Community-Acquired Bacterial Pneumonia MedDRA version: 19.0 Level: LLT Classification code 10010120 Term: Community acquired pneumonia System Organ Class: 100000004862
Conditions
Interventions
Product Name: Nafithromycin
Product Code: WCK 4873
Pharmaceutical Form: Tablet
INN or Proposed INN: Nafithromycin
CAS Number: 1395044-49-1
Current Sponsor code: WCK 4873
Other descriptive name: WCK 4
Sponsors
Wockhardt Bio AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female = 18 years of age 2. Willing to participate in the study and provide written informed consent before any protocol specific assessment is performed 3. Meet the following clinical criteria for CABP: a. Have at least TWO of the following symptoms (new or worsening): • Dyspnea (shortness of breath) • Cough • Production of purulent sputum • Pleuritic chest pain b. Have at least TWO of the following vital sign abnormalities: • Fever or hypothermia documented by the Investigator (oral, rectal, or tympanic temperature > 38.0°C [100.4°F] or 90 beats per minute • Tachypnea, defined as respiratory rate > 20 breaths per minute c. Have at least ONE of the following laboratory abnormalities: • Hypoxemia defined as arterial oxygen saturation 10,000 cells/mm3) or leucopenia (WBC 15% band forms), regardless of total peripheral WBC count d. Radiographic evidence of CABP: • Radiographically-confirmed pneumonia, i.e., new or progressive pulmonary infiltrate(s) on CXR or CT scan consistent with acute bacterial pneumonia within 48 h prior to randomization e. PORT score of 51 to 105 (PORT Risk Class of II, III or IV) (Appendix II) 4. All females must have a negative urine or serum pregnancy test (ß-HCG) at Screening AND agree to the use of one of the following acceptable methods of contraception from Screening through TOC: surgical sterilization (defined as bilateral oophorectomy or bilateral salpingectomy, but excluding bilateral tubal occlusion), post-menopausal (defined by amenorrhea for at least 12 months following cessation of all exogenous hormonal treatments), barrier contraception (e.g., condom, intrauterine device), levonorgestrel intrauterine system (e.g., Mirena®), regular medroxyprogesterone injections (e.g., Depo-Provera®), sexual intercourse with only vasectomised partners, or abstinence. Note that oral contraceptives should not be used as the sole method of birth control because the effect of nafithromycin on the efficacy of oral contraceptives has not yet been established; subjects who take oral contraceptives must also use one of the acceptable forms of birth control (listed above) from Screening through TOC. Males must agree to use an acceptable barrier method of birth control (i.e., condom) with female partner(s) and must not donate sperm from Screening through TOC. 5. Ability to ingest oral study drug (e.g., able to swallow large capsules intact, and no significant nausea, vomiting, diarrhea, or any other condition that might impair ingestion or absorption of oral study drug) 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 203 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 22
Exclusion criteria
Exclusion criteria: 1. Subjects with any of the following confirmed or suspected types of pneumonia: • Aspiration pneumonia • HABP, defined as pneumonia with onset of clinical signs and symptoms after at least 48 h hospitalization in an acute in-subject health care facility. • HCAP, defined as pneumonia acquired in a long-term care or subacute healthcare facility or pneumonia with onset after recent hospital discharge (within 90 days of current admission and previously hospitalized for = 48 h) • VABP, defined as pneumonia with onset of clinical signs and symptoms after at least 48 h endotracheal intubation • Pneumonia that may be caused by pathogen(s) resistant to either study drug (nafithromycin or moxifloxacin), including viral, mycobacterial, or fungal pneumonia • Post-obstructive pneumonia • Pneumonia associated with cystic fibrosis 2. Suspected or confirmed pleural empyema (a parapneumonic pleural effusion is not an exclusion criterion) or lung abscess 3. Suspected or confirmed non-infectious causes of pulmonary infiltrates 4. Receipt of 1 or more dose(s) of a potentially-effective systemic antibacterial treatment for treatment of the current CABP within 72 h prior to randomization with the exception of: • Receipt of a single dose of a short-acting antibacterial agent within 72 h of randomization OR • Failure (worsening of symptoms) of at least 48 h of treatment for the current episode of CABP with an antibacterial agent other than a ketolide or fluoroquinolone 5. Subjects requiring concomitant adjunctive or additional potentially effective systemic antibacterial treatment for management of CABP 6. Evidence of significant immunologic disease determined by any of the following: • Current or anticipated neutropenia defined as 2 times ULN (unless associated with an elevated indirect bilirubin typical of Gilbert syndrome), AST or ALT > 3 times ULN, serum creatinine > 2.0 mg/dl and/or BUN > 30 mg/dl. Other clinically-significant abnormal laboratory findings should be discussed with the Medical Monitor prior to the subject's entry. 9. History of Clostridium difficile-associated disease within 6 months prior to enrolment 10. History of hypersensitivity, known contraindication (e.g. lactose intolerance,lactase deficiency and glucose
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: · To assess the overall safety and tolerability of oral nafithromycin; · To assess the clinical response in the ITT population at Day 4;;Secondary Objective: · To assess the clinical response in the micro-ITT population at Day 4; · To assess the clinical outcome in the ITT and CE populations at EOT and TOC; · To assess early improvement in clinical symptoms and normalization of vital signs in the ITT population at Day 4; · To assess clinical outcome in micro-ITT population at TOC; · To assess by-subject and by-pathogen microbiological response in micro-ITT and ME populations at TOC; · To assess readmission to the hospital (or admission to the hospital if not previously hospitalized) for any reason prior to FU;Primary end point(s): · Clinical Response at Day 4 in the ITT population ;Timepoint(s) of evaluation of this end point: Response at Day 4 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): · Clinical Response at Day 4, as described above, in the micro-ITT population · Clinical Outcome at EOT (ITT and CE populations) and TOC (ITT, CE, and micro-ITT populations) · Improvement in CABP Symptoms and Normalization in Vital Signs at Study Day 4 (ITT population) · Hospitalization Prior to FU (ITT population): Hospital readmission for any reason between Day 1 and FU Visit, if previously hospitalized and discharged, or initial hospital admission for any reason between Day 2 and FU Visit, if not previously hospitalized on Day 1 Safety Endpoints: Safety evaluation is based on TEAEs, clinical laboratory evaluation, vital signs, physical examination findings and electrocardiograms (ECGs) collected during the study.;Timepoint(s) of evaluation of this end point: Response at Day 4, Day 7 or within 2 days following Day 7 (EOT), Day 15 ±3 days (TOC) Time points for PK sample collection will be: · Pre-dose: pre-dose PK sample will be collected within 10 minutes before dosing. · Post-dose at 2-4 h (Day 3) and 24-28 h (Day 4). Subjects who have been hospitalized are also required to have a post-dose PK sample at 6-10 h (Day 3). FU is to be conducted on Day 31 ±3 days | — |
Countries
Bulgaria, Georgia, Latvia, Romania, Russian Federation, Serbia, South Africa, United States
Contacts
Public ContactAssociate VP, Piotr Iwanowski, MD,
Wockhardt
Outcome results
None listed