Pharmacokinetic Drug-Drug Interaction Study

NCT03892213 | Completed Phase 1

• 1 other identifier: DNDi-CH-E1224-002
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chagas Disease

Keywords

Chagas Disease; drug-drug interaction; benznidazole; E1224; pharmacokinetics

Outcome Measures

Primary Outcomes (8)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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)

  Through study completion, i.e up to 22 days.

• Clinically significant alterations in pulse rate

  Through study completion, i.e up to 22 days.

• Clinically significant alterations in blood pressure

  Through study completion, i.e up to 22 days.

• Clinically significant alterations in 12-lead ECG

  Through study completion, i.e up to 22 days.

• Clinically significant Haematology abnormalities (hemoglobin, RBC, hematocrit, MCV, MCH, MCHC, WBC, including differential, platelet counts)

  Day 1, Day 4, Day 7, Day 9, Day 10, Day 12, Day 13, Day 14 and Day 15 pre morning dose

Study Arms (1)

Benznidazole and E1224

OTHER

Benznidazole and E1224

Drug: Benznidazole; Drug: E1224

Interventions

Benznidazole DRUG

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.

Also known as: Abarax® (Benznidazole 100mg or 50mg).

Benznidazole and E1224

E1224 DRUG

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.

Also known as: E1224 is a prodrug monolysine form of ravuconazole.

Benznidazole and E1224

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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;

You may not qualify if:

• 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);

Sponsors & Collaborators

• Drugs for Neglected Diseases: lead
• PhinC Development: collaborator

Study Sites (1)

FP Clinical Pharma - Juncal 4484 - 3o piso

Buenos Aires, C1425BAB, Argentina

Location

MeSH Terms

Conditions

Chagas Disease

Interventions

benzonidazole

Condition Hierarchy (Ancestors)

Trypanosomiasis; Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Vector Borne Diseases

Study Officials

• Isabela Ribeiro, MD

  Drugs for Neglected Diseases initiative

  STUDY CHAIR

• Ethel Feleder, MD

  F.P. Clinical Pharma Clinical Research Unit

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 20, 2014
• First Posted: March 27, 2019
• Study Start: October 1, 2014
• Primary Completion: December 1, 2014
• Study Completion: January 1, 2015
• Last Updated: March 27, 2019

Record last verified: 2019-03

Locations

AR (1)