Study to Assess the Safety and PK of Oral and IV Xenleta in Adults With Cystic Fibrosis

NCT05225805 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: NAB-BC-3781-1014
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 6

Brief Summary

This study is intended to assess the pharmacokinetic (PK) and safety of a single dose of IV and oral formulations of lefamulin in adults with cystic fibrosis (CF).

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (5)

• The Median for Lefamulin and Its Main Metabolite BC-8041 for PK Plasma Parameter Tmax in Cystic Fibrosis (CF) Patients.

  Appropriate non-compartmental techniques were used to obtain estimates for the PK parameter Tmax in plasma for lefamulin and its metabolite BC-8041. Time to reach maximum plasma concentration of lefamulin following drug administration (Tmax) Tmax will be determined by direct inspection of the concentration versus time data by WinNonlin.

  Pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 4 hrs, 8 hrs, 12 hrs & 24 hrs Post-dose

• The Key Geometric Mean for Lefamulin and Its Main Metabolite BC-8041 for PK Plasma Parameter Cmax in CF Patients.

  Appropriate non-compartmental techniques will be used to obtain estimates for the PK parameter Cmax in plasma for lefamulin and its metabolite BC-8041. Maximum observed plasma concentration (Cmax) Cmax was determined by direct inspection of the concentration versus time data by WinNonlin.

  Pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 4 hrs, 8 hrs, 12 hrs & 24 hrs Post-dose

• The Key Geometric Mean for Lefamulin and Its Main Metabolite BC-8041 for PK Plasma Parameter AUC(0-last) in CF Patients.

  Appropriate non-compartmental techniques will be used to obtain estimates for the PK parameter (AUC0-last) in plasma for lefamulin and its metabolite BC-8041. AUC calculations will be performed using the linear/log trapezoidal rule. AUC0-last will be calculated between t0hr and the last measurable concentration. Area under the drug concentration curve from time zero (0 h) to 24 h (AUC0-last)

  Pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 4 hrs, 8 hrs, 12 hrs & 24 hrs Post-dose

• The Key Geometric Mean for Lefamulin and Its Main Metabolite BC-8041 for PK Plasma Parameter AUC(0-inf) in CF Patients.

  Appropriate non-compartmental techniques will be used to obtain estimates for PK parameter AUC(0-inf) in plasma for lefamulin and its metabolite BC-8041. AUC calculations will be performed using the linear/log trapezoidal rule. AUC(0-inf) will be will be calculated between t0hr and infinity. Area under the drug concentration curve from time zero (0 h) to infinity (AUC(0-inf)

  Pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 4 hrs, 8 hrs, 12 hrs & 24 hrs Post-dose

• The Key Geometric Mean for Lefamulin and Its Main Metabolite BC-8041 for PK Plasma Parameter t1/2 in CF Patients.

  Appropriate non-compartmental techniques will be used to obtain estimates for thr PK parameter t1/2 in plasma for lefamulin and its metabolite BC-8041. Apparent elimination half-life calculated as ln(2)/ke (t½)

  Pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 4 hrs, 8 hrs, 12 hrs & 24 hrs Post-dose

Study Arms (2)

Group A

EXPERIMENTAL

Group A will receive one dose of 150 mg lefamulin IV followed by one dose of 600 mg lefamulin oral

Drug: Lefamulin

Group B

EXPERIMENTAL

Group B will receive one dose of 600 mg lefamulin oral followed by one dose of 150 mg lefamulin IV

Drug: Lefamulin

Interventions

Lefamulin DRUG

Antibiotic

Also known as: BC-3781

Group A; Group B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent.
• Adult patients, ≥ 18 years of age.
• Genetic confirmation of CF diagnosis by a report from a genetic test, such as "F508 deletion detected."
• Weight \> 40 kgs.
• Forced expiration volume (FEV)1 \> 40% predicted, as measured during the most recent evaluation.
• Mentally and physically able to participate in the study as determined by the Investigator, ie, clinically stable with no significant changes in health status within 28 days prior to, and including, Day 1.
• Vital signs within the following ranges:
• Tympanic temperature, \< 38°C
• Systolic blood pressure, 90 to 160 mmHg
• Diastolic blood pressure, 50 to 90 mmHg
• Heart rate \< 100 beats per minute at rest
• Respiration rate 12 to 20 breaths per minute
• Oxygen saturation to be documented. No selection criteria; supplemental oxygen use is acceptable.
• Negative beta-human chorionic gonadotropin (β-hCG) urine or serum pregnancy test for females of childbearing potential.
• Willing to commit to acceptable methods of contraception as defined in the protocol.

You may not qualify if:

• Known history of chronic liver or biliary disease, Gilbert's syndrome, or any of the following at Screening: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2 x upper limit of normal (ULN), total bilirubin \> 1.5 x ULN.
• Prolonged baseline corrected QT interval corrected according to Fridericia (QTcF) defined as \> 440 ms (females) and \> 430 ms (males).
• Family history or presence of prolonged QTc syndrome, Torsades de Pointes, or known conduction defects (eg, bundle branch block, atrioventricular block).
• Use of Orkambi® (lumacaftor/ivacaftor) within 28 days prior to Day 1.
• Use of cytochrome P450 (CYP)3A substrates that prolong the QT interval within 24 hours prior to Day 1.
• Use of strong and moderate Cytochrome P450 (CYP3A) inducers or P-glycoprotein (P-gp) inducers within 28 days prior to Day 1.
• Use of strong inhibitors of CYP3A4 within 24 hours prior to Day 1.
• Serum potassium level below the normal reference range at Screening.
• Known allergy to pleuromutilin class of antibiotic or any of the excipients of the lefamulin formulations.
• Consumption of grapefruit, grapefruit juice, grapefruit products, pomelo, or Seville oranges within 24 hours before Day 1.
• Use of vaporized nicotine or cannabidiol products, smoking (regularly or intermittently) more than 5 cigarettes (or equivalent) per day, or any use of tobacco other than in cigarettes or cigars within 28 days of Day 1.
• Positive blood test for hepatitis C, human immunodeficiency virus (HIV), or hepatitis B antigen or core antibody (indicating active infection).
• Positive test for drugs of abuse or alcohol at Screening or Day 1 that cannot be satisfactorily supported by medical history.
• Use of an investigational product within the 30 days prior to Day 1 (3 months prior to Day 1 if the study drug was a new chemical entity).
• Difficulty swallowing tablets.

Sponsors & Collaborators

• Nabriva Therapeutics AG: lead

Study Sites (6)

University of Kansas School of Medicine

Kansas City, Kansas, 66160, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Penn State University College of Medicine

Hershey, Pennsylvania, 17033, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• Sawicki GS, Wicha WW, Hiley TS, Close NC, Gelone SP, Guico-Pabia CJ. Safety and Pharmacokinetics Following Oral or Intravenous Lefamulin in Adults With Cystic Fibrosis. Clin Ther. 2024 Feb;46(2):96-103. doi: 10.1016/j.clinthera.2023.12.002. Epub 2024 Jan 8.

  PMID: 38195348 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

lefamulin

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Results Point of Contact

• Title: Christine Guico-Pabia, MD, MBA, MPH
• Organization: Nabriva Therapeutics US, Inc.

christine.guico-pabia@nabriva.com

610-981-2874

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Model Details: Open-label, Crossover Study

Study Record Dates

• First Submitted: January 7, 2022
• First Posted: February 7, 2022
• Study Start: March 1, 2022
• Primary Completion: September 20, 2022
• Study Completion: January 13, 2023
• Last Updated: June 17, 2024
• Results First Posted: June 17, 2024

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)