Study to compare how the safety and efficacy of Omadacycline compares to Linezolid in the treatment of adult subjects with skin Infections.

• Register: EUCTR
• Last refreshed on: 13 June 2016
• Main ID: EUCTR2013-003644-23-LV
• Date of registration: 13/04/2015
• Prospective Registration: Yes
• Primary sponsor: Paratek Pharma LLC
• Public title: Study to compare how the safety and efficacy of Omadacycline compares to Linezolid in the treatment of adult subjects with skin Infections.
• Scientific title: A Phase 3 Randomized, Double-Blind, Multi-Center Study to Compare the Safety and Efficacy of Omadacycline IV/PO to Linezolid IV/PO for Treating Adult Subjects with Acute Bacterial Skin and Skin Structure Infection (ABSSSI)
• Date of first enrolment: 02/07/2015
• Target sample size: 650
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-003644-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria, Croatia, Germany, Greece, Hungary, Israel, Latvia, Lithuania, Mexico, Peru, Poland, Romania, Russian Federation, South Africa, Spain, Turkey, Ukraine, United States

Contacts

• Name: Head of Research and Development
• Affiliation: Paratek Pharma LLC

• Name: Head of Research and Development
• Affiliation: Paratek Pharma LLC

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written and signed informed consent must be obtained before any assessment is performed.
2. Male or female, age 18 years or older.
3. Has a qualifying skin and skin structure infection
4.Has evidence of a systemic inflammatory response within the 24 hours prior to randomization as indicated by ONE of the following:
- Elevated white blood cell (WBC) count (= 10,000 cells/mm3) or leukopenia (= 4,000 cells/mm3)
- Elevated immature neutrophils (= 15% band forms) regardless of total peripheral WBC count.
- Lymphatic involvement: lymphangitis or lymphadenopathy that is proximal to and in a location that suggests drainage from the qualifying infection
-Fever or hypothermia documented by the investigator (oral or rectal temperature > 38.0°C or < 36.0°C
5. Females of child-bearing potential who are less than 2 years post-menopausal must have a negative pregnancy test (beta-human Chorionic Gonadotropin [ß-hCG]) at Screening, and agree to comply with using a highly effective form of birth control (eg, abstinence, oral contraceptive, intrauterine device [IUD], barrier contraception [condom], tubal ligation, hysterectomy, bilateral oophorectomy, or vasectomized partner) from Screening through Post Therapy Evaluation (PTE). Males must use a highly effective method of birth control with female partner(s) and must not donate sperm from Screening through Post Therapy Evaluation (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 600
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion criteria:
1-Has received 1 or more doses of a potentially effective systemic antibacterial treatment within the 72 hour period prior to first dose of study drug.
2. Has, for any reason, used a topical antibacterial agent(s) with specific antibacterial activity (eg, mupirocin, retapamulin, fusidic acid) continuously within the 72 hour period prior to first dose of study drug, if applied to the skin for = 72 hours.
3. Infections where the outcome is strongly influenced by factors other than protocol-defined treatment and procedures, that require antibacterial treatment for greater than 14 days, are associated with chronic skin lesions that may obscure determination of response even after successful bacterial eradication has been achieved, or are suspected or known to be caused by a pathogen resistant to either study drug.
4. Has known or is clinically suspected for one or more of the following prior to randomization:
• Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) = 2 × Upper Limit of Normal (ULN),
• total bilirubin > 1.5 × ULN, or
• evidence of end-stage liver disease (eg, ascites, hepatic encephalopathy)
5. Has a known history of having experienced unstable cardiac disease (eg, unstable angina, myocardial infarction, congestive heart failure, cardiac arrhythmia, etc.) within the 3 months prior to screening.
6. Requires any form of dialysis (eg, hemodialysis, peritoneal dialysis).
7. History or evidence of severe renal disease or is known to have a calculated creatinine clearance (CrCl) of < 30 mL/min, using the Cockcroft-Gault equation.
8. Evidence of significant immunological disease
9. Requires acute pharmacologic intervention to stabilize blood pressure and/or adequate tissue perfusion, OR has evidence of septic shock.
10. Pregnant or nursing (breastfeeding) women.
11. Has a history of hypersensitivity or allergic reaction (eg, anaphylaxis, urticaria, other significant reaction) to any tetracycline (eg, minocycline, doxycycline or tigecycline) or to linezolid.
12. Has a history of pseudotumor cerebri, or prior (within 2 weeks prior to Screening) or planned concomitant use of isotretinoin.
13. Has a history of systemic lupus erythematosus or lupus-like syndrome.
14. Has current evidence of pancreatitis
15. Has received a monoamine oxidase inhibitor within 14 days prior to Screening (eg, phenelzine, isocarboxazid, selegiline, moclobemide; which are typically used to treat depression or Parkinson's Disease).
16. Use of other investigational drugs within 5 half-lives or within 30 days prior to Screening.
17. Has previously been treated with omadacycline or previously enrolled in this study.
18. Any planned medical intervention that might interfere with the ability to comply with the study requirements.
19. Has 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 adverse events, or completion of the expected course of treatment


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

Acute Bacterial Skin and Skin Structure Infection
MedDRA version: 18.1 Level: PT Classification code 10040872 Term: Skin infection System Organ Class: 10021881 - Infections and infestations

Intervention(s)

Product Name: Omadacycline
Product Code: PTK 0796
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Omadacycline
CAS Number: 1075240 43 5
Current Sponsor code: PTK 0796
Other descriptive name: Neopentyl aminomethylminocycline
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intravenous use

Product Name: Omadacycline
Product Code: PTK 0796
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Omadacycline;
CAS Number: 1075240 43 5
Current Sponsor code: PTK 0796
Other descriptive name: Neopentyl aminomethylminocycline
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Zyvox
Product Name: Linezolid
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Linezolid
CAS Number: 165800-03-3
Other descriptive name: LINEZOLID
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Trade Name: Zyvox
Product Name: Zyvox
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Linezolid
CAS Number: 165800-03-3
Other descriptive name: LINEZOLID
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 600-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: -Successful Early Clinical Response is evaluated at 48-72 hours after the first dose of study drug.
-Successful Investigator’s Assessment of Clinical Response assessment at the Post Therapy Evaluation (PTE) visit.

Primary end point(s): Primary efficacy outcome:
In order to satisfy different health authority requirements, the primary variables assessing efficacy will be tested with 2 response endpoints:
-Successful Early Clinical Response, defined as survival with a = 20% reduction of lesion size compared to Screening measurements without receiving any rescue antibacterial therapy.
-Successful Investigator’s Assessment of Clinical Response at the Post Therapy Evaluation (PTE) visit defined as survival after completion of a study drug regimen, with resolution or improvement of signs and symptoms of infection to the extent that further antibacterial therapy is not necessary

Main Objective: The primary objective of this study is to demonstrate that omadacycline 100 mg iv every 12 hours (q12h) for 2 doses, followed by 100 mg iv every 24 hours (q24h)/300 mg po q24h is non-inferior to linezolid 600 mg iv q12h/600 mg po q12h in the treatment of adults with ABSSSI known or suspected to be due to Gram-positive pathogens

Secondary Objective: • To evaluate the safety of omadacycline in the treatment of adult subjects with ABSSSI 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 ABSSSI

Secondary Outcome(s)

Secondary end point(s): 1-The number and percentage of subjects classified as a Clinical Success, Clinical Failure and Indeterminate by the Investigator’s Assessment at PTE in the modified intent-to-treat population (mITT) and Clinical Evaluable (CE) populations for each treatment group.
2-The number and percentage of subjects in each treatment group in each response category for Early Clinical Response for the micro-mITT population.
3-The number and percentage of subjects who are classified as a Clinical Success and Clinical Failure by the investigator at the PTE visit in the Microbiologically Evaluable (ME) population.
4-The number and percentage of subjects with an Early Clinical Response of success and an Investigator’s Assessment of Clinical Response at PTE of Clinical Success by pathogen (including Gram-negative causative pathogens and Methicillin-Resistant Staphylococcus aureus (MRSA) will be provided in the micro-mITT and ME populations.
5-All-cause mortality (ACM) in the ITT population.

Timepoint(s) of evaluation of this end point: 1-At PTE
2-At 48-72h first study dose
3-PTE
4-PTE
5- At 15 and 30 days after the first dose of study drug

Secondary ID(s)

PTK0796-ABSI-1108

Source(s) of Monetary Support

Paratek Pharma LLC