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

Community Acquired Pneumonia Clinical Trial

— LEAP  

Official title:

A Phase 3, Randomized, Double-Blind, Double-Dummy Study to Compare the Efficacy and Safety of Lefamulin (BC 3781) Versus Moxifloxacin (With or Without Adjunctive Linezolid) in Adults With Community-Acquired Bacterial Pneumonia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02559310
• Other study ID #: NAB-BC-3781-3101
• Status: Completed
• Phase: Phase 3
• Start date: September 2015
• Est. completion date: May 2017

Study information

• Verified date: October 2019
• Source: Nabriva Therapeutics AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 551
• Est. completion date: May 2017
• Est. primary completion date: April 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Community Acquired Pneumonia
• Pneumonia

Intervention

Drug:
• lefamulin
antibacterial agent
• Moxifloxacin
antibacterial agent
• Linezolid
antibacterial agent

Locations

Country	Name	City	State
Argentina	Site 3004	Cordoba
Argentina	Site 3001	Córdoba
Argentina	Site 3003	Córdoba
Argentina	Site 3007	Córdoba
Argentina	Site 3005	La Plata	Buenos Aires
Argentina	Site 3006	Rosario	Santa Fe
Bosnia and Herzegovina	Site 4003	Mostar
Bosnia and Herzegovina	Site 4001	Tuzla
Bosnia and Herzegovina	Site 4004	Zenica
Brazil	Site 3104	Belo Horizonte	Minas Gerais
Brazil	Site 3103	Campinas	Sao Paulo
Brazil	Site 3102	Passo Fundo	Rio Grande Do Sol
Brazil	Site 3101	Sao Paulo Do Rio Preto	Sao Paulo
Bulgaria	Site 4105	Gabrovo
Bulgaria	Site 4107	Lovech
Bulgaria	Site 4112	Pernik
Bulgaria	Site 4103	Ruse
Bulgaria	Site 4108	Smolyan
Bulgaria	Site 4101	Sofia
Bulgaria	Site 4102	Sofia
Bulgaria	Site 4106	Sofia
Bulgaria	Site 4110	Sofia
Bulgaria	Site 4111	Sofia
Bulgaria	Site 4104	Veliko Tarnovo
Bulgaria	Site 4109	Vidin
Georgia	Site 4201	Tbilisi
Georgia	Site 4202	Tbilisi
Georgia	Site 4204	Tbilisi
Georgia	Site 4205	Tbilisi
Georgia	Site 4206	Tbilisi
Hungary	Site 4305	Budapest
Hungary	Site 4306	Csorna
Hungary	Site 4304	Debrecen
Hungary	Site 4302	Farkasgyepu
Hungary	Site 4307	Miskolc
Hungary	Site 4308	Miskolc
Hungary	Site 4303	Törökbálint
Latvia	Site 4403	Daugavpils
Latvia	Site 4401	Liepaja
Latvia	Site 4402	Riga
Netherlands	Site 4603	Almelo	Overijssel
Netherlands	Site 4602	Helmond
Peru	Site 3201	Lima
Peru	Site 3202	Lima
Peru	Site 3204	Lima
Peru	Site 3205	Trujillo	La Libertad
Philippines	Site 2005	Iloilo City
Philippines	Site 2004	Manila
Philippines	Site 2003	Manila City
Philippines	Site 2001	Quezon City
Philippines	Site 2002	Quezon City
Poland	Site 4701	Lódz
Poland	Site 4703	Skierniewice	Lódzkie
Poland	Site 4704	Warszawa	Mazowieckie
Poland	Site 4702	Wilkowice
Romania	Site 4801	Bucharest
Romania	Site 4806	Bucharest
Romania	Site 4810	Bucuresti
Romania	Site 4811	Cluj-Napoca
Romania	Site 4803	Craiova
Romania	Site 4808	Craiova
Romania	Site 4802	Palazu Mare	Constanta
Romania	Site 4807	Timisoara
Romania	Site 4809	Timisoara
Russian Federation	Site 4904	Chelyabinsk
Russian Federation	Site 4902	Novosibirsk
Russian Federation	Site 4906	Smolensk
Russian Federation	Site 4901	St. Petersburg
Russian Federation	Site 4903	St. Petersburg
Russian Federation	Site 4905	Yaroslavl
Serbia	Site 5002	Belgrade
Serbia	Site 5001	Kragujevac	Šumadijski Okrug
Serbia	Site 5003	Nis	Nišavski Okrug
Serbia	Site 5004	Sremska Kamenica
South Africa	Site 5103	Benoni	Gauteng
South Africa	Site 5102	Krugersdorp
South Africa	Site 5101	Middelburg	Mpumalanga
South Africa	Site 5104	Pretoria	Gauteng
South Africa	Site 5105	Thabazimbi	Limpopo
Thailand	Site 2103	Nonthaburi
Ukraine	Site 5203	Chernivtsi	Chernivets'ka Oblast
Ukraine	Site 5204	Ivano-Frankivsk	Ivano-Frankivs'ka Oblast
Ukraine	Site 5201	Kharkiv	Kharkivs'ka Oblast
Ukraine	Site 5209	Kherson	Khersons'ka Oblast
Ukraine	Site 5202	Kyiv
Ukraine	Site 5205	Kyiv
Ukraine	Site 5207	Kyïv
Ukraine	Site 5211	Odesa	Odes'ka Oblast
Ukraine	Site 5208	Sumy
Ukraine	Site 5210	Zaporizhzhia	Zaporiz'ka Oblast
Ukraine	Site 5212	Zaporizhzhia
Ukraine	Site 5206	Zhytomyr
United States	Site 1009	Akron	Ohio
United States	Site 1001	Butte	Montana
United States	Site 1002	Dayton	Ohio
United States	Site 1006	Hazard	Kentucky
United States	Site 1005	Minneapolis	Minnesota
United States	Site 1008	Shreveport	Louisiana
United States	Site 1004	Splendora	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Nabriva Therapeutics AG

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Early Clinical Response (ECR)	ECR was defined as survival with improvement in at least 2 signs and symptoms of CABP (relative to baseline), no worsening of any CABP sign or symptom, and no use of concomitant antibiotics (other than adjunctive linezolid, as allowed by the study protocol) for the treatment of CABP through the ECR assessment.	ECR was assessed 96 +/- 24 hours after the first dose of study drug.
Secondary	Investigator's Assessment of Clinical Response (IACR)	IACR was defined as resolution or improvement of a subject's clinical signs and symptoms such that no additional antibacterial therapy was administered for the treatment of the current episode of CABP	IACR was assessed at the Test-of-Cure visit; 5-10 days after the last dose of study drug.
Secondary	Investigator's Assessment of Clinical Response (IACR)	IACR was defined as resolution or improvement of a subject's clinical signs and symptoms such that no additional antibacterial therapy was administered for the treatment of the current episode of CABP.	IACR was assessed at the Test of Cure visit, 5 - 10 days after the last dose of study drug.