Clinical trial NCT02813694: Study to Compare Lefamulin to Moxifloxacin for the Treatment of Adults With Pneumonia
Official title: A Phase 3, Randomized, Double-Blind, Double-Dummy Study to Compare the Efficacy and Safety of Oral Lefamulin (BC 3781) Versus Oral Moxifloxacin in Adults With Community-Acquired Bacterial Pneumonia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Community Acquired Pneumonia
Keywords: Pneumonia
CABP
CAP
Community acquired bacterial pneumonia
Lead sponsor: Nabriva Therapeutics AG
Sponsor class: INDUSTRY
First posted: 2016-06-27
Enrollment: 738
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Early Clinical Response (ECR)
timeFrame: 96 hours +/- 24 hours after first dose of study drug
Secondary outcomes:
measure: Investigator's Assessment of Clinical Response (IACR)
timeFrame: IACR was assessed at the Test-of-Cure Visit; 5 to 10 days after last dose of study drug
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: 1080
state: California
city: Fresno
country: United States
facility: Site 1065
state: California
city: Northridge
country: United States
facility: 1078
state: California
city: Oxnard
country: United States
facility: Site 1072
state: California
city: Sacramento
country: United States
facility: Site 1070
state: California
city: Sherman Oaks
country: United States
facility: 1079
state: California
city: Sylmar
country: United States
facility: Site 1053
state: California
city: DeBary
country: United States
facility: Site 1064
state: Florida
city: DeLand
country: United States
facility: Site 1052
state: Florida
city: Miami
country: United States
facility: 1076
state: Florida
city: Michigan City
country: United States
facility: Site 1051
state: Indiana
city: Natchitoches
country: United States
facility: Site 1057
state: Louisiana
city: New Bedford
country: United States
facility: Site 1073
state: Massachusetts
city: Detroit
country: United States
facility: Site 1055
state: Michigan
city: Detroit
country: United States
facility: Site 1062
state: Michigan
city: Royal Oak
country: United States
facility: Site 1068
state: Michigan
city: Saint Louis
country: United States
facility: Site 1058
state: Missouri
city: Butte
country: United States
facility: Site 1054
state: Montana
city: Lima
country: United States
facility: Site 1067
state: Ohio
city: Rapid City
country: United States
facility: Site 1056
state: South Dakota
city: Hendersonville
country: United States
facility: 1077
state: Tennessee
city: Houston
country: United States
facility: Site 1060
state: Texas
city: Houston
country: United States
facility: Site 1069
state: Texas
city: Splendora
country: United States
facility: Site 1066
state: Texas
city: Charlottesville
country: United States
facility: Site 1059
state: Virginia
city: Buenos Aires AV
country: Argentina
facility: Site 3059
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Site 3056
city: Cordoba
country: Argentina
facility: Site 3054
city: Cordoba
country: Argentina
facility: Site 3052
city: Cordoba
country: Argentina
facility: Site 3057
city: General Pacheco
country: Argentina
facility: Site 3058
city: La Plata
country: Argentina
facility: Site 3051
city: La Plata
country: Argentina
facility: Site 3053
city: Belo Horizonte
country: Brazil
facility: Site 3154
city: Passo Fundo
country: Brazil
facility: Site 3153
city: Sao Jose do Rio Preto
country: Brazil
facility: Site 3152
city: Ruse
country: Bulgaria
facility: 4162
city: Sliven
country: Bulgaria
facility: Site 4154
city: Sofia
country: Bulgaria
facility: Site 4160
city: Sofia
country: Bulgaria
facility: Site 4157
city: Sofia
country: Bulgaria
facility: Site 4153
city: Sofia
country: Bulgaria
facility: Site 4156
city: Sofia
country: Bulgaria
facility: Site 4161
city: Sofia
country: Bulgaria
facility: 4163
city: Sofia
country: Bulgaria
facility: 4164
city: Sofia
country: Bulgaria
facility: 4165
city: Stara Zagora
country: Bulgaria
facility: Site 4158
city: Vidin
country: Bulgaria
facility: Site 4159
city: Vratsa
country: Bulgaria
facility: Site 4152
city: Santiago
country: Chile
facility: Site 3353
city: Santiago
country: Chile
facility: Site 3356
city: Santiago
country: Chile
facility: Site 3357
city: Talca
country: Chile
facility: Site 3354
city: Temuco
country: Chile
facility: Site 3352
city: Valdivia
country: Chile
facility: Site 3355
city: Batumi
country: Georgia
facility: Site 4256
city: Tbilisi
country: Georgia
facility: Site 4253
city: Tbilisi
country: Georgia
facility: Site 4255
city: Tbilisi
country: Georgia
facility: Site 4252
city: Tbilisi
country: Georgia
facility: Site 4254
city: Budapest
country: Hungary
facility: Site 4354
city: Budapest
country: Hungary
facility: Site 4353
city: Matrahaza
country: Hungary
facility: Site 4352
city: Torokbalint
country: Hungary
facility: Site 4351
city: Uijeongbu Si
country: Korea, Republic of
facility: Site 2254
state: Gyeonggi-do
city: Bucheon-si
country: Korea, Republic of
facility: Site 2257
city: Daegu
country: Korea, Republic of
facility: Site 2253
city: Seoul
country: Korea, Republic of
facility: Site 2255
city: Seoul
country: Korea, Republic of
facility: Site 2256
city: Seoul
country: Korea, Republic of
facility: Site 2251
city: Seoul
country: Korea, Republic of
facility: Site 2252
city: Liepāja
country: Latvia
facility: Site 4451
city: Rīga
country: Latvia
facility: Site 4453
city: Valmiera
country: Latvia
facility: Site 4452
city: Aguascalientes
country: Mexico
facility: Site 1153
city: Guadalajara
country: Mexico
facility: Site 1154
city: Monterrey
country: Mexico
facility: Site 1151
city: Toluca
country: Mexico
facility: Site 1152
city: Grau
country: Peru
facility: Site 3264
state: Lima
city: Arequipa
country: Peru
facility: Site 3262
city: Cusco
country: Peru
facility: Site 3263
city: Cuzco
country: Peru
facility: Site 3261
city: Ica
country: Peru
facility: Site 3254
city: Iquitos
country: Peru
facility: Site 3259
city: La Libertad
country: Peru
facility: Site 3251
city: Lima Lima
country: Peru
facility: Site 3258
city: Lima
country: Peru
facility: Site 3252
city: Lima
country: Peru
facility: Site 3253
city: Lima
country: Peru
facility: Site 3255
city: Lima
country: Peru
facility: Site 3257
city: Lima
country: Peru
facility: Site 3260
city: Lima
country: Peru
facility: Site 3265
city: Piura
country: Peru
facility: Site 3256
city: Caloocan City
country: Philippines
facility: Site 2053
city: Cebu
country: Philippines
facility: Site 2055
city: Iloilo City
country: Philippines
facility: Site 2052
city: Quezon City
country: Philippines
facility: Site 2056
city: Quezon City
country: Philippines
facility: Site 2051
city: Quezon
country: Philippines
facility: Site 2054
city: Bochnia
country: Poland
facility: Site 4755
city: Chodziez
country: Poland
facility: Site 4754
city: Krakow
country: Poland
facility: Site 4753
city: Kraków
country: Poland
facility: Site 4756
city: Siedlce
country: Poland
facility: Site 4757
city: Bucuresti
country: Romania
facility: Site 4858
city: Bucureşti
country: Romania
facility: Site 4855
city: Bucureşti
country: Romania
facility: Site 4854
city: Cluj-Napoca
country: Romania
facility: Site 4853
city: Codlea
country: Romania
facility: Site 4851
city: Craiova
country: Romania
facility: Site 4857
city: Timisoara
country: Romania
facility: Site 4856
city: Barnaul
country: Russian Federation
facility: Site 4953
city: Moscow
country: Russian Federation
facility: Site 4957
city: Moscow
country: Russian Federation
facility: Site 4952
city: Novosibirsk
country: Russian Federation
facility: Site 4954
city: Saratov
country: Russian Federation
facility: Site 4959
city: Smolensk
country: Russian Federation
facility: Site 4958
city: St. Petersburg
country: Russian Federation
facility: Site 4955
city: St. Petersburg
country: Russian Federation
facility: Site 4951
city: Belgrade
country: Serbia
facility: Site 5052
city: Belgrade
country: Serbia
facility: Site 5056
city: Belgrade
country: Serbia
facility: Site 5051
city: Belgrade
country: Serbia
facility: 5057
city: Knez Selo
country: Serbia
facility: Site 5055
city: Kragujevac
country: Serbia
facility: Site 5054
city: Sremska Kamenica
country: Serbia
facility: Site 5053
city: Bloemfontein
country: South Africa
facility: Site 5151
city: Krugersdorp
country: South Africa
facility: Site 5154
city: Middelburg
country: South Africa
facility: Site 5155
city: Pretoria
country: South Africa
facility: Site 5156
city: Queenswood
country: South Africa
facility: Site 5152
city: Witbank
country: South Africa
facility: Site 5153
city: Alicante
country: Spain
facility: Site 4554
city: Badalona
country: Spain
facility: Site 4556
city: Barcelona
country: Spain
facility: Site 4552
city: Barcelona
country: Spain
facility: Site 4555
city: Madrid
country: Spain
facility: Site 4553
city: Madrid
country: Spain
facility: Site 4551
city: Kaohsiung
country: Taiwan
facility: Site 2352
city: Kaohsiung
country: Taiwan
facility: Site 2351
city: Taipei
country: Taiwan
facility: Site 2354
city: Chernivtsi
country: Ukraine
facility: Site 5264
city: Ivano-Frankivs'k
country: Ukraine
facility: Site 5261
city: Ivano-Frankivs'k
country: Ukraine
facility: Site 5258
city: Kharkiv
country: Ukraine
facility: Site 5256
city: Kharkiv
country: Ukraine
facility: Site 5254
city: Kherson
country: Ukraine
facility: Site 5255
city: Kyiv
country: Ukraine
facility: Site 5263
city: Kyiv
country: Ukraine
facility: SIte 5252
city: Kyiv
country: Ukraine
facility: Site 5251
city: Kyiv
country: Ukraine
facility: Site 5265
city: Poltava
country: Ukraine
facility: Site 5259
city: Vinnytsya
country: Ukraine
facility: Site 5260
city: Zaporizhzhya
country: Ukraine
facility: Site 5253
city: Zaporizhzhya
country: Ukraine
facility: Site 5257
Study officials:
affiliation: Nabriva Therapeutics AG
name: Leanne Gasink, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.