| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Acute bacterial skin and skin structure infections (ABSSSI). |
|
| E.1.1.1 | Medical condition in easily understood language |
| Acute Bacterial Skin and Skin Structure Infections (ABSSSI) |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10052891 |
| E.1.2 | Term | Skin bacterial infection |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| 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 |
| The primary objective is to use descriptive statistics to evaluate the safety of intravenous (IV) and/or oral 6- to 10-day tedizolid phosphate with 10- to 14-day IV and/or oral comparator in subjects from birth to <12 years of age with acute bacterial skin and skin structure infections (ABSSSI). No formal hypothesis tests will be used to evaluate this endpoint. |
|
| E.2.2 | Secondary objectives of the trial |
| To use descriptive statistics to evaluate investigator’s assessment of clinical response in the tedizolid phosphate and comparator groups at the test-of-cure (TOC) visit on Day 25 in the intention to treat (ITT) and clinically evaluable at TOC (CE-TOC) populations. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Have a parent/legally acceptable representative (LAR) who is able to give documented informed consent and willing and able to comply with all required study procedures . Assent is required of subjects who in the investigator’s judgment are capable of understanding the nature of the study.
2. Be male or female from birth to < 12 years of age at the time of consent. Preterm neonates should have a gestational age of at least 26 weeks at birth.
3. Have adequate venous access for collection of protocol-specified samples and administration of study drug (for subjects receiving IV study medication)
4. Have ABSSSI, defined by meeting the definition of at least 1 of the following 3 clinical syndromes:
a. Cellulitis/erysipelas defined as a diffuse skin infection, characterized as defined in the protocol
b. Major cutaneous abscess, defined as an infection characterized by a collection of pus apparent upon visual examination within the dermis or deeper that is accompanied by all conditions defined in the protocol
c. Wound infection, defined as an infection characterized by purulent drainage from a wound with surrounding erythema, edema, and induration (EEI); and is further defined by the conditions defined in the protocol
5. Have local symptoms of ABSSSI that started within 7 days before Study Day -1
6. Have a suspected or documented gram-positive infection from baseline Gram stain or culture. Specimens for culture are required for abscesses and wounds at the Screening Visit; specimens for cellulitis are to be collected according to standard practice at the site. Note: the microbiological sample must have been collected using a valid sampling technique, such as an aspirate, biopsy, incision, deep swab, etc. A superficial swab is not acceptable.
7. Have body weight ≥ 3.2 kg for children from 28 days to <12 years old; for children under 28 days old, weight eligibility criterion will be updated in future amendment. |
|
| E.4 | Principal exclusion criteria |
1. Has an uncomplicated skin and skin structure infection such as furuncles, minor abscesses (area of suppuration not surrounded by cellulitis/erysipelas), impetiginous lesions, superficial or limited cellulitis/erysipelas, and minor wound -associated foreign body reactions (e.g., stitch abscesses)
2. Has ABSSSI due to or associated with any of the conditions listed in the protocol
3. Has received antibacterial therapy for treatment of the current episode of ABSSSI unless:
• ≤ 24 hours of effective antibacterial drug therapy with a short-acting antibacterial drug (defined as administration frequency of 1 or more doses per 24 hours)
OR
• Response to prior antibacterial therapy for the primary infection site of ABSSSI is considered by the investigator to be failure (no improvement in signs and symptoms [e.g., fever, pain, tenderness, lesion size increase]) after at least 48 hours of therapy
4. Has topical antibacterial applied and remaining on the primary lesion > 24 hours prior to randomization, except for antibiotic/antiseptic-coated dressing applied to a clean postsurgical wound
5. Has known bacteremia, severe sepsis, or septic shock at the Screening Visit
6. Has significant or life-threatening condition, disease, or organ system condition (e.g., endocarditis, meningitis)
7. Has recent history of opportunistic infections where the underlying cause of these infections is still active (e.g., leukemia, transplant, acquired immunodeficiency syndrome), or is suspected to be at risk of opportunistic infections or infection with unusual pathogens (e.g., primary immune deficiency, cystic fibrosis)
8. Has received or is receiving treatment for active tuberculosis (within 1 month)
9. Has known or suspected severe neutropenia (absolute neutrophil count [ANC] <1000 cells/mm3)
10. Is human immunodeficiency virus (HIV) positive and has known or suspected CD4 cell count < 15%
11. Has renal impairment that requires peritoneal dialysis, plasmapheresis, hemodialysis, venovenous dialysis, or other forms of renal filtration
12. Has known or suspected severe hepatic impairment
13. Has cardiac or electrocardiogram (ECG) finding which in the opinion of the investigator would limit the subject’s ability to complete and/or participate in this clinical study. For neonates, an ECG is not required, but ECG data will be collected if available.
14. Has received investigational medicinal product within 30 days before the first administration of study drug. (Investigational product in this case refers to a product that is not approved in the country in which the subject is enrolled, for either adults or children, for any indication.)
15. Has an investigational device present or removed within 30 days before the first administration of study drug or presence of device-related infection
16. Was previously treated in tedizolid phosphate clinical studies (including this protocol)
17. Has contraindication, including hypersensitivity to tedizolid phosphate, other oxazolidinones, or any component in the formulation
18.Has contraindication, including hypersensitivity to all available comparator drugs.
19.Has a wound infection, and meets either of the conditions listed in the protocol
20. Needs oral administration of methotrexate, topotecan, irinotecan, or rosuvastatin, during administration of oral study drug (administration during the follow-up period, ie, after the EOT Visit, is allowed, as is administration during treatment with IV study drug).
21. Is a female who is pregnant or nursing, or who is of childbearing potential and not abstinent or a male who is not abstinent
22. Has circumstances, including those of parent(s)/legal guardian(s), that make adherence to the protocol, compliance with study drug administration, or completion of the study unlikely
23. Is or has an immediate family member (e.g., spouse, parent/legal guardian or sibling) who is investigational site or sponsor staff directly involved with this trial
24.Uses monoamine oxidase inhibitors, tricyclic antidepressants, buspirone, selective serotonin reuptake inhibitors, and serotonin 5 hydroxytryptamine receptor agonists (triptans) within 14 days prior to study drug administration
25. Is identified as having used illicit drug(s) (urine drug screening not required for entry).
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoint is the overall safety assessment of tedizolid phosphate within the pediatric population. Multiple assessments are conducted to evaluate the safety:
1. Adverse events;
2. Vital signs;
3. Physical exams including specific neurological and visual acuity assessments;
4. Hematology and clinical chemistry. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
At each scheduled visits until the Late follow up
|
|
| E.5.2 | Secondary end point(s) |
| The investigator’s assessment of clinical response at the TOC visit, 22-29 days after the first infusion, in the Intent to Treat (ITT) and Clinically Evaluable at Test of Cure (CE-TOC) populations; |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| At TOC (Test of Cure) which is about 22-29 days after the first dose. |
|
| 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 | No |
| 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 | Yes |
| E.8.1.4 | Double blind | No |
| 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 | No |
| 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 | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 17 |
| 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 |
| Brazil |
| Georgia |
| Guatemala |
| Mexico |
| Russian Federation |
| South Africa |
| Turkey |
| Ukraine |
| United States |
| Bulgaria |
| Germany |
| Latvia |
| Lithuania |
| Poland |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
