Zoliflodacin Bioequivalence and Drug-Drug Interaction Study

NCT05635305 | Completed Phase 1 FDA Drug

• 1 other identifier: STI_Zoli003
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Keywords

Bioequivalence; Drug Drug Interaction

Outcome Measures

Primary Outcomes (10)

• Cmax

  Maximum observed plasma concentration

  through study completion, an average of 5 months

• AUC(0-t)

  Area under the plasma concentration versus time curve, from time zero to t, where t is the time of the last quantifiable concentration

  through study completion, an average of 5 months

• AUC(0-∞)

  Area under the plasma concentration versus time curve, with extrapolation to infinity

  through study completion, an average of 5 months

• clinically significant changes from baseline for vital signs: HR

  clinically significant changes from baseline for heart rate

  through study completion, an average of 5 months

• clinically significant changes from baseline for vital signs: SBP

  clinically significant changes from baseline for Systolic Blood Pressure

  through study completion, an average of 5 months

• clinically significant changes from baseline for vital signs: DBP

  clinically significant changes from baseline for Diastolic Blood Pressure

  through study completion, an average of 5 months

• clinically significant changes from baseline for ECG: PR

  clinically significant changes from baseline for PR

  through study completion, an average of 5 months

• clinically significant changes from baseline for ECG: QRS

  clinically significant changes from baseline for QRS

  through study completion, an average of 5 months

• clinically significant changes from baseline for ECG: QTcF

  clinically significant changes from baseline for QTcF

  through study completion, an average of 5 months

• TEAE

  drug-related treatment-emergent

  through study completion, an average of 5 months

Secondary Outcomes (1)

• tmax

  through study completion, an average of 5 months

Study Arms (2)

BE study

EXPERIMENTAL

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

Drug: Zoliflodacin Patheon

DDI study

EXPERIMENTAL

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).

Drug: Zoliflodacin Patheon

Interventions

Zoliflodacin Patheon DRUG

Zoliflodacin Patheon formulation to be compared with Zoliflodacin Dr Reddy's formulation during BE study (cohort 1). Itraconazole will be administered with Zoliflodacin Patheon formulation during DDI study (cohort 2)

BE study; DDI study

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• o Not of childbearing potential, e.g., have a documentation of irreversible surgical sterilization by hysterectomy and/or bilateral oophorectomy and/or bilateral salpingectomy and/or bilateral tubal ligation, at least 6 weeks before the Screening visit, amenorrhea for ≥ 12 months and follicle stimulating hormone (FSH) in the post menopausal range according to local laboratory ranges.
• ii. Not lactating iii. The female subject must agree to use, with their partner, an approved method of highly effective contraception in combination with a barrier method from at least 1 month before the Screening visit until 1 month after last dosing of IMP. Female subjects must agree not to attempt to become pregnant, must not donate ova from the Screening visit until at least 1 month after last dosing of IMP.
• The following are considered to be highly effective methods of birth control:
• Hormonal contraception (i.e., combined oral contraceptives, injectable or implantable hormonal contraceptives
• Hormonal or non-hormonal intrauterine device/system with a proven failure rate \<1%

You may not qualify if:

• 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).
• Receipt of zoliflodacin, vaccines, biologics, or any other investigational product within 3 months prior to study start or during the study, or 5-times the half-life of the drug tested in the previous clinical study, whichever is longer (time calculated relative to the last dose in the previous clinical study). Influenza vaccination and SARS-CoV-2 vaccination prior to Screening will be allowed.
• Presence of clinically significant abnormality following review of pre-study laboratory tests (i.e., aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], alkaline phosphatase \[ALP\], or creatinine \> upper limit of normal \[ULN\]), vital signs, full physical examination, and ECG.
• History of serious allergy, allergic skin rash, history of drug allergy to itraconazole or other azole antifungals or allergy/sensitivity to any drug.
• Excessive intake of caffeine (more than 8 cups daily of beverage containing caffeine).
• Current alcohol use \>21 units of alcohol per week for males and \>14 units of alcohol per week for females (one unit = 8 g or about 10 mL of pure alcohol) and/or positive urine alcohol test at Screening.

Sponsors & Collaborators

• Global Antibiotics Research and Development Partnership: lead
• Parexel: collaborator
• KCAS: collaborator

Study Sites (1)

Parexel Early Phase Clinical Unit

Berlin, 14050, Germany

Location

Study Officials

• Salman Nasr, MD

  Parexel CPU Berlin, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: BE study (cohort 1) will be managed in parallel with the DDI study (cohort 2)

Study Record Dates

• First Submitted: November 2, 2022
• First Posted: December 2, 2022
• Study Start: November 9, 2022
• Primary Completion: February 7, 2023
• Study Completion: February 7, 2023
• Last Updated: March 1, 2023

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)