FilariasisPhase 1NCT03383523
Relative Bioavailability Study of Emodepside IR-tablets and Solution
A Phase 1 study testing Emodepside (BAY 44-4400) in people with Filariasis, run by Drugs for Neglected Diseases at 1 site in United Kingdom.
Trial 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) Read more about this study
- Who is it for?
- Ages 18 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Filariasis
- What is being tested?
- Emodepside (BAY 44-4400)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 77 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 26 Oct 2017to 26 Mar 2018
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male, Caucasian volunteers, deemed healthy based on a clinical history, physical examination, ECG, vital signs, and laboratory tests of blood and urine.
- 18 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
Who cannot join
- 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.)
Show all 24Show fewer
- 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
- Use, within 14 days before the dose of study medication, of dietary supplements or herbal remedies (such as St John's Wort) that are known to be inducers or inhibitors of CYP3A4, or other co-medications known to be relevant substrates of CYP3A4 (see list in the Study Procedures Manual)
- Use, within 14 days before the dose of study medication, of dietary supplements or herbal remedies that are known to be strong inhibitors of P-gp, or other co-medications known to be relevant substrates of P-gp (see list in the Study Procedures Manual)
- Relevant pathological abnormalities in the ECG at screening, such as:
- second or third-degree atrioventricular (AV) block prolongation of the QRS complex > 120 msec, QTc-interval (QTcB or QTcF) > 450 msec. The mean of the triplicate ECG readings will be used to assess eligibility.
- Evidence of drug abuse (via urine testing) at the screening assessment or admission to the ward
- Use of excluded therapies that may impact on the interpretation of study results in the opinion of the Investigator or Sponsor
- Objection by General Practitioner (GP) to subject entering trial
- History of residing for 6 or more continuous months during the last 3 years in regions with endemic parasitic infections, as determined by the Investigator
- Possibility that subject will not cooperate with the requirements of the protocol
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Hammersmith Medicines Research (HMR) Limited
London, NW10 7EW
About this study
Official title: Phase1,Randomized,Open-Label,Parallel-Group,Relative Bioavailability Study to Investigate PK,Including Food Effect,Safety and Tolerability of Single Doses of New Immediate Release Tablet Formulations of Emodepside (BAY 44-4400),Compared to Oral Solution,in Healthy Male Subjects
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)
Read the detailed description
There is an urgent need for a macrofilaricidal drug, killing or sterilizing permanently O. volvulus adult worms, which could be used in individual case management and, after appropriate testing, as an alternative drug to ivermectin in MDA programs. Emodepside is a promising candidate to kill the adult and sexually mature O. volvulus. Emodepside was shown to be macrofilaricidal against a variety of filarial nematodes and is a registered drug for animal health, commercialized by Bayer AG under the name of Profender® (in combination with praziquantel) or Procox® (in combination with toltrazuril).
A first-in-human (FIH) double-blind, placebo-controlled study of single ascending doses of emodepside in healthy Caucasian men has been conducted and the preliminary results are favourable, and support continuing the Phase I development program. For this reason, new tablet formulations have been developped and the present study will evaluate bioavailability, PK safety and tolerability, and as well food effect of single doses of 2 new immediate release (IR)-tablet formulations of emodepside compared to the oral liquid service formulation (LSF) used in the FIH study.
- Conditions
- Filariasis
- Being tested
- Emodepside (BAY 44-4400)
- Medical subject headings
- Filariasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Emodepside (BAY 44-4400)Drug
Also called Profender® (in combination with praziquantel) FOR VETERINARY USE, Procox® (in combination with toltrazuril) FOR VETERINARY USE
2 tablets compared to the liquid formulation
| Study group | Role | What they receive |
|---|---|---|
| Part 1a - treatment A | Experimental | 5 mg emodepside LSF, fasted Receives: Drug: Emodepside (BAY 44-4400) |
| Part 1a - treatment B | Experimental | 5 mg emodepside IR-tablet #406, fasted Receives: Drug: Emodepside (BAY 44-4400) |
| Part 1a - treatment C | Experimental | 5 mg emodepside IR-tablet #416, fasted Receives: Drug: Emodepside (BAY 44-4400) |
| Part 1b - treatment D | Experimental | 5 mg emodepside IR-tablet #406, fed Receives: Drug: Emodepside (BAY 44-4400) |
| Part 1b - treatment E | Experimental | 5 mg emodepside IR-tablet #416, fed Receives: 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) Receives: 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) Receives: Drug: Emodepside (BAY 44-4400) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 7 days
Secondary outcomes (6)
Safety and Tolerability as Measured by Number of Participants With Treatment-related Adverse Events
number of participants with treatment-related adverse events
Measured: 7 days
Safety and Tolerability as Measured by Number of Participants With Physical Examination Findings
number of participants with abnormal physical examination (PE) findings. Standard examination done on head, ears, eyes, nose, thyroid, lymph node, back, neck, lungs, skin, abdomen, chest. The details are listed in protocol section 8.11.3
Measured: 7 days
Safety and Tolerability as Measured by Number of Participants With Neurological Examination Findings
Number of participants with abnormal neurological examination (NE) findings
Measured: 7 days
Safety and Tolerability as Measured by Number of Participants With Vital Signs Findings
number of participants with vital signs (VS) findings. The vital signs ranges are the following Supine Systolic BP : 85-160mm HG, Supine Diastolic BP: 40-90mm HG, Supine HR: 35-100 beats/min. Details are described in the protocol section 8.11.2
Measured: 7 days
Safety and Tolerability as Measured by Number of Participants With 12-lead ECG Findings
number of participants with 12-lead ECG findings. The ECG reference ranges used are the following: ventricular rate: 45-100beats/min, PR interval:120-220msec, QRS:<120msec, QTc:<430msec
Measured: 7 days
Safety and Tolerability as Measured by Number of Participants With Clinical Laboratory Tests Findings
number of participants with relevant abnormal laboratory tests results
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2017
- Study start26 Oct 2017
- Primary completion26 Mar 2018
- Study completion26 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for FilariasisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 77 participants (actual)
Sponsor and investigators
- Lead sponsor
- Drugs for Neglected Diseases
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer, Bill and Melinda Gates Foundation
- Responsible party
- Sponsor
- Investigators
- Jeremy Dennison, Principal investigator, Hammersmith Medicines Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03383523
- Sponsor's protocol ID
- DNDI-EMO-03
- Other IDs
- 2017-003091-31, 2017
- Status last verified
- Feb 2020
- First submitted
- 27 Nov 2017
- Last updated
- 9 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase1,Randomized,Open-Label,Parallel-Group,Relative Bioavailability Study to Investigate PK,Including Food Effect,Safety and Tolerability of Single Doses of New Immediate Release Tablet Formulations of Emodepside (BAY 44-4400),Compared to Oral Solution,in Healthy Male Subjects
- ClinicalTrials.gov ID
- NCT03383523
- Acronym / sponsor ID
- DNDI-EMO-03
- Conditions
- Filariasis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 77 participants (actual)
- Lead sponsor
- Drugs for Neglected DiseasesUniversity, hospital or other
- Collaborators
- Bayer, Bill and Melinda Gates Foundation
- Study start
- 26 Oct 2017 (actual)
- Primary completion
- 26 Mar 2018 (actual)
- Study completion
- 26 Mar 2018 (actual)
- First posted
- 26 Dec 2017 (actual)
- Results
- Posted 9 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Detailed description
There is an urgent need for a macrofilaricidal drug, killing or sterilizing permanently O. volvulus adult worms, which could be used in individual case management and, after appropriate testing, as an alternative drug to ivermectin in MDA programs. Emodepside is a promising candidate to kill the adult and sexually mature O. volvulus. Emodepside was shown to be macrofilaricidal against a variety of filarial nematodes and is a registered drug for animal health, commercialized by Bayer AG under the name of Profender® (in combination with praziquantel) or Procox® (in combination with toltrazuril).
A first-in-human (FIH) double-blind, placebo-controlled study of single ascending doses of emodepside in healthy Caucasian men has been conducted and the preliminary results are favourable, and support continuing the Phase I development program. For this reason, new tablet formulations have been developped and the present study will evaluate bioavailability, PK safety and tolerability, and as well food effect of single doses of 2 new immediate release (IR)-tablet formulations of emodepside compared to the oral liquid service formulation (LSF) used in the FIH study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Part 1a - treatment A | Experimental | Drug: Emodepside (BAY 44-4400)5 mg emodepside LSF, fasted |
| Part 1a - treatment B | Experimental | Drug: Emodepside (BAY 44-4400)5 mg emodepside IR-tablet #406, fasted |
| Part 1a - treatment C | Experimental | Drug: Emodepside (BAY 44-4400)5 mg emodepside IR-tablet #416, fasted |
| Part 1b - treatment D | Experimental | Drug: Emodepside (BAY 44-4400)5 mg emodepside IR-tablet #406, fed |
| Part 1b - treatment E | Experimental | Drug: Emodepside (BAY 44-4400)5 mg emodepside IR-tablet #416, fed |
| Part 2 - treatment F | Experimental | Drug: Emodepside (BAY 44-4400)2 x 5 mg emodepside IR-tablet #406, fasted (may be tested or not, depending on the results of the part 1) |
| Part 2 - treatment G | Experimental | Drug: Emodepside (BAY 44-4400)2 x 5 mg emodepside IR-tablet #416, fasted (may be tested or not, depending on the results of the part 1) |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Male, Caucasian volunteers, deemed healthy based on a clinical history, physical examination, ECG, vital signs, and laboratory tests of blood and urine.
- 18 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
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Emodepside (BAY 44-4400)Also: Profender® (in combination with praziquantel) FOR VETERINARY USE, Procox® (in combination with toltrazuril) FOR VETERINARY USE2 tablets compared to the liquid formulation | Drug | 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 |
Primary outcome
PK (AUC0-7d) of Two New Tablet Formulations of Emodepside in Comparison to the Liquid Formulation (LSF) Oral Solution.
Time frame: means from zero to 7 days
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
PK (Cmax) of Two New Tablet Formulations of Emodepside in Comparison to the Liquid Formulation (LSF) Oral Solution.
Time frame: 7 days
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
6 secondary outcomes
Safety and Tolerability as Measured by Number of Participants With Treatment-related Adverse Events
Time frame: 7 days
Safety and Tolerability as Measured by Number of Participants With Physical Examination Findings
Time frame: 7 days
Safety and Tolerability as Measured by Number of Participants With Neurological Examination Findings
Time frame: 7 days
Safety and Tolerability as Measured by Number of Participants With Vital Signs Findings
Time frame: 7 days
Safety and Tolerability as Measured by Number of Participants With 12-lead ECG Findings
Time frame: 7 days
Safety and Tolerability as Measured by Number of Participants With Clinical Laboratory Tests Findings
Time frame: 7 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeremy Dennison principal investigator
Hammersmith Medicines Research
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Emodepside (BAY 44-4400) in people with Filariasis, run by Drugs for Neglected Diseases at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PK (AUC0-7d) of Two New Tablet Formulations of Emodepside in Comparison to the Liquid Formulation (LSF) Oral Solution. (time frame: means from zero to 7 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2020.