AZD0914 Phase 1 ADME Study in Healthy Volunteers

• Sponsor: Entasis Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02298920
• Collaborator: (none)
• Enrollment: 6
• Locations: 2
• Arm: 1
• Duration (Months): 1
• Patients Per Site: 3
• Patients Per Site Per Month: 2.9

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: AZD0914	Phase 1

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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 6 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• 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 Start Date: Jan 1, 2015
• Actual Primary Completion Date: Feb 1, 2015
• Actual Study Completion Date: Feb 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single Group Open Label ADME Study	Drug: AZD0914; Radiolabelled AZD0914 for study of absorption, disposition, metabolism, and excretion in healthy volunteers.

Outcome Measures

Primary Outcome Measures

1. PK Parameters [Up to 11 days]

   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.

2. Urine and Feces PK Parameters [Up to 11 days]

   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).

3. Metabolites [Up to 11 days]

   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.

Secondary Outcome Measures

1. Number and severity of adverse events, abnormal labs, signs, ECGs, and PEs [Up to 17 days]

   Signs, symptoms, incidence, and severity of adverse events (AE), abnormalities in clinical laboratory assessments, vital signs, electrocardiograms (ECGs), and physical examinations.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

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;

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Covance Clinical Research Unit	Madison	Wisconsin	United States	53704
2	Research Site	Madison	Wisconsin	United States

Sponsors and Collaborators

• Entasis Therapeutics

Investigators

• Principal Investigator: Irene Mirkin, MD, Covance Clinical Research Unit

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Entasis Therapeutics
• ClinicalTrials.gov Identifier: NCT02298920
• Other Study ID Numbers: D4930C00003
• First Posted: Nov 24, 2014
• Last Update Posted: Jun 3, 2015
• Last Verified: Jun 1, 2015

Study Results

No Results Posted as of Jun 3, 2015