Clinical trial NCT02661178: First in Man Clinical Trial of Emodepside (BAY 44-4400)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Parasitic Diseases
Helminthiasis
Nematode Infections
Secernentea Infections
Spirurida Infections
Filariasis
Skin Diseases, Parasitic
Skin and Connective Tissue Diseases
Skin Diseases
Skin Diseases, Infectious
Depsipeptides
Emodepside
Neglected disease
Africa
New drug
Oral drug
Parasite
Anthelmintic drug
Cyclooctadepsipeptide
Single ascending dose
Volunteers
Phase 1
Safety
Tolerability
Pharmacokinetics
Relative bioavailability
Onchocerciasis
Lead sponsor: Drugs for Neglected Diseases
Sponsor class: OTHER
Collaborators: name: Bayer
name: Bill and Melinda Gates Foundation
First posted: 2016-01-22
Enrollment: 79
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Safety and Tolerability as Measured by Adverse Events
timeFrame: Up to 14 days post dose (may be extended to 21 days)
measure: Safety and Tolerability as Measured by Physical and Neurological Examination Findings
timeFrame: Up to 14 days post dose (may be extended to 21 days)
measure: Safety and Tolerability as Measured by Vital Signs
timeFrame: Up to 14 days post dose (may be extended to 21 days)
measure: Safety and Tolerability as Measured by 12-lead ECG
timeFrame: Up to 14 days post dose (may be extended to 21 days)
measure: Safety and Tolerability as Measured by Clinical Laboratory Parameters
timeFrame: Up to 14 days post dose (may be extended to 21 days)
measure: Safety and Tolerability as Measured by Ophthalmological Examination Findings in One Study Arm Only
timeFrame: Up to 14 days post dose (may be extended to 21 days)
Secondary outcomes:
measure: The AUC∞ of Emodepside in Plasma
timeFrame: From pre-dose until 336h post-dose (may be extended to 504h post-dose)
measure: The AUC∞/D of Emodepside in Plasma
timeFrame: From pre-dose until 336h post-dose (may be extended to 504h post-dose)
measure: The Cmax of Emodepside in Plasma
timeFrame: From pre-dose until 336h post-dose (may be extended to 504h post-dose)
measure: The Cmax/D of Emodepside in Plasma
timeFrame: From pre-dose until 336h post-dose (may be extended to 504h post-dose)
measure: The Cmax, Norm of Emodepside in Plasma
timeFrame: From pre-dose until 336h post-dose (may be extended to 504h post-dose)
measure: The Tmax of Emodepside in Plasma
timeFrame: From pre-dose until 336h post-dose (may be extended to 504h post-dose)
measure: The t½ of Emodepside in Plasma
timeFrame: From pre-dose until 336h post-dose (may be extended to 504h post-dose)
measure: The MRT of Emodepside in Plasma
timeFrame: From pre-dose until 336h post-dose (may be extended to 504h post-dose)
measure: The CL/F of Emodepside in Plasma
timeFrame: From pre-dose until 336h post-dose (may be extended to 504h post-dose)
measure: The AUC 0-24 of Emodepside in Plasma
timeFrame: From pre-dose until 336h post-dose (may be extended to 504h post-dose)
measure: The AUC 0-24/D of Emodepside in Plasma
timeFrame: From pre-dose until 336h post-dose (may be extended to 504h post-dose)
measure: The AUC 24, Norm of Emodepside in Plasma
timeFrame: From pre-dose until 336h post-dose (may be extended to 504h post-dose)
measure: The Vz/F of Emodepside in Plasma
timeFrame: From pre-dose until 336h post-dose (may be extended to 504h post-dose)
measure: The AUC Last of Emodepside in Plasma
timeFrame: From pre-dose until 336h post-dose (may be extended to 504h post-dose)
measure: Frel of the IR (Immediate Release) Tablet of Emodepside
timeFrame: From pre-dose until 336h post-dose (may be extended to 504h post-dose)
measure: The AUC Last, Norm of Emodepside in Plasma
timeFrame: From pre-dose until 336h post-dose (may be extended to 504h post-dose)
measure: 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
timeFrame: From pre-dose until 336h post-dose (may be extended to 504h post-dose)
measure: 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
timeFrame: From pre-dose until 336h post-dose (may be extended to 504h post-dose)
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Hammersmith Medicines Research
Study officials:
affiliation: Hammersmith Medicines Research
name: Malcolm Boyce, MD, BSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Drugs for Neglected Diseases initiative
name: Frederic Monnot
role: STUDY_DIRECTOR
References: