Clinical trial NCT02298920: AZD0914 Phase 1 ADME Study in Healthy Volunteers
Official title: A Phase I, Open-Label Study to Assess the Absorption, Metabolism, Excretion, Safety and Tolerability of a Single Oral Dose of Radiolabeled [14C]-AZD0914 in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Entasis Therapeutics
Sponsor class: INDUSTRY
First posted: 2014-11-24
Enrollment: 6
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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

Detailed description: This is an open-label, single dose study in 6 healthy male subjects aged 18 to 55 years. Each subject will be admitted to the clinical pharmacology unit on the day prior to dosing Check in (Day -1) and will remain in the clinical pharmacology unit until up to at least target Day 8 (168 hours post-dose).

All subjects will receive 3000 mg AZD0914 incorporating 18.5 MBq (500 Ci) of \[14C\] administered as a single oral dose following at least an 8 hour fast from food. Subjects can have water. For specific food and water restrictions.

This study will investigate the metabolic fate and routes of excretion of AZD0914.

Eligibility criteria: Inclusion Criteria:

1. Healthy male subjects between 18 and 55 years of age, inclusive, at the time of consent with suitable veins for cannulation or repeated venipuncture;
2. Subjects must be able to understand and be willing to comply with study procedures, restrictions, and requirements;
3. Within body mass index (BMI) range 19 to 30 kg/m2, inclusive, at screening;
4. Non-smokers in past 6 months;
5. 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;

Exclusion Criteria:

1. 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;
2. 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;
3. Any clinically significant abnormalities in clinical chemistry, hematology, or UA results as judged by the Investigator;
4. 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;
5. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IP;

Primary outcomes:
measure: PK Parameters
timeFrame: Up to 11 days
measure: Urine and Feces PK Parameters
timeFrame: Up to 11 days
measure: Metabolites
timeFrame: Up to 11 days
Secondary outcomes:
measure: Number and severity of adverse events, abnormal labs, signs, ECGs, and PEs
timeFrame: Up to 17 days
Other outcomes:
Locations:
city: Madison
country: United States
facility: Covance Clinical Research Unit
state: Wisconsin
city: Madison
country: United States
facility: Research Site
state: Wisconsin
Study officials:
affiliation: Covance Clinical Research Unit
name: Irene Mirkin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.