Clinical trial NCT02453529: Study to Determine and Compare Plasma and Intrapulmonary Concentrations of WCK 4873 in Healthy Adult Human Subjects
Official title: A Phase 1, Multiple-Dose, Open-Label Study to Determine and Compare Plasma and Intrapulmonary Concentrations of WCK 4873 in Healthy Adult Human Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: plasma concentration
pulmonary concentration
Lead sponsor: Wockhardt
Sponsor class: INDUSTRY
Collaborators: name: Clinartis
First posted: 2015-05-25
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: • Epithelial lining fluid (ELF) and alveolar macrophage (AM) will be used to assess the concentrations of oral WCK 4873 in healthy adult subjects
timeFrame: 48 hrs per dose
Secondary outcomes:
measure: • Safety and tolerability of oral WCK 4873 in healthy adult subjects as measure by safety lab assesments, ECGs, physical examinations and AEs captured.
timeFrame: 8 weeks
measure: • Pharmacokinetic (PK) profile of multiple doses (800 mg) of WCK 4873 in healthy adult subjects
timeFrame: 48 hrs last dose
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Pulmonary Associates, 1112 E. McDowell Rd.
state: Arizona
Study officials:
References:
citation: 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.