Safety, Tolerability and PK of Multiple-ascending Doses of Emodepside

NCT03383614 | Completed Phase 1 Results DMC

• 2 other identifiers: DNDI-EMO-022017-003020-75
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The study evaluates safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of emodepside, after administration as a Liquid Service Formulation (LSF), over 10 days, in healthy male caucasian subjects.

Conditions

Filariasis

Outcome Measures

Primary Outcomes (8)

• 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.

  up to 10 days

• Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Physical Examination Findings

  Abnormal or clinically significant physical examination findings during the study or reported as an adverse event.

  up to 120 days

• Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Neurological Examination Findings

  Abnormal or clinically significant neurological examination findings during the study or reported as an adverse event.

  up to 120 days

Secondary Outcomes (40)

• Geometric Mean Emodepside Plasma Pharmacokinetic Concentration-Time Data During the Repeated Dosing Period

  From Day 1, pre-dose to Day 9, 24 hours post-dose

• The AUClast of Emodepside in Plasma

  AUClast in plasma after the last dose (Day 9)

• The AUClast/D of Emodepside in Plasma

  AUClast /D in plasma after the last dose (Day 9)

• The AUClast,Norm of Emodepside in Plasma

  AUClast,norm in plasma after the last (Day 9) dose

• The AUC12 of Emodepside in Plasma

  AUC12 in plasma after the first (Day 0) and last (Day 9) dose

Other Outcomes (1)

• Drug-related Adverse Events

  Drug-related AEs were reported throughout the study

Study Arms (3)

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

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); cohort 3 (8 subjects)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: only male subjects will be included
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male, Caucasian volunteers, deemed healthy based on a clinical history, physical examination, ECG, vital signs, and laboratory tests of blood and urine.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

Hammersmith Medicines Research Limited

London, NW10 7EW, United Kingdom

Location

MeSH Terms

Conditions

Filariasis

Interventions

Bay 44-4400

Condition Hierarchy (Ancestors)

Spirurida Infections; Secernentea Infections; Nematode Infections; Helminthiasis; Parasitic Diseases; Infections

Results Point of Contact

• Title: Jean Yves Gillon
• Organization: DNDi

jygillon@dndi.org

+41.22.906.92.32

Study Officials

• Jeremy Dennison, PhD MBChB

  Hammersmith Medicines Research Limited

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2017
• First Posted: December 26, 2017
• Study Start: November 14, 2017
• Primary Completion: October 15, 2018
• Study Completion: October 15, 2018
• Last Updated: April 15, 2020
• Results First Posted: April 15, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)