First in Man Clinical Trial of Emodepside (BAY 44-4400)

Healthy Volunteers Clinical Trial

Official title:

A Phase 1, Blinded, Randomized, Placebo Controlled, Parallel-Group, Single-Dose, Dose-Escalation Study to Investigate Safety, Tolerability, and Pharmacokinetics of Emodepside (BAY 44-4400) After Oral Dosing in Healthy Male Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02661178
• Other study ID #: DNDI-EMO-001
• Secondary ID: 2015-003592-29
• Status: Completed
• Phase: Phase 1
• Start date: December 2015
• Est. completion date: March 27, 2017

Study information

• Verified date: October 2019
• Source: Drugs for Neglected Diseases
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will investigate the safety, tolerability, and pharmacokinetics of single ascending doses of emodepside (BAY 44-4400) in healthy male volunteers. This study will also conduct an exploratory investigation of the relative bioavailability of emodepside administered as tablets and determine the effect of food on the pharmacokinetics.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: March 27, 2017
• Est. primary completion date: March 27, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Male, Caucasian volunteers, deemed healthy on the basis of a clinical history, physical examination, ECG, vital signs, and laboratory tests of blood and urine. Optionally, after further evaluation during the study, at the sponsor's discretion other ethnic groups may be recruited.

• Aged 18 to 55 years.

• With a body mass index (BMI; Quetelet index) in the range of 18 to 30.1 kg/m2 at screening.

• Sufficient intelligence to understand the nature of the trial and any hazards of participating in it. Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of, the entire trial.

• Willingness to give written consent to participate, after reading the information and consent form, and after having the opportunity to discuss the trial with the investigator or his delegate

Exclusion Criteria:

• Participation in another clinical trial within 3 months prior and during the study, or 5-times the half-life of the drug tested in the previous clinical trial, whichever is longer (time calculated relative to the last dose in the previous clinical trial)

• Clinically relevant abnormal medical history, concurrent medical condition, acute or chronic illness or history of chronic illness sufficient to invalidate the subject's participation in the trial or make it unnecessarily hazardous.

• Surgery (eg stomach bypass) or medical condition that might affect absorption of study drug taken orally.

• Presence of abnormal physical findings, ECG, or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the subject.

• Positive tests for hepatitis B & C, HIV

• Presence or history of drug or alcohol abuse during the last 10 years, or intake of more than 21 units of alcohol weekly.

• Regular daily consumption of more than one liter of xanthine-containing beverages

• Regular daily consumption of more than 5 cigarettes daily, or use more than 3 grams (1/8 ounce) of tobacco

• Use of a prescription medicine during the 28 days before the first dose of trial medication or use of an over-the-counter medicine, with the exception of acetaminophen (paracetamol), during the 7 days before the first dose of trial medication

• Use of dietary supplements or herbal remedies (such as St John's Wort) known to interfere with the CYP3A4 and/or P-gp metabolic pathways during the 28 days before the first dose of trial medication (see list in Study Procedures Manual)

Additional exclusion criteria for cohort with ophthalmological assessments:

• No contact lenses wear within 1 month prior to first dose of IMP. Contact lenses wear 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

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• emodepside (BAY 44-4400)

• placebo

Locations

Country	Name	City	State
United Kingdom	Hammersmith Medicines Research	London

Sponsors (3)

Lead Sponsor	Collaborator
Drugs for Neglected Diseases	Bayer, Bill and Melinda Gates Foundation

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
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	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,	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.	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	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.	Up to 14 days post dose (may be extended to 21 days)
Secondary	The AUC8 of Emodepside in Plasma	The area under the plasma drug concentration versus time curve from time zero to infinity (AUC8)	From pre-dose until 336h post-dose (may be extended to 504h post-dose)
Secondary	The AUC8/D of Emodepside in Plasma	Dose-normalized area under the plasma drug concentration versus time curve from time zero to infinity (AUC8/D), calculated as AUC8/Dose administered.	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	From pre-dose until 336h post-dose (may be extended to 504h post-dose)
Secondary	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)
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)	From pre-dose until 336h post-dose (may be extended to 504h post-dose)
Secondary	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)
Secondary	The t½ of Emodepside in Plasma	Terminal half-life (t½), calculated according to the equation t½ = ln2/?z, where ?z 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)
Secondary	The MRT of Emodepside in Plasma	The mean residence time (MRT) was calculated as MRT = AUMC/AUC8, 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)
Secondary	The CL/F of Emodepside in Plasma	Apparent total clearance from plasma (CL/F) was calculated as CL/F = Dose/AUC8	From pre-dose until 336h post-dose (may be extended to 504h post-dose)
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	From pre-dose until 336h post-dose (may be extended to 504h post-dose)
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	From pre-dose until 336h post-dose (may be extended to 504h post-dose)
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)	From pre-dose until 336h post-dose (may be extended to 504h post-dose)
Secondary	The Vz/F of Emodepside in Plasma	Apparent volume of distribution (Vz/F) was calculated as Vz/F = Dose/(?z × AUC8), where ?z 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)
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	From pre-dose until 336h post-dose (may be extended to 504h post-dose)
Secondary	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)
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))	From pre-dose until 336h post-dose (may be extended to 504h post-dose)
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.	From pre-dose until 336h post-dose (may be extended to 504h post-dose)
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.	From pre-dose until 336h post-dose (may be extended to 504h post-dose)