Study to Compare Lefamulin to Moxifloxacin (With or Without Linezolid) for the Treatment of Adults With Pneumonia

NCT ID: NCT02559310

Last Updated: 2019-10-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 551 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2017-05-31

Brief Summary

This study evaluates the safety and efficacy of lefamulin, a pleuromutilin, for the treatment of adults with moderate to severe community-acquired bacterial pneumonia.

Detailed Description

Lefamulin is a potent, semi-synthetic antibacterial belonging to a novel class known as the pleuromutilins. Both the intravenous (IV) and oral dosage forms of lefamulin are under investigation in this study. Lefamulin's in vitro antibacterial profile includes the most important bacterial pathogens causing respiratory tract infection (RTI). The antibacterial spectrum comprises S. pneumoniae, H. influenzae, M. catarrhalis, the atypical respiratory pathogens L. pneumophila, C. pneumoniae, and M. pneumoniae, S. aureus including MRSA and CA-MRSA, ß-haemolytic streptococci including S. pyogenes and S. agalactiae, and Enterococcus faecium including vancomycin-resistant enterococci (VRE). Moreover, as demonstrated in cross-resistance studies, lefamulin remains active against clinical isolates resistant to the following antimicrobial(s) (classes): macrolides, lincosamides, streptogramin B, oxazolidinones, tetracyclines, ß lactams, quinolones, trimethoprim-sulfametoxazole, mupirocin, and vancomycin.

Conditions

Community Acquired Pneumonia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Lefamulin

Intravenous lefamulin with potential step-down to oral lefamulin

Group Type: EXPERIMENTAL

lefamulin

Intervention Type: DRUG

antibacterial agent

Moxifloxacin +/- Linezolid

Intravenous moxifloxacin with potential step-down to oral moxifloxacin +/- linezolid

Group Type: ACTIVE_COMPARATOR

Moxifloxacin

Intervention Type: DRUG

antibacterial agent

Linezolid

Intervention Type: DRUG

antibacterial agent

Interventions

lefamulin

antibacterial agent

Intervention Type: DRUG

Moxifloxacin

antibacterial agent

Intervention Type: DRUG

Linezolid

antibacterial agent

Intervention Type: DRUG

Other Intervention Names

BC-3781; Avelox; Zyvox

Eligibility Criteria

Inclusion Criteria

1. Be male or female at least 18 years of age.

2. Provide written informed consent and be willing and able to adhere to the study-specified procedures and restrictions.

3. Have an acute illness (7 days duration) with at least 3 of the following symptoms consistent with a lower respiratory tract infection (new or worsening):

• Dyspnea
• New or increased cough
• Purulent sputum production
• Chest pain due to pneumonia

4. Have at least 2 of the following vital sign abnormalities:

• Fever (body temperature >38.0°C (100.4°F) measured orally or equivalent temperature from an alternate body site) or hypothermia (body temperature <35.0°C (95.0°F) measured orally or equivalent temperature from an alternate body site)
• Hypotension (systolic blood pressure <90 mmHg)
• Tachycardia (heart rate >100 beats/min)
• Tachypnea (respiratory rate >20 breaths/min)

5. Have at least 1 other clinical sign or laboratory finding of CABP:

• Hypoxemia (i.e., O2 saturation <90% on room air or while receiving supplemental oxygen at subject's baseline requirement or PaO2 <60 mmHg)
• Auscultatory and/or percussion findings consistent with pneumonia (e.g., crackles, egophony, dullness)
• White blood cell (WBC) count >10,000 cells/mm3 or <4500 cells/mm3 or >15% immature neutrophils (bands) regardless of total WBC count

6. Have radiographically-documented pneumonia within 48 hours before enrollment (i.e., infiltrates in a lobar or multilobar distribution or diffuse opacities on chest x-ray or chest computed tomography scan consistent with acute bacterial pneumonia).

7. Have a Pneumonia Outcomes Research Team (PORT) Risk Class ≥III.

Exclusion Criteria

1. Have received more than a single dose of a short-acting oral or IV antibacterial for CABP within 72 hours before randomization

2. Require concomitant systemic antibacterial therapy potentially effective against CABP pathogens

3. Have been hospitalized for 2 or more days within 90 days prior to the onset of symptoms or have resided in a nursing home or long-term healthcare facility within 30 days prior to the onset of symptoms. NOTE: Residence in an independent living facility is permitted.

4. Have confirmed or suspected CABP caused by a pathogen known to be resistant to any of the study drugs (e.g., Pseudomonas aeruginosa, any pathogen of the Enterobacteriaceae Family) or attributable to etiologies other than community acquired bacterial pathogens (e.g., ventilator associated pneumonia, hospital acquired bacterial pneumonia, bacterial aspiration pneumonia, Pneumocystis jiroveci pneumonia or other fungal pneumonia, viral or mycobacterial infection of the lung).

5. Have a noninfectious cause of pulmonary infiltrates (e.g., pulmonary embolism, chemical pneumonitis from aspiration, hypersensitivity pneumonia, congestive heart failure, bronchial obstruction, lung cancer, cystic fibrosis).

6. Have confirmed or suspected pleural empyema (does not include sterile parapneumonic effusions).

7. Require mechanical ventilation.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nabriva Therapeutics AG

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jennifer Schranz, MD

Role: STUDY_CHAIR

Nabriva Therapeutics

Locations

Site 1006

Hazard, Kentucky, United States

Site 1008

Shreveport, Louisiana, United States

Site 1005

Minneapolis, Minnesota, United States

Site 1001

Butte, Montana, United States

Site 1009

Akron, Ohio, United States

Site 1002

Dayton, Ohio, United States

Site 1004

Splendora, Texas, United States

Site 3005

La Plata, Buenos Aires, Argentina

Site 3006

Rosario, Santa Fe Province, Argentina

Site 3003

Córdoba, , Argentina

Site 3007

Córdoba, , Argentina

Site 3001

Córdoba, , Argentina

Site 3004

Córdoba, , Argentina

Site 4003

Mostar, , Bosnia and Herzegovina

Site 4001

Tuzla, , Bosnia and Herzegovina

Site 4004

Zenica, , Bosnia and Herzegovina

Site 3104

Belo Horizonte, Minas Gerais, Brazil

Site 3102

Passo Fundo, Rio Grande Do Sol, Brazil

Site 3103

Campinas, São Paulo, Brazil

Site 3101

Sao Paulo Do Rio Preto, São Paulo, Brazil

Site 4105

Gabrovo, , Bulgaria

Site 4107

Lovech, , Bulgaria

Site 4112

Pernik, , Bulgaria

Site 4103

Rousse, , Bulgaria

Site 4108

Smolyan, , Bulgaria

Site 4102

Sofia, , Bulgaria

Site 4101

Sofia, , Bulgaria

Site 4106

Sofia, , Bulgaria

Site 4110

Sofia, , Bulgaria

Site 4111

Sofia, , Bulgaria

Site 4104

Veliko Tarnovo, , Bulgaria

Site 4109

Vidin, , Bulgaria

Site 4206

Tbilisi, , Georgia

Site 4204

Tbilisi, , Georgia

Site 4205

Tbilisi, , Georgia

Site 4201

Tbilisi, , Georgia

Site 4202

Tbilisi, , Georgia

Site 4305

Budapest, , Hungary

Site 4306

Csorna, , Hungary

Site 4304

Debrecen, , Hungary

Site 4302

Farkasgyepű, , Hungary

Site 4307

Miskolc, , Hungary

Site 4308

Miskolc, , Hungary

Site 4303

Törökbálint, , Hungary

Site 4403

Daugavpils, , Latvia

Site 4401

Liepāja, , Latvia

Site 4402

Riga, , Latvia

Site 4603

Almelo, Overijssel, Netherlands

Site 4602

Helmond, , Netherlands

Site 3205

Trujillo, La Libertad, Peru

Site 3202

Lima, , Peru

Site 3204

Lima, , Peru

Site 3201

Lima, , Peru

Site 2005

Iloilo City, , Philippines

Site 2003

Manila, , Philippines

Site 2004

Manila, , Philippines

Site 2002

Quezon City, , Philippines

Site 2001

Quezon City, , Philippines

Site 4703

Skierniewice, Lódzkie, Poland

Site 4704

Warsaw, Masovian Voivodeship, Poland

Site 4701

Lódz, , Poland

Site 4702

Wilkowice, , Poland

Site 4802

Palazu Mare, Constanța County, Romania

Site 4810

Bucharest, , Romania

Site 4801

Bucharest, , Romania

Site 4806

Bucharest, , Romania

Site 4811

Cluj-Napoca, , Romania

Site 4803

Craiova, , Romania

Site 4808

Craiova, , Romania

Site 4807

Timișoara, , Romania

Site 4809

Timișoara, , Romania

Site 4904

Chelyabinsk, , Russia

Site 4902

Novosibirsk, , Russia

Site 4903

Saint Petersburg, , Russia

Site 4901

Saint Petersburg, , Russia

Site 4906

Smolensk, , Russia

Site 4905

Yaroslavl, , Russia

Site 5003

Niš, Nišavski Okrug, Serbia

Site 5002

Belgrade, , Serbia

Site 5004

Kamenitz, , Serbia

Site 5001

Kragujevac, Šumadijski Okrug, Serbia

Site 5103

Benoni, Gauteng, South Africa

Site 5104

Pretoria, Gauteng, South Africa

Site 5105

Thabazimbi, Limpopo, South Africa

Site 5101

Middelburg, Mpumalanga, South Africa

Site 5102

Krugersdorp, , South Africa

Site 2103

Nonthaburi, , Thailand

Site 5203

Chernivtsi, Chernivtsi Oblast, Ukraine

Site 5204

Ivano-Frankivsk, Ivano-Frankivsk Oblast, Ukraine

Site 5201

Kharkiv, Kharkivs’ka Oblast’, Ukraine

Site 5209

Kherson, Kherson Oblast, Ukraine

Site 5211

Odesa, Odesa Oblast, Ukraine

Site 5210

Zaporizhzhia, Zaporizhzhia Oblast, Ukraine

Site 5207

Kiyiv, , Ukraine

Site 5202

Kyiv, , Ukraine

Site 5205

Kyiv, , Ukraine

Site 5208

Sumy, , Ukraine

Site 5212

Zaporizhzhia, , Ukraine

Site 5206

Zhytomyr, , Ukraine

Countries

United States; Argentina; Bosnia and Herzegovina; Brazil; Bulgaria; Georgia; Hungary; Latvia; Netherlands; Peru; Philippines; Poland; Romania; Russia; Serbia; South Africa; Thailand; Ukraine

References

File TM Jr, Alexander E, Goldberg L, Das AF, Sandrock C, Paukner S, Moran GJ. Lefamulin efficacy and safety in a pooled phase 3 clinical trial population with community-acquired bacterial pneumonia and common clinical comorbidities. BMC Pulm Med. 2021 May 8;21(1):154. doi: 10.1186/s12890-021-01472-z.

Reference Type: DERIVED

PMID: 33964925 (View on PubMed)

File TM, Goldberg L, Das A, Sweeney C, Saviski J, Gelone SP, Seltzer E, Paukner S, Wicha WW, Talbot GH, Gasink LB. Efficacy and Safety of Intravenous-to-oral Lefamulin, a Pleuromutilin Antibiotic, for the Treatment of Community-acquired Bacterial Pneumonia: The Phase III Lefamulin Evaluation Against Pneumonia (LEAP 1) Trial. Clin Infect Dis. 2019 Nov 13;69(11):1856-1867. doi: 10.1093/cid/ciz090.

Reference Type: DERIVED

PMID: 30722059 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

NAB-BC-3781-3101

Identifier Type: -

Identifier Source: org_study_id