Chagas DiseasePhase 1NCT03892213

Pharmacokinetic Drug-Drug Interaction Study

A Phase 1 study testing Benznidazole and E1224 in people with Chagas Disease, run by Drugs for Neglected Diseases at 1 site in Argentina.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to determine whether benznidazole and E1224 should be administered concomitantly in patients with Chagas Disease as not enough data are available. This study aims to assess cross interactions of these two compounds. 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: Chagas Disease
What is being tested?: Benznidazole and E1224
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 28 participants
Where: 1 siteArgentina
Study dates: Oct 2014to Jan 2015
Phase: Phase 1
Are there results?: None posted in the registry

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 healthy volunteers 18 to 45 years of age;
Light smokers (less than 5 cigarettes per day) or subjects who are non-smokers;
Male subjects with a body weight of at least 50 kg and a body mass index (BMI) calculated as weight in kg/height (in m2) from 18 to 28 kg/m2 at screening;
Able to communicate well with the Investigator and research staff and to comply with the requirements of the entire study;
Provision of written informed consent to participate as shown by a signature on the volunteer consent form;

Who cannot join

Who on direct questioning and physical examination have evidence of any clinically significant acute or chronic disease, including known or suspected HIV, hepatites B virus (HBV) or hepatites C virus (HCV) infection;
Who has positive diagnosis of T. cruzi infection indicated by Conventional serology;
With any clinically significant abnormality following review of pre-study laboratory tests, vital signs, full physical examination and 12-lead ECG;
Who forfeit their freedom by administrative or legal award or who were under guardianship;
Unwilling to give their informed consent;
Who have a positive laboratory test for Hepatitis B surface antigen (HbsAg), or anti-HIV 1/2 or anti- HCV antibodies;
Who have a history of allergy (serious or not), allergic skin rash, asthma, intolerance, sensitivity or photosensitivity to any drug;
Who are known or suspected alcohol or drug abusers (more than 14 units of alcohol per week, one unit = 8 g or about 10 mL of pure alcohol);

Trial locations and contacts

1 site in 1 country.

Argentina1 site

FP Clinical Pharma - Juncal 4484 - 3o piso
Buenos Aires, C1425BAB

Other trials in Argentina

About this study

Official title: A Phase 1 Pharmacokinetic Drug-Drug Interaction Study of Benznidazole and E1224 in Healthy Male Volunteers

Read the detailed description

Benznidazole and E1224 are intended to be administered concomitantly in patients with Chagas disease. Thus, an in vivo interaction study in healthy volunteers may be justified as the two drugs are intended to be administered concomitantly in patients and no in vivo nor in vitro data are available.

In addition both interactions (potential for benznidazole to interact on the pharmacokinetic (PK) of E1224 and potential for E1224 on the PK of benznidazole should be studied.

Benznidazole t1/2 is quite short (12 h) whereas E1224 t1/2 is very long (more than 200 h). Therefore it was chosen to study the interaction of E1224 at steady-state while interaction of benznidazole after single dose appears more appropriate instead of a classical randomized cross-over design.

Conditions: Chagas Disease
Being tested: Benznidazole, E1224
Keywords: Chagas Disease, drug-drug interaction, benznidazole, E1224, pharmacokinetics
Medical subject headings: Chagas Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BenznidazoleDrug
Also called Abarax® (Benznidazole 100mg or 50mg).
Benznidazole single dose (2.5 mg/kg) at Day 1. Benznidazole single dose (2.5 mg/kg) at Day 9*. Benznidazole multiple dose (2.5 mg/kg twice daily) from Day 12* until Day 15.
E1224Drug
Also called E1224 is a prodrug monolysine form of ravuconazole.
E1224 multiple dose 400 mg loading dose once daily for 3 days (i.e. from Day 4 to Day 6 followed by maintenance dose 100mg once daily for 9 days (from Day 7 to Day15).
On Day 9 and from Day 12 to Day 15, E1224 and benznidazole will be given concomitantly.

Study groups in NCT03892213
Study group	Role	What they receive
Benznidazole and E1224	Other	Benznidazole and E1224 Receives: Drug: Benznidazole; Drug: E1224

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximum serum concentration (Cmax) of Benznidazole
BNZ PK parameter following single dose to investigate the possible drug-drug interaction between BNZ and E1224 through evaluation of the PK characteristics of both drugs when given alone or concomitantly.
Measured: Day 1 and day 9
Time of occurrence of maximum plasma concentration (tmax) of Benznidazole
BNZ PK parameter following single dose to investigate the possible drug-drug interaction between BNZ and E1224 through evaluation of the PK characteristics of both drugs when given alone or concomitantly.
Measured: Day 1 and day 9
Area under the serum concentration versus time curve from time zero to the time (t) corresponding to the last quantifiable concentration (AUC 0-t) of Benznidazole
BNZ PK parameter following single dose to investigate the possible drug-drug interaction between BNZ and E1224 through evaluation of the PK characteristics of both drugs when given alone or concomitantly.
Measured: Day 1 and day 9
Area under the concentration-time curve from time zero to infinity with extrapolation of the terminal phase (AUC 0-∞) of Benznidazole
BNZ PK parameter following single dose to investigate the possible drug-drug interaction between BNZ and E1224 through evaluation of the PK characteristics of both drugs when given alone or concomitantly.
Measured: Day 1 and day 9
Terminal half-life (t1/2) of Benznidazole
BNZ PK parameter following single dose to investigate the possible drug-drug interaction between BNZ and E1224 through evaluation of the PK characteristics of both drugs when given alone or concomitantly.
Measured: Day 1 and day 9
Maximum serum concentration (Cmax) of Ravuconazole.
PK parameter of ravuconazole following multiple dose to investigate the possible drug-drug interaction between BNZ and E1224 (prodrug of ravuconazole) through evaluation of the PK characteristics of both drugs when given alone or concomitantly.
Measured: Day 8 and day 15, day 6 (morning pre-dose), day 7 (morning pre-dose), day 8 (morning pre-dose), day 13 (morning pre-dose), day 14 (morning pre-dose), and day 15 (morning pre-dose)
Time of occurrence of maximum plasma concentration (tmax) of Ravuconazole.
PK parameter of ravuconazole following multiple dose to investigate the possible drug-drug interaction between BNZ and E1224 (prodrug of ravuconazole) through evaluation of the PK characteristics of both drugs when given alone or concomitantly.
Measured: Day 8 and day 15, day 6 (morning pre-dose), day 7 (morning pre-dose), day 8 (morning pre-dose), day 13 (morning pre-dose), day 14 (morning pre-dose), and day 15 (morning pre-dose)
The area under the blood drug concentration vs. time curve from time zero (pre-dose) to 24 h post-dose (AUC 0-24)
PK parameter of ravuconazole following multiple dose to investigate the possible drug-drug interaction between BNZ and E1224 (prodrug of ravuconazole) through evaluation of the PK characteristics of both drugs when given alone or concomitantly.
Measured: Day 8 and day 15, day 6 (morning pre-dose), day 7 (morning pre-dose), day 8 (morning pre-dose), day 13 (morning pre-dose), day 14 (morning pre-dose), and day 15 (morning pre-dose)

Secondary outcomes (7)

Incidence of Adverse Events (AEs)
Monitoring for the occurrence of adverse events (AEs)
Measured: Through study completion, i.e up to 22 days.
Clinically significant alterations in pulse rate
Parameter to assess the safety and tolerability of multiple oral doses of BNZ and E1224 given in healthy male subjects.
Measured: Through study completion, i.e up to 22 days.
Clinically significant alterations in blood pressure
Parameter to assess the safety and tolerability of multiple oral doses of BNZ and E1224 given in healthy male subjects.
Measured: Through study completion, i.e up to 22 days.
Clinically significant alterations in 12-lead ECG
Parameter to assess the safety and tolerability of multiple oral doses of BNZ and E1224 given in healthy male subjects
Measured: Through study completion, i.e up to 22 days.
Clinically significant Haematology abnormalities (hemoglobin, RBC, hematocrit, MCV, MCH, MCHC, WBC, including differential, platelet counts)
Parameter to assess the safety and tolerability of multiple oral doses of BNZ and E1224 given in healthy male subjects.
Measured: Day 1, Day 4, Day 7, Day 9, Day 10, Day 12, Day 13, Day 14 and Day 15 pre morning dose
Clinically significant Biochemistry abnormalities (albumin (ALB), ALP, ALT, AST, gamma-glutamyl transferase (GGT), chlorides (Cl-), creatinine, glucose (GLU), potassium (K+), sodium (Na+), total bilirubin (TBIL), total proteins (TP), Urea.
Parameter to assess the safety and tolerability of multiple oral doses of BNZ and E1224 given in healthy male subjects.
Measured: Day 1, Day 4, Day 7, Day 9, Day 10, Day 12, Day 13, Day 14 and Day 15 pre morning dose
Clinically significant Urinalysis abnormalities (leukocytes, pH, proteins, urobilinogen, blood, nitrites, glucose, ketone bodies, bilirubin).
Parameter to assess the safety and tolerability of multiple oral doses of BNZ and E1224 given in healthy male subjects.
Measured: Screening and day 22

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2014Jan 2015

First posted27 Mar 2019
Study startOct 2014
Primary completionDec 2014
Study completionJan 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Chagas DiseaseStudies 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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 28 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03892213
Sponsor's protocol ID: DNDi-CH-E1224-002
Status last verified: Mar 2019
First submitted: 20 Aug 2014
Last updated: 27 Mar 2019
Results posted: No
Data monitoring committee: No
Individual data sharing: Undecided

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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An Observational Pregnancy Safety Study in Women Who Were Exposed to the Drug Nifurtimox During Pregnancy to Learn About the Risk of Pregnancy Complications and About the Mother's and Baby's Health
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Active, not recruitingPhase 3
Prospective Study of Benznidazole for Chagas' Disease Children With Chronic Indeterminate Chagas Disease
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All Chagas Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 27 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1 Pharmacokinetic Drug-Drug Interaction Study of Benznidazole and E1224 in Healthy Male Volunteers
ClinicalTrials.gov ID: NCT03892213
Acronym / sponsor ID: DNDi-CH-E1224-002
Conditions: Chagas Disease
Keywords: Chagas Disease, drug-drug interaction, benznidazole, E1224, pharmacokinetics
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 28 participants (actual)
Lead sponsor: Drugs for Neglected DiseasesUniversity, hospital or other
Collaborators: PhinC Development
Study start: Oct 2014
Primary completion: Dec 2014 (actual)
Study completion: Jan 2015 (actual)
First posted: 27 Mar 2019 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

In addition both interactions (potential for benznidazole to interact on the pharmacokinetic (PK) of E1224 and potential for E1224 on the PK of benznidazole should be studied.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Benznidazole and E1224	Other	Drug: Benznidazole, Drug: E1224Benznidazole and E1224

Who may qualify

Ages: 18 to 45 years
Sex: Male only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (5 listed)

Male healthy volunteers 18 to 45 years of age;
Light smokers (less than 5 cigarettes per day) or subjects who are non-smokers;
Male subjects with a body weight of at least 50 kg and a body mass index (BMI) calculated as weight in kg/height (in m2) from 18 to 28 kg/m2 at screening;
Able to communicate well with the Investigator and research staff and to comply with the requirements of the entire study;
Provision of written informed consent to participate as shown by a signature on the volunteer consent form;

Key exclusion criteria (8 listed)

Who on direct questioning and physical examination have evidence of any clinically significant acute or chronic disease, including known or suspected HIV, hepatites B virus (HBV) or hepatites C virus (HCV) infection;
Who has positive diagnosis of T. cruzi infection indicated by Conventional serology;
With any clinically significant abnormality following review of pre-study laboratory tests, vital signs, full physical examination and 12-lead ECG;
Who forfeit their freedom by administrative or legal award or who were under guardianship;
Unwilling to give their informed consent;

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
BenznidazoleAlso: Abarax® (Benznidazole 100mg or 50mg).Benznidazole single dose (2.5 mg/kg) at Day 1. Benznidazole single dose (2.5 mg/kg) at Day 9. Benznidazole multiple dose (2.5 mg/kg twice daily) from Day 12 until Day 15.	Drug	Benznidazole and E1224
E1224Also: E1224 is a prodrug monolysine form of ravuconazole.E1224 multiple dose 400 mg loading dose once daily for 3 days (i.e. from Day 4 to Day 6 followed by maintenance dose 100mg once daily for 9 days (from Day 7 to Day15). On Day 9 and from Day 12 to Day 15, E1224 and benznidazole will be given concomitantly.	Drug	Benznidazole and E1224

Primary outcome

Maximum serum concentration (Cmax) of Benznidazole
Time frame: Day 1 and day 9
BNZ PK parameter following single dose to investigate the possible drug-drug interaction between BNZ and E1224 through evaluation of the PK characteristics of both drugs when given alone or concomitantly.
Time of occurrence of maximum plasma concentration (tmax) of Benznidazole
Time frame: Day 1 and day 9
BNZ PK parameter following single dose to investigate the possible drug-drug interaction between BNZ and E1224 through evaluation of the PK characteristics of both drugs when given alone or concomitantly.
Area under the serum concentration versus time curve from time zero to the time (t) corresponding to the last quantifiable concentration (AUC 0-t) of Benznidazole
Time frame: Day 1 and day 9
BNZ PK parameter following single dose to investigate the possible drug-drug interaction between BNZ and E1224 through evaluation of the PK characteristics of both drugs when given alone or concomitantly.
Area under the concentration-time curve from time zero to infinity with extrapolation of the terminal phase (AUC 0-∞) of Benznidazole
Time frame: Day 1 and day 9
BNZ PK parameter following single dose to investigate the possible drug-drug interaction between BNZ and E1224 through evaluation of the PK characteristics of both drugs when given alone or concomitantly.
Terminal half-life (t1/2) of Benznidazole
Time frame: Day 1 and day 9
BNZ PK parameter following single dose to investigate the possible drug-drug interaction between BNZ and E1224 through evaluation of the PK characteristics of both drugs when given alone or concomitantly.
Maximum serum concentration (Cmax) of Ravuconazole.
Time frame: Day 8 and day 15, day 6 (morning pre-dose), day 7 (morning pre-dose), day 8 (morning pre-dose), day 13 (morning pre-dose), day 14 (morning pre-dose), and day 15 (morning pre-dose)
PK parameter of ravuconazole following multiple dose to investigate the possible drug-drug interaction between BNZ and E1224 (prodrug of ravuconazole) through evaluation of the PK characteristics of both drugs when given alone or concomitantly.
Time of occurrence of maximum plasma concentration (tmax) of Ravuconazole.
Time frame: Day 8 and day 15, day 6 (morning pre-dose), day 7 (morning pre-dose), day 8 (morning pre-dose), day 13 (morning pre-dose), day 14 (morning pre-dose), and day 15 (morning pre-dose)
PK parameter of ravuconazole following multiple dose to investigate the possible drug-drug interaction between BNZ and E1224 (prodrug of ravuconazole) through evaluation of the PK characteristics of both drugs when given alone or concomitantly.
The area under the blood drug concentration vs. time curve from time zero (pre-dose) to 24 h post-dose (AUC 0-24)
Time frame: Day 8 and day 15, day 6 (morning pre-dose), day 7 (morning pre-dose), day 8 (morning pre-dose), day 13 (morning pre-dose), day 14 (morning pre-dose), and day 15 (morning pre-dose)
PK parameter of ravuconazole following multiple dose to investigate the possible drug-drug interaction between BNZ and E1224 (prodrug of ravuconazole) through evaluation of the PK characteristics of both drugs when given alone or concomitantly.

7 secondary outcomes

Incidence of Adverse Events (AEs)
Time frame: Through study completion, i.e up to 22 days.
Clinically significant alterations in pulse rate
Time frame: Through study completion, i.e up to 22 days.
Clinically significant alterations in blood pressure
Time frame: Through study completion, i.e up to 22 days.
Clinically significant alterations in 12-lead ECG
Time frame: Through study completion, i.e up to 22 days.
Clinically significant Haematology abnormalities (hemoglobin, RBC, hematocrit, MCV, MCH, MCHC, WBC, including differential, platelet counts)
Time frame: Day 1, Day 4, Day 7, Day 9, Day 10, Day 12, Day 13, Day 14 and Day 15 pre morning dose
Clinically significant Biochemistry abnormalities (albumin (ALB), ALP, ALT, AST, gamma-glutamyl transferase (GGT), chlorides (Cl-), creatinine, glucose (GLU), potassium (K+), sodium (Na+), total bilirubin (TBIL), total proteins (TP), Urea.
Time frame: Day 1, Day 4, Day 7, Day 9, Day 10, Day 12, Day 13, Day 14 and Day 15 pre morning dose
Clinically significant Urinalysis abnormalities (leukocytes, pH, proteins, urobilinogen, blood, nitrites, glucose, ketone bodies, bilirubin).
Time frame: Screening and day 22

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2019.
Individual participant dataSharing planned: Undecided

Related trials for Chagas Disease

Not yet recruitingObservational study
Assessment of the Risk of Zoonotic Infections in Prisons in French Guiana
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RecruitingPhase 2
A Study of Efficacy, Safety, Tolerability of LXE408 in Participants With Chronic Chagas Disease.
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Not yet recruitingObservational study
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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.

Isabela Ribeiro, MD study chair

Drugs for Neglected Diseases initiative

Ethel Feleder, MD principal investigator

F.P. Clinical Pharma Clinical Research Unit

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 Benznidazole and E1224 in people with Chagas Disease, run by Drugs for Neglected Diseases at 1 site in Argentina.

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 5 inclusion and 8 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 27 Mar 2019. 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 Argentina. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Maximum serum concentration (Cmax) of Benznidazole (time frame: Day 1 and day 9). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03892213.

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 27 Mar 2019.