Relative Bioavailability Study of Emodepside IR-tablets and Solution

NCT03383523 | Completed Phase 1 Results DMC

• 2 other identifiers: DNDI-EMO-032017-003091-31
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates 2 new immediate release (IR)-tablet formulations of emodepside and they will be compared to the oral liquid service formulation (LSF) used in the FIH Single Ascending Dose study (DNDi-EMO-001 study) (CT.gov identifier: NCT02661178)

Conditions

Filariasis

Outcome Measures

Primary Outcomes (2)

• PK (AUC0-7d) of Two New Tablet Formulations of Emodepside in Comparison to the Liquid Formulation (LSF) Oral Solution.

  Means AUC from zero to 7 days (AUC0-7d) = means area under the plasma concentration-time curve from time zero (pre-dose) to 7 days. To create the curve, the following PK Timepoints have been collected: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3,4,6,8,12,36,48,72,120 and 168h post dose

  means from zero to 7 days

• PK (Cmax) of Two New Tablet Formulations of Emodepside in Comparison to the Liquid Formulation (LSF) Oral Solution.

  Cmax means maximum observed plasma concentration. To create the PK curve, the following PK timepoints have been collected: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3,4,6,8,12,36,48,72,120 and 168h post dose

  7 days

Secondary Outcomes (6)

• Safety and Tolerability as Measured by Number of Participants With Treatment-related Adverse Events

  7 days

• Safety and Tolerability as Measured by Number of Participants With Physical Examination Findings

  7 days

• Safety and Tolerability as Measured by Number of Participants With Neurological Examination Findings

  7 days

• Safety and Tolerability as Measured by Number of Participants With Vital Signs Findings

  7 days

• Safety and Tolerability as Measured by Number of Participants With 12-lead ECG Findings

  7 days

Study Arms (7)

Part 1a - treatment A

EXPERIMENTAL

5 mg emodepside LSF, fasted

Drug: Emodepside (BAY 44-4400)

Part 1a - treatment B

EXPERIMENTAL

5 mg emodepside IR-tablet #406, fasted

Drug: Emodepside (BAY 44-4400)

Part 1a - treatment C

EXPERIMENTAL

5 mg emodepside IR-tablet #416, fasted

Drug: Emodepside (BAY 44-4400)

Part 1b - treatment D

EXPERIMENTAL

5 mg emodepside IR-tablet #406, fed

Drug: Emodepside (BAY 44-4400)

Part 1b - treatment E

EXPERIMENTAL

5 mg emodepside IR-tablet #416, fed

Drug: Emodepside (BAY 44-4400)

Part 2 - treatment F

EXPERIMENTAL

2 x 5 mg emodepside IR-tablet #406, fasted (may be tested or not, depending on the results of the part 1)

Drug: Emodepside (BAY 44-4400)

Part 2 - treatment G

EXPERIMENTAL

2 x 5 mg emodepside IR-tablet #416, fasted (may be tested or not, depending on the results of the part 1)

Drug: Emodepside (BAY 44-4400)

Interventions

Emodepside (BAY 44-4400) DRUG

2 tablets compared to the liquid formulation

Also known as: Profender® (in combination with praziquantel) FOR VETERINARY USE, Procox® (in combination with toltrazuril) FOR VETERINARY USE

Part 1a - treatment A; Part 1a - treatment B; Part 1a - treatment C; Part 1b - treatment D; Part 1b - treatment E; Part 2 - treatment F; Part 2 - treatment G

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: male only
• 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 (Body Mass Index (BMI); Quetelet index) in the range 18.0 to 30.1 kg/m2 at screening
• Mean blood pressure and heart rate (from the triplicate readings) in the supine position at the screening assessment outside one (or more) of the ranges: 90-140 mm Hg systolic BP 60-90 mm Hg diastolic BP 45-100 beats/min HR
• 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 (TOPS)
• Willingness to follow contraception requirements of the study, from the first dose of the IMP until 90 days after dosing and inform HMR as soon as possible if their partner becomes pregnant in the 90 days after dosing

You may not qualify if:

• Administration of a licensed or unlicensed medicinal product as part of another clinical trial in the 3 months before the first dose of study medication, or within 5 half-lives of administration of a medicinal product given in the previous study (whichever is longer), or otherwise 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 the study drug when taken orally
• Presence of abnormal physical findings, ECG, or laboratory values at the 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 the 3 months before admission
• Clinically relevant history of vital organ disease, or other organ or central nervous system disease (e.g. diabetes mellitus, liver disease, seizures, etc.)
• Current or previous medical or psychiatric disorder that, in the opinion of the Investigator or the Sponsor, would increase the risk and ability to participate in and/or complete the study
• Positive test for hepatitis B, hepatitis C or HIV
• Febrile illness (e.g. fever) within 1 week before the first dose of study medication
• History of a severe allergy, non-allergic drug reaction, severe adverse reaction to any drug, or multiple drug allergies
• Hypersensitivity to any ingredient of the study medication, including the active ingredient (emodepside)
• Presence or history of drug or alcohol abuse in the last year, or intake of more than 21 units (1 unit = 1/2 pint of beer, 1 small glass of wine or 1 measure of spirits) of alcohol weekly
• Regular daily consumption of more than one litre of beverages containing xanthine
• Daily consumption of more than 10 cigarettes or more than 6 grams (1/4 ounce) of tobacco
• Use of a prescription medicine during the 28 days before the dose of study medication, or use of an over-the-counter medicine (with exception of acetaminophen (paracetamol)), during the 7 days before the 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 (HMR) Limited

London, NW10 7EW, United Kingdom

Location

MeSH Terms

Conditions

Filariasis

Interventions

emodepside; Bay 44-4400; Praziquantel; toltrazuril

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Jean Yves Gillon
• Organization: Drugs for Neglected Diseases Initiative

jygillon@dndi.org

+41229069232

Study Officials

• Jeremy Dennison

  Hammersmith Medicines Research

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a single-centre, open-label, randomized, parallel-group relative bioavailability study in healthy men. The study will be done in 2 parts, as follows: Part 1 - single oral doses of 5 mg emodepside will be tested: * Part 1a - the LSF (reference formulation) and 2 new IR-tablet formulations (test formulations) will be administered in the fasted state. * Part 1b - the 2 new IR-tablet formulations will be administered in the fed state (high-fat, high-calorie meal). Part 2 - single oral doses of 10 mg emodepside will be tested: depending on the results from Part 1, one or both IR-tablet formulations will be administered in the fasted state.

Study Record Dates

• First Submitted: November 27, 2017
• First Posted: December 26, 2017
• Study Start: October 26, 2017
• Primary Completion: March 26, 2018
• Study Completion: March 26, 2018
• Last Updated: March 9, 2020
• Results First Posted: March 9, 2020

Record last verified: 2020-02

Locations

GB (1)