.65 mmol/L | Standard Deviation 0.362 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Serum Glucose Concentration at Day 1 | Predose (Baseline) | 4.88 mmol/L | Standard Deviation 0.264 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Serum Glucose Concentration at Day 1 | 2 h | 9.25 mmol/L | Standard Deviation 2.74 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Serum Glucose Concentration at Day 1 | 1 h | 12.03 mmol/L | Standard Deviation 0.989 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Serum Glucose Concentration at Day 1 | 4 h | 4.02 mmol/L | Standard Deviation 0.204 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Serum Glucose Concentration at Day 1 | Predose (Baseline) | 4.87 mmol/L | Standard Deviation 0.273 |
| Placebo Group | Mean Serum Glucose Concentration at Day 1 | 4 h | 4.15 mmol/L | Standard Deviation 0.575 |
| Placebo Group | Mean Serum Glucose Concentration at Day 1 | 1 h | 7.58 mmol/L | Standard Deviation 2.242 |
| Placebo Group | Mean Serum Glucose Concentration at Day 1 | Predose (Baseline) | 4.97 mmol/L | Standard Deviation 0.228 |
| Placebo Group | Mean Serum Glucose Concentration at Day 1 | 2 h | 5.88 mmol/L | Standard Deviation 1.174 |
Secondary
Mean Serum Glucose Concentration at Day 120
Oral glucose tolerance test: mean serum glucose concentration at Day 120, before and up to 4 hours after intake of a high-glucose solution, in subjects receiving repeated doses of emodepside or placebo for 10 days (Days 0-9). Baseline=pre-glucose intake on each respective day. Note: At Day 120, serum glucose concentration was only measured in Cohort 3 (10 mg BID)
Time frame: Mean serum glucose concentration at Day 120, before and up to 4 hours after intake of a high-glucose solution
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Glucose Concentration at Day 120 | 0 h (Baseline) | 4.93 mmol/L | Standard Deviation 0.294 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Glucose Concentration at Day 120 | 1 h | 8.12 mmol/L | Standard Deviation 2.542 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Glucose Concentration at Day 120 | 2 h | 6.08 mmol/L | Standard Deviation 0.54 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Glucose Concentration at Day 120 | 4 h | 4.26 mmol/L | Standard Deviation 0.305 |
Secondary
Mean Serum Glucose Concentration at Day -2
Oral glucose tolerance test: mean serum glucose concentration at Day -2, before and up to 4 hours after intake of a high-glucose solution, in subjects receiving repeated doses of emodepside or placebo for 10 days (Days 0-9). Baseline=pre-glucose intake on each respective day.
Time frame: Mean serum glucose concentration at Day -2, before and up to 4 hours after intake of a high-glucose solution
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Glucose Concentration at Day -2 | 0 h (Baseline) | 4.72 mmol/L | Standard Deviation 0.319 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Glucose Concentration at Day -2 | 1 h | 8.78 mmol/L | Standard Deviation 1.659 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Glucose Concentration at Day -2 | 2 h | 5.98 mmol/L | Standard Deviation 1.512 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Glucose Concentration at Day -2 | 4 h | 4.57 mmol/L | Standard Deviation 0.979 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Serum Glucose Concentration at Day -2 | 1 h | 7.03 mmol/L | Standard Deviation 0.301 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Serum Glucose Concentration at Day -2 | 2 h | 5.05 mmol/L | Standard Deviation 0.589 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Serum Glucose Concentration at Day -2 | 4 h | 3.95 mmol/L | Standard Deviation 0.622 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Serum Glucose Concentration at Day -2 | 0 h (Baseline) | 4.92 mmol/L | Standard Deviation 0.256 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Serum Glucose Concentration at Day -2 | 2 h | 5.48 mmol/L | Standard Deviation 0.608 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Serum Glucose Concentration at Day -2 | 1 h | 7.00 mmol/L | Standard Deviation 0.867 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Serum Glucose Concentration at Day -2 | 4 h | 4.22 mmol/L | Standard Deviation 0.371 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Serum Glucose Concentration at Day -2 | 0 h (Baseline) | 4.97 mmol/L | Standard Deviation 0.294 |
| Placebo Group | Mean Serum Glucose Concentration at Day -2 | 4 h | 4.53 mmol/L | Standard Deviation 0.294 |
| Placebo Group | Mean Serum Glucose Concentration at Day -2 | 1 h | 6.48 mmol/L | Standard Deviation 1.45 |
| Placebo Group | Mean Serum Glucose Concentration at Day -2 | 0 h (Baseline) | 4.78 mmol/L | Standard Deviation 0.133 |
| Placebo Group | Mean Serum Glucose Concentration at Day -2 | 2 h | 4.95 mmol/L | Standard Deviation 0.965 |
Secondary
Mean Serum Glucose Concentration at Day 8
Oral glucose tolerance test: mean serum glucose concentration at Day 8, before and up to 4 hours after intake of a high-glucose solution, in subjects receiving repeated doses of emodepside or placebo for 10 days (Days 0-9). Baseline=pre-glucose intake on each respective day.
Time frame: Mean serum glucose concentration at Day 8, before and up to 4 hours after intake of a high-glucose solution
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Glucose Concentration at Day 8 | Predose (Baseline) | 4.87 mmol/L | Standard Deviation 0.314 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Glucose Concentration at Day 8 | 1 h | 10.02 mmol/L | Standard Deviation 1.857 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Glucose Concentration at Day 8 | 2 h | 7.05 mmol/L | Standard Deviation 1.533 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Glucose Concentration at Day 8 | 4 h | 3.93 mmol/L | Standard Deviation 0.965 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Serum Glucose Concentration at Day 8 | 1 h | 11.75 mmol/L | Standard Deviation 4.574 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Serum Glucose Concentration at Day 8 | 2 h | 8.98 mmol/L | Standard Deviation 4.311 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Serum Glucose Concentration at Day 8 | 4 h | 4.12 mmol/L | Standard Deviation 0.933 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Serum Glucose Concentration at Day 8 | Predose (Baseline) | 5.10 mmol/L | Standard Deviation 0.533 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Serum Glucose Concentration at Day 8 | 2 h | 8.97 mmol/L | Standard Deviation 2.837 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Serum Glucose Concentration at Day 8 | 1 h | 11.27 mmol/L | Standard Deviation 2.738 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Serum Glucose Concentration at Day 8 | 4 h | 4.52 mmol/L | Standard Deviation 0.806 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Serum Glucose Concentration at Day 8 | Predose (Baseline) | 4.90 mmol/L | Standard Deviation 0.303 |
| Placebo Group | Mean Serum Glucose Concentration at Day 8 | 4 h | 4.13 mmol/L | Standard Deviation 0.197 |
| Placebo Group | Mean Serum Glucose Concentration at Day 8 | 1 h | 7.77 mmol/L | Standard Deviation 1.679 |
| Placebo Group | Mean Serum Glucose Concentration at Day 8 | Predose (Baseline) | 4.83 mmol/L | Standard Deviation 0.258 |
| Placebo Group | Mean Serum Glucose Concentration at Day 8 | 2 h | 5.52 mmol/L | Standard Deviation 0.783 |
Secondary
Mean Serum Insulin Concentration at Day 1
Oral glucose tolerance test: mean serum insulin concentration at Day 1, before and up to 4 hours after intake of a high-glucose solution, in subjects receiving repeated doses of emodepside or placebo for 10 days (Days 0-9). Baseline=pre-glucose intake on each respective day.
Time frame: Mean serum insulin concentration at Day 1, before and up to 4 hours after intake of a high-glucose solution
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Insulin Concentration at Day 1 | Predose (Baseline) | 36.7 pmol/L | Standard Deviation 15.49 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Insulin Concentration at Day 1 | 1 h | 312.2 pmol/L | Standard Deviation 153.67 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Insulin Concentration at Day 1 | 2 h | 268.5 pmol/L | Standard Deviation 107.14 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Insulin Concentration at Day 1 | 4 h | 28.8 pmol/L | Standard Deviation 22.35 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Serum Insulin Concentration at Day 1 | 1 h | 288.8 pmol/L | Standard Deviation 171.44 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Serum Insulin Concentration at Day 1 | 2 h | 377.3 pmol/L | Standard Deviation 224.73 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Serum Insulin Concentration at Day 1 | 4 h | 30.8 pmol/L | Standard Deviation 12.35 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Serum Insulin Concentration at Day 1 | Predose (Baseline) | 41.2 pmol/L | Standard Deviation 14.51 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Serum Insulin Concentration at Day 1 | 2 h | 336.2 pmol/L | Standard Deviation 165.71 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Serum Insulin Concentration at Day 1 | 1 h | 332.2 pmol/L | Standard Deviation 228.84 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Serum Insulin Concentration at Day 1 | 4 h | 35.7 pmol/L | Standard Deviation 4.59 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Serum Insulin Concentration at Day 1 | Predose (Baseline) | 30.3 pmol/L | Standard Deviation 11.43 |
| Placebo Group | Mean Serum Insulin Concentration at Day 1 | 4 h | 33.8 pmol/L | Standard Deviation 19.56 |
| Placebo Group | Mean Serum Insulin Concentration at Day 1 | 1 h | 606.7 pmol/L | Standard Deviation 157.35 |
| Placebo Group | Mean Serum Insulin Concentration at Day 1 | Predose (Baseline) | 35.2 pmol/L | Standard Deviation 16.59 |
| Placebo Group | Mean Serum Insulin Concentration at Day 1 | 2 h | 238.0 pmol/L | Standard Deviation 165.06 |
Secondary
Mean Serum Insulin Concentration at Day 120
Oral glucose tolerance test: mean serum insulin concentration at Day 120, before and up to 4 hours after intake of a high-glucose solution, in subjects receiving repeated doses of emodepside or placebo for 10 days (Days 0-9). Baseline=pre-glucose intake on each respective day. Note: At Day 120, serum glucose concentration was only measured in Cohort 3 (10 mg BID)
Time frame: Mean serum insulin concentration at Day 120, before and up to 4 hours after intake of a high-glucose solution
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Insulin Concentration at Day 120 | 0 h (Baseline) | 28.0 pmol/L | Standard Deviation 13.74 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Insulin Concentration at Day 120 | 1 h | 417.8 pmol/L | Standard Deviation 379.72 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Insulin Concentration at Day 120 | 2 h | 152.8 pmol/L | Standard Deviation 114.92 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Insulin Concentration at Day 120 | 4 h | 18.8 pmol/L | Standard Deviation 11.39 |
Secondary
Mean Serum Insulin Concentration at Day -2
Oral glucose tolerance test: mean serum insulin concentration at Day -2, before and up to 4 hours after intake of a high-glucose solution, in subjects receiving repeated doses of emodepside or placebo for 10 days (Days 0-9). Baseline=pre-glucose intake on each respective day.
Time frame: Mean serum insulin concentration at Day -2, before and up to 4 hours after intake of a high-glucose solution
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Insulin Concentration at Day -2 | 0 h (Baseline) | 24.5 pmol/L | Standard Deviation 13.81 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Insulin Concentration at Day -2 | 1 h | 334.8 pmol/L | Standard Deviation 207.66 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Insulin Concentration at Day -2 | 2 h | 174.7 pmol/L | Standard Deviation 206.08 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Insulin Concentration at Day -2 | 4 h | 44.3 pmol/L | Standard Deviation 72.56 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Serum Insulin Concentration at Day -2 | 1 h | 305.3 pmol/L | Standard Deviation 65.59 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Serum Insulin Concentration at Day -2 | 2 h | 103.7 pmol/L | Standard Deviation 32.38 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Serum Insulin Concentration at Day -2 | 4 h | 17.2 pmol/L | Standard Deviation 6.11 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Serum Insulin Concentration at Day -2 | 0 h (Baseline) | 25.7 pmol/L | Standard Deviation 8.55 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Serum Insulin Concentration at Day -2 | 2 h | 136.0 pmol/L | Standard Deviation 70.52 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Serum Insulin Concentration at Day -2 | 1 h | 306.7 pmol/L | Standard Deviation 180 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Serum Insulin Concentration at Day -2 | 4 h | 20.8 pmol/L | Standard Deviation 7.44 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Serum Insulin Concentration at Day -2 | 0 h (Baseline) | 27.0 pmol/L | Standard Deviation 14 |
| Placebo Group | Mean Serum Insulin Concentration at Day -2 | 4 h | 21.8 pmol/L | Standard Deviation 9.33 |
| Placebo Group | Mean Serum Insulin Concentration at Day -2 | 1 h | 338.3 pmol/L | Standard Deviation 189.61 |
| Placebo Group | Mean Serum Insulin Concentration at Day -2 | 0 h (Baseline) | 29.0 pmol/L | Standard Deviation 14.68 |
| Placebo Group | Mean Serum Insulin Concentration at Day -2 | 2 h | 186.8 pmol/L | Standard Deviation 83.55 |
Secondary
Mean Serum Insulin Concentration at Day 8
Oral glucose tolerance test: mean serum insulin concentration at Day 8, before and up to 4 hours after intake of a high-glucose solution, in subjects receiving repeated doses of emodepside or placebo for 10 days (Days 0-9). Baseline=pre-glucose intake on each respective day.
Time frame: Mean serum insulin concentration at Day 8, before and up to 4 hours after intake of a high-glucose solution
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Insulin Concentration at Day 8 | Predose (Baseline) | 32.5 pmol/L | Standard Deviation 9.85 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Insulin Concentration at Day 8 | 1 h | 302.5 pmol/L | Standard Deviation 145.61 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Insulin Concentration at Day 8 | 2 h | 337.0 pmol/L | Standard Deviation 110.23 |
| Cohort 1: 5mg EMODEPSIDE OD | Mean Serum Insulin Concentration at Day 8 | 4 h | 63.0 pmol/L | Standard Deviation 86.69 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Serum Insulin Concentration at Day 8 | 1 h | 286.8 pmol/L | Standard Deviation 179.53 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Serum Insulin Concentration at Day 8 | 2 h | 225.7 pmol/L | Standard Deviation 101.02 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Serum Insulin Concentration at Day 8 | 4 h | 63.3 pmol/L | Standard Deviation 83.32 |
| Cohort 2: 10mg EMODEPSIDE OD | Mean Serum Insulin Concentration at Day 8 | Predose (Baseline) | 39.3 pmol/L | Standard Deviation 22.59 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Serum Insulin Concentration at Day 8 | 2 h | 229.8 pmol/L | Standard Deviation 79 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Serum Insulin Concentration at Day 8 | 1 h | 225.3 pmol/L | Standard Deviation 148.93 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Serum Insulin Concentration at Day 8 | 4 h | 36.8 pmol/L | Standard Deviation 21.17 |
| Cohort 3: 10mg EMODEPSIDE BID | Mean Serum Insulin Concentration at Day 8 | Predose (Baseline) | 34.5 pmol/L | Standard Deviation 15.83 |
| Placebo Group | Mean Serum Insulin Concentration at Day 8 | 4 h | 21.7 pmol/L | Standard Deviation 19.97 |
| Placebo Group | Mean Serum Insulin Concentration at Day 8 | 1 h | 690.5 pmol/L | Standard Deviation 342.1 |
| Placebo Group | Mean Serum Insulin Concentration at Day 8 | Predose (Baseline) | 33.8 pmol/L | Standard Deviation 12.94 |
| Placebo Group | Mean Serum Insulin Concentration at Day 8 | 2 h | 238.3 pmol/L | Standard Deviation 92.34 |
Secondary
The AUC12/D of Emodepside in Plasma
Summary of AUC12/D of emodepside after the first (Day 0) and last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15h after the morning dose. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120h (Day 14) after the morning dose. AUC12/D: the area under the concentration-time curve from time zero (pre-dose) to 12h, corrected for dose. Note: AUC12/D was collected only in Cohort 3. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).
Time frame: AUC12/D in plasma after the first (Day 0) and last (Day 9) dose
Population: BID=twice daily.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | The AUC12/D of Emodepside in Plasma | Day 0 | 74.2 h*ng/mL/mg | Geometric Coefficient of Variation 29.4 |
| Cohort 1: 5mg EMODEPSIDE OD | The AUC12/D of Emodepside in Plasma | Day 9 | 281 h*ng/mL/mg | Geometric Coefficient of Variation 35 |
Secondary
The AUC12,Norm of Emodepside in Plasma
Summary of AUC12,norm of emodepside after the first (Day 0) and last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15 h after the morning dose. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose. AUC12,norm: the area under the concentration-time curve from time zero (pre-dose) to 12 h corrected by dose and body weight. Note: AUC12,norm was calculated only in Cohort 3. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).
Time frame: AUC12,norm in plasma after the first (Day 0) and last (Day 9) dose
Population: BID=twice daily.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | The AUC12,Norm of Emodepside in Plasma | Day 0 | 0.985 (h*ng/mL)/(mg*kg) | Geometric Coefficient of Variation 39.2 |
| Cohort 1: 5mg EMODEPSIDE OD | The AUC12,Norm of Emodepside in Plasma | Day 9 | 3.73 (h*ng/mL)/(mg*kg) | Geometric Coefficient of Variation 46.6 |
Secondary
The AUC12 of Emodepside in Plasma
Summary of AUC12 of emodepside after the first (Day 0) and last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15h after the morning dose. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120h (Day 14) after the morning dose. AUC12: the area under the concentration-time curve from time zero (pre-dose) to 12h. Note: AUC12 was calculated only in Cohort 3. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).
Time frame: AUC12 in plasma after the first (Day 0) and last (Day 9) dose
Population: BID=twice daily.
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | The AUC12 of Emodepside in Plasma | Day 0 | 742 h*ng/mL | Geometric Coefficient of Variation 29.4 |
| Cohort 1: 5mg EMODEPSIDE OD | The AUC12 of Emodepside in Plasma | Day 9 | 2810 h*ng/mL | Geometric Coefficient of Variation 35 |
Secondary
The AUC24/D of Emodepside in Plasma
Summary of AUC24/D of emodepside after the first (Day 0) and last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15 h after the morning dose. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose. AUC24/D: the area under the concentration-time curve from time zero (pre-dose) to 24h corrected for dose. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).
Time frame: AUC24/D in plasma after the first (Day 0) and last (Day 9) dose
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | The AUC24/D of Emodepside in Plasma | Day 0 | 115 h*ng/mL/mg | Geometric Coefficient of Variation 19.7 |
| Cohort 1: 5mg EMODEPSIDE OD | The AUC24/D of Emodepside in Plasma | Day 9 | 338 h*ng/mL/mg | Geometric Coefficient of Variation 31.3 |
| Cohort 2: 10mg EMODEPSIDE OD | The AUC24/D of Emodepside in Plasma | Day 0 | 113 h*ng/mL/mg | Geometric Coefficient of Variation 32.7 |
| Cohort 2: 10mg EMODEPSIDE OD | The AUC24/D of Emodepside in Plasma | Day 9 | 349 h*ng/mL/mg | Geometric Coefficient of Variation 44.2 |
| Cohort 3: 10mg EMODEPSIDE BID | The AUC24/D of Emodepside in Plasma | Day 0 | 71.4 h*ng/mL/mg | Geometric Coefficient of Variation 26.5 |
| Cohort 3: 10mg EMODEPSIDE BID | The AUC24/D of Emodepside in Plasma | Day 9 | 490 h*ng/mL/mg | Geometric Coefficient of Variation 35.8 |
Secondary
The AUC24,Norm of Emodepside in Plasma
Summary of AUC24,norm of emodepside after the first (Day 0) and last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15h after the morning dose. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120h (Day 14) after the morning dose. AUC24,norm: the area under the concentration-time curve from time zero (pre-dose) to 24h corrected by dose and body weight. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).
Time frame: AUC24,norm in plasma at Day 0 and Day 9
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | The AUC24,Norm of Emodepside in Plasma | Day 9 | 4.70 (h*ng/mL)/(mg*kg) | Geometric Coefficient of Variation 34.1 |
| Cohort 1: 5mg EMODEPSIDE OD | The AUC24,Norm of Emodepside in Plasma | Day 0 | 1.60 (h*ng/mL)/(mg*kg) | Geometric Coefficient of Variation 21.5 |
| Cohort 2: 10mg EMODEPSIDE OD | The AUC24,Norm of Emodepside in Plasma | Day 0 | 1.48 (h*ng/mL)/(mg*kg) | Geometric Coefficient of Variation 56.7 |
| Cohort 2: 10mg EMODEPSIDE OD | The AUC24,Norm of Emodepside in Plasma | Day 9 | 4.54 (h*ng/mL)/(mg*kg) | Geometric Coefficient of Variation 69.7 |
| Cohort 3: 10mg EMODEPSIDE BID | The AUC24,Norm of Emodepside in Plasma | Day 0 | 0.948 (h*ng/mL)/(mg*kg) | Geometric Coefficient of Variation 36.5 |
| Cohort 3: 10mg EMODEPSIDE BID | The AUC24,Norm of Emodepside in Plasma | Day 9 | 6.50 (h*ng/mL)/(mg*kg) | Geometric Coefficient of Variation 47.7 |
Secondary
The AUC24 of Emodepside in Plasma
Summary of AUC24 of emodepside after the first (Day 0) and last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15 h after the morning dose. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose. AUC24: the area under the concentration-time curve from time zero (pre-dose) to 24 h. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).
Time frame: AUC24 in plasma after the first (Day 0) and last (Day 9) dose
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | The AUC24 of Emodepside in Plasma | Day 0 | 574 h*ng/mL | Geometric Coefficient of Variation 19.7 |
| Cohort 1: 5mg EMODEPSIDE OD | The AUC24 of Emodepside in Plasma | Day 9 | 1689 h*ng/mL | Geometric Coefficient of Variation 31.3 |
| Cohort 2: 10mg EMODEPSIDE OD | The AUC24 of Emodepside in Plasma | Day 0 | 1135 h*ng/mL | Geometric Coefficient of Variation 32.7 |
| Cohort 2: 10mg EMODEPSIDE OD | The AUC24 of Emodepside in Plasma | Day 9 | 3487 h*ng/mL | Geometric Coefficient of Variation 44.2 |
| Cohort 3: 10mg EMODEPSIDE BID | The AUC24 of Emodepside in Plasma | Day 0 | 1428 h*ng/mL | Geometric Coefficient of Variation 26.5 |
| Cohort 3: 10mg EMODEPSIDE BID | The AUC24 of Emodepside in Plasma | Day 9 | 4897 h*ng/mL | Geometric Coefficient of Variation 35.8 |
Secondary
The AUClast/D of Emodepside in Plasma
Summary of AUClast/D of emodepside after the last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120h (Day 14) after the morning dose. AUClast/D: the area under the concentration-time curve from time zero (pre-dose) to the time of last quantifiable concentration corrected for dose. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).
Time frame: AUClast /D in plasma after the last dose (Day 9)
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | The AUClast/D of Emodepside in Plasma | 3872 h*ng/mL/mg | Geometric Coefficient of Variation 29.9 |
| Cohort 2: 10mg EMODEPSIDE OD | The AUClast/D of Emodepside in Plasma | 4065 h*ng/mL/mg | Geometric Coefficient of Variation 43.5 |
| Cohort 3: 10mg EMODEPSIDE BID | The AUClast/D of Emodepside in Plasma | 5955 h*ng/mL/mg | Geometric Coefficient of Variation 29.1 |
Secondary
The AUClast,Norm of Emodepside in Plasma
Summary of AUClast,norm of emodepside after the last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120h (Day 14) after the morning dose. AUClast,norm: the area under the concentration-time curve from time zero (pre-dose) to the time of last quantifiable concentration corrected by dose and body weight. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).
Time frame: AUClast,norm in plasma after the last (Day 9) dose
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | The AUClast,Norm of Emodepside in Plasma | 53.9 (h*ng/mL)/(mg*kg) | Geometric Coefficient of Variation 33.1 |
| Cohort 2: 10mg EMODEPSIDE OD | The AUClast,Norm of Emodepside in Plasma | 52.9 (h*ng/mL)/(mg*kg) | Geometric Coefficient of Variation 69.5 |
| Cohort 3: 10mg EMODEPSIDE BID | The AUClast,Norm of Emodepside in Plasma | 79.1 (h*ng/mL)/(mg*kg) | Geometric Coefficient of Variation 40.6 |
Secondary
The AUClast of Emodepside in Plasma
Summary of AUClast of emodepside after the last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120h (Day 14) after the morning dose. AUClast: the area under the concentration-time curve from time zero (pre-dose) to the time of last quantifiable concentration. PK=pharmacokinetic. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).
Time frame: AUClast in plasma after the last dose (Day 9)
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | The AUClast of Emodepside in Plasma | 19359 h*ng/mL | Geometric Coefficient of Variation 29.9 |
| Cohort 2: 10mg EMODEPSIDE OD | The AUClast of Emodepside in Plasma | 40655 h*ng/mL | Geometric Coefficient of Variation 43.5 |
| Cohort 3: 10mg EMODEPSIDE BID | The AUClast of Emodepside in Plasma | 59554 h*ng/mL | Geometric Coefficient of Variation 29.1 |
Secondary
The CLss/F of Emodepside in Plasma
Summary of CLss/F of emodepside after the last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose. CLss/F: apparent total clearance from plasma on Day 9. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).
Time frame: CLss/F in plasma after the last (Day 9) dose
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | The CLss/F of Emodepside in Plasma | 2.96 L/h | Geometric Coefficient of Variation 31.3 |
| Cohort 2: 10mg EMODEPSIDE OD | The CLss/F of Emodepside in Plasma | 2.87 L/h | Geometric Coefficient of Variation 44.2 |
| Cohort 3: 10mg EMODEPSIDE BID | The CLss/F of Emodepside in Plasma | 3.56 L/h | Geometric Coefficient of Variation 35 |
Secondary
The Cmax/D of Emodepside in Plasma
Summary of Cmax/D of emodepside after the first (Day 0) and last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15 h after the morning dose. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose. Cmax/D: the observed maximum plasma concentration measured in a subject after dosing identified by inspection of the drug concentration vs. time data, corrected for dose. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).
Time frame: Cmax/D in plasma after the first (Day 0) and last (Day 9) dose
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | The Cmax/D of Emodepside in Plasma | Day 0 | 18.8 ng/mL/mg | Geometric Coefficient of Variation 17.8 |
| Cohort 1: 5mg EMODEPSIDE OD | The Cmax/D of Emodepside in Plasma | Day 9 | 29.9 ng/mL/mg | Geometric Coefficient of Variation 17.9 |
| Cohort 2: 10mg EMODEPSIDE OD | The Cmax/D of Emodepside in Plasma | Day 0 | 18.6 ng/mL/mg | Geometric Coefficient of Variation 21.3 |
| Cohort 2: 10mg EMODEPSIDE OD | The Cmax/D of Emodepside in Plasma | Day 9 | 28.7 ng/mL/mg | Geometric Coefficient of Variation 39.7 |
| Cohort 3: 10mg EMODEPSIDE BID | The Cmax/D of Emodepside in Plasma | Day 0 | 16.0 ng/mL/mg | Geometric Coefficient of Variation 20.4 |
| Cohort 3: 10mg EMODEPSIDE BID | The Cmax/D of Emodepside in Plasma | Day 9 | 34.9 ng/mL/mg | Geometric Coefficient of Variation 27.1 |
Secondary
The Cmax,Norm of Emodepside in Plasma
Summary of Cmax,norm of emodepside after the first (Day 0) and last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15 h after the morning dose. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose. Cmax,norm: the observed maximum plasma concentration measured in a subject after dosing identified by inspection of the drug concentration vs. time data, corrected for dose and body weight. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).
Time frame: Cmax,norm in plasma after the first (Day 0) and last (Day 9) dose
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | The Cmax,Norm of Emodepside in Plasma | Day 9 | 0.416 (ng/mL)*(mg*kg) | Geometric Coefficient of Variation 20.6 |
| Cohort 1: 5mg EMODEPSIDE OD | The Cmax,Norm of Emodepside in Plasma | Day 0 | 0.261 (ng/mL)*(mg*kg) | Geometric Coefficient of Variation 18.4 |
| Cohort 2: 10mg EMODEPSIDE OD | The Cmax,Norm of Emodepside in Plasma | Day 0 | 0.242 (ng/mL)*(mg*kg) | Geometric Coefficient of Variation 42.8 |
| Cohort 2: 10mg EMODEPSIDE OD | The Cmax,Norm of Emodepside in Plasma | Day 9 | 0.374 (ng/mL)*(mg*kg) | Geometric Coefficient of Variation 65.4 |
| Cohort 3: 10mg EMODEPSIDE BID | The Cmax,Norm of Emodepside in Plasma | Day 0 | 0.212 (ng/mL)*(mg*kg) | Geometric Coefficient of Variation 28.7 |
| Cohort 3: 10mg EMODEPSIDE BID | The Cmax,Norm of Emodepside in Plasma | Day 9 | 0.464 (ng/mL)*(mg*kg) | Geometric Coefficient of Variation 38.2 |
Secondary
The Cmax of Emodepside in Plasma
Summary of Cmax of emodepside after the first (Day 0) and last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15 h after the morning dose. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose. Cmax: the observed maximum plasma concentration measured in a subject after dosing identified by inspection of the drug concentration vs. time data. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).
Time frame: Cmax in plasma after the first (Day 0) and last (Day 9) dose
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | The Cmax of Emodepside in Plasma | Day 0 | 93.8 ng/mL | Geometric Coefficient of Variation 17.8 |
| Cohort 1: 5mg EMODEPSIDE OD | The Cmax of Emodepside in Plasma | Day 9 | 149 ng/mL | Geometric Coefficient of Variation 17.9 |
| Cohort 2: 10mg EMODEPSIDE OD | The Cmax of Emodepside in Plasma | Day 0 | 186 ng/mL | Geometric Coefficient of Variation 21.3 |
| Cohort 2: 10mg EMODEPSIDE OD | The Cmax of Emodepside in Plasma | Day 9 | 287 ng/mL | Geometric Coefficient of Variation 39.7 |
| Cohort 3: 10mg EMODEPSIDE BID | The Cmax of Emodepside in Plasma | Day 0 | 160 ng/mL | Geometric Coefficient of Variation 20.4 |
| Cohort 3: 10mg EMODEPSIDE BID | The Cmax of Emodepside in Plasma | Day 9 | 349 ng/mL | Geometric Coefficient of Variation 27.1 |
Secondary
The Ctrough of Emodepside in Plasma
Summary of Ctrough (log-transformed) of emodepside after last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose. Ctrough: trough plasma concentration (measured concentration at the end of a dosing interval on Day 9 \[taken directly before next administration\]) obtained directly from the concentration-time data. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).
Time frame: Ctrough in plasma after the last (Day 9) dose
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | The Ctrough of Emodepside in Plasma | 49.7 ng/mL | Geometric Coefficient of Variation 36.8 |
| Cohort 2: 10mg EMODEPSIDE OD | The Ctrough of Emodepside in Plasma | 97.1 ng/mL | Geometric Coefficient of Variation 50.8 |
| Cohort 3: 10mg EMODEPSIDE BID | The Ctrough of Emodepside in Plasma | 185 ng/mL | Geometric Coefficient of Variation 39.5 |
Secondary
The MRTlast of Emodepside in Plasma
Summary of MRTlast of emodepside after the first (Day 0) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15 h after the morning dose. MRTlast: mean residence time from time zero (pre-dose) to the time of last quantifiable concentration (measurable up to 24h after dosing on Day 0). The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).
Time frame: MRTlast in plasma after the first (Day 0) dose
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | The MRTlast of Emodepside in Plasma | 7.28 Hours | Geometric Coefficient of Variation 10.7 |
| Cohort 2: 10mg EMODEPSIDE OD | The MRTlast of Emodepside in Plasma | 7.00 Hours | Geometric Coefficient of Variation 11 |
| Cohort 3: 10mg EMODEPSIDE BID | The MRTlast of Emodepside in Plasma | 10.8 Hours | Geometric Coefficient of Variation 2.8 |
Secondary
The Rac(AUC12) of Emodepside in Plasma
Summary of emodepside plasma Rac(AUC12) after 10 days' repeated doses of 10 mg emodepside (Day 9): PK parameter population. Rac(AUC12): accumulation ratio calculated from AUC12, where AUC12 is the area under the concentration-time curve from time zero (pre-dose) to 12h. Note: measure of dispersion is 'percentage coefficient of variation' (the between-subject coefficient of variation \[%CVb\]). Note: Rac(AUC12) was calculated only in Cohort 3.
Time frame: Rac(AUC12) after 10 days' repeated doses of 10 mg emodepside (Day 9)
Population: BID=twice daily.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | The Rac(AUC12) of Emodepside in Plasma | 3.83 Ratio | Standard Deviation 15.5 |
Secondary
The Rac(AUC24) of Emodepside in Plasma
Summary of emodepside plasma Rac(AUC24) after 10 days' repeated doses of 10 mg emodepside (Day 9): PK parameter population. Rac(AUC24): accumulation ratio calculated from AUC24, where AUC24 is the area under the concentration-time curve from time zero (pre-dose) to 24h. Note: measure of dispersion is 'percentage coefficient of variation' (the between-subject coefficient of variation \[%CVb\]).
Time frame: Rac(AUC24) after 10 days' repeated doses of 10 mg emodepside (Day 9)
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | The Rac(AUC24) of Emodepside in Plasma | 2.97 Ratio | Standard Deviation 16.1 |
| Cohort 2: 10mg EMODEPSIDE OD | The Rac(AUC24) of Emodepside in Plasma | 3.09 Ratio | Standard Deviation 11.3 |
| Cohort 3: 10mg EMODEPSIDE BID | The Rac(AUC24) of Emodepside in Plasma | 3.47 Ratio | Standard Deviation 17.1 |
Secondary
The Rac(Cmax) of Emodepside in Plasma
Summary of emodepside plasma Rac(Cmax) after 10 days' repeated doses of 10 mg emodepside (Day 9): PK parameter population. Rac(Cmax): accumulation ratio calculated from Cmax, where Cmax is the observed maximum plasma concentration measured in a subject after dosing identified by inspection of the drug concentration vs. time data. Note: measure of dispersion is 'percentage coefficient of variation' (the between-subject coefficient of variation \[%CVb\]).
Time frame: Rac(Cmax) after 10 days' repeated doses of 10 mg emodepside (Day 9)
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | The Rac(Cmax) of Emodepside in Plasma | 1.61 Ratio | Standard Deviation 16.5 |
| Cohort 2: 10mg EMODEPSIDE OD | The Rac(Cmax) of Emodepside in Plasma | 1.58 Ratio | Standard Deviation 24.1 |
| Cohort 3: 10mg EMODEPSIDE BID | The Rac(Cmax) of Emodepside in Plasma | 2.21 Ratio | Standard Deviation 17.4 |
Secondary
The t1/2,(0-24) of Emodepside in Plasma
Summary of t1/2,(0-24) of emodepside after the last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose. t1/2,(0-24): half-life calculated from the terminal slope of the log concentration-time (0-24h) curve. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).
Time frame: t1/2,(0-24) in plasma after the last (Day 9) dose
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | The t1/2,(0-24) of Emodepside in Plasma | 26.9 Hours | Geometric Coefficient of Variation 52.4 |
| Cohort 2: 10mg EMODEPSIDE OD | The t1/2,(0-24) of Emodepside in Plasma | 18.4 Hours | Geometric Coefficient of Variation 30 |
| Cohort 3: 10mg EMODEPSIDE BID | The t1/2,(0-24) of Emodepside in Plasma | 33.2 Hours | Geometric Coefficient of Variation 55 |
Secondary
The t1/2 of Emodepside in Plasma
Summary of t1/2 of emodepside after the last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose. t1/2: terminal half-life. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).
Time frame: t1/2 in plasma after the last (Day 9) dose
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | The t1/2 of Emodepside in Plasma | 419 Hours | Geometric Coefficient of Variation 42.6 |
| Cohort 2: 10mg EMODEPSIDE OD | The t1/2 of Emodepside in Plasma | 450 Hours | Geometric Coefficient of Variation 30.6 |
| Cohort 3: 10mg EMODEPSIDE BID | The t1/2 of Emodepside in Plasma | 508 Hours | Geometric Coefficient of Variation 56.9 |
Secondary
The Tmax of Emodepside in Plasma
Summary of tmax of emodepside after the first (Day 0) and last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 0 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 15 h after the morning dose. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose. tmax: the time at which Cmax was apparent, identified by inspection of the drug concentration vs. time data.
Time frame: tmax in plasma after the first (Day 0) and last (Day 9) dose
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | The Tmax of Emodepside in Plasma | Day 0 | 1.00 Hours |
| Cohort 1: 5mg EMODEPSIDE OD | The Tmax of Emodepside in Plasma | Day 9 | 1.00 Hours |
| Cohort 2: 10mg EMODEPSIDE OD | The Tmax of Emodepside in Plasma | Day 0 | 1.25 Hours |
| Cohort 2: 10mg EMODEPSIDE OD | The Tmax of Emodepside in Plasma | Day 9 | 1.25 Hours |
| Cohort 3: 10mg EMODEPSIDE BID | The Tmax of Emodepside in Plasma | Day 0 | 1.00 Hours |
| Cohort 3: 10mg EMODEPSIDE BID | The Tmax of Emodepside in Plasma | Day 9 | 1.50 Hours |
Secondary
The Vz/F of Emodepside in Plasma
Summary of Vz/F of emodepside after the last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose. Vz/F: apparent volume of distribution on Day 9. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).
Time frame: Vz/F in plasma after the last (Day 9) dose
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | The Vz/F of Emodepside in Plasma | 1788 litre(s) | Geometric Coefficient of Variation 74.2 |
| Cohort 2: 10mg EMODEPSIDE OD | The Vz/F of Emodepside in Plasma | 1861 litre(s) | Geometric Coefficient of Variation 68.5 |
| Cohort 3: 10mg EMODEPSIDE BID | The Vz/F of Emodepside in Plasma | 2607 litre(s) | Geometric Coefficient of Variation 102.1 |
Secondary
The λz of Emodepside in Plasma
Summary of λz of emodepside after the last (Day 9) dose for 10-day oral treatment courses in healthy men: PK parameter population. Data on Day 9 was collected at the following time points: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 15, 24, 36 (Day 10), 48 (Day 11), 72 (Day 12), 96 (Day 13) and 120 h (Day 14) after the morning dose. λz: terminal rate constant. The geometric coefficient of variation is the between-subject coefficient of variation (%CVb).
Time frame: λz in plasma after the last (Day 9) dose
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | The λz of Emodepside in Plasma | 0.00166 1/h | Geometric Coefficient of Variation 42.6 |
| Cohort 2: 10mg EMODEPSIDE OD | The λz of Emodepside in Plasma | 0.00154 1/h | Geometric Coefficient of Variation 30.6 |
| Cohort 3: 10mg EMODEPSIDE BID | The λz of Emodepside in Plasma | 0.00137 1/h | Geometric Coefficient of Variation 56.9 |
Other Pre-specified
Drug-related Adverse Events
Subjects presenting drug-related treatment-emergent adverse events listed by preferred term. Note: subjects with ≥1 adverse event are counted only once per preferred term.
Time frame: Drug-related AEs were reported throughout the study
Population: OD=once daily; BID=twice daily.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | Drug-related Adverse Events | Dizziness | 1 Participants |
| Cohort 1: 5mg EMODEPSIDE OD | Drug-related Adverse Events | Euphoric mood | 1 Participants |
| Cohort 1: 5mg EMODEPSIDE OD | Drug-related Adverse Events | Nervousness | 1 Participants |
| Cohort 1: 5mg EMODEPSIDE OD | Drug-related Adverse Events | Visual impairment | 2 Participants |
| Cohort 2: 10mg EMODEPSIDE OD | Drug-related Adverse Events | Dizziness | 0 Participants |
| Cohort 2: 10mg EMODEPSIDE OD | Drug-related Adverse Events | Visual impairment | 1 Participants |
| Cohort 2: 10mg EMODEPSIDE OD | Drug-related Adverse Events | Euphoric mood | 1 Participants |
| Cohort 2: 10mg EMODEPSIDE OD | Drug-related Adverse Events | Nervousness | 0 Participants |
| Cohort 3: 10mg EMODEPSIDE BID | Drug-related Adverse Events | Visual impairment | 3 Participants |
| Cohort 3: 10mg EMODEPSIDE BID | Drug-related Adverse Events | Euphoric mood | 0 Participants |
| Cohort 3: 10mg EMODEPSIDE BID | Drug-related Adverse Events | Dizziness | 0 Participants |
| Cohort 3: 10mg EMODEPSIDE BID | Drug-related Adverse Events | Nervousness | 0 Participants |
| Placebo Group | Drug-related Adverse Events | Dizziness | 0 Participants |
| Placebo Group | Drug-related Adverse Events | Nervousness | 0 Participants |
| Placebo Group | Drug-related Adverse Events | Euphoric mood | 0 Participants |
| Placebo Group | Drug-related Adverse Events | Visual impairment | 1 Participants |