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

NCT02661178 | Completed Phase 1 Results

• 2 other identifiers: DNDI-EMO-0012015-003592-29
• Study Type: interventional
• Target: 79
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (6)

• 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.

  Up to 14 days post dose (may be extended to 21 days)

Secondary Outcomes (18)

• The AUC∞ of Emodepside in Plasma

  From pre-dose until 336h post-dose (may be extended to 504h post-dose)

• The AUC∞/D of Emodepside in Plasma

  From pre-dose until 336h post-dose (may be extended to 504h post-dose)

• The Cmax of Emodepside in Plasma

  From pre-dose until 336h post-dose (may be extended to 504h post-dose)

• The Cmax/D of Emodepside in Plasma

  From pre-dose until 336h post-dose (may be extended to 504h post-dose)

• The Cmax, Norm of Emodepside in Plasma

  From pre-dose until 336h post-dose (may be extended to 504h post-dose)

Study Arms (2)

emodepside (BAY 44-4400)

EXPERIMENTAL

Up to 10 cohorts with single ascending dose

Drug: emodepside (BAY 44-4400)

placebo of emodepside (BAY 44-4400)

PLACEBO COMPARATOR

Up to 10 cohorts with single ascending dose

Drug: placebo

Interventions

emodepside (BAY 44-4400) DRUG

emodepside (BAY 44-4400)

placebo DRUG

placebo of emodepside (BAY 44-4400)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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)

Sponsors & Collaborators

• Drugs for Neglected Diseases: lead
• Bayer: collaborator
• Bill and Melinda Gates Foundation: collaborator

Study Sites (1)

Hammersmith Medicines Research

London, NW10 7EW, United Kingdom

Location

MeSH Terms

Conditions

Parasitic Diseases; Helminthiasis; Nematode Infections; Secernentea Infections; Spirurida Infections; Filariasis; Skin Diseases, Parasitic; Skin and Connective Tissue Diseases; Skin Diseases; Skin Diseases, Infectious; Neglected Diseases; Onchocerciasis

Interventions

emodepside; Bay 44-4400

Condition Hierarchy (Ancestors)

Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Sophie Delhomme
• Organization: Drugs for Neglected Diseases initiative

sdelhomme@dndi.org

+41229069230

Study Officials

• Malcolm Boyce, MD, BSc

  Hammersmith Medicines Research

  PRINCIPAL INVESTIGATOR

• Frederic Monnot

  Drugs for Neglected Diseases initiative

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2016
• First Posted: January 22, 2016
• Study Start: December 1, 2015
• Primary Completion: March 27, 2017
• Study Completion: March 27, 2017
• Last Updated: April 13, 2020
• Results First Posted: April 13, 2020

Record last verified: 2019-10

Locations

GB (1)