A Phase 1, Single-dose, Open-label, Randomized, 4-way Crossover Zoliflodacin Bioequivalence Study of the Reference Product (ZoliPa) With the Test Product (ZoliDr) in Healthy Adult Volunteers Under Fasted and Specific Fed Conditions Paired With an Investigation of the Effect of Cytochrome P450 3A4 Inhibition by Itraconazole on 3g Zoliflodacin (ZoliPa) Single-dose Pharmacokinetics

Global Antibiotics Research and Development Partnership1 site in 1 country50 target enrollmentNovember 9, 2022

Overview

Brief Summary

this study will be a Phase 1, single-dose, two parallel cohorts, open-label, randomized study in healthy subjects with Cohort 1 as bioequivalence (BE) and food effect study and Cohort 2 as a drug-drug interaction (DDI) study.

Detailed Description

Cohort 1 (BE) is a four-period, four-sequence, four-treatment crossover BE and food effect study of zoliflodacin granules for oral suspension manufactured by Dr. Reddy's (test product, ZoliDr) and those manufactured by Patheon (reference product, ZoliPa) as a 3 g oral dose under fasting and a \[specific\] fed condition. This cohort will comprise of approximately 32 subjects (8 healthy subjects per treatment sequence) in 4 x 4 BE treatment arms in fasted and \[specific\] fed conditions. Healthy subjects will be randomized into 4 parallel treatment sequences to receive sequential Treatments A, B, C, and D in William's Square design pattern where: * Treatment A is ZoliPa fasted * Treatment B is ZoliDr fasted * Treatment C is ZoliPa \[specific\] fed condition * Treatment D is ZoliDr \[specific\] fed condition Based on William's Square design, below treatment sequences will be followed: A-B-C-D B-A-D-C C-D-A-B D-C-B-A There will be 4 treatment periods, each with a single dose of the investigational medicinal products (IMP). The washout period between each IMP administration will be at least 72 hours. Food regimen: Subjects, who are in a treatment period in which they are \[specific\] fed, will be dosed 30 minutes after the start of food intake. The subjects are expected to consume the entire meal within 30 minutes prior to dosing. Cohort 2 (DDI): This is an open-label, 2-period, 2-treatment, fixed sequence crossover DDI study in healthy subjects. It will investigate PK of zoliflodacin (ZoliPa) in the absence and presence of itraconazole. Approximately 18 subjects will receive ZoliPa on Day 1 under fasting condition. After a washout of 72 hours after dosing of ZoliPa, on Day 4, subjects will receive a 400 mg loading dose of itraconazole followed by 200 mg of itraconazole once daily from Day 5-8. From Day 4 to Day 8, itraconazole will be administered immediately after a full meal. On Day 9, both itraconazole and zoliflodacin (ZoliPa) will be administered under fasting conditions at -1 hours and 0 hours, respectively. Itraconazole will then be administered with food at 24 hours (Day 10) and 48 hours (Day 11) after administration of zoliflodacin (ZoliPa).

Registry

clinicaltrials.gov

Start Date

November 9, 2022

End Date

February 7, 2023

Last Updated

3 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Global Antibiotics Research and Development Partnership

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Healthy male and female subjects, 18 to 55 years of age at the time of signing of informed consent.
•Body mass index (BMI, Quetelet index, calculated as weight in kg/height in m2) between 18.0 and 30.0 kg/m2 (both inclusive) and weigh at least 50 kg and no more than 95 kg inclusive at Screening.
•Healthy subjects, defined as individuals who are free from clinically significant illness or disease as determined by their medical/surgical history, normal vital signs, normal physical examination, normal standard 12-lead electrocardiogram (ECG), and laboratory investigations.
•At the Screening visit, supine vital signs must be within the following ranges:
•Systolic blood pressure (SBP) between 90 and 139 mmHg
•Diastolic blood pressure (DBP) between 60 and 89 mmHg
•Pulse between 50 and 90 beats per minute (bpm)
•Tympanic temperature between 35.0 and 37.5°C Note: These will be measured after resting for 10 min.
•Able to understand and communicate in German/or native language of the site with the Investigator and research staff and to comply with the requirements of the entire study. Provision of written informed consent to participate in the study.
•Female subjects, if:

Exclusion Criteria

•For Cohort 2, DDI Study only: Female subjects of childbearing potential.
•Subject has a positive RT PCR test for SARS-CoV-2 prior to randomization.
•Subject has clinical signs and symptoms consistent with SARS-CoV-2 infection, e.g., fever, dry cough, dyspnea, sore throat, fatigue, or positive SARS-CoV-2 test result within 4 weeks prior to Screening.
•Subject had severe course of COVID-19 (i.e., hospitalization, extracorporeal membrane oxygenation \[ECMO\], or mechanically ventilated) less than 3 months prior to Screening.
•Subject received or is planning to receive a COVID-19 vaccine within 3 weeks prior to the first IMP administration until Post-study visit.
•Recent (within previous 14 days) exposure to someone who has COVID-19 symptoms or positive test result.
•Has a current occupation that involves routine exposure to potential COVID-19 patients or sources of SARS-CoV-2 (e.g., healthcare worker).
•History of orthostatic hypotension (drop of \>20 mmHg at systolic blood pressure, drop of \> 10 at diastolic blood pressure, and/or heart rate increase of \>30 bpm and \>120 bpm after 3 minutes in standing position).
•Evidence of psychiatric disorder, antagonistic personality, poor motivation, emotional or intellectual problems likely to limit the validity of consent to participate in the study or limit the ability to comply with protocol requirements.
•History or presence of any clinically significant acute or chronic disease, including known or suspected human immunodeficiency virus (HIV), hepatitis A virus (HAV), HBV, or HCV infection (confirmed by positive laboratory test for anti-HAV IgM antibodies, hepatitis B surface antigen (HbsAg), or anti-HIV1/2 or anti-HCV antibodies).

Arms & Interventions

BE study

Cohort 1 (BE) is a four-period, four-sequence, four-treatment crossover BE and food effect study of zoliflodacin granules for oral suspension manufactured by Dr. Reddy's (test product, ZoliDr) and those manufactured by Patheon (reference product, ZoliPa) as a 3 g oral dose under fasting and a \[specific\] fed condition. This cohort will comprise of approximately 32 subjects (8 healthy subjects per treatment sequence) in 4 x 4 BE treatment arms in fasted and \[specific\] fed conditions. Healthy subjects will be randomized into 4 parallel treatment sequences to receive sequential Treatments A, B, C, and D in William's Square design pattern where: * Treatment A is ZoliPa fasted * Treatment B is ZoliDr fasted * Treatment C is ZoliPa \[specific\] fed condition * Treatment D is ZoliDr \[specific\] fed condition Based on William's Square design, below treatment sequences will be followed: A-B-C-D B-A-D-C C-D-A-B D-C-B-A

Intervention: Zoliflodacin Patheon

DDI study

This is an open-label, 2-period, 2-treatment, fixed sequence crossover DDI study in healthy subjects. It will investigate PK of zoliflodacin (ZoliPa) in the absence and presence of itraconazole. Approximately 18 subjects will receive ZoliPa on Day 1 under fasting condition. After a washout of 72 hours after dosing of ZoliPa, on Day 4, subjects will receive a 400 mg loading dose of itraconazole followed by 200 mg of itraconazole once daily from Day 5-8. From Day 4 to Day 8, itraconazole will be administered immediately after a full meal. On Day 9, both itraconazole and zoliflodacin (ZoliPa) will be administered under fasting conditions at -1 hours and 0 hours, respectively. Itraconazole will then be administered with food at 24 hours (Day 10) and 48 hours (Day 11) after administration of zoliflodacin (ZoliPa).

Intervention: Zoliflodacin Patheon