Benznidazole Absorption, Metabolism and Excretion Study

NCT03739541 | Completed Phase 1

• 1 other identifier: LPRI747-103
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy Male Subjects

Outcome Measures

Primary Outcomes (23)

• Cmax of BNZ in plasma

  maximum observed concentration (Cmax) in plasma

  Days 1-29

• Mass balance of [14C]-BNZ

  Mass balance of \[14C\]-BNZ in urine and faeces

  Days 1-29

• Chemical structure of [14C]-BNZ metabolites

  Characterization of the chemical structure and identification of metabolites of \[14C\]-BNZ in plasma, urine, and faeces

  Days 1-29

• tmax of BNZ in plasma

  time to maximum concentration (tmax) in plasma

  Days 1-29

• AUC0-t of BNZ in plasma

  area under the concentration-time curve (AUC) from hour zero to the last measurable concentration (AUC0-t) in plasma

  Days 1-29

• AUC0-∞ of BNZ in plasma

  AUC from time zero to infinity (AUC0-∞) in plasma

  Days 1-29

• % AUC extrap of BNZ in plasma

  percentage extrapolation (% AUCextrap) in plasma

  Days 1-29

• t1/2 of BNZ in plasma

  apparent terminal elimination half-life (t1/2) in plasma

  Days 1-29

• CL/Fof BNZ in plasma

  apparent oral clearance (CL/F) in plasma

  Days 1-29

• Vz/F of BNZ in plasma

  volume of distribution during the elimination phase for BNZ (Vz/F) in plasma

  Days 1-29

• Cmax of [14C]-BNZ in plasma

  maximum observed concentration (Cmax) in plasma

  Days 1-29

• tmax of [14C]-BNZ in plasma

  time to maximum concentration (tmax) in plasma

  Days 1-29

• AUC0-t of [14C]-BNZ in plasma

  area under the concentration-time curve (AUC) from hour zero to the last measurable concentration (AUC0-t) in plasma

  Days 1-29

• AUC0-∞ of [14C]-BNZ in plasma

  AUC from time zero to infinity (AUC0-∞) in plasma

  Days 1-29

• % AUC extrap of [14C]-BNZ in plasma

  percentage extrapolation (% AUCextrap) in plasma

  Days 1-29

• t1/2 of [14C]-BNZ in plasma

  apparent terminal elimination half-life (t1/2) in plasma

  Days 1-29

• Cmax of [14C]-BNZ in whole blood

  maximum observed concentration (Cmax) in whole blood

  Days 1-29

• tmax of [14C]-BNZ in whole blood

  time to maximum concentration (tmax) in whole blood

  Days 1-29

• AUC0-t of [14C]-BNZ in whole blood

  area under the concentration-time curve (AUC) from hour zero to the last measurable concentration (AUC0-t) in whole blood

  Days 1-29

• AUC0-∞ of [14C]-BNZ in whole blood

  AUC from time zero to infinity (AUC0-∞) in whole blood

  Days 1-29

• % AUCextrap of [14C]-BNZ in whole blood

  percentage extrapolation (% AUCextrap) in whole blood

  Days 1-29

• t1/2 of [14C]-BNZ in whole blood

  apparent terminal elimination half-life (t1/2) in whole blood

  Days 1-29

• Total radioactivity AUC ratio

  Total radioactivity AUC ratio (blood/plasma)

  Days 1-29

Secondary Outcomes (17)

• The incidence and severity of Adverse Events (AEs)

  Days 1-29

• The incidence of laboratory abnormalities (haematology)

  Days 1-29

• The incidence of laboratory abnormalities (clinical chemistry)

  Days 1-29

• The incidence of laboratory abnormalities (urinalysis)

  Days 1-29

• Measurement of QT interval (QTcB)

  Days 1-29

Study Arms (1)

[14C]-Benznidazole

EXPERIMENTAL

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

Drug: [14C]-Benznidazole

Interventions

[14C]-Benznidazole DRUG

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

Also known as: BNZ

[14C]-Benznidazole

Eligibility Criteria

• Age: 35 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males of any race, between 35 and 65 years of age, inclusive, at screening.
• Body mass index between 18.0 and 32.0 kg/m2, inclusive, at screening.
• 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).
• Will agree to use contraception as detailed in Section 7.6.
• History of a minimum of 1 bowel movement per day.
• Able to comprehend and willing to sign an Inform Consent Form and to abide by the study restrictions.

You may not qualify if:

• 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).
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).
• History of dermatological conditions within the 6 months prior to dosing, such as rash, pruritus, and dermatitis, as determined by the Investigator (or designee).
• 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.
• History of alcoholism or drug/chemical abuse within 2 years prior to check-in.
• 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.
• Positive alcohol breath test or positive urine cotinine test result, or positive urine drug screen (confirmed by repeat) at screening or check-in.
• Positive hepatitis panel and/or positive human immunodeficiency virus test (Appendix 3).
• Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 3 months prior to check-in.
• 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.
• Use or intend to use any prescription medications/products within 14 days prior to check-in, unless deemed acceptable by the Investigator (or designee).
• 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).
• 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.
• Use of tobacco- or nicotine-containing products within 3 months prior to check-in.

Sponsors & Collaborators

• Exeltis France: lead
• Insud Pharma: collaborator

Study Sites (1)

Covance

Leeds, LS2 9LH, United Kingdom

Location

Study Officials

• Sunu Valasseri, MBBS, MSc

  Covance

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 6, 2018
• First Posted: November 14, 2018
• Study Start: July 16, 2018
• Primary Completion: September 2, 2018
• Study Completion: September 2, 2018
• Last Updated: November 14, 2018

Record last verified: 2018-09

Locations

GB (1)