Benznidazole Absorption, Metabolism and Excretion Study

NCT ID: NCT03739541

Last Updated: 2018-11-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-16
• Study Completion Date: 2018-09-02

Brief Summary

This Phase I ADME study will be conducted to evaluate the pharmacokinetics of benznidazole.

Detailed Description

This will be a single-site, open-label, non-randomized, single oral dose absorption, metabolism and excretion study in healthy male subjects. Potential subjects will be screened to assess their eligibility to enter the study within 28 days prior to dosing on Day 1. Subjects will be admitted into the Clinical Research Unit (CRU) on Day -1. Subjects will be confined to the CRU until at least Day 11 (240 hours postdose), and will be discharged from the CRU on Day 11 if all the following discharge criteria are met: >90% mass balance recovery; OR plasma/blood radioactivity levels below the limit of quantitation for 2 consecutive collections; and <1% of the total radioactive dose recovered in combined excreta (urine and faeces) in 2 consecutive 24-hour periods. If these criteria are not met by Day 11, subjects will remain in the CRU until all discharge criteria are met up to a maximum of Day 15 to continue 24-hour blood, urine and faeces collections for the analysis of total radioactivity, unless otherwise agreed upon by the Sponsor and Investigator. If the discharge criteria are not met by Day 15, subjects may be asked to collect 24-hour excreta samples on up to 2 further occasions on a nonresidential basis to allow extrapolation of urinary and faecal excretion. If needed, the 2 additional 24-hour nonresidential collections will occur on Day 21 (±1 day) and Day 28 (±1 day). If on the second occasion the subject has still not met the desired criterion, then the subject will be discharged from the study, per Investigator and Sponsor decision. Pharmacokinetic samples and radioanalytical samples will be obtained through at least 240 hours postdose, and possibly up to 4 weeks postdose (radioanalytical samples only), in case of not meeting discharge criteria. Samples for metabolite profiling/identification will be obtained through 240 hours postdose.

Conditions

Healthy Male Subjects

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

[14C]-Benznidazole

A single dose of 100 mg \[14C\]-BNZ, orally administered on Day 1 following an overnight fast.

Group Type: EXPERIMENTAL

[14C]-Benznidazole

Intervention Type: DRUG

A single dose level of 100 mg; 200 μCi (7.4 MBq)

Interventions

[14C]-Benznidazole

A single dose level of 100 mg; 200 μCi (7.4 MBq)

Intervention Type: DRUG

Other Intervention Names

BNZ

Eligibility Criteria

Inclusion Criteria

1. Males of any race, between 35 and 65 years of age, inclusive, at screening.

2. Body mass index between 18.0 and 32.0 kg/m2, inclusive, at screening.

3. In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia [eg, Gilbert's syndrome] is acceptable) at screening or check-in as assessed by the Investigator (or designee).

4. Will agree to use contraception as detailed in Section 7.6.

5. History of a minimum of 1 bowel movement per day.

6. Able to comprehend and willing to sign an Inform Consent Form and to abide by the study restrictions.

Exclusion Criteria

1. Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, haematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator (or designee).

2. History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).

3. History of dermatological conditions within the 6 months prior to dosing, such as rash, pruritus, and dermatitis, as determined by the Investigator (or designee).

4. History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair will be allowed). Cholecystectomy is acceptable.

5. History of alcoholism or drug/chemical abuse within 2 years prior to check-in.

6. Alcohol consumption of >28 units per week for males. One unit of alcohol equals

½ pint (285 mL) of beer or lager, 1 glass (125 mL) of wine, or 1/6 gill (25 mL) of spirits.

7. Positive alcohol breath test or positive urine cotinine test result, or positive urine drug screen (confirmed by repeat) at screening or check-in.

8. Positive hepatitis panel and/or positive human immunodeficiency virus test (Appendix 3).

9. Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 3 months prior to check-in.

10. Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to check-in, unless deemed acceptable per Investigator (or designee) and Sponsor decision.

11. Use or intend to use any prescription medications/products within 14 days prior to check-in, unless deemed acceptable by the Investigator (or designee).

12. Use or intend to use slow-release medications/products considered to still be active within 14 days prior to check-in, unless deemed acceptable by the Investigator (or designee).

13. Use or intend to use any nonprescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations within 7 days prior to check-in, unless deemed acceptable per Investigator (or designee) and Sponsor decision.

14. Use of tobacco- or nicotine-containing products within 3 months prior to check-in.

15. Receipt of blood products within 2 months prior to check-in.

16. Donation of blood from 3 months prior to screening, plasma from 2 weeks prior to screening, or platelets from 6 weeks prior to screening.

17. Poor peripheral venous access.

18. Have previously completed or withdrawn from this study or any other study investigating BNZ, and have previously received the investigational product.

19. Subjects with exposure to significant diagnostic or therapeutic radiation (eg, serial X-ray, computed tomography scan, barium meal) or current employment in a job requiring radiation exposure monitoring within 12 months prior to check-in.

20. Subjects who have participated in any clinical trial involving a radiolabelled investigational product within 12 months prior to check-in.

21. Subjects who, in the opinion of the Investigator (or designee), should not participate in this study.

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Insud Pharma

INDUSTRY

Sponsor Role: collaborator

Exeltis France

UNKNOWN

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sunu Valasseri, MBBS, MSc

Role: PRINCIPAL_INVESTIGATOR

Covance

Locations

Covance

Leeds, , United Kingdom

Countries

United Kingdom

Other Identifiers

LPRI747-103

Identifier Type: -

Identifier Source: org_study_id