Study to compare the safety and efficacy of Omadacycline versus Levofloxacin for adults with acute pyelonephritis
- Conditions
- Acute PyelonephritisMedDRA version: 20.1Level: LLTClassification code 10001032Term: Acute pyelonephritisSystem Organ Class: 100000004862Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]
- Registration Number
- EUCTR2018-000037-13-LV
- Lead Sponsor
- Paratek Pharma, LLC, a wholly-owned subsidiary of Paratek Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 200
1.Written and signed informed consent must be obtained before any assessment is performed.
2.a. Females age 18-65 years.
b. Females age 18 years or older.
Inclusion 2a will be followed for first 100 subjects enrolled. Following an interim analysis, see adaptive design section for additional information, inclusion 2b may be allowed. An administrative memo will be issued to sites to formally notify them if/when Inclusion 2b will be followed. No subjects >65 years may be enrolled until an administrative memo is received and acknowledged by the investigator.
3. Clinical signs and symptoms of acute uncomplicated pyelonephritis with onset or worsening within 96 hours prior to randomization. Clinical signs and symptoms are defined as:
• Flank pain or costovertebral angle tenderness on physical examination plus at least one of the following:
- Chills or rigors or warmth associated with fever (oral, tympanic, rectal or core temperature > 38°C [> 100.4°F], which must be observed and documented by a health care provider), or
- Nausea or Vomiting
4. A clean-catch midstream urine sample with dipstick analysis positive (at least ++) for leukocyte esterase or pyuria (white blood cell [WBC] count > 10/µL in unspun urine or = 10 per high power field in spun urine sediment).
5. Female subjects must have a negative pregnancy test at Screening, and agree to comply with using an acceptable form of birth control (eg, abstinence, oral contraceptive, intrauterine device [IUD], barrier contraception [condom], tubal ligation, hysterectomy, bilateral oophorectomy, postmenopausal or vasectomized partner) from Screening through PTE.
6. Ability to communicate well with the investigator, to understand and comply with the requirements of the study.
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 170
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30
1. Pregnant or nursing (breastfeeding) women.
2. Receipt of any dose of a potentially therapeutic antibacterial agent from 72 hours prior to randomization until the first dose of test article.
3. Anticipated need for systemic antibacterial therapy other than test article during the study period.
4. Infection at baseline that in the Investigator’s judgment would require more than 10 days of antibacterial therapy.
5. Symptoms of AP present longer than 7 days prior to randomization.
6. Confirmed or suspected AP caused by a pathogen that is resistant to tetracyclines or fluoroquinolones, including infection caused by fungi or mycobacteria.
7. Known or suspected rapidly-progressing or life-threatening illness including septic shock. Septic shock can be identified using the clinical criteria of hypotension requiring vasopressor therapy to maintain mean arterial blood pressure of 65mmHg or greater and having a serum lactate level greater than 2 mmol/L after adequate fluid resuscitation.
8. Use of an indwelling urinary catheter, nephrostomy tubes or other indwelling urinary tract device within the 30 days prior to randomization.
9. Confirmed or suspected urinary retention from any cause, including neurogenic bladder or obstruction.
10. History of surgically modified or abnormal urinary tract anatomy (eg, bladder diverticula or redundant urine collection system).
11. Confirmed or suspected complete or partial obstruction of the urinary tract, or obstructive uropathy that is scheduled to be medically or surgically relieved during the study therapy period.
12. Confirmed or suspected renal disease or condition that, in the opinion of the investigator, may confound the assessment of efficacy, including but not limited to the following:
•Perinephric or intrarenal abscess
•Emphysematous pyelonephritis
•Chronic pyelonephritis, including xanthogranulomatous pyelonephritis
•Polycystic kidney disease
•Renal carcinoma
13. History of renal transplant or a surgically created intestinal conduit for urinary diversion.
14. Suspected or confirmed non-renal source of infection.
15. Confirmed or suspected vaginitis or sexually transmitted infection or lower UTI without symptoms/signs of AP.
16. Has any of the following at Screening:
• ALT or aspartate aminotransferase (AST) = 3 × Upper Limit of Normal (ULN)
• total bilirubin > 1.5 × ULN
• suspected or confirmed clinical evidence of end-stage liver disease (eg, ascites, hepatic encephalopathy)
17. History of unstable cardiac disease within the 3 months prior to randomization.
18. Significant immunological disease determined by any of the following:
•Current or anticipated neutropenia defined as less than 500 neutrophils/mm3
•Known infection with Human Immunodeficiency Virus (HIV) and a cluster of differentiation 4 (CD4) count that is unknown or documented to be less than 200 cells/mm3 within the last year, or other Acquired Immune Deficiency Syndrome (AIDS) defining illness as determined by the investigator.
19. Receipt of cancer chemotherapy, radiotherapy, or potent, non corticosteroid immunosuppressant drugs within the 3 months prior to randomization, or the receipt of systemic corticosteroids equivalent to or greater than 40 mg of prednisone per day (see equivalent corticosteroid doses in Appendix 2) or 40 mg of prednisone per day for more than 14 days in the 30 days prior to randomization.
20. History of hypersensitivity or allergic reaction to any tetracycline or fluoroquinolone antibiotic.
21. Inability
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy of intravenous (iv) and iv to oral (iv/po) dosing regimens of omadacycline and levofloxacin in the treatment of adults with Acute Pyelonephritis (AP);Secondary Objective: - To evaluate the safety of omadacycline in the treatment of adults with AP. <br>- To evaluate the pharmacokinetics (PK) of omadacycline in adults with AP.;Primary end point(s): The primary efficacy outcome is overall response at the Post Therapy Evaluation (PTE) Visit in the microbiological intent-to-treat (micro-ITT) population, which is a composite of per-subject microbiologic response and investigator’s assessment of clinical response.;Timepoint(s) of evaluation of this end point: PTE Visit
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Safety endpoints: all treatment-emergent adverse events (TEAEs).<br><br>Efficacy endpoints: the number and percentage of subjects with an overall response of success, failure and indeterminate at the EOT (micro-ITT and microbiologically evaluable (ME) populations) and PTE Visits will be determined by treatment group. ;Timepoint(s) of evaluation of this end point: Safety endpoints: at each Visit;<br><br>Efficacy endpoints: at the EOT and PTE Visits.