A PHASE 3, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, COMPARATOR-CONTROLLED STUDY TO EVALUATE THE SAFETY AND EFFICACY OF INTRAVENOUS TO ORAL DELAFLOXACIN IN ADULT SUBJECTS WITH COMMUNITY-ACQUIRED BACTERIAL PNEUMONIA

• Register: RPEC
• Last refreshed on: 4 September 2023
• Main ID: PER-016-17
• Date of registration: 26/07/2017
• Prospective Registration: Yes
• Primary sponsor: Melinta Therapeutics, Inc.,
• Public title: A PHASE 3, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, COMPARATOR-CONTROLLED STUDY TO EVALUATE THE SAFETY AND EFFICACY OF INTRAVENOUS TO ORAL DELAFLOXACIN IN ADULT SUBJECTS WITH COMMUNITY-ACQUIRED BACTERIAL PNEUMONIA
• Scientific title: A PHASE 3, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, COMPARATOR-CONTROLLED STUDY TO EVALUATE THE SAFETY AND EFFICACY OF INTRAVENOUS TO ORAL DELAFLOXACIN IN ADULT SUBJECTS WITH COMMUNITY-ACQUIRED BACTERIAL PNEUMONIA
• Date of first enrolment: 04/09/2017
• Target sample size: 25
• Recruitment status: Complete
• URL: https://www.ins.gob.pe/ensayosclinicos/rpec/recuperarECPBNuevoEN.asp?numec=016-17
• Study type: Interventional
• Study design: Subjects who meet the entry criteria will be randomly assigned in a 1:1 ratio to receive delafloxacin or moxifloxacin. Randomization will be stratified by PORT Class, medical history of chronic obstructive pulmonary disease (COPD)/asthma, and prior systemic antimicrobial use. Enrollment will be limited to no more than 25% Port Class II and no more than 25% of subjects with prior antibacterial use.; Subjects will be randomized to receive either IV delafloxacin 300 mg every 12 hours (BID), with an option to switch to oral delafloxacin 450 mg BID; or IV moxifloxacin 400 mg every 24 hours (QD), with an option to switch to oral moxifloxacin 400 mg QD for the remaining doses. Subjects randomized to receive IV moxifloxacin 400 mg QD will receive alternating IV placebo QD to preserve the double blind nature of the study, such that all randomized subjects will receive an IV infusion on a BID basis.; The investigator may elect to switch subjects from moxifloxacin/moxif
• Phase: III

Countries of recruitment

Argentina, Australia, Belarus, Brazil, Bulgaria, Canada, Chile, Colombia, Dominican Republic, Georgia, Germany, Hungary, Latovia, Mexico, Modalvia, New Zealand, Peru, Poland, Romania, Russian Federation, Serbia, Slovenia, South Africa, Spain, Ukraine, United States

Contacts

• Name: Cecilia Dignani
• Affiliation: PSI CRO Peru S.A.C.

• Name: Eugenia Paez
• Affiliation: PSI CRO Peru S.A.C.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male and female subjects 18 years of age or older.
• Patients from a nursing home setting may be enrolled if they are normally ambulatory and are not on enteral feeding
2. Evidence of acute onset of CABP.
Subjects must have at least 2 of the following clinical signs and symptoms (new or worsening):
• Cough
• Production of purulent sputum consistent with a bacterial infection
• Difficulty breathing (dyspnea)
• Chest pain due to pneumonia
AND
Subjects must also have at least 2 of the following findings:
• Fever (oral temperature > 38°C or equivalent) within 24 hours prior to randomization
• Hypothermia (oral temperature < 35°C or equivalent) within 24 hours prior to randomization
• Tachycardia (> 100 beats per minute)
• Tachypnea (elevated respiratory rate >18 breaths per minute)
AND
Subjects must also have at least 1 of the following findings:
• Hypoxemia (oxygen saturation < 90% or PaO2 < 60 mmHg on room air or with subject’s baseline [pre-CABP under study] supplemental oxygen flow rate)
• Clinical evidence of pulmonary consolidation and/or presence of pulmonary rales
• An elevated white blood cell count (WBC) > 10,000/mm3 or 15% immature neutrophils (bands), regardless of total peripheral WBC count or leukopenia with WBC < 4500/mm3
3. Presence of lobar, multilobar, or patchy parenchymal infiltrate(s) consistent with acute bacterial pneumonia on a pulmonary imaging study (e.g., chest radiograph [CXR] [posteroanterior and lateral preferred; single view acceptable if conclusive] or computed tomography [CT] of thorax) as per local standard of care within 48 hours before the first dose of study drug.
4. PORT risk class of II, III, IV, or V PSI score (greater than 50). Subjects may be initially screened based on meeting CURB-65 score of 2 to 4. PORT risk class II will be limited to 25% of randomized subjects.
5. In the opinion of the investigator, the subject must be a suitable candidate for possible IV to oral switch antibiotic therapy and must also be able to swallow large tablets/capsules intact without crushing.
6. Females of childbearing potential (including females less than 2 years post-menopausal) must have a negative pregnancy test prior to enrollment. Sexually active women and men with partners of childbearing potential must agree to use an acceptable form of contraception, as determined by the investigator (e.g., abstinence, oral contraceptives, double barrier methods, hormonal injectable, transdermal, or implanted contraceptives, tubal ligation, or vasectomy) during participation in the study and through the Follow-up Visit (Day 28). Female partners of male subjects should also use an additional reliable method of contraception, such as spermicide with male or female condoms, cervical sponge, intrauterine device, cervical cap or diaphragm, or oral, implantable, transdermal, or injectable contraceptives during study and through the Follow-up Visit (Day 28).
7. In the opinion of the investigator, the subject must be able and willing to comply with protocol requirements.
8. A written, voluntarily signed informed consent must be obtained from the subject or where allowed by local regulations, legally authorized representative, in accordance with local regulations, before the initiation of any study-related procedures. The subject or legally authorized representative must be able to read and/or understand the informed consent form
Exclusion criteria:
1. Medical history of significant hypersensitivity or allergic reaction to antibiotics of the quinolone or oxazolidinone class or study drug excipients according to the judgment of the investigator.
2. Women who are pregnant or lactating.
3. Any infection expected to require other systemic antibacterial agents in addition to study drug.
4. Receipt of systemic antibiotic therapy in the 7 days before enrollment unless one of the following is documented:
• The subject received at least 48 hours of antibiotic therapy for CABP and the clinic notes document treatment failure (i.e., not by patient history or pulmonary imaging alone) with new or worsening symptoms while on pre-study therapy or identification of a respiratory pathogen that is resistant to a pre-study antibiotic, which would be susceptible to study drug (delafloxacin or moxifloxacin) in subjects with new or worsening signs and symptoms of CABP.
• The subject received 1 dose of a single, potentially effective, short-acting antimicrobial drug or a short-acting antimicrobial drug regimen for treatment of the CABP under study within 24 hours of enrollment. (Note: 1 dose of a regimen is defined as the standard therapy for CABP at the study site.) Subjects who received prior antimicrobial drug under this criterion will be limited to no more than 25% of total randomized subjects.
5. Respiratory infection confirmed or suspected to be secondary to hospital-acquired or ventilator-associated pneumonia or that requires treatment in an intensive care setting at the time of informed consent.
6. Intubated at the time of informed consent or clinical presentation with pneumonia that would require invasive mechanical ventilation.
7. Current or suspected diagnosis of:
• Viral pneumonia, fungal pneumonia, including Pneumocystis jiroveci pneumonia
• Aspiration pneumonia
• Other noninfectious causes of pulmonary infiltrates (e.g., pulmonary embolism, hypersensitivity pneumonia, congestive heart failure)
• Primary or metastatic lung cancer
• Cystic fibrosis
• Active or suspected tuberculosis
• Empyema (not including sterile parapneumonic effusions)
8. Known anatomical or pathological bronchial obstruction or a history of bronchiectasis or documented Global initiative for chronic Obstructive Lung Disease (GOLD) Stage 4 chronic obstructive pulmonary disease or a history of post obstructive pneumonia.
9. Severely compromised immune system, e.g.:
• Known absolute neutropenia (absolute neutrophil count < 500 cells/µL)
• Known human immunodeficiency virus infection (HIV) with a CD4 count < 350 cells/µL within the last 4 months
• Cancer chemotherapy or radiation in the last 3 months
• Hematological malignancy
• Bone marrow transplantation
• Chronic steroid use (> 20 mg prednisone per day or equivalent) prior to enrollment
10. Known history of Child-Pugh Class B or C liver disease and/or presence or possible signs of significant hepatic disease or alanine aminotransferase (ALT) > 3× the upper limit of normal (ULN).
11. Severe renal disease or creatinine clearance (CrCl) ≤ 29 mL/min using Cockcroft-Gault formula or need for hemodialysis or peritoneal dialysis.
12. Uncorrected hypokalemia or known uncorrected hypomagnesemia at time of enrollment.
13. Ongoing treatment for seizures or untreated history of seizures.
14. History of peripheral neuropathy.
15. History of tendon damage/disord

Age minimum:
Age maximum:
Gender: --

Health Condition(s) or Problem(s) studied

Bacterial pneumonia, unspecified

J159

-J159 Bacterial pneumonia, unspecified
Bacterial pneumonia, unspecified

Intervention(s)

Delafloxacin 300 mg will be administered as a 1-hour IV infusion every 12 hours (± 2 hours) for a minimum of 6 doses with an option to switch to delafloxacin 450 mg tablet administered orally every 12 hours (± 2 hours) for the remaining doses.
Moxifloxacin 400 mg will be administered as a 1-hour IV infusion every 24 (± 2 hours) hours for a minimum of 3 active doses with an option to switch to moxifloxacin 400 mg (over-encapsulated tablet) administered orally every 24 hours (± 2) for the remaining doses.
At local investigator discretion, subjects in the moxifloxacin arm with confirmed MRSA, in place of remaining moxifloxacin doses, can receive linezolid 600 mg administered as a 1-hour IV infusion every 12 hours (± 2 hours) for the remaining doses.
Each site will document a blinding plan prior to study start. All blinded IV dosing will be maintained with a 12-hour schedule. IV bags will be blinded.
Subjects in the moxifloxacin arm, when on IV therapy, will receive once-daily active therapy via alternating doses of IV moxifloxacin and IV placebo every 12 (± 2) hours.
Subjects in the delafloxacin arm, when on oral therapy, will receive oral placebo moxifloxacin QD or IV placebo linezolid BID to maintain blinding.
Subjects in the moxifloxacin/linezolid arm, when on oral therapy or when meet criteria for oral therapy, will receive placebo delafloxacin oral formulation to maintain blinding.

Secondary ID(s)

2015-003026-14

NCT02679573

Source(s) of Monetary Support

Melinta Therapeutics, Inc.

Ethics review

Status: Approved
Approval date: 09/03/2017
Contact:

[e-mail]

Hospital Nacional Arzobispo Loayza

88339014 - 3301677

[e-mail]

Status: Approved
Approval date: 16/03/2017
Contact:

[e-mail]

Hospital Nacional Dos de Mayo

3280028

[e-mail]

Status: Approved
Approval date: 28/03/2017
Contact:

[e-mail]

Comite Institucional de Etica en Investigacion de la Asociacion Benefica Prisma

616-5500 Anx. 246

[e-mail]

Status: Approved
Approval date: 06/04/2017
Contact:

[e-mail]

Hospital Cayetano Heredia

97254626

[e-mail]

Results

• Results available: Yes
• Date Completed: 06/08/2018