Community-Acquired Bacterial Pneumonia (CABP) MedDRA version: 20.1 Level: LLT Classification code 10010120 Term: Community acquired pneumonia System Organ Class: 100000004862
Conditions
Interventions
Product Name: Omadacycline
Product Code: PTK0796
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: OMADACYCLINE
CAS Number: 389139-89-3
Current Sponsor code: P
Sponsors
Paratek Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written and signed informed consent must be obtained before any protocol specific assessment is performed. 2. Male or female, aged 18 years or older. 3. Has at least 3 of the following symptoms: • Cough • Production of purulent sputum • Dyspnea (shortness of breath) • Pleuritic chest pain 4. Has at least TWO of the following abnormal vital signs: • Fever or hypothermia documented by the investigator (temperature > 38.0°C [100.4°F] or 90 beats per minute (bpm) • RR > 20 breaths/minute 5. Has at least 1 clinical sign or laboratory finding associated with CABP: • Hypoxemia (PaO2 12,000 cells/mm3) or leucopenia (WBC 15% band forms) (regardless of total peripheral WBC count) 6. Has disease categorized as being PORT Risk Class III or IV at Screening (see PORT Risk Class calculation in Appendix 5). 7. Radiographically-confirmed pneumonia, ie, new or progressive pulmonary infiltrate(s) on chest X-ray (CXR) or chest computed tomography (CT) scan consistent with acute bacterial pneumonia within 48 hours prior to the first dose of test article. 8. Is expected to require a minimum of at least 2 days of iv therapy for the initial treatment of CABP. 9. Females must have a negative pregnancy test at Screening and agree to comply with using an acceptable method of birth control as per your local requirements (eg, abstinence, po contraceptive, intrauterine device [IUD], barrier contraception [condom], tubal ligation, hysterectomy, bilateral oophorectomy, postmenopausal or vasectomized partner) from Screening through PTE. Males must agree to use an acceptable method of birth control with female partner(s) and must not donate sperm from Screening through PTE. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 670 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 670
Exclusion criteria
Exclusion criteria: 1.Has received 1 or more dose(s) of a potentially effective systemic antibacterial treatment within the 72 hours prior to the first dose of IMP(a subject will be considered to have received a potentially effective systemic antibacterial treatment if the pathogen identified as causing infection is shown to be susceptible to the antibacterial given or, in the circumstance where a pathogen is not identified, if the antibacterial agent is approved for treatment of pneumonia or is known to have activity against any of the leading causes of CABP [eg, S. pneumoniae, H. influenzae, M.catarrhalis, S. aureus, L. pneumophila]). 2.Is known or suspected to have CABP caused by a pathogen that may be resistant to either test article (eg, P. aeruginosa, Proteus spp., M. morganii, Providencia spp., P. jiroveci, obligate anaerobes, mycobacteria, fungal pathogens). 3.Suspected or confirmed empyema or lung abscess. 4.Confirmed or suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection based on local SoC assessments. 5.Subjects who reside in a long-term care or subacute/intermediate healthcare facility or a subject with pneumonia following a recent hospitalization. 6.Has a known history of having experienced unstable cardiac disease within the 3 months prior to Screening or presents with a tachyarrhythmia (excl sinus tachycardia). 7.Has a QT interval corrected for heart rate using Fridericia’s formula (QTcF) > 450 msec (males) or > 470 msec (females), are known to have long QT syndrome, use drugs of potential proarrhythmic or QT prolonging effect. 8.Has other contraindications to receiving a systemic fluoroquinolone antibiotic, including confirmed or suspected peripheral neuropathy, tendon disorder, myasthenia gravis, cirrhosis, aortic aneurysm, or central nervous system (CNS) disorder that may predispose to seizures or lower the seizure threshold. 9.History or evidence of severe renal disease or has a calculated creatinine clearance (CrCl) of < 30 mL/minute, using the Cockcroft-Gault equation . Requires dialysis (eg, hemodialysis, peritoneal dialysis). 10.Significant immunological disease determined by any of the following: •Current or anticipated neutropenia defined as < 500 neutrophils/mm3 •Known infection with HIV and a cluster of differentiation 4 (CD4) count that is unknown or documented to be < 200 cells/mm3 within the last year, or an AIDS-defining illness 11.Cancer chemotherapy, radiotherapy, or potent, non-corticosteroid immunosuppressant drugs within the past 3 months, or the receipt of corticosteroids equivalent to or greater than 40 mg of prednisone per day or for more than 14 days in the prior 30 days (. Exception: Systemic corticosteroids added within 24 hours of randomization or after randomization as adjunctive therapy for the current episode of CABP is allowed. 12.Requires acute pharmacologic intervention to stabilize BP and/or adequate tissue perfusion OR meets septic shock criteria (ALL): •Meets at least 2 criteria for sepsis as defined by the quick Sequential Organ Failure Assessment (qSOFA) score: (a) Altered mental status with Glasgow Coma Scale (GCS) < 15, (b) RR = 22 breaths per minute, and (c) SBP = 100 mmHg •Despite adequate fluid resuscitation, persistent hypotension requiring vasopressors to maintain mean MAP = 65 mmHg. •Serum lactate = 2 mmol/L 13.PORT Risk Class I, II, and V patients. 14.Requires or expected to require Intensive Care Unit admittance or invasive or non-invasive ventilation. 1
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate that iv to po omadacycline is non-inferior to iv to po moxifloxacin in the treatment of adults with PORT Risk Class III and IV CABP.;Secondary Objective: •To evaluate the safety of omadacycline in the treatment of adult subjects with CABP in the Safety population. •To evaluate the Clinical Response according to the identified causative pathogen. •To evaluate the pharmacokinetics (PK) of omadacycline in adult subjects with CABP. ;Primary end point(s): - ECR Success (72 to 120 hours after first dose) will be determined programmatically and defined as survival with improvement in at least 2 of 4 subject symptoms (cough, sputum production, pleuritic chest pain, dyspnea), as assessed by the investigator, without deterioration in any of these 4 symptoms. - Investigator’s Assessment of Clinical Success at the PTE visit, defined as survival after completion of a test article regimen, with resolution of signs and symptoms of the infection to the extent that further antibacterial therapy is not necessary. Assessment of signs and symptoms of CABP by the investigator. ;Timepoint(s) of evaluation of this end point: •CR Success (72 to 120 hours after first dose) -Clinical Success at the PTE visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Assessment of signs and symptoms of CABP by the investigator. • Microbiological assessment of the infection. • Patient reported outcome assessment. • Clinical stability.;Timepoint(s) of evaluation of this end point: Clinical success at the PTE visit | — |
Countries
Bulgaria, Croatia, Georgia, Hungary, Poland, Russian Federation, Serbia, Ukraine
Contacts
Public ContactChief Development and Regulatory
Paratek Pharmaceutical Inc.
Outcome results
None listed