A Study to Compare the Effect of Omadacycline Versus Moxifloxacin in Healthy Adult Volunteers

A Phase 1, Randomized, Double-Blind Study to Compare the Effect of Omadacycline PO Versus Moxifloxacin PO on the Gut Microbiota in Healthy Adult Volunteers

This is a randomized (1:1), double-blind, double-dummy, phase I study to compare the effects of Omadacycline versus Moxifloxacin on gut microbiota and the resistomes in healthy adult volunteers.The study consists of 3 phases: Screening, double-blind treatment, and follow-up. Healthy volunteers aged 18-40 years, who meet entry criteria, are randomly assigned to a treatment group using an Interactive Voice Response System/Interactive Web Response System (IxRS) and receive the first dose of the study drug.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: Moxifloxacin Oral Tablet; Drug: Omadacycline Oral Tablet

Detailed Description

The study consists of 3 phases: Screening, double-blind treatment, and follow-up. Healthy volunteers aged 18-40 years, who meet entry criteria, are randomly assigned to a treatment group using an Interactive Voice Response System/Interactive Web Response System (IxRS) and receive the first dose of the study drug.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Hangzhou, China
    • The First Affiliated Hospital of Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Sign an Informed Consent Form (ICF) prior to the commencement of any study-related procedures.
2. Chinese healthy male and female subjects aged between 18 and 40 years (inclusive).
3. Body mass index (BMI) between 18.5 and 23.9 kg/m2 (inclusive).
4. Complete the stool sample collections required during screening.

Exclusion Criteria:

1. Subjects with clinically significant medical history of cardiovascular, hepatic, renal, gastrointestinal or psychiatric conditions, or any other condition as deemed by the investigators that may potentially jeopardize subject safety or impact study outcomes.
2. Subjects who have undergone any major surgery within 4 weeks prior to the first dose of study drug administration.
3. Subjects who have previously undergone gastrointestinal surgery that may affect the absorption of the study drug (eg. Intestinal resection surgery, fistula surgery).
4. During screening, subjects with positive tests for hepatitis C antibodies, hepatitis B surface antigen, or hepatitis B virus (HBV) DNA or HBV RNA, or known positive tests for human immunodeficiency virus (HIV).
5. Subjects with Fridericia-corrected QT interval (QTcF) > 450 milliseconds (males) or > 470 milliseconds (females); or known to have long QT syndrome; or using medications that may cause arrhythmia or prolong QT interval, and/or experiencing tachyarrhythmia.
6. Subjects with a history of irritable bowel syndrome (with or without constipation) -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Moxifloxacin; Moxifloxacin PO (400 mg)q24h D1-D10	Drug: Moxifloxacin Oral Tablet; 400mg per tablet; Other Names: Avelox
Experimental: Omadacycline; Omadacycline PO (450 mg) q24h D1-D2 PO (300 mg) q24h D3-D10	Drug: Omadacycline Oral Tablet; 150 mg per tablet; Other Names: NUZYRA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the types of microbial resistomes.	Metagenome will be extracted from fecal samples of ME population and subjected to second-generation high-throughput sequencing. Bioinformatics will be employed to study the changes in the types of resistance-related genes of microbiota during the drug administration process in the microbiologically evaluable population. This outcome is based on second-generation high-throughput sequencing. the outcome is to test the genes to confirm the changes in types of microbial resistors in different stages.	3months
Changes in the quantity of microbial resistomes.	Metagenome will be extracted from fecal samples of ME population and subjected to second-generation high-throughput sequencing. Bioinformatics will be employed to study the changes in the quantity of resistance-related genes of microbiota during the drug administration process in the microbiologically evaluable population.This outcome is based on second-generation high-throughput sequencing. the outcome is to test the gene to confirm the changes in quantity of microbial resistors in different stages .	3months
Changes in the abundance of microbial resistomes.	Metagenome will be extracted from fecal samples of ME population and subjected to second-generation high-throughput sequencing. Bioinformatics will be employed to study the changes in the abundance of resistance-related genes of microbiota during the drug administration process in the microbiologically evaluable population.This outcome is based on second-generation high-throughput sequencing. the outcome is to test the genes to confirm the changes in abundance of microbial resistors in different stages.	3months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the microbial composition	Metagenome will be extracted from fecal samples of ME population and subjected to second-generation high-throughput sequencing. Principal component analysis will be employed to study the changes in the structure of microbiota during the drug administration process in the microbiologically evaluable population. This outcome is based on the result of principal component analysis to confirm the microbial composition in different stages based on different genes.	3months
Changes in the microbial functionality	Metagenome will be extracted from fecal samples of ME population and subjected to second-generation high-throughput sequencing. Principal coordinates analysis will be employed to study the changes in the structure of microbiota during the drug administration process in the microbiologically evaluable population. This outcome is based on result of principal coordinates analysis to confirm the microbial functionality in different stages based on different genes.	3months

Collaborators and Investigators

• Sponsor: Zai Lab (Hong Kong), Ltd.
• Investigators: Principal Investigator: Jian Liu, Zhejiang University; Principal Investigator: Yonghong Xiao, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2024
• Primary Completion (Actual): September 29, 2024
• Study Completion (Actual): September 29, 2024

Study Registration Dates

• First Submitted: April 29, 2024
• First Submitted That Met QC Criteria: June 11, 2024
• First Posted (Actual): June 17, 2024

Study Record Updates

• Last Update Posted (Estimated): November 1, 2024
• Last Update Submitted That Met QC Criteria: October 29, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Bacterial Agents; Anti-Infective Agents; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Topoisomerase Inhibitors; Topoisomerase II Inhibitors; Moxifloxacin
• Other Study ID Numbers: ZL-2401-005

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No