Study to Determine and Compare Plasma and Intrapulmonary Concentrations of WCK 4873 in Healthy Adult Human Subjects

A Phase 1, Multiple-Dose, Open-Label Study to Determine and Compare Plasma and Intrapulmonary Concentrations of WCK 4873 in Healthy Adult Human Subjects

This is a Phase 1, multiple dose, open-label pharmacokinetic study conducted in healthy adult male and female subjects.

Subjects will receive 3 oral doses of WCK 4873 administered once-daily starting on Day 1. Blood collection for determining plasma WCK 4873 concentrations will be conducted within 15 minutes prior to and at 1, 2, 3, 4, 6, 9, 12, and 24 hours after the first dose of WCK 4873. The 24 hours post-dose sample after the first dose will be collected prior to Day 2 dosing. Blood samples for determining plasma WCK 4873 concentrations will also be collected within 15 minutes prior to and at 1, 2, 3, 4, 6, 9, 12, 24 and 36 hours after the third dose. Each subject will undergo one standardized bronchoscopy with bronchoalveolar lavage (BAL) in the outpatient bronchoscopy suite at 3, 6, 9, 12, 24 or 48 hours after the third oral dose of WCK 4873. Subjects scheduled for bronchoscopy at 48 hours will also have blood sample drawn for determining plasma WCK 4873 concentrations at 48 hours after the third dose.

Safety will be assessed throughout the study by adverse event monitoring, clinical laboratory tests (including liver function tests), ECG, physical examination and vital sign monitoring. Subjects will discontinue study drug administration in the event of AST/ALT elevation of greater than 3 times the upper limit of normal.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: WCK 4873

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Pulmonary Associates, 1112 E. McDowell Rd.

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:

• Body mass index (BMI) 18.5 and 30 (kg/m2) and weight between 55.0 and 100.0 kg (both inclusive).
• Medical history without any major pathology as judged by the Principal Investigator.
• Resting supine blood pressure 100-139 (systolic) or 60-89 (diastolic) mm Hg, a resting pulse rate of 40 beats per minute or higher, and showing no clinically relevant deviations as judged by the Principal Investigator.

Exclusion Criteria:

• History or presence of significant oncologic, cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease.
• Positive alcohol breath test or urine drug screen test at screening or confinement.
• Positive testing for HIV, Hepatitis B or Hepatitis C.
• Clinically significant pulmonary or any other disease that prevents a subject from undergoing bronchoscopy with pulmonary lavage.

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: WCK 4873; Oral tablets	Drug: WCK 4873; Oral tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
• Epithelial lining fluid (ELF) and alveolar macrophage (AM) will be used to assess the concentrations of oral WCK 4873 in healthy adult subjects	48 hrs per dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
• Safety and tolerability of oral WCK 4873 in healthy adult subjects as measure by safety lab assesments, ECGs, physical examinations and AEs captured.		8 weeks
• Pharmacokinetic (PK) profile of multiple doses (800 mg) of WCK 4873 in healthy adult subjects	Plasma concentrations of WCK 4873; plasma PK parameters (Cmax, tmax, kel, t½, AUC0-t, AUC0-24, Vd, CL); ELF concentrations of WCK 4873; concentration of WCK 4873 in alveolar macrophages	48 hrs last dose

Collaborators and Investigators

• Sponsor: Wockhardt
• Collaborators: Clinartis

Publications and helpful links

General Publications

• Rodvold KA, Gotfried MH, Chugh R, Gupta M, Friedland HD, Bhatia A. Comparison of Plasma and Intrapulmonary Concentrations of Nafithromycin (WCK 4873) in Healthy Adult Subjects. Antimicrob Agents Chemother. 2017 Aug 24;61(9):e01096-17. doi: 10.1128/AAC.01096-17. Print 2017 Sep.

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: April 17, 2015
• First Submitted That Met QC Criteria: May 20, 2015
• First Posted (Estimate): May 25, 2015

Study Record Updates

• Last Update Posted (Estimate): August 3, 2015
• Last Update Submitted That Met QC Criteria: July 31, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: plasma concentration; pulmonary concentration
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Nafithromycin
• Other Study ID Numbers: W-4873-101