Safety, Tolerability and PK of Multiple-ascending Doses o... | NCT03383614

NCT03383614

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
2017-003020-75	EudraCT Number

Status Module

Sponsor/Collaborators Module

Name	Class
Bayer	INDUSTRY
Bill and Melinda Gates Foundation	OTHER

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
cohort 1 (8 subjects)	Experimental	6 subjects with LSF emodepside 5mg, OD 2 subjects with matching placebo	Drug: LSF emodepside (BAY 44-4400) or matching placebo
cohort 2 (8 subjects)	Experimental	6 subjects with LSF emodepside 10mg, OD 2 subjects with matching placebo	Drug: LSF emodepside (BAY 44-4400) or matching placebo
cohort 3 (8 subjects)	Experimental	6 subjects with LSF emodepside 10mg, BID 2 subjects with matching placebo	Drug: LSF emodepside (BAY 44-4400) or matching placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
LSF emodepside (BAY 44-4400) or matching placebo	Drug	Emodepside administered as an LSF oral solution (1mg/mL)	cohort 1 (8 subjects) cohort 2 (8 subjects)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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).	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.	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.	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.	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.	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.

Secondary Outcomes

Measure	Description	Time Frame
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.

Other Outcomes

Measure	Description	Time Frame
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.	Drug-related AEs were reported throughout the study

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male, Caucasian volunteers, deemed healthy based on a clinical history, physical examination, ECG, vital signs, and laboratory tests of blood and urine.
18 to 45 years of age.
Normal body weight (BMI; Quetelet index) in the range 18 to 30.1 kg/m2 at screening.
Blood pressure and heart rate in the supine position prior to randomisation must be within the ranges 90-140 mm Hg systolic, 60-90 mm Hg diastolic; heart rate 45-100 beats/min.
Sufficient intelligence to understand the nature of the trial and any hazards of participating in it. Ability to communicate satisfactorily with the Investigator and to participate in, and comply with the requirements of, the entire trial.
Willingness to give written consent to participate, after reading the information and consent form, and after having the opportunity to discuss the trial with the Investigator or his delegate.
Willingness to give written consent to have data entered into the Overvolunteering Prevention System.
Willingness to agree to the contraceptive requirements of the study from the first dose until 120 days after the last dose of study medication.

Exclusion Criteria:

Administration of a licensed or unlicensed medicinal product as part of another clinical trial within the 3 months before, or within 5 half-lives of, their first dose of study medication, whichever is longer, or is currently in the follow-up period for any clinical trial.
Clinically relevant abnormal medical history, concurrent medical condition, acute or chronic illness or history of chronic illness (such as diabetes mellitus or other abnormalities of glucose homeostasis) sufficient to invalidate the subject's participation in the trial or make it unnecessarily hazardous.
Past surgery (e.g., stomach bypass) or medical condition that might affect absorption of study drug taken orally.
Presence of abnormal physical findings, ECG, or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the subject.
Loss of more than 400 mL of blood within 3 months before admission.
Clinically relevant history of vital organ disease or other disease of an organ or the central nervous system.
Current or previous medical or psychiatric disorder, condition or history of such (e.g., seizures) that, in the opinion of the Investigator or the Sponsor, would increase the risk associated with study participation, or impair the subject's ability to participate or complete this study.
Positive test for hepatitis B, hepatitis C or HIV.
Febrile illness within 1 week before the first dose of study medication.
History of severe allergy, non-allergic drug reactions, severe adverse reaction to any drug, or multiple drug allergies.
Subjects with hypersensitivity to any ingredient of the study medication, including the active ingredient, emodepside.
Presence or history of drug or alcohol abuse in the last 10 years, or intake of more than 21 units of alcohol weekly.
Regular daily consumption of more than one liter of xanthine-containing beverages.
Regular daily consumption of more than 5 cigarettes daily, or use more than 3 grams (1/8 ounce) of tobacco.
Use of a prescription medicine during the 28 days before the first dose of study medication or use of an over-the-counter medicine (with exception of acetaminophen [paracetamol]), during the 7 days before the first dose of study medication.
Use of dietary supplements or herbal remedies (such as St John's Wort) that are known to be inducers or inhibitors of CYP3A4, or other co-medications known to be relevant substrates of CYP3A4, during the 28 days before the first dose of study medication (see list in the Study Procedures Manual).
Use of dietary supplements or herbal remedies (such as St John's Wort) that are known to be strong inhibitors of P-gp, or other co-medications known to be relevant substrates of P-gp, during the 28 days before the first dose of study medication (see list in the Study Procedures Manual).
Relevant pathological abnormalities in the ECG at screening, such as a second or third-degree atrioventricular (AV) block or prolongation of the QRS complex over 120 msec or QTc-interval over 450 msec (corrected using Bazett's [QTcB] or Fridericia's [QTcF] formulae).
Evidence of drug abuse (via urine testing) at the screening assessment or admission to the ward.
Use of excluded therapies that may impact on the interpretation of study results in the opinion of the Investigator or Sponsor.
Objection by General Practitioner (GP) to subject entering trial.
History of residing for 6 or more continuous months, within the last 3 years, in regions with endemic parasitic infections as determined by the Investigator.
Possibility that subject will not cooperate with the requirements of the protocol.
No contact lenses wear within 1 month before dosing. Wearing contact lenses is not permitted during the study.
Any ocular disorder for which topical ocular therapy is currently or chronically prescribed, including inflammatory eye disease (dry eye allergic conjunctivitis [seasonal allergic conjunctivitis, vernal keratoconjunctivitis, atopic keratoconjunctivitis], uveitis and glaucoma).
Past history of ocular disease requiring ongoing treatment.
Past ocular surgery including laser or other refractive corneal surgery.
Evidence of eye irritation, visual difficulties, corneal opacity, ocular surface (corneal or conjunctival damage, with or without ocular symptoms).
Evidence of narrow anterior chamber angles causing increased risk of acute glaucoma.
Evidence of ocular media opacity including lens opacity/vitreous opacities.
Evidence of retinal or optic nerve pathology.
Evidence of pronounced colour blindness, as indicated by an Ishihara score of 9/13 or below.

Contacts/Locations Module

Name	Affiliation	Role
Jeremy Dennison, PhD MBChB	Hammersmith Medicines Research Limited	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Hammersmith Medicines Research Limited		London		NW10 7EW	United Kingdom

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

24 healthy subjects were randomized and received study drug or matching placebo.

Arm/Group Information

ID	Title	Description
FG000	Cohort 1: 5mg EMODEPSIDE OD	6 subjects with LSF emodepside 5mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)
FG001	Cohort 2: 10mg EMODEPSIDE OD	6 subjects with LSF emodepside 10mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)
FG002	Cohort 3: 10mg EMODEPSIDE BID	6 subjects with LSF emodepside 10mg, BID LSF emodepside (BAY 44-4400) oral solution (1mg/mL)
FG003	Placebo Group	6 subjects with matching placebo (2 subjects per dose group)

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG0006 subjects FG0016 subjects FG0026 subjects FG0036 subjects
COMPLETED		FG0006 subjects FG0015 subjects FG0026 subjects FG0036 subjects
NOT COMPLETED		FG0000 subjects FG0011 subjects FG0020 subjects FG0030 subjects

Type	Comment	Reasons
Withdrawal by Subject		FG0000 subjects FG0011 subjects FG0020 subjects FG003

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Cohort 1: 5mg EMODEPSIDE OD	6 subjects with LSF emodepside 5mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)
BG001	Cohort 2: 10mg EMODEPSIDE OD	6 subjects with LSF emodepside 10mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

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 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).

Adverse events were determined in the Safety population. Adverse events were monitored from Screening (Day -28 and until Day -3) to Follow-up (up to Day 120 ±2 days).

AE=adverse event; OD=once daily; BID=twice daily.

Posted

Number

Participants

up to 120 days

ID	Title	Description
OG000	Cohort 1: 5mg EMODEPSIDE OD	6 subjects with LSF emodepside 5mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)
OG001	Cohort 2: 10mg EMODEPSIDE OD

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cohort 1: 5mg EMODEPSIDE OD	6 subjects with LSF emodepside 5mg, OD LSF emodepside (BAY 44-4400) oral solution (1mg/mL)

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anal fistula	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	The fistula was downgraded by the investigator to a nonserious AE on 05 NOV 2018; after final database lock. That decision was based on the fact that the subject was hospitalised because of the AE of anal abscess, and not the fistula.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Sebaceous cyst excision	Surgical and medical procedures	MedDRA (21.1)	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Jean Yves Gillon	DNDi	+41.22.906.92.32		jygillon@dndi.org

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jul 25, 2018	Feb 19, 2020	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Aug 29, 2018	Feb 19, 2020	SAP_001.pdf

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

ID	Term
D005368	Filariasis

ID	Term
D017205	Spirurida Infections
D017190	Secernentea Infections
D009349	Nematode Infections
D006373	Helminthiasis

Intervention Browse Module

ID	Term
C439266	Bay 44-4400

Masking Info

cohort 3 (8 subjects)

6 subjects with LSF emodepside 10mg, OD

LSF emodepside (BAY 44-4400) oral solution (1mg/mL)

EG0000 events0 affected6 at risk

EG0011 events1 affected6 at risk

EG0020 events0 affected6 at risk

EG0030 events0 affected6 at risk