A Phase 1 interventional study of LSF emodepside (BAY 44-4400) or matching placebo in Filariasis, sponsored by Drugs for Neglected Diseases. Completed at 1 site in United Kingdom. Open to male participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-04-15.
Sponsored by Drugs for Neglected Diseases · Phase 1, Interventional, and Treatment
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.
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.
23 studies on the registry are indexed under Filariasis; 2 are open to participants now.
This study's enrollment of 24 is below the median of 100 across 12 interventional studies indexed under Filariasis.
Browse Filariasis studies →Drugs for Neglected Diseases is the lead sponsor of 58 studies on the registry; 3 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
6 subjects with LSF emodepside 5mg, OD 2 subjects with matching placebo
Drug: LSF emodepside (BAY 44-4400) or matching placebo
6 subjects with LSF emodepside 10mg, OD 2 subjects with matching placebo
Drug: LSF emodepside (BAY 44-4400) or matching placebo
6 subjects with LSF emodepside 10mg, BID 2 subjects with matching placebo
Drug: LSF emodepside (BAY 44-4400) or matching placebo
Emodepside administered as an LSF oral solution (1mg/mL)
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
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
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
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
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
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
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
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
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
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)
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)
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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)
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)
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)
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
| Milestone | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group |
|---|---|---|---|---|
| Started | 6 | 6 | 6 | 6 |
| Completed | 6 | 5 | 6 | 6 |
| Not completed | 0 | 1 | 0 | 0 |
| Withdrew: Withdrawal by subject | 0 | 1 | 0 | 0 |
Death, serious adverse events (SAEs) and treatment-emergent adverse events (TEAEs).
| Participants | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group |
|---|---|---|---|---|
| AEs | 5 | 6 | 6 | 4 |
| TEAEs | 5 | 6 | 6 | 4 |
| Drug-related TEAEs | 2 | 1 | 3 | 1 |
| SAEs | 1 | 0 | 0 | 0 |
| Deaths | 0 | 0 | 0 | 0 |
| Withdrawals from the study owing to a TEAE | 0 | 0 | 0 | 0 |
Number of subjects with a TEAE, by highest level of severity.
| Participants | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group |
|---|---|---|---|---|
| Mild | 2 | 3 | 4 | 3 |
| Moderate | 2 | 3 | 2 | 1 |
| Severe | 1 | 0 | 0 | 0 |
Vital signs included heart rate, systolic and diastolic blood pressure and temperature.
| Participants | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group |
|---|---|---|---|---|
| Clinically significant change in HR | 0 | 0 | 0 | 0 |
| Clinically significant change in systolic BP | 0 | 0 | 0 | 0 |
| Clinically significant change in diastolic BP | 0 | 0 | 0 | 0 |
| Clinically significant change in temperature | 0 | 0 | 0 | 0 |
The following variables were recorded in 12-lead ECGs: ventricular rate, PR interval, QRS interval, QTcB and QTcF interval.
| Participants | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group |
|---|---|---|---|---|
| Clinically significant changes in ventricular rate | 0 | 0 | 0 | 0 |
| Clinically significant changes in PR interval | 0 | 0 | 0 | 0 |
| Clinically significant changes in QRS interval | 0 | 0 | 0 | 0 |
| Clinically significant changes in QTcB interval | 0 | 0 | 0 | 0 |
Clinical laboratory parameters included clinical chemistry, hematology, coagulation and urinalysis.
| Participants | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group |
|---|---|---|---|---|
| Clinically significant clinical chemistry changes | 0 | 0 | 1 | 0 |
| Clinically significant hematology changes | 0 | 0 | 0 | 0 |
| Clinically significant coagulation changes | 0 | 0 | 0 | 0 |
| Clinically significant urinalysis changes | 0 | 0 | 0 | 0 |
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.
| Participants | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group |
|---|---|---|---|---|
| Clinically significant ocular symptoms | 3 | 0 | 3 | 1 |
| Clinically significant Amsler grid assessment | 1 | 0 | 0 | 0 |
Abnormal or clinically significant physical examination findings during the study or reported as an adverse event.
| Participants | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group |
|---|---|---|---|---|
| Abnormal physical examination | 2 | 1 | 2 | 0 |
| Physical examination reported as an AE | 2 | 1 | 1 | 0 |
Abnormal or clinically significant neurological examination findings during the study or reported as an adverse event.
| Participants | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group |
|---|---|---|---|---|
| Abnormal neurological examination | 2 | 1 | 1 | 1 |
| Neurological examination reported as an AE | 1 | 1 | 1 | 1 |
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.
| ng/mL | Cohort 1: Emodepside 5 mg OD | Cohort 2: Emodepside 10 mg OD | Cohort 3: Emodepside 10 mg BID |
|---|---|---|---|
| Day 1, pre-dose | 8.77 ± 35.8 | 15.78 ± 42.9 | 45.94 ± 35.1 |
| Day 2, pre-dose | 15.24 ± 31.1 | 28.80 ± 40.0 | 64.62 ± 38.5 |
| Day 3, pre-dose | 21.22 ± 35.0 | 39.08 ± 45.6 | 84.65 ± 37.7 |
| Day 4, pre-dose | 24.81 ± 37.4 | 47.38 ± 42.2 | 98.01 ± 32.0 |
| Day 5, pre-dose | 31.46 ± 36.3 | 60.07 ± 42.9 | 120.98 ± 31.1 |
| Day 6, pre-dose | 36.68 ± 36.7 | 70.88 ± 39.6 | 137.60 ± 35.2 |
| Day 7, pre-dose | 40.57 ± 31.4 | 83.31 ± 43.0 | 149.41 ± 33.3 |
| Day 8, pre-dose | 46.91 ± 36.8 | 91.63 ± 42.4 | 179.90 ± 35.3 |
| Day 9, pre-dose | 49.73 ± 35.1 | 97.11 ± 44.0 | 184.94 ± 37.1 |
| Day 9, 24 hour post-dose | 51.76 ± 36.6 | 108.17 ± 49.1 | 176.10 ± 39.8 |
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).
| h*ng/mL | Cohort 1: Emodepside 5 mg OD | Cohort 2: Emodepside 10 mg OD | Cohort 3: Emodepside 10 mg BID |
|---|---|---|---|
| The AUClast of Emodepside in Plasma | 19359 ± 29.9 | 40655 ± 43.5 | 59554 ± 29.1 |
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).
| h*ng/mL/mg | Cohort 1: Emodepside 5 mg OD | Cohort 2: Emodepside 10 mg OD | Cohort 3: Emodepside 10 mg BID |
|---|---|---|---|
| The AUClast/D of Emodepside in Plasma | 3872 ± 29.9 | 4065 ± 43.5 | 5955 ± 29.1 |
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).
| (h*ng/mL)/(mg*kg) | Cohort 1: Emodepside 5 mg OD | Cohort 2: Emodepside 10 mg OD | Cohort 3: Emodepside 10 mg BID |
|---|---|---|---|
| The AUClast,Norm of Emodepside in Plasma | 53.9 ± 33.1 | 52.9 ± 69.5 | 79.1 ± 40.6 |
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).
| h*ng/mL | Cohort 3: Emodepside 10 mg BID |
|---|---|
| Day 0 | 742 ± 29.4 |
| Day 9 | 2810 ± 35.0 |
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).
| h*ng/mL/mg | Cohort 3: Emodepside 10 mg BID |
|---|---|
| Day 0 | 74.2 ± 29.4 |
| Day 9 | 281 ± 35.0 |
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).
| (h*ng/mL)/(mg*kg) | Cohort 3: Emodepside 10 mg BID |
|---|---|
| Day 0 | 0.985 ± 39.2 |
| Day 9 | 3.73 ± 46.6 |
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).
| h*ng/mL | Cohort 1: Emodepside 5 mg OD | Cohort 2: Emodepside 10 mg OD | Cohort 3: Emodepside 10 mg BID |
|---|---|---|---|
| Day 0 | 574 ± 19.7 | 1135 ± 32.7 | 1428 ± 26.5 |
| Day 9 | 1689 ± 31.3 | 3487 ± 44.2 | 4897 ± 35.8 |
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).
| h*ng/mL/mg | Cohort 1: Emodepside 5 mg OD | Cohort 2: Emodepside 10 mg OD | Cohort 3: Emodepside 10 mg BID |
|---|---|---|---|
| Day 0 | 115 ± 19.7 | 113 ± 32.7 | 71.4 ± 26.5 |
| Day 9 | 338 ± 31.3 | 349 ± 44.2 | 490 ± 35.8 |
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).
| (h*ng/mL)/(mg*kg) | Cohort 1: Emodepside 5 mg OD | Cohort 2: Emodepside 10 mg OD | Cohort 3: Emodepside 10 mg BID |
|---|---|---|---|
| Day 0 | 1.60 ± 21.5 | 1.48 ± 56.7 | 0.948 ± 36.5 |
| Day 9 | 4.70 ± 34.1 | 4.54 ± 69.7 | 6.50 ± 47.7 |
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).
| ng/mL | Cohort 1: Emodepside 5 mg OD | Cohort 2: Emodepside 10 mg OD | Cohort 3: Emodepside 10 mg BID |
|---|---|---|---|
| Day 0 | 93.8 ± 17.8 | 186 ± 21.3 | 160 ± 20.4 |
| Day 9 | 149 ± 17.9 | 287 ± 39.7 | 349 ± 27.1 |
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).
| ng/mL/mg | Cohort 1: Emodepside 5 mg OD | Cohort 2: Emodepside 10 mg OD | Cohort 3: Emodepside 10 mg BID |
|---|---|---|---|
| Day 0 | 18.8 ± 17.8 | 18.6 ± 21.3 | 16.0 ± 20.4 |
| Day 9 | 29.9 ± 17.9 | 28.7 ± 39.7 | 34.9 ± 27.1 |
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).
| (ng/mL)*(mg*kg) | Cohort 1: Emodepside 5 mg OD | Cohort 2: Emodepside 10 mg OD | Cohort 3: Emodepside 10 mg BID |
|---|---|---|---|
| Day 0 | 0.261 ± 18.4 | 0.242 ± 42.8 | 0.212 ± 28.7 |
| Day 9 | 0.416 ± 20.6 | 0.374 ± 65.4 | 0.464 ± 38.2 |
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).
| ng/mL | Cohort 1: Emodepside 5 mg OD | Cohort 2: Emodepside 10 mg OD | Cohort 3: Emodepside 10 mg BID |
|---|---|---|---|
| The Ctrough of Emodepside in Plasma | 49.7 ± 36.8 | 97.1 ± 50.8 | 185 ± 39.5 |
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.
| Hours | Cohort 1: Emodepside 5 mg OD | Cohort 2: Emodepside 10 mg OD | Cohort 3: Emodepside 10 mg BID |
|---|---|---|---|
| Day 0 | 1.00 (1.00 to 1.07) | 1.25 (1.00 to 2.00) | 1.00 (1.00 to 1.58) |
| Day 9 | 1.00 (1.00 to 1.50) | 1.25 (1.00 to 2.00) | 1.50 (1.03 to 2.50) |
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).
| Hours | Cohort 1: Emodepside 5 mg OD | Cohort 2: Emodepside 10 mg OD | Cohort 3: Emodepside 10 mg BID |
|---|---|---|---|
| The t1/2 of Emodepside in Plasma | 419 ± 42.6 | 450 ± 30.6 | 508 ± 56.9 |
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).
| Hours | Cohort 1: Emodepside 5 mg OD | Cohort 2: Emodepside 10 mg OD | Cohort 3: Emodepside 10 mg BID |
|---|---|---|---|
| The t1/2,(0-24) of Emodepside in Plasma | 26.9 ± 52.4 | 18.4 ± 30.0 | 33.2 ± 55.0 |
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).
| 1/h | Cohort 1: Emodepside 5 mg OD | Cohort 2: Emodepside 10 mg OD | Cohort 3: Emodepside 10 mg BID |
|---|---|---|---|
| The λz of Emodepside in Plasma | 0.00166 ± 42.6 | 0.00154 ± 30.6 | 0.00137 ± 56.9 |
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).
| L/h | Cohort 1: Emodepside 5 mg OD | Cohort 2: Emodepside 10 mg OD | Cohort 3: Emodepside 10 mg BID |
|---|---|---|---|
| The CLss/F of Emodepside in Plasma | 2.96 ± 31.3 | 2.87 ± 44.2 | 3.56 ± 35.0 |
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).
| litre(s) | Cohort 1: Emodepside 5 mg OD | Cohort 2: Emodepside 10 mg OD | Cohort 3: Emodepside 10 mg BID |
|---|---|---|---|
| The Vz/F of Emodepside in Plasma | 1788 ± 74.2 | 1861 ± 68.5 | 2607 ± 102.1 |
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).
| Hours | Cohort 1: Emodepside 5 mg OD | Cohort 2: Emodepside 10 mg OD | Cohort 3: Emodepside 10 mg BID |
|---|---|---|---|
| The MRTlast of Emodepside in Plasma | 7.28 ± 10.7 | 7.00 ± 11.0 | 10.8 ± 2.8 |
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.
| Ratio | Cohort 3: Emodepside 10 mg BID |
|---|---|
| The Rac(AUC12) of Emodepside in Plasma | 3.83 ± 15.5 |
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 \[%CVb\]).
| Ratio | Cohort 1: Emodepside 5 mg OD | Cohort 2: Emodepside 10 mg OD | Cohort 3: Emodepside 10 mg BID |
|---|---|---|---|
| The Rac(AUC24) of Emodepside in Plasma | 2.97 ± 16.1 | 3.09 ± 11.3 | 3.47 ± 17.1 |
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 \[%CVb\]).
| Ratio | Cohort 1: Emodepside 5 mg OD | Cohort 2: Emodepside 10 mg OD | Cohort 3: Emodepside 10 mg BID |
|---|---|---|---|
| The Rac(Cmax) of Emodepside in Plasma | 1.61 ± 16.5 | 1.58 ± 24.1 | 2.21 ± 17.4 |
Mean glucose concentrations (mmol/L) after repeated once or twice daily dosing with up to 10 mg emodepside or placebo at Day -1.
| mmol/L | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group |
|---|---|---|---|---|
| -24 h | 4.72 ± 0.286 | 4.68 ± 0.349 | 4.80 ± 0.245 | 4.77 ± 0.468 |
| -23 h | 4.90 ± 0.308 | 4.85 ± 0.259 | 4.85 ± 0.281 | 4.92 ± 0.313 |
| -22 h | 4.77 ± 0.378 | 4.72 ± 0.371 | 4.72 ± 0.279 | 4.82 ± 0.360 |
| -20 h | 4.63 ± 0.388 | 4.57 ± 0.207 | 4.55 ± 0.207 | 4.73 ± 0.480 |
| -12 h | 5.17 ± 0.712 | 5.55 ± 0.451 | 5.52 ± 0.556 | 5.48 ± 0.806 |
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.
| mmol/L | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group |
|---|---|---|---|---|
| Predose (Baseline) | 4.96 ± 0.321 | 4.85 ± 0.409 | 4.85 ± 0.351 | 4.85 ± 0.288 |
| 1 h | 5.07 ± 0.367 | 5.57 ± 0.816 | 5.42 ± 0.445 | 4.78 ± 0.214 |
| 2 h | 5.05 ± 0.327 | 5.28 ± 0.508 | 5.27 ± 0.472 | 4.70 ± 0.310 |
| 4 h | 4.73 ± 0.378 | 4.75 ± 0.274 | 4.82 ± 0.279 | 4.70 ± 0.276 |
| 12 h | 5.68 ± 0.268 | 6.22 ± 0.343 | 5.57 ± 0.554 | 6.27 ± 0.761 |
| 24 h | 5.07 ± 0.314 | 4.88 ± 0.264 | 4.87 ± 0.273 | 4.97 ± 0.288 |
Mean glucose concentrations (mmol/L) after repeated once or twice daily dosing with up to 10 mg emodepside or placebo at Day 9.
| mmol/L | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group |
|---|---|---|---|---|
| Predose | 4.52 ± 0.306 | 4.95 ± 0.362 | 4.97 ± 0.314 | 4.67 ± 0.234 |
| 1 h | 5.10 ± 0.352 | 5.98 ± 1.972 | 5.65 ± 0.771 | 4.80 ± 0.219 |
| 2 h | 5.03 ± 0.250 | 5.72 ± 1.543 | 5.57 ± 0.761 | 4.74 ± 0.329 |
| 4 h | 4.60 ± 0.363 | 4.62 ± 0.377 | 5.08 ± 0.662 | 4.70 ± 0.374 |
| 12 h | 5.58 ± 0.319 | 6.00 ± 0.745 | 7.03 ± 1.111 | 6.02 ± 0.615 |
| 24 h | 4.92 ± 0.264 | 5.10 ± 0.490 | 5.17 ± 0.273 | 4.82 ± 0.160 |
| 48 h | 5.02 ± 0.194 | 5.07 ± 0.532 | 5.10 ± 0.390 | 4.90 ± 0.379 |
| 72 h | 4.87 ± 0.350 | 5.13 ± 0.589 | 5.03 ± 0.308 | 5.03 ± 0.280 |
| 96 h | 4.80 ± 0.276 | 5.10 ± 0.540 | 4.85 ± 0.315 | 4.87 ± 0.320 |
| 120 h | 5.00 ± 0.352 | 4.98 ± 0.458 | 5.05 ± 0.288 | 4.90 ± 0.352 |
Mean glucose concentrations (mmol/L) after repeated once or twice daily dosing with up to 10 mg emodepside or placebo at Day 30.
| mmol/L | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group |
|---|---|---|---|---|
| Mean Glucose Concentration at Day 30 | 4.83 ± 0.288 | 5.23 ± 0.993 | 4.97 ± 0.234 | 4.53 ± 0.350 |
Mean insulin concentration (pmol/L) after repeated once or twice daily dosing with up to 10 mg emodepside or placebo at Day -1.
| pmol/L | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group |
|---|---|---|---|---|
| -24 h | 29.0 ± 8.60 | 25.8 ± 8.11 | 33.2 ± 17.90 | 32.3 ± 12.31 |
| -23 h | 25.8 ± 3.87 | 26.2 ± 7.73 | 28.0 ± 11.33 | 26.5 ± 8.92 |
| -22 h | 24.0 ± 6.69 | 25.7 ± 8.91 | 28.3 ± 14.50 | 33.0 ± 5.73 |
| -20 h | 22.7 ± 6.02 | 22.7 ± 7.97 | 24.3 ± 9.18 | 24.5 ± 12.76 |
| -12 h | 129.5 ± 54.14 | 157.0 ± 81.51 | 204.7 ± 78.37 | 136.5 ± 64.30 |
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.
| pmol/L | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group |
|---|---|---|---|---|
| Predose (Baseline) | 27.8 ± 15.41 | 29.3 ± 5.09 | 32.2 ± 14.34 | 30.5 ± 12.55 |
| 1 h | 25.0 ± 3.79 | 23.2 ± 10.85 | 29.2 ± 14.86 | 33.0 ± 9.10 |
| 2 h | 24.3 ± 5.20 | 25.3 ± 9.99 | 36.3 ± 20.39 | 31.2 ± 12.89 |
| 4 h | 21.7 ± 5.01 | 21.7 ± 5.39 | 27.7 ± 11.69 | 20.2 ± 6.85 |
| 12 h | 127.2 ± 67.59 | 203.2 ± 83.22 | 175.3 ± 64.59 | 195.0 ± 88.03 |
| 24 h | 36.7 ± 15.49 | 41.2 ± 14.51 | 30.3 ± 11.43 | 35.2 ± 16.59 |
Mean insulin concentration (pmol/L) after repeated once or twice daily dosing with up to 10 mg emodepside or placebo at Day 9.
| pmol/L | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group |
|---|---|---|---|---|
| Predose | 31.5 ± 8.62 | 32.7 ± 15.02 | 29.2 ± 10.19 | 31.3 ± 9.83 |
| 1 h | 29.2 ± 9.66 | 24.4 ± 15.39 | 22.2 ± 8.89 | 27.8 ± 9.77 |
| 2 h | 27.7 ± 4.84 | 31.2 ± 10.53 | 30.2 ± 13.91 | 29.8 ± 10.26 |
| 4 h | 23.0 ± 7.35 | 28.4 ± 13.24 | 19.5 ± 9.12 | 21.8 ± 6.37 |
| 12 h | 147.2 ± 77.58 | 143.0 ± 113.7 | 215.8 ± 128.1 | 215.7 ± 151.8 |
| 24 h | 34.5 ± 11.88 | 36.5 ± 12.24 | 32.7 ± 17.44 | 36.3 ± 13.03 |
| 48 h | 36.2 ± 5.60 | 44.8 ± 17.89 | 36.3 ± 13.59 | 38.2 ± 19.17 |
| 72 h | 48.3 ± 23.53 | 40.7 ± 13.88 | 39.8 ± 15.61 | 38.7 ± 14.42 |
| 96 h | 37.8 ± 10.42 | 39.3 ± 12.31 | 37.2 ± 17.66 | 30.0 ± 11.63 |
| 120 h | 39.0 ± 8.63 | 42.3 ± 17.92 | 36.0 ± 15.24 | 33.2 ± 21.68 |
Mean insulin concentration (pmol/L) after repeated once or twice daily dosing with up to 10 mg emodepside or placebo at Day 30.
| pmol/L | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group |
|---|---|---|---|---|
| Mean Insulin Concentration at Day 30 | 29.2 ± 12.50 | 60.3 ± 90.19 | 24.3 ± 9.79 | 29.2 ± 20.21 |
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.
| mmol/L | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group |
|---|---|---|---|---|
| 0 h (Baseline) | 4.72 ± 0.319 | 4.92 ± 0.256 | 4.97 ± 0.294 | 4.78 ± 0.133 |
| 1 h | 8.78 ± 1.659 | 7.03 ± 0.301 | 7.00 ± 0.867 | 6.48 ± 1.450 |
| 2 h | 5.98 ± 1.512 | 5.05 ± 0.589 | 5.48 ± 0.608 | 4.95 ± 0.965 |
| 4 h | 4.57 ± 0.979 | 3.95 ± 0.622 | 4.22 ± 0.371 | 4.53 ± 0.294 |
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.
| mmol/L | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group |
|---|---|---|---|---|
| Predose (Baseline) | 5.07 ± 0.314 | 4.88 ± 0.264 | 4.87 ± 0.273 | 4.97 ± 0.228 |
| 1 h | 10.10 ± 1.170 | 12.37 ± 2.826 | 12.03 ± 0.989 | 7.58 ± 2.242 |
| 2 h | 6.17 ± 1.600 | 7.95 ± 1.653 | 9.25 ± 2.740 | 5.88 ± 1.174 |
| 4 h | 3.95 ± 0.339 | 3.65 ± 0.362 | 4.02 ± 0.204 | 4.15 ± 0.575 |
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.
| mmol/L | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group |
|---|---|---|---|---|
| Predose (Baseline) | 4.87 ± 0.314 | 5.10 ± 0.533 | 4.90 ± 0.303 | 4.83 ± 0.258 |
| 1 h | 10.02 ± 1.857 | 11.75 ± 4.574 | 11.27 ± 2.738 | 7.77 ± 1.679 |
| 2 h | 7.05 ± 1.533 | 8.98 ± 4.311 | 8.97 ± 2.837 | 5.52 ± 0.783 |
| 4 h | 3.93 ± 0.965 | 4.12 ± 0.933 | 4.52 ± 0.806 | 4.13 ± 0.197 |
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)
| mmol/L | Cohort 3: 10mg EMODEPSIDE BID |
|---|---|
| 0 h (Baseline) | 4.93 ± 0.294 |
| 1 h | 8.12 ± 2.542 |
| 2 h | 6.08 ± 0.540 |
| 4 h | 4.26 ± 0.305 |
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.
| pmol/L | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group |
|---|---|---|---|---|
| 0 h (Baseline) | 24.5 ± 13.81 | 25.7 ± 8.55 | 27.0 ± 14.00 | 29.0 ± 14.68 |
| 1 h | 334.8 ± 207.66 | 305.3 ± 65.59 | 306.7 ± 180.00 | 338.3 ± 189.61 |
| 2 h | 174.7 ± 206.08 | 103.7 ± 32.38 | 136.0 ± 70.52 | 186.8 ± 83.55 |
| 4 h | 44.3 ± 72.56 | 17.2 ± 6.11 | 20.8 ± 7.44 | 21.8 ± 9.33 |
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.
| pmol/L | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group |
|---|---|---|---|---|
| Predose (Baseline) | 36.7 ± 15.49 | 41.2 ± 14.51 | 30.3 ± 11.43 | 35.2 ± 16.59 |
| 1 h | 312.2 ± 153.67 | 288.8 ± 171.44 | 332.2 ± 228.84 | 606.7 ± 157.35 |
| 2 h | 268.5 ± 107.14 | 377.3 ± 224.73 | 336.2 ± 165.71 | 238.0 ± 165.06 |
| 4 h | 28.8 ± 22.35 | 30.8 ± 12.35 | 35.7 ± 4.59 | 33.8 ± 19.56 |
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.
| pmol/L | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group |
|---|---|---|---|---|
| Predose (Baseline) | 32.5 ± 9.85 | 39.3 ± 22.59 | 34.5 ± 15.83 | 33.8 ± 12.94 |
| 1 h | 302.5 ± 145.61 | 286.8 ± 179.53 | 225.3 ± 148.93 | 690.5 ± 342.10 |
| 2 h | 337.0 ± 110.23 | 225.7 ± 101.02 | 229.8 ± 79.00 | 238.3 ± 92.34 |
| 4 h | 63.0 ± 86.69 | 63.3 ± 83.32 | 36.8 ± 21.17 | 21.7 ± 19.97 |
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)
| pmol/L | Cohort 3: 10mg EMODEPSIDE BID |
|---|---|
| 0 h (Baseline) | 28.0 ± 13.74 |
| 1 h | 417.8 ± 379.72 |
| 2 h | 152.8 ± 114.92 |
| 4 h | 18.8 ± 11.39 |
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.
| Participants | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group |
|---|---|---|---|---|
| Visual impairment | 2 | 1 | 3 | 1 |
| Euphoric mood | 1 | 1 | 0 | 0 |
| Nervousness | 1 | 0 | 0 | 0 |
| Dizziness | 1 | 0 | 0 | 0 |
Collected over Adverse events were monitored from Screening (Day -28 and until Day -3) to Follow-up (up to Day 120 ±2 days).. Non-serious events are listed at a 4% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Cohort 1: 5mg EMODEPSIDE OD | 0/6 (0%) | 1/6 (16.7%) | 5/6 (83.3%) |
| Cohort 2: 10mg EMODEPSIDE OD | 0/6 (0%) | 0/6 (0%) | 6/6 (100%) |
| Cohort 3: 10mg EMODEPSIDE BID | 0/6 (0%) | 0/6 (0%) | 6/6 (100%) |
| Placebo Group | 0/6 (0%) | 0/6 (0%) | 4/6 (66.7%) |
| Event | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group |
|---|---|---|---|---|
| Anal fistulaGastrointestinal disorders | 1/6 | 0/6 | 0/6 | 0/6 |
| Anal abscessInfections and infestations | 1/6 | 0/6 | 0/6 | 0/6 |
| Event | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group |
|---|---|---|---|---|
| Visual impairmentEye disorders | 2/6 | 1/6 | 3/6 | 1/6 |
| NasopharyngitisInfections and infestations | 3/6 | 3/6 | 0/6 | 0/6 |
| HeadacheNervous system disorders | 1/6 | 0/6 | 0/6 | 2/6 |
| DizzinessNervous system disorders | 2/6 | 0/6 | 0/6 | 0/6 |
| NauseaGastrointestinal disorders | 0/6 | 0/6 | 0/6 | 2/6 |
| Sebaceous cyst excisionSurgical and medical procedures | 0/6 | 1/6 | 0/6 | 0/6 |
| Allergy to animalImmune system disorders | 0/6 | 0/6 | 1/6 | 0/6 |
| FatigueGeneral disorders | 0/6 | 0/6 | 0/6 | 1/6 |
| Influenza like illnessGeneral disorders | 0/6 | 0/6 | 1/6 | 0/6 |
| MalaiseGeneral disorders | 1/6 | 0/6 | 0/6 | 0/6 |
| Age, Categorical(Participants) | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group | Total |
|---|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 6 | 6 | 6 | 6 | 24 |
| >=65 years | 0 | 0 | 0 | 0 | 0 |
| Age, Continuous(years) | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group | Total |
|---|---|---|---|---|---|
| Mean | 31.0 (19 to 41) | 33.3 (19 to 42) | 28.0 (20 to 43) | 32.7 (27 to 41) | 31.3 (19 to 43) |
| Sex: Female, Male(Participants) | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group | Total |
|---|---|---|---|---|---|
| Female | 0 | 0 | 0 | 0 | 0 |
| Male | 6 | 6 | 6 | 6 | 24 |
| Ethnicity (NIH/OMB)(Participants) | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group | Total |
|---|---|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 | 0 | 0 |
| Not Hispanic or Latino | 6 | 6 | 6 | 6 | 24 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group | Total |
|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 | 0 | 0 |
| White | 6 | 6 | 6 | 6 | 24 |
| More than one race | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment(participants) | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group | Total |
|---|---|---|---|---|---|
| United Kingdom | 6 | 6 | 6 | 6 | 24 |
| Height(cm) | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group | Total |
|---|---|---|---|---|---|
| Mean | 179.3 ± 4.18 | 179.7 ± 4.59 | 181.8 ± 6.74 | 182.7 ± 8.80 | 180.9 ± 6.10 |
| Weight(kg) | Cohort 1: 5mg EMODEPSIDE OD | Cohort 2: 10mg EMODEPSIDE OD | Cohort 3: 10mg EMODEPSIDE BID | Placebo Group | Total |
|---|---|---|---|---|---|
| Mean | 72.18 ± 6.204 | 77.70 ± 17.570 | 75.23 ± 9.520 | 74.73 ± 8.999 | 74.96 ± 10.807 |
4 further baseline measures are reported on the registry.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Nov 2017 to primary completion in Oct 2018, 11 months.
Results were first posted in Apr 2020, 1 year 6 months after primary completion.
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Drugs for Neglected Diseases