AZD0914 Phase 1 ADME Study in Healthy Volunteers

NCT02298920 | Completed Phase 1

• 1 other identifier: D4930C00003
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief Summary

This study will investigate the metabolic fate and routes of excretion of 14CAZD0914 in six male healthy volunteers.

Conditions

Healthy

Outcome Measures

Primary Outcomes (3)

• PK Parameters

  Maximum observed concentration (Cmax), time to maximum observed concentration (tmax), area under the concentration-time curve from hour 0 to the last measurable concentration (AUC0-t), area under the concentration-time curve extrapolated to infinity (AUC0-inf), apparent terminal elimination rate constant (lambdaZ), apparent terminal elimination half-life (t1/2), apparent clearance (Cl/F) (oral and AZD0914 only), and apparent volume of distribution (Vz/F) (AZD0914 only). Ratios for area under the concentration-time curve extrapolated to infinity including the ratio of total radioactivity in whole blood/plasma and the ratio of non-radiolabeled AZD0914 in plasma/total radioactivity in plasma, will be calculated as appropriate.

  Up to 11 days

• Urine and Feces PK Parameters

  The following pharmacokinetic parameters will be calculated, whenever possible, based on the urine total radioactivity concentrations: amount excreted in urine (Aeu) over the sampling interval, renal clearance (CLR), and the percent excreted in urine (%Feu). For fecal total radioactivity concentrations, the following pharmacokinetic parameters will be calculated for \[14C\] AZD0914 derived radioactivity: amount excreted in feces (Aef) over the sampling interval and the percent excreted in feces (%Fef).

  Up to 11 days

• Metabolites

  Metabolites of \[14C\]-AZD0914 will be identified. Pharmacokinetic parameters for the metabolites of \[14C\]-AZD0914 will be calculated, as deemed appropriate, based on plasma and urine concentration levels. Data may be presented in a separate report.

  Up to 11 days

Secondary Outcomes (1)

• Number and severity of adverse events, abnormal labs, signs, ECGs, and PEs

  Up to 17 days

Study Arms (1)

Single Group

EXPERIMENTAL

Open Label ADME Study

Drug: AZD0914

Interventions

AZD0914 DRUG

Radiolabelled AZD0914 for study of absorption, disposition, metabolism, and excretion in healthy volunteers.

Single Group

Eligibility Criteria

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

You may qualify if:

• Healthy male subjects between 18 and 55 years of age, inclusive, at the time of consent with suitable veins for cannulation or repeated venipuncture;
• Subjects must be able to understand and be willing to comply with study procedures, restrictions, and requirements;
• Within body mass index (BMI) range 19 to 30 kg/m2, inclusive, at screening;
• Non-smokers in past 6 months;
• In good health, as determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, and vital signs as judged by the Investigator;

You may not qualify if:

• Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, interfere with absorption, distribution, metabolism or excretion of drugs, or influence the results or the subject's ability to participate in the study;
• Any clinically significant abnormalities in rhythm, conduction, or morphology of the resting ECG and any clinically significant abnormalities in the 12-lead ECG as considered by the Investigator that may interfere with the interpretation of QT interval corrected for heart rate (QTc) changes;
• Any clinically significant abnormalities in clinical chemistry, hematology, or UA results as judged by the Investigator;
• Abnormal vital signs, after 10 minutes supine rest, confirmed by repeat, defined as any of the following: systolic blood pressure \<90 mmHg or \>140 mmHg; diastolic blood pressure \<50 mmHg or \>90 mmHg; or heart rate \<40 or \>100 beats per minute;
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IP;

Sponsors & Collaborators

• Entasis Therapeutics: lead

Study Sites (2)

Covance Clinical Research Unit

Madison, Wisconsin, 53704, United States

Location

Research Site

Madison, Wisconsin, United States

Location

Related Publications (1)

• O'Donnell J, Lawrence K, Vishwanathan K, Hosagrahara V, Mueller JP. Single-Dose Pharmacokinetics, Excretion, and Metabolism of Zoliflodacin, a Novel Spiropyrimidinetrione Antibiotic, in Healthy Volunteers. Antimicrob Agents Chemother. 2018 Dec 21;63(1):e01808-18. doi: 10.1128/AAC.01808-18. Print 2019 Jan.

  PMID: 30373802 DERIVED

MeSH Terms

Interventions

zoliflodacin

Study Officials

• Irene Mirkin, MD

  Covance Clinical Research Unit

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 19, 2014
• First Posted: November 24, 2014
• Study Start: January 1, 2015
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: June 3, 2015

Record last verified: 2015-06

Locations

US (2)