Study to Compare Lefamulin to Moxifloxacin for the Treatment of Adults With Pneumonia

NCT ID: NCT02813694

Last Updated: 2019-10-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 738 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-31
• Study Completion Date: 2018-01-31

Brief Summary

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

Detailed Description

Lefamulin is a potent, semi-synthetic antibacterial belonging to a novel class known as the pleuromutilins. The oral dosage form of lefamulin is 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

oral lefamulin, 600mg

Group Type: EXPERIMENTAL

lefamulin

Intervention Type: DRUG

antibacterial agent

Moxifloxacin

oral moxifloxacin, 400mg

Group Type: ACTIVE_COMPARATOR

Moxifloxacin

Intervention Type: DRUG

antibacterial agent

Interventions

lefamulin

antibacterial agent

Intervention Type: DRUG

Moxifloxacin

antibacterial agent

Intervention Type: DRUG

Other Intervention Names

BC-3781; Avelox

Eligibility Criteria

Inclusion Criteria

Each subject must:

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 (less than or equal to 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 < 4 500 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 of II, III, or IV and be an appropriate candidate for oral antibiotic therapy as treatment for the current episode of CABP.

Exclusion Criteria

Each subject must NOT:

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., MRSA, 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).

• 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

Leanne Gasink, MD

Role: STUDY_CHAIR

Nabriva Therapeutics AG

Locations

1080

Beverly Hills, California, United States

Site 1065

Fresno, California, United States

1078

Northridge, California, United States

Site 1072

Oxnard, California, United States

Site 1070

Sacramento, California, United States

1079

Sherman Oaks, California, United States

Site 1053

Sylmar, California, United States

Site 1064

DeBary, Florida, United States

Site 1052

DeLand, Florida, United States

1076

Miami, Florida, United States

Site 1051

Michigan City, Indiana, United States

Site 1057

Natchitoches, Louisiana, United States

Site 1073

New Bedford, Massachusetts, United States

Site 1055

Detroit, Michigan, United States

Site 1062

Detroit, Michigan, United States

Site 1068

Royal Oak, Michigan, United States

Site 1058

St Louis, Missouri, United States

Site 1054

Butte, Montana, United States

Site 1067

Lima, Ohio, United States

Site 1056

Rapid City, South Dakota, United States

1077

Hendersonville, Tennessee, United States

Site 1060

Houston, Texas, United States

Site 1069

Houston, Texas, United States

Site 1066

Splendora, Texas, United States

Site 1059

Charlottesville, Virginia, United States

Site 3056

Buenos Aires, , Argentina

Site 3059

Buenos Aires AV, , Argentina

Site 3054

Córdoba, , Argentina

Site 3052

Córdoba, , Argentina

Site 3057

Córdoba, , Argentina

Site 3058

General Pacheco, , Argentina

Site 3051

La Plata, , Argentina

Site 3053

La Plata, , Argentina

Site 3154

Belo Horizonte, , Brazil

Site 3153

Passo Fundo, , Brazil

Site 3152

São José do Rio Preto, , Brazil

4162

Rousse, , Bulgaria

Site 4154

Sliven, , Bulgaria

Site 4160

Sofia, , Bulgaria

Site 4157

Sofia, , Bulgaria

Site 4153

Sofia, , Bulgaria

Site 4156

Sofia, , Bulgaria

Site 4161

Sofia, , Bulgaria

4163

Sofia, , Bulgaria

4164

Sofia, , Bulgaria

4165

Sofia, , Bulgaria

Site 4158

Stara Zagora, , Bulgaria

Site 4159

Vidin, , Bulgaria

Site 4152

Vratsa, , Bulgaria

Site 3353

Santiago, , Chile

Site 3356

Santiago, , Chile

Site 3357

Santiago, , Chile

Site 3354

Talca, , Chile

Site 3352

Temuco, , Chile

Site 3355

Valdivia, , Chile

Site 4256

Batumi, , Georgia

Site 4253

Tbilisi, , Georgia

Site 4255

Tbilisi, , Georgia

Site 4252

Tbilisi, , Georgia

Site 4254

Tbilisi, , Georgia

Site 4354

Budapest, , Hungary

Site 4353

Budapest, , Hungary

Site 4352

Mátraháza, , Hungary

Site 4351

Törökbálint, , Hungary

Site 4451

Liepāja, , Latvia

Site 4453

Riga, , Latvia

Site 4452

Valmiera, , Latvia

Site 1153

Aguascalientes, , Mexico

Site 1154

Guadalajara, , Mexico

Site 1151

Monterrey, , Mexico

Site 1152

Toluca, , Mexico

Site 3264

Grau, Lima region, Peru

Site 3262

Arequipa, , Peru

Site 3263

Cusco, , Peru

Site 3261

Cuzco, , Peru

Site 3254

Ica, , Peru

Site 3259

Iquitos, , Peru

Site 3251

La Libertad, , Peru

Site 3252

Lima, , Peru

Site 3253

Lima, , Peru

Site 3255

Lima, , Peru

Site 3257

Lima, , Peru

Site 3260

Lima, , Peru

Site 3265

Lima, , Peru

Site 3258

Lima Lima, , Peru

Site 3256

Piura, , Peru

Site 2053

Caloocan City, , Philippines

Site 2055

Cebu, , Philippines

Site 2052

Iloilo City, , Philippines

Site 2054

Quezon, , Philippines

Site 2056

Quezon City, , Philippines

Site 2051

Quezon City, , Philippines

Site 4755

Bochnia, , Poland

Site 4754

Chodzież, , Poland

Site 4753

Krakow, , Poland

Site 4756

Krakow, , Poland

Site 4757

Siedlce, , Poland

Site 4855

Bucharest, , Romania

Site 4858

Bucharest, , Romania

Site 4854

Bucharest, , Romania

Site 4853

Cluj-Napoca, , Romania

Site 4851

Codlea, , Romania

Site 4857

Craiova, , Romania

Site 4856

Timișoara, , Romania

Site 4953

Barnaul, , Russia

Site 4957

Moscow, , Russia

Site 4952

Moscow, , Russia

Site 4954

Novosibirsk, , Russia

Site 4955

Saint Petersburg, , Russia

Site 4951

Saint Petersburg, , Russia

Site 4959

Saratov, , Russia

Site 4958

Smolensk, , Russia

Site 5052

Belgrade, , Serbia

Site 5056

Belgrade, , Serbia

Site 5051

Belgrade, , Serbia

5057

Belgrade, , Serbia

Site 5053

Kamenitz, , Serbia

Site 5055

Knez-Selo, , Serbia

Site 5054

Kragujevac, , Serbia

Site 5151

Bloemfontein, , South Africa

Site 5154

Krugersdorp, , South Africa

Site 5155

Middelburg, , South Africa

Site 5156

Pretoria, , South Africa

Site 5152

Queenswood, , South Africa

Site 5153

Witbank, , South Africa

Site 2254

Uijeongbu-si, Gyeonggi-do, South Korea

Site 2257

Bucheon-si, , South Korea

Site 2253

Daegu, , South Korea

Site 2255

Seoul, , South Korea

Site 2256

Seoul, , South Korea

Site 2251

Seoul, , South Korea

Site 2252

Seoul, , South Korea

Site 4554

Alicante, , Spain

Site 4556

Badalona, , Spain

Site 4552

Barcelona, , Spain

Site 4555

Barcelona, , Spain

Site 4553

Madrid, , Spain

Site 4551

Madrid, , Spain

Site 2352

Kaohsiung City, , Taiwan

Site 2351

Kaohsiung City, , Taiwan

Site 2354

Taipei, , Taiwan

Site 5264

Chernivtsi, , Ukraine

Site 5261

Ivano-Frankivsk, , Ukraine

Site 5258

Ivano-Frankivsk, , Ukraine

Site 5256

Kharkiv, , Ukraine

Site 5254

Kharkiv, , Ukraine

Site 5255

Kherson, , Ukraine

Site 5263

Kyiv, , Ukraine

SIte 5252

Kyiv, , Ukraine

Site 5251

Kyiv, , Ukraine

Site 5265

Kyiv, , Ukraine

Site 5259

Poltava, , Ukraine

Site 5260

Vinnytsia, , Ukraine

Site 5253

Zaporizhzhya, , Ukraine

Site 5257

Zaporizhzhya, , Ukraine

Countries

United States; Argentina; Brazil; Bulgaria; Chile; Georgia; Hungary; Latvia; Mexico; Peru; Philippines; Poland; Romania; Russia; Serbia; South Africa; South Korea; Spain; Taiwan; 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)

Alexander E, Goldberg L, Das AF, Moran GJ, Sandrock C, Gasink LB, Spera P, Sweeney C, Paukner S, Wicha WW, Gelone SP, Schranz J. Oral Lefamulin vs Moxifloxacin for Early Clinical Response Among Adults With Community-Acquired Bacterial Pneumonia: The LEAP 2 Randomized Clinical Trial. JAMA. 2019 Nov 5;322(17):1661-1671. doi: 10.1001/jama.2019.15468.

Reference Type: DERIVED

PMID: 31560372 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

NAB-BC-3781-3102

Identifier Type: -

Identifier Source: org_study_id