E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Community-Acquired Bacterial Pneumonia (CABP) |
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E.1.1.1 | Medical condition in easily understood language |
Pneumonia acquired infectiously from normal contact |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010120 |
E.1.2 | Term | Community acquired pneumonia |
E.1.2 | System Organ Class | 100000004862 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
•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.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 < 36.0°C [95.5°F]) • Hypotension with SBP < 90 mm Hg • Heart rate > 90 beats per minute (bpm) • RR > 20 breaths/minute 5. Has at least 1 clinical sign or laboratory finding associated with CABP: • Hypoxemia (PaO2 < 60 mm Hg by ABG or oxygen saturation < 90% by pulse oximetry) • Physical examination findings of pulmonary consolidation (eg, dullness on percussion, bronchial breath sounds, or egophony) • An elevated total white blood cell (WBC) count (> 12,000 cells/mm3) or leucopenia (WBC < 4,000 cells/mm3) or elevated immature neutrophils (> 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.
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E.4 | Principal 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. 15.Known or suspected primary or metastatic neoplastic lung disease, aspiration pneumonia, active tuberculosis, cystic fibrosis, bronchiectasis, bronchial obstruction , chronic neurological disorder preventing clearance of pulmonary secretions, or severe COPD ). 16.Pregnant or nursing (breastfeeding) women. 17.Has a history of hypersensitivity or allergy (eg, anaphylaxis, urticaria, other significant reaction) to any tetracycline (eg, minocycline, doxycycline or tigecycline) or to any fluoroquinolone or any component of the IMP or comparator. 18.Has a history of pseudotumor cerebri, or prior (within 2 weeks prior to Screening) or planned concomitant use of isotretinoin. 19.Has a history of systemic lupus erythematosus or lupus-like syndrome. 20.History of lactose intolerance, lactase deficiency, or glucose-galactose malabsorption. 21.Has current evidence of pancreatitis. 22.Use of other investigational drugs within 5 half-lives or 30 days prior to Screening, whichever is longer. 23.Has previously been treated with omadacycline or previously enrolled in this study. 24.Any planned medical intervention that might interfere with the ability to comply with the study requirements. 25.Has a life expectancy of less than or equal to 3 months or any concomitant condition that, in the opinion of the investigator, is likely to interfere with evaluation of the response of the infection under study, determination of AEs, or completion of the expected course of treatment.
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E.5 End points |
E.5.1 | 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.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
•CR Success (72 to 120 hours after first dose) -Clinical Success at the PTE visit
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E.5.2 | 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. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Clinical success at the PTE visit |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Ukraine |
Bulgaria |
Croatia |
Georgia |
Hungary |
Poland |
Russian Federation |
Serbia |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The study will be completed when the last subject has either discontinued or completed the final Follow-up assessment. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |