A Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD0914

A Phase I, Randomized, Placebo-controlled, Single-center Study to Assess the Safety, Tolerability, and Pharmacokinetics of AZD0914 After a Single Oral Administration and to Assess the Effect of Food in Healthy Adult Volunteers

The purpose of this study is to assess the safety and tolerability of orally administered AZD0914 in healthy adult subjects.

Study Overview

• Status: Completed
• Conditions: Gonococcal (GC) Infection
• Intervention / Treatment: Drug: Part A; Drug: Part B

Detailed Description

A Phase I, Randomized, Placebo-controlled, Single-center Study to Assess the Safety, Tolerability, and Pharmacokinetics of AZD0914 After a Single Oral Administration and to Assess the Effect of Food in Healthy Adult Volunteers

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male and female (of non-childbearing potential)subjects aged 18 to55 years (inclusive).
• Have a body mass index (BMI) between 18.00 and 30.50 kg/m2 and weigh at least 50 kg and no more than 100 kg
• Male subjects should be willing to use barrier contraception, ie, condoms, from the day of dose administration until at least 3 months after dose administration of the IP

Exclusion Criteria:

• History of any important clinically significant disease or disorder which, in the opinion of the PI, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study
• History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
• Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks from the first administration of IP as judged by the PI
• History of gastrointestinal ulcer disease, inflammatory bowel disease, indigestion symptoms >3 times a week, or blood in stool in previous 6 months not related to anal trauma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo fasting; Single or multiple dosing placebo	Drug: Part A; Single ascending doses
EXPERIMENTAL: Active fed condition; AZD0914 given as single dose	Drug: Part B; Single doses food effect. Subjects to receive 2 single doses, one in fed and one in fasted.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Description of the safety profile in terms of adverse events; blood pressure, heart rate and body temperature; electrocardiograms; telemetry; clinical chemistry ; haematology and physical examination	Applies to Part A and B	From admission on day -1 until follow up. ( Max 16 days)

Secondary Outcome Measures

Outcome Measure	Time Frame
Description of pharmacokinetics(PK) for AZD0914 study part A and B in terms of maximum observed plasma concentration (Cmax)	Samples taken at predose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours postdose
Description of pharmacokinetics(PK) for AZD0914 study part A and B in terms of time to reach maximum observed plasma concentration (tmax)	Samples taken at predose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours postdose
Description of pharmacokinetics(PK) for AZD0914(Part A and B) in terms of AUC from time zero to time of last quantifiable AZD0914 concentration [AUC(0-last)]	Samples taken at predose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours postdose
Description of pharmacokinetics(PK) for AZD0914(Part A and B) in terms of AUC from time zero to 24 hours after dosing [AUC(0-24)]	Samples taken at predose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours postdose
Description of pharmacokinetics(PK) for AZD0914(Part A and B) in terms of terminal half-life (t1/2λz) and apparent plasma clearance (CL/F)	Samples taken at predose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours postdose
Description of pharmacokinetics(PK) for AZD0914(Part A and B) in terms of apparent terminal phase volume of distribution (Vz/F), and at steady state (Vss/F),mean residence time	Samples taken at predose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours postdose
Description of pharmacokinetics(PK) for AZD0914 (Part A and B) in terms of cumulative amount of investigation product (IP) excreted unchanged into urine from zero to time t [Ae(0-t)],	Samples taken from collections between -12 to 0 hours predose, and 0 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 48, and 48 to 72 hours after the 1st dose
Description of pharmacokinetics(PK) for AZD0914 (Part A and B) in terms of fraction of dose excreted unchanged into urine (fe), and renal clearance (CLr)	Samples taken from collections between -12 to 0 hours predose, and 0 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 48, and 48 to 72 hours after the 1st dose

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Humphrey Gardener, MD, AstraZeneca

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (ACTUAL): March 1, 2014
• Study Completion (ACTUAL): March 1, 2014

Study Registration Dates

• First Submitted: August 23, 2013
• First Submitted That Met QC Criteria: August 23, 2013
• First Posted (ESTIMATE): August 28, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): April 15, 2014
• Last Update Submitted That Met QC Criteria: April 14, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Healthy Volunteers; Phase 1; First Time in Man
• Additional Relevant MeSH Terms: Infections; Communicable Diseases; Sexually Transmitted Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Neisseriaceae Infections; Sexually Transmitted Diseases, Bacterial; Gonorrhea
• Other Study ID Numbers: D4930C00001