Study to Determine the Excretion and Metabolism of 14C-ETX2514 Administered Intravenously in Healthy Male Subjects

NCT04018950 | Completed Phase 1 FDA Drug

• 1 other identifier: CS2514-2018-0002
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This study will be conducted to determine the routes and rates of excretion of radio label arising from 14C-ETX2514 and to characterize metabolites of ETX2514 arising from 14C-ETX2514 administered intravenously in healthy participants.

Conditions

Acinetobacter Baumannii-calcoaceticus Complex Infections

Keywords

Acinetobacter baumannii-calcoaceticus; complex infections; ETX2514; excretion; metabolism

Outcome Measures

Primary Outcomes (6)

• Cumulative urinary recovery of total radioactivity

  -12-0 hours (pre-dose), and at 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144, and 144-168 hours after the initiation of the intravenous (IV) dose

• Cumulative fecal recovery of total radioactivity

  -12-0 hours (pre-dose), and at 0-24, 24-48, 48-72, 72-96, 96-120, 120-144, and 144-168 hours after the initiation of the IV dose

• Mass balance as a sum of the percent of total radioactivity recovered in urine and feces

  urine: -12-0 hours (pre-dose), and at 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144, and 144-168 hours after the IV dose; feces: -12-0 hours (pre-dose), and at 0-24, 24-48, 48-72, 72-96, 96-120, 120-144, and 144-168 hours after the IV dose

• Metabolite profiles in plasma

  pre-dose (-30 minutes) and at 1, 2 (± 2 minutes), 3 (just prior to shutting off infusion), 4, 6, 8, 10, 12 (± 5 minutes), 18, 24, 36, 48, 72, 96, 120, 144, and 168 hours (± 10 minutes) after the initiation of the IV dose or early termination

• Metabolite profiles in urine samples

  -12-0 hours (pre-dose) and over the following collection periods: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120,120-144, and 144-168 hours after the initiation of the IV dose

• Metabolite profiles in fecal samples

  -12-0 hours (pre-dose) and over the following collection periods: 0-24, 24-48, 48-72, 72-96, 96-120, 120-144, and 144-168 hours after the initiation of the IV dose

Secondary Outcomes (5)

• Number of participants with any treatment-emergent adverse event

  up to Day 8

• Number of participants with any clinically significant clinical laboratory evaluation

  up to Day 8

• Number of participants with any clinically significant vital sign measurement

  up to Day 8

• Number of participants with any clinically significant electrocardiogram finding

  up to Day 8

• Number of participants with any clinically significant physical examination finding

  up to Day 8

Study Arms (1)

ETX2514 and 14C-ETX2514

EXPERIMENTAL

Participants will receive a single intravenous infusion of 1 gram non-labeled ETX2514 and 1 microCurie (µCi) of 14C-ETX2514 in normal saline, administered as a 3-hour infusion.

Drug: ETX2514; Drug: 14C-ETX2514

Interventions

ETX2514 DRUG

intravenous infusion

ETX2514 and 14C-ETX2514

14C-ETX2514 DRUG

intravenous infusion

ETX2514 and 14C-ETX2514

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male participants, between 18 and 55 years of age (inclusive) at the time of Screening
• Body mass index (BMI) ≥ 18.0 kilograms per meters squared (kg/m\^2) and ≤ 32.0 kg/m\^2 at Screening and weight between 55.0 and 100.0 kg (both inclusive) at Screening and Day -1
• Able to understand and willing to sign the Informed Consent Form (ICF), and willing and able to comply with the study restrictions and investigative site rules for participants
• Judged to be in good health in the opinion of the Investigator on the basis of a medical evaluation (including a physical examination, medical history, electrocardiograms vital signs, and the results of biochemistry and hematology tests and urinalysis carried out at Screening, Day -1 and pre-dose on Day 1) that does not reveal any clinically significant abnormality, which evaluation will consider acceptable the presence of a stable condition (e.g., hypertension, hyperlipidemia, diabetes mellitus, hypothyroidism) that may be under medical control (i.e., adequate and stable treatment) having no clinical consequences of the condition that, in the judgment of the Investigator, would increase risk to the participant's health by participating in this study or would increase risk of not achieving the study objectives
• Participants with normal renal function as evidenced by creatinine clearance (CLcr) estimated by Cockcroft Gault formula
• Non-tobacco/nicotine-containing product users for a minimum of 6 months prior to Screening.
• Male participants with female partners of childbearing potential may be enrolled if they are:
• documented to be surgically sterile (vasectomy); or
• using two adequate forms of highly effective contraception (together with the female partner), out of which one will be a physical barrier (i.e., condom combined with partner oral contraceptive, implant, injectable, or indwelling intrauterine device), for 90 days after the study drug administration
• Must agree not to donate sperm from the Screening period through 90 days after the last dose
• Has sufficiently good venous access in both arms to confidently enable intravenous administration of study drug in one arm and serial blood sampling from the other arm
• Content of 14C in one or both (at Investigator's discretion) of urine and blood (or plasma) samples obtained at Screening does not significantly exceed the general environmental background 14C level

You may not qualify if:

• History or presence of oncologic, cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, psychiatric or other disease or condition that in the Investigator's judgment poses a significant risk to the safety of the volunteer or the achievement of study objectives
• Clinically significant abnormal medical history, abnormal findings on physical examination, vital signs, electrocardiograms, or laboratory tests at Screening, Day -1 or pre-dose on Day 1 that the Investigator judges may put at risk achieving the objectives of the trial or protecting the safety of the volunteer
• History of cancer judged not to be in full remission for at least 5 years (except basal cell skin cancer or squamous cell skin cancer with history of curative treatment and no recurrence for at least 1 year prior to screening), as judged by the Investigator
• Any acute illness including clinically significant infection within 30 days prior to Screening
• Acute illness within 14 days prior to study drug administration unless mild in severity and enrollment is approved by both Investigator and Sponsor's medical representative
• Presence of active infection requiring antibiotic treatment
• History of multiple and/or severe allergies to drugs or foods or a history of anaphylactic reaction
• Uncontrolled hyperuricemia (serum uric acid \> upper limit of normal \[ULN\])
• Concomitant use of medications known to affect the elimination of serum creatinine (e.g., trimethoprim or cimetidine) or to compete for renal tubular secretion (e.g., probenecid) within 60 days prior to study drug administration
• Documented congenital or acquired long QT syndrome
• Corrected QT interval (QTc) using Fridericia correction (QTcF) at Screening, Day -1, or pre-dose (Day 1) \> 450 milliseconds
• Family history of long QT syndrome or of unexplained sudden death in a first-degree relative under age 50
• Uncontrolled treated/untreated hypertension (defined as a mean of 3 repeated measurements with approximately 5 minutes of resting time between each measurement for systolic blood pressure \[SBP\] ≥ 140 millimeters of mercury (mmHg) and/or diastolic blood pressure \[DBP\] ≥ 100 mmHg
• Current presence of clinically significant hypotension (systolic blood pressure \[SBP\] \< 90 mmHg and/or diastolic blood pressure \[DBP\] \< 50 mmHg)
• Positive alcohol breath test or urine drug screen test at screening and/or Day -1

Sponsors & Collaborators

• Entasis Therapeutics: lead

Study Sites (1)

Pharmaron Clinical Pharmacology Center

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Interventions

durlobactam

Study Design

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

Study Record Dates

• First Submitted: July 10, 2019
• First Posted: July 15, 2019
• Study Start: June 21, 2019
• Primary Completion: July 26, 2019
• Study Completion: July 26, 2019
• Last Updated: August 30, 2019

Record last verified: 2019-08

Locations

US (1)