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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-003592-29 | EudraCT Number |
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| Name | Class |
|---|---|
| Bayer | INDUSTRY |
| Bill and Melinda Gates Foundation | OTHER |
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This study will investigate the safety, tolerability, and pharmacokinetics of single ascending doses of emodepside (BAY 44-4400) in healthy male volunteers. This study will also conduct an exploratory investigation of the relative bioavailability of emodepside administered as tablets and determine the effect of food on the pharmacokinetics.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| emodepside (BAY 44-4400) | Experimental | Up to 10 cohorts with single ascending dose |
|
| placebo of emodepside (BAY 44-4400) | Placebo Comparator | Up to 10 cohorts with single ascending dose |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| emodepside (BAY 44-4400) | Drug |
| ||
| placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Safety and Tolerability as Measured by Adverse Events | Deaths, serious adverse events (SAEs) and treatment-emergent adverse events (TEAEs) | Up to 14 days post dose (may be extended to 21 days) |
| Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal or clinically significant neurological examination findings during the study or reported as an AE | Up to 14 days post dose (may be extended to 21 days) |
| Safety and Tolerability as Measured by Vital Signs | Vital signs included heart rate, systolic and diastolic blood pressure, | Up to 14 days post dose (may be extended to 21 days) |
| Safety and Tolerability as Measured by 12-lead ECG | The following variables were recorded in 12-lead ECGs and extracted from continuous 12-lead ECG recordings: ventricular rate, PR interval, QRS interval, QTcB and QTcF interval. | Up to 14 days post dose (may be extended to 21 days) |
| Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinical laboratory parameters included hematology, biochemistry, serology and coagulation in blood samples and urinalysis in urine samples | Up to 14 days post dose (may be extended to 21 days) |
| Safety and Tolerability as Measured by Ophthalmological Examination Findings in One Study Arm Only | Subjects attended a specialist eye hospital for ophthalmology assessments by a Consultant Ophthalmologist. Opthalmology assessments included:ocular symptoms, past ocular history, auto-refraction, best corrected distance visual acuity, color vision assessment, amsler grid assessment, ocular alignment and ocular motility assessment, confrontation visual field assessment, slit lamp examination (anterior segment), intraocular pressure (Goldmann Tonometry), optical coherence scanning of tomography, post mydriatic ocular media (at Screening visit 2 only) and retinal examination with slit lamp and lens. |
| Measure | Description | Time Frame |
|---|---|---|
| The AUC∞ of Emodepside in Plasma | The area under the plasma drug concentration versus time curve from time zero to infinity (AUC∞) | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
| The AUC∞/D of Emodepside in Plasma |
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Inclusion Criteria:
Exclusion Criteria:
Additional exclusion criteria for cohort with ophthalmological assessments:
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| Name | Affiliation | Role |
|---|---|---|
| Malcolm Boyce, MD, BSc | Hammersmith Medicines Research | Principal Investigator |
| Frederic Monnot | Drugs for Neglected Diseases initiative | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hammersmith Medicines Research | London | NW10 7EW | United Kingdom |
79 healthy subjects were randomized and received study drug. Protocol Enrollment reflects the total number of participants enrolled in both Part 1 (63 participants) and Part 2 (16 participants).
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| ID | Title | Description |
|---|---|---|
| FG000 | Emodepside 0.1mg Solution, Fasted (Part 1) | Emodepside (BAY 44-4400) 0.1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) |
| FG001 | Emodepside 1mg Solution, Fasted (Part 1) | Emodepside (BAY 44-4400) 1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) |
| FG002 | Emodepside 2.5mg Solution, Fasted (Part 1) | Emodepside (BAY 44-4400) 2.5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) |
| FG003 | Emodepside 5mg Solution, Fasted (Part 1) | Emodepside (BAY 44-4400) 5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) |
| FG004 | Emodepside 5mg Tablet, Fasted (Part 1) | Emodepside (BAY 44-4400) 5mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase) |
| FG005 | Emodepside 10mg Solution, Fasted (Part 1) | Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) |
| FG006 | Emodepside 20mg Solution, Fasted (Part 1) | Emodepside (BAY 44-4400) 20mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) |
| FG007 | Emodepside 20mg Tablet, Fasted (Part 1) | Emodepside (BAY 44-4400) 20mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase) |
| FG008 | Emodepside 40mg Solution, Fasted (Part 1) | Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) |
| FG009 | Placebo Solution, Fasted (Part 1) | Matching placebo of emodepside (BAY 44-4400), solution, administered in fasted state Part one of study (FIH, single ascending dose phase) |
| FG010 | Placebo Tablet, Fasted (Part 1) | Matching placebo of emodepside (BAY 44-4400), tablet, administered in fasted state Part one of study (FIH, single ascending dose phase) |
| FG011 | Emodepside 10mg Solution, Fed (Part 2) | Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fed state This cohort was not classed as first in human Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events) |
| FG012 | Emodepside 40mg Solution, Fasted, (Part 2) | Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events) |
| FG013 | Placebo Solution, Fed (Part 2) | Matching placebo of emodepside (BAY 44-4400), solution, administered in fed state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events) |
| FG014 | Placebo Solution, Fasted (Part 2) | Matching placebo of emodepside (BAY 44-4400), solution, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events) |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1 |
|
| ||||||||||||||||||
| Part 2 |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Emodepside 0.1mg Solution, Fasted (Part 1) | Emodepside (BAY 44-4400) 0.1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) |
| BG001 | Emodepside 1mg Solution, Fasted (Part 1) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Totals were calculated seperately for Parts 1 and 2 |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Safety and Tolerability as Measured by Adverse Events | Deaths, serious adverse events (SAEs) and treatment-emergent adverse events (TEAEs) | AEs were determined in the Safety Population. In Part 1 n=63 (n=62 subjects completed). One subject in the 1mg emodepside group was withdrawn after receiving 0.1mg emodepside LSF, owing to an AE. He consented to follow-up safety assessment until Day 7 as a 0.1mg emodepside group. In Part 2, n=16 (n=16 subjects completed) | Posted | Number | participants | Up to 14 days post dose (may be extended to 21 days) |
|
The AE reporting period for this trial began after subject enrolment in the trial (after signature of informed consent) and ended at the follow-up visit (3 weeks after their dose of study medicine) .
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Emodepside 0.1mg Solution, Fasted (Part 1) | Emodepside (BAY 44-4400) 0.1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| TEAEs by primary system organ classes (SOCs) | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Sophie Delhomme | Drugs for Neglected Diseases initiative | +41229069230 | sdelhomme@dndi.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 18, 2017 | Oct 17, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 10, 2017 | Oct 17, 2019 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D010272 | Parasitic Diseases |
| D006373 | Helminthiasis |
| D009349 | Nematode Infections |
| D017190 | Secernentea Infections |
| D017205 | Spirurida Infections |
| D005368 | Filariasis |
| D012876 | Skin Diseases, Parasitic |
| D017437 | Skin and Connective Tissue Diseases |
| D012871 | Skin Diseases |
| D012874 | Skin Diseases, Infectious |
| D058069 | Neglected Diseases |
| D009855 | Onchocerciasis |
| ID | Term |
|---|---|
| D007239 | Infections |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C468987 | emodepside |
| C439266 | Bay 44-4400 |
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|
| Up to 14 days post dose (may be extended to 21 days) |
Dose-normalized area under the plasma drug concentration versus time curve from time zero to infinity (AUC∞/D), calculated as AUC∞/Dose administered.
| From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
| The Cmax of Emodepside in Plasma | Maximum observed plasma concentration (Cmax) was obtained directly from the concentration-time data | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
| The Cmax/D of Emodepside in Plasma | Dose-normalized observed maximum plasma concentration (Cmax/D) was calculated as Cmax/Dose administered | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
| The Cmax, Norm of Emodepside in Plasma | The observed maximum plasma concentration (Cmax) normalized by dose and body weight was calculated as Cmax/(Dose administered*body weight) | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
| The Tmax of Emodepside in Plasma | Time to reach maximum plasma concentration (Tmax) was obtained directly from the concentration-time data | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
| The t½ of Emodepside in Plasma | Terminal half-life (t½), calculated according to the equation t½ = ln2/λz, where λz is the apparent terminal elimination rate constant, estimated by linear regression of log-transformed concentration versus time data | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
| The MRT of Emodepside in Plasma | The mean residence time (MRT) was calculated as MRT = AUMC/AUC∞, where AUMC is the area under the first moment of the concentration-time curve from zero time (pre-dose) extrapolated to infinite time | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
| The CL/F of Emodepside in Plasma | Apparent total clearance from plasma (CL/F) was calculated as CL/F = Dose/AUC∞ | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
| The AUC 0-24 of Emodepside in Plasma | Area under the plasma concentration-time curve from time zero (pre-dose) to 24 h was calculated using the trapezoidal method | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
| The AUC 0-24/D of Emodepside in Plasma | Dose-normalized area under the concentration-time curve (AUC) from time zero (pre-dose) to 24 h was calculated as AUC0-24/Dose administered | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
| The AUC 24, Norm of Emodepside in Plasma | Area under the concentration-time curve from time zero (pre-dose) to 24 h, normalized by dose and body weight (AUC 24, norm) was calculated as AUC0-24/(Dose administered*body weight) | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
| The Vz/F of Emodepside in Plasma | Apparent volume of distribution (Vz/F) was calculated as Vz/F = Dose/(λz × AUC∞), where λz is the apparent terminal elimination rate constant, estimated by linear regression of log-transformed concentration versus time data | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
| The AUC Last of Emodepside in Plasma | The area under the concentration-time curve from time zero (pre-dose) to the time of last quantifiable concentration (t), calculated using the linear trapezoidal method for increasing concentrations and the log trapezoidal method for decreasing concentrations | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
| Frel of the IR (Immediate Release) Tablet of Emodepside | The average relative bioavailability (Frel) of the IR tablet was calculated | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
| The AUC Last, Norm of Emodepside in Plasma | The area under the concentration-time curve from time zero (pre-dose) to the time of last quantifiable concentration normalized by dose and body weight (AUClast/(Dose administered*body weight)) | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
| Effect of Food on the Bioavailability (Cmax) of Emodepside (BAY 44-4400) After Single Oral Dose Administered as Solution or IR Tablets in One Arm Only | Results of the statistical analysis of the effect of food on Emodepside exposure, after a single dose of 10 mg Emodepside LSF solution. | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
| Effect of Food on the Bioavailability (AUC24) of Emodepside (BAY 44-4400) After Single Oral Dose Administered as Solution or IR Tablets in One Arm Only | Results of the statistical analysis of the effect of food on Emodepside exposure, after a single dose of 10 mg Emodepside LSF solution. | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
| COMPLETED |
|
| NOT COMPLETED |
|
Emodepside (BAY 44-4400) 1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) |
| BG002 | Emodepside 2.5mg Solution, Fasted (Part 1) | Emodepside (BAY 44-4400) 2.5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) |
| BG003 | Emodepside 5mg Solution, Fasted (Part 1) | Emodepside (BAY 44-4400) 5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) |
| BG004 | Emodepside 5mg Tablet, Fasted (Part 1) | Emodepside (BAY 44-4400) 5mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase) |
| BG005 | Emodepside 10mg Solution, Fasted (Part 1) | Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) |
| BG006 | Emodepside 20mg Solution, Fasted (Part 1) | Emodepside (BAY 44-4400) 20mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) |
| BG007 | Emodepside 20mg Tablet, Fasted (Part 1) | Emodepside (BAY 44-4400) 20mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase) |
| BG008 | Emodepside 40mg Solution, Fasted (Part 1) | Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) |
| BG009 | Placebo Solution, Fasted (Part 1) | Matching placebo of emodepside (BAY 44-4400), solution, administered in fasted state Part one of study (FIH, single ascending dose phase) |
| BG010 | Placebo Tablet, Fasted (Part 1) | Matching placebo of emodepside (BAY 44-4400), tablet, administered in fasted state Part one of study (FIH, single ascending dose phase) |
| BG011 | Emodepside 10mg Solution, Fed (Part 2) | Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fed state This cohort was not classed as first in human Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events) |
| BG012 | Emodepside 40mg Solution, Fasted, AE Follow-up Arm (Part 2) | Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events) |
| BG013 | Placebo Solution, Fed (Part 2) | Matching placebo of emodepside (BAY 44-4400), solution, administered in fed state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events) |
| BG014 | Placebo Solution, Fasted (Part 2) | Matching placebo of emodepside (BAY 44-4400), solution, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events) |
| BG015 | Total | Total of all reporting groups |
| Mean |
| Standard Deviation |
| years |
|
| Sex: Female, Male | Totals were calculated seperately for Parts 1 and 2 | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Totals were calculated seperately for Parts 1 and 2 | Count of Participants | Participants |
|
| Race (NIH/OMB) | Totals were calculated seperately for Parts 1 and 2 | Count of Participants | Participants |
|
| Height | Totals were calculated seperately for Parts 1 and 2 | Mean | Standard Deviation | cm |
|
| Weight | Totals were calculated seperately for Parts 1 and 2 | Mean | Standard Deviation | kg |
|
| BMI | Totals were calculated seperately for Parts 1 and 2 | Mean | Standard Deviation | kg/m^2 |
|
| Emodepside 1mg Solution, Fasted (Part 1) |
Emodepside (BAY 44-4400) 1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) |
| OG002 | Emodepside 2.5mg Solution, Fasted (Part 1) | Emodepside (BAY 44-4400) 2.5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) |
| OG003 | Emodepside 5mg Solution, Fasted (Part 1) | Emodepside (BAY 44-4400) 5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) |
| OG004 | Emodepside 5mg Tablet, Fasted (Part 1) | Emodepside (BAY 44-4400) 5mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase) |
| OG005 | Emodepside 10mg Solution, Fasted (Part 1) | Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) |
| OG006 | Emodepside 20mg Solution, Fasted (Part 1) | Emodepside (BAY 44-4400) 20mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) |
| OG007 | Emodepside 20mg Tablet, Fasted (Part 1) | Emodepside (BAY 44-4400) 20mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase) |
| OG008 | Emodepside 40mg Solution, Fasted (Part 1) | Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) |
| OG009 | Emodepside 10mg Solution, Fed (Part 2) | Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fed state This cohort was not classed as first in human Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events) |
| OG010 | Emodepside 40mg Solution, Fasted, (Part 2) | Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events) |
| OG011 | Placebo Solution, Fasted (Part 1) | Matching placebo of emodepside (BAY 44-4400), solution, administered in fasted state Part one of study (FIH, single ascending dose phase) |
| OG012 | Placebo Tablet, Fasted (Part 1) | Matching placebo of emodepside (BAY 44-4400), tablet, administered in fasted state Part one of study (FIH, single ascending dose phase) |
| OG013 | Placebo Solution, Fed (Part 2) | Matching placebo of emodepside (BAY 44-4400), solution, administered in fed state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events) |
| OG014 | Placebo Solution, Fasted (Part 2) | Matching placebo of emodepside (BAY 44-4400), solution, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events) |
|
|
| Primary | Safety and Tolerability as Measured by Physical and Neurological Examination Findings | Abnormal or clinically significant neurological examination findings during the study or reported as an AE | AEs were determined in the Safety Population. In Part 1 n=63 (n=62 subjects completed). One subject in the 1mg emodepside group was withdrawn after receiving 0.1mg emodepside LSF, owing to an AE. He consented to follow-up safety assessment until Day 7 as a 0.1mg emodepside group. | Posted | Number | participants | Up to 14 days post dose (may be extended to 21 days) |
|
|
|
| Primary | Safety and Tolerability as Measured by Vital Signs | Vital signs included heart rate, systolic and diastolic blood pressure, | AEs were determined in the Safety Population. In Part 1 n=63 (n=62 subjects completed). One subject in the 1mg emodepside group was withdrawn after receiving 0.1mg emodepside LSF, owing to an AE. He consented to follow-up safety assessment until Day 7 as a 0.1mg emodepside group. | Posted | Number | participants | Up to 14 days post dose (may be extended to 21 days) |
|
|
|
| Primary | Safety and Tolerability as Measured by 12-lead ECG | The following variables were recorded in 12-lead ECGs and extracted from continuous 12-lead ECG recordings: ventricular rate, PR interval, QRS interval, QTcB and QTcF interval. | AEs were determined in the Safety Population. In Part 1 n=63 (n=62 subjects completed). One subject in the 1mg emodepside group was withdrawn after receiving 0.1mg emodepside LSF, owing to an AE. He consented to follow-up safety assessment until Day 7 as a 0.1mg emodepside group. | Posted | Number | participants | Up to 14 days post dose (may be extended to 21 days) |
|
|
|
| Primary | Safety and Tolerability as Measured by Clinical Laboratory Parameters | Clinical laboratory parameters included hematology, biochemistry, serology and coagulation in blood samples and urinalysis in urine samples | AEs were determined in the Safety Population. In Part 1 n=63 (n=62 subjects completed). One subject in the 1mg emodepside group was withdrawn after receiving 0.1mg emodepside LSF, owing to an AE. He consented to follow-up safety assessment until Day 7 as a 0.1mg emodepside group. | Posted | Number | participants | Up to 14 days post dose (may be extended to 21 days) |
|
|
|
| Primary | Safety and Tolerability as Measured by Ophthalmological Examination Findings in One Study Arm Only | Subjects attended a specialist eye hospital for ophthalmology assessments by a Consultant Ophthalmologist. Opthalmology assessments included:ocular symptoms, past ocular history, auto-refraction, best corrected distance visual acuity, color vision assessment, amsler grid assessment, ocular alignment and ocular motility assessment, confrontation visual field assessment, slit lamp examination (anterior segment), intraocular pressure (Goldmann Tonometry), optical coherence scanning of tomography, post mydriatic ocular media (at Screening visit 2 only) and retinal examination with slit lamp and lens. | AEs were determined in the Safety Population. Opthalmology examinations were only performed for the Emodepside 40mg group (n=6) and the corresponding placebo group (n=2) | Posted | Number | participants | Up to 14 days post dose (may be extended to 21 days) |
|
|
|
| Secondary | The AUC∞ of Emodepside in Plasma | The area under the plasma drug concentration versus time curve from time zero to infinity (AUC∞) | It is unacceptable to use AUCinf data if>40% of the AUC has been extrapolated.This is in line with literature(Gabrielson&Weiner, 2000).The AUCinf values with<20% of the area extrapolated (reliable results) have not been summarised in the tables because n is either 1 or 2 per treatment (n=2 only for 1m solution). | Posted | Geometric Mean | Standard Deviation | h*ng/ml | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
|
|
|
| Secondary | The AUC∞/D of Emodepside in Plasma | Dose-normalized area under the plasma drug concentration versus time curve from time zero to infinity (AUC∞/D), calculated as AUC∞/Dose administered. | It is unacceptable to use AUCinf data if>40% of the AUC has been extrapolated.This is in line with literature(Gabrielson&Weiner, 2000).The AUCinf values with<20% of the area extrapolated (reliable results) have not been summarised in the tables because n is either 1 or 2 per treatment (n=2 only for 1m solution). | Posted | Number | No values calculated | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
|
|
|
| Secondary | The Cmax of Emodepside in Plasma | Maximum observed plasma concentration (Cmax) was obtained directly from the concentration-time data | PK Concentration were summarized using PK concentration population (all subjects who received at least one dose of study drug and for whom a PK sample was analyzed). PK parameters were summarized using the PK Parameter population (all subjects in the PK Concentration Population for whom PK parameters could be derived). | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
|
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| Secondary | The Cmax/D of Emodepside in Plasma | Dose-normalized observed maximum plasma concentration (Cmax/D) was calculated as Cmax/Dose administered | PK Concentration data were summarized using the PK concentration population (all subjects who received at least one dose of study drug and for whom a PK sample was analyzed). PK parameters were summarized using the PK Parameter population (all subjects in the PK Concentration Population for whom PK parameters could be derived). | Posted | Geometric Mean | Geometric Coefficient of Variation | (ng/mL)/mg | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
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| Secondary | The Cmax, Norm of Emodepside in Plasma | The observed maximum plasma concentration (Cmax) normalized by dose and body weight was calculated as Cmax/(Dose administered*body weight) | PK Concentration data were summarized using the PK concentration population (all subjects who received at least one dose of study drug and for whom a PK sample was analyzed). PK parameters were summarized using the PK Parameter population (all subjects in the PK Concentration Population for whom PK parameters could be derived). | Posted | Geometric Mean | Geometric Coefficient of Variation | (ng/mL)/(mg*kg) | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
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| Secondary | The Tmax of Emodepside in Plasma | Time to reach maximum plasma concentration (Tmax) was obtained directly from the concentration-time data | PK Concentration data were summarized using the PK concentration population (all subjects who received at least one dose of study drug and for whom a PK sample was analyzed). PK parameters were summarized using the PK Parameter population (all subjects in the PK Concentration Population for whom PK parameters could be derived) | Posted | Mean | Full Range | Hours | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
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| Secondary | The t½ of Emodepside in Plasma | Terminal half-life (t½), calculated according to the equation t½ = ln2/λz, where λz is the apparent terminal elimination rate constant, estimated by linear regression of log-transformed concentration versus time data | PK Concentration data were summarized using the PK concentration population (all subjects who received at least one dose of study drug and for whom a PK sample was analyzed). PK parameters were summarized using the PK Parameter population (all subjects in the PK Concentration Population for whom PK parameters could be derived) | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
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| Secondary | The MRT of Emodepside in Plasma | The mean residence time (MRT) was calculated as MRT = AUMC/AUC∞, where AUMC is the area under the first moment of the concentration-time curve from zero time (pre-dose) extrapolated to infinite time | PK Concentration data were summarized using the PK concentration population (all subjects who received at least one dose of study drug and for whom a PK sample was analyzed). PK parameters were summarized using the PK Parameter population (all subjects in the PK Concentration Population for whom PK parameters could be derived). | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
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| Secondary | The CL/F of Emodepside in Plasma | Apparent total clearance from plasma (CL/F) was calculated as CL/F = Dose/AUC∞ | PK Concentration data were summarized using the PK concentration population (all subjects who received at least one dose of study drug and for whom a PK sample was analyzed). PK parameters were summarized using the PK Parameter population (all subjects in the PK Concentration Population for whom PK parameters could be derived). | Posted | Geometric Mean | Geometric Coefficient of Variation | L/hour | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
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| Secondary | The AUC 0-24 of Emodepside in Plasma | Area under the plasma concentration-time curve from time zero (pre-dose) to 24 h was calculated using the trapezoidal method | PK Concentration data were summarized using the PK concentration population (all subjects who received at least one dose of study drug and for whom a PK sample was analyzed). PK parameters were summarized using the PK Parameter population (all subjects in the PK Concentration Population for whom PK parameters could be derived). | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
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| Secondary | The AUC 0-24/D of Emodepside in Plasma | Dose-normalized area under the concentration-time curve (AUC) from time zero (pre-dose) to 24 h was calculated as AUC0-24/Dose administered | PK Concentration data were summarized using the PK concentration population (all subjects who received at least one dose of study drug and for whom a PK sample was analyzed). PK parameters were summarized using the PK Parameter population (all subjects in the PK Concentration Population for whom PK parameters could be derived). | Posted | Geometric Mean | Geometric Coefficient of Variation | (h.ng/mL)/mg) | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
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| Secondary | The AUC 24, Norm of Emodepside in Plasma | Area under the concentration-time curve from time zero (pre-dose) to 24 h, normalized by dose and body weight (AUC 24, norm) was calculated as AUC0-24/(Dose administered*body weight) | PK Concentration data were summarized using the PK concentration population (all subjects who received at least one dose of study drug and for whom a PK sample was analyzed). PK parameters were summarized using the PK Parameter population (all subjects in the PK Concentration Population for whom PK parameters could be derived). | Posted | Geometric Mean | Geometric Coefficient of Variation | (h*ng/mL)/(mg*kg) | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
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| Secondary | The Vz/F of Emodepside in Plasma | Apparent volume of distribution (Vz/F) was calculated as Vz/F = Dose/(λz × AUC∞), where λz is the apparent terminal elimination rate constant, estimated by linear regression of log-transformed concentration versus time data | PK Concentration data were summarized using the PK concentration population (all subjects who received at least one dose of study drug and for whom a PK sample was analyzed). PK parameters were summarized using the PK Parameter population (all subjects in the PK Concentration Population for whom PK parameters could be derived). | Posted | Geometric Mean | Geometric Coefficient of Variation | Litres | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
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| Secondary | The AUC Last of Emodepside in Plasma | The area under the concentration-time curve from time zero (pre-dose) to the time of last quantifiable concentration (t), calculated using the linear trapezoidal method for increasing concentrations and the log trapezoidal method for decreasing concentrations | PK Concentration data were summarized using the PK concentration population (all subjects who received at least one dose of study drug and for whom a PK sample was analyzed). PK parameters were summarized using the PK Parameter population (all subjects in the PK Concentration Population for whom PK parameters could be derived). | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
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| Secondary | Frel of the IR (Immediate Release) Tablet of Emodepside | The average relative bioavailability (Frel) of the IR tablet was calculated | PK Concentration data were summarized using the PK concentration population (all subjects who received at least one dose of study drug and for whom a PK sample was analyzed). PK parameters were summarized using the PK Parameter population (all subjects in the PK Concentration Population for whom PK parameters could be derived). | Posted | Number | 90% Confidence Interval | Frel percentage | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
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| Secondary | The AUC Last, Norm of Emodepside in Plasma | The area under the concentration-time curve from time zero (pre-dose) to the time of last quantifiable concentration normalized by dose and body weight (AUClast/(Dose administered*body weight)) | PK Concentration data were summarized using the PK concentration population (all subjects who received at least one dose of study drug and for whom a PK sample was analyzed). PK parameters were summarized using the PK Parameter population (all subjects in the PK Concentration Population for whom PK parameters could be derived). | Posted | Geometric Mean | Geometric Coefficient of Variation | (h*ng/mL)/(mg*kg) | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
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| Secondary | Effect of Food on the Bioavailability (Cmax) of Emodepside (BAY 44-4400) After Single Oral Dose Administered as Solution or IR Tablets in One Arm Only | Results of the statistical analysis of the effect of food on Emodepside exposure, after a single dose of 10 mg Emodepside LSF solution. | emodepside assessed in fasted condition: only one cohort (10mg solution) assessed with high fat high calories meal. | Posted | Least Squares Mean | Full Range | ng/ml | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
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| Secondary | Effect of Food on the Bioavailability (AUC24) of Emodepside (BAY 44-4400) After Single Oral Dose Administered as Solution or IR Tablets in One Arm Only | Results of the statistical analysis of the effect of food on Emodepside exposure, after a single dose of 10 mg Emodepside LSF solution. | emodepside assessed in fasted condition: only one cohort (10mg solution) assessed with high fat high calories meal. | Posted | Least Squares Mean | Full Range | ng*h/mL | From pre-dose until 336h post-dose (may be extended to 504h post-dose) |
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| 0 |
| 1 |
| 0 |
| 1 |
| 1 |
| 1 |
| EG001 | Emodepside 1mg Solution, Fasted (Part 1) | Emodepside (BAY 44-4400) 1mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) | 0 | 5 | 0 | 5 | 3 | 5 |
| EG002 | Emodepside 2.5mg Solution, Fasted (Part 1) | Emodepside (BAY 44-4400) 2.5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) | 0 | 6 | 0 | 6 | 0 | 6 |
| EG003 | Emodepside 5mg Solution, Fasted (Part 1) | Emodepside (BAY 44-4400) 5mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) | 0 | 6 | 0 | 6 | 3 | 6 |
| EG004 | Emodepside 5mg Tablet, Fasted (Part 1) | Emodepside (BAY 44-4400) 5mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase) | 0 | 5 | 0 | 5 | 3 | 5 |
| EG005 | Emodepside 10mg Solution, Fasted (Part 1) | Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) | 0 | 6 | 0 | 6 | 5 | 6 |
| EG006 | Emodepside 20mg Solution, Fasted (Part 1) | Emodepside (BAY 44-4400) 20mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) | 0 | 6 | 0 | 6 | 3 | 6 |
| EG007 | Emodepside 20mg Tablet, Fasted (Part 1) | Emodepside (BAY 44-4400) 20mg tablet (immediate release), administered in fasted state Part one of study (FIH, single ascending dose phase) | 0 | 6 | 0 | 6 | 2 | 6 |
| EG008 | Emodepside 40mg Solution, Fasted (Part 1) | Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part one of study (FIH, single ascending dose phase) | 0 | 6 | 0 | 6 | 5 | 6 |
| EG009 | Emodepside 10mg Solution, Fed (Part 2) | Emodepside (BAY 44-4400) 10mg solution, as oral liquid service formulation, administered in fed state This cohort was not classed as first in human Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events) | 0 | 6 | 0 | 6 | 3 | 6 |
| EG010 | Emodepside 40mg Solution, Fasted, (Part 2) | Emodepside (BAY 44-4400) 40mg solution, as oral liquid service formulation, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events) | 0 | 6 | 0 | 6 | 5 | 6 |
| EG011 | Placebo Solution, Fasted (Part 1) | Matching placebo of emodepside (BAY 44-4400), solution, administered in fasted state Part one of study (FIH, single ascending dose phase) | 0 | 12 | 0 | 12 | 5 | 12 |
| EG012 | Placebo Tablet, Fasted (Part 1) | Matching placebo of emodepside (BAY 44-4400), tablet, administered in fasted state Part one of study (FIH, single ascending dose phase) | 0 | 4 | 0 | 4 | 1 | 4 |
| EG013 | Placebo Solution, Fed (Part 2) | Matching placebo of emodepside (BAY 44-4400), solution, administered in fed state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events) | 0 | 2 | 0 | 2 | 0 | 2 |
| EG014 | Placebo Solution, Fasted (Part 2) | Matching placebo of emodepside (BAY 44-4400), solution, administered in fasted state Part two of study (not FIH, exploratory effect of food on the bioavailability of emodepside and to assess relationship between emodepside and adverse events) | 0 | 2 | 0 | 2 | 0 | 2 |
| TEAEs by primary system organ classes (SOCs) | Eye disorders | MedDRA (19.0) | Systematic Assessment |
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| TEAEs by primary system organ classes (SOCs) | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
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| TEAEs by primary system organ classes (SOCs) | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
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| TEAEs by primary system organ classes (SOCs) | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
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| TEAEs by primary system organ classes (SOCs) | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
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| TEAEs by primary system organ classes (SOCs) | General disorders | MedDRA (19.0) | Systematic Assessment |
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| TEAEs by primary system organ classes (SOCs) | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
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| TEAEs by primary system organ classes (SOCs) | Psychiatric disorders | MedDRA (19.0) | Systematic Assessment |
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The Institution (HMR) could not make any public communication related to the Results or Trial Subjects, notably, without DNDi's prior written approval. The Institution shall inform DNDi in advance of any media visits to the Clinical Trial site and comply with the guidance provided by DNDi.
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Neurological examination reported as AE |
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| Abnormal physcial examination |
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| Physical examination reported as AE |
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| Clinically significant change in systolic BP |
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| Clinically significant change in diastolic BP |
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| Notable changes in PR interval |
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| Notable changes in QRS interval |
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| Notable changes in QTcB |
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| Notable changes in QTcF interval |
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| Clinically significant biochemical changes |
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| Clinically significant serological changes |
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| Clinically significant coagulation changes |
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| Clinically significant urinalysis changes |
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| Clinically significant changes in remaining exams |
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