Clinical trial NCT01929629: A Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD0914
Official title: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Gonococcal (GC) Infection
Keywords: Phase 1
Healthy Volunteers
First Time in Man
Pharmacokinetics
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2013-08-28
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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

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

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: From admission on day -1 until follow up. ( Max 16 days)
Secondary outcomes:
measure: Description of pharmacokinetics(PK) for AZD0914 study part A and B in terms of maximum observed plasma concentration (Cmax)
timeFrame: 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
measure: Description of pharmacokinetics(PK) for AZD0914 study part A and B in terms of time to reach maximum observed plasma concentration (tmax)
timeFrame: 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
measure: 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)]
timeFrame: 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
measure: 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)]
timeFrame: 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
measure: Description of pharmacokinetics(PK) for AZD0914(Part A and B) in terms of terminal half-life (t1/2λz) and apparent plasma clearance (CL/F)
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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)],
timeFrame: 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
measure: 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)
timeFrame: 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
Other outcomes:
Locations:
city: Overland Park
country: United States
facility: Research Site
state: Kansas
Study officials:
affiliation: Quintiles Phase I unit, Kansas
name: David Mathews, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: AstraZeneca
name: Humphrey Gardener, MD
role: STUDY_DIRECTOR
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.