A study to evaluate the effectiveness, safety and the body's ability to absorb, distribute, metabolize and excrete Daptomycin compared to Vancomycin or nafcillin in children who suffer from infection of the bone or bone marrow due to bacteria

Phase 1

• Conditions: Acute Hematogenous Osteomyelitis Due to Gram-Positive Organisms; MedDRA version: 19.1Level: LLTClassification code 10009081Term: Chronic osteomyelitisSystem Organ Class: 100000004862; Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]; MedDRA version: 19.1Level: LLTClassification code 10046076Term: Unspecified osteomyelitisSystem Organ Class: 100000004862; MedDRA version: 19.1Level: LLTClassification code 10009091Term: Chronic osteomyelitis, site unspecifiedSystem Organ Class: 100000004862

• Registration Number: EUCTR2013-000864-28-EE
• Lead Sponsor: Cubist Pharmaceuticals LLC, an indirect wholly-owned subsidiary of Merck Sharp & Dohme Corp.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-08-04
• Last Update Posted: 6 February 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 144

Inclusion Criteria

1. Informed consent in writing from parent(s) or legally-acceptable representative(s) and, informed assent from subject (if age appropriate according to local requirements)
2. Male or female 1 year to < 18 years of age (subject must be randomized before 18th birthday). A stepwise approach will be implemented to gate enrollment as follows: enrollment will begin with children aged 2-17 years; after an external Drug Safety Monitoring Board (DSMB) review, enrollment will be broadened to 1-17 years.
3. Presence of suspected or confirmed AHO warranting hospitalization and IV antibacterial therapy
4.2 Confirmed (I, II and III) or suspected (I and III) presence of AHO meeting the following criteria:
I. Acute onset or worsening within =21 days before randomization of at least 2 of the following 7 clinical symptom parameters (organized into 3 general categories) such that at least 1 category will be present and if only 1 (Pain, Inflammation or Limb Function) category is present it needs to be of at least moderate severity.
• Pain
? Localized pain
? Point tenderness (on palpation)
• Inflammation
? Localized warmth in the affected area
? Localized swelling in the affected area
? Area of induration
• Limb Function
? Difficulty bearing weight on affected limb
? Motion restriction and/or loss of function in affected limb
AND
II. At least 1 of the following:
• Radiologic imaging (magnetic resonance imaging [MRI], bone scan, x-ray, or computed tomography [CT] scan) consistent with osteomyelitis performed within 7 days before randomization (or planned to occur within 7 days after randomization). If a qualifying radiologic imaging study is inconclusive, follow-up radiologic imaging must be done to confirm the diagnosis of AHO.
OR
• A positive microbiological culture from a bone biopsy or bone aspirate (if available), or blood culture, or presumptive evidence of gram-positive infection by Gram-stain of specimen.
AND
III. Presence of at least 1 of the following:
• CRP > 10 mg/dL
• Erythrocyte sedimentation rate (ESR) > 20 mm/hour
• Leukocytosis (> 12,000 white blood cells [WBC]/mm3), leukopenia (< 4000 WBC/mm3), or immature neutrophils [bands] (> 10% regardless of total peripheral WBC)
• Fever > 38°C (100.4ºF) or hypothermia < 36°C (96.8ºF)
Note: Subjects enrolled with suspected AHO (I and III) will need radiologic or microbiologic confirmation post-randomization for inclusion in MITT population.
5. Female subjects who have reached menarche must have a negative serum or urine pregnancy test
6. Female subjects who have reached menarche and are sexually active must be willing to practice sexual abstinence or dual methods of birth control (eg, condom or diaphragm with spermicidal foam or gel) during treatment and for at least 28 days after the last dose of IV study drug (if no PO switch) or PO therapy
Are the trial subjects under 18? yes
Number of subjects for this age range: 144
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.1 Documented history of any hypersensitivity or allergic reaction to daptomycin
2.1 Septic arthritis only (without AHO)
3.1 AHO of the spine or pelvis
4. Chronic osteomyelitis (i.e. symptoms of osteomyelitis > 21 days) or osteomyelitis with complications requiring non routine surgical
treatment (i.e. sequestration)
5. Major trauma, penetrating trauma (including a puncture wound of the foot), postoperative osteomyelitis, foreign body in or adjacent to affected bone or joint, or other iatrogenic bone or joint infections present at the site of infection
6. AHO due to a proven gram-negative organism
7. Presence of transient tenosynovitis, juvenile rheumatoid arthritis (JRA), reactive arthritis, bony tumors, and other osteoarticular diseases suspected to be due to a nonbacterial (e.g., fungal or mycobacterial) etiology
8.1 More than 24 hours of effective IV antibacterial therapy for AHO within 96 hours before randomization. Exceptions: a) microbiological or clinical treatment failure with a nonstudy IV antibacterial therapy that was administered for at least 48 hours. Failure must be confirmed by either microbiological laboratory report or documented worsening or no improvement of clinical signs or symptoms; b) low-dose tetracycline derivative for acne (e.g., doxycycline 50 mg q12h); c) Prior treatment with oral antibiotics if subject has worsening or no improvement of clinical signs and symptoms
9. Requirement for any potentially effective concomitant systemic antibacterial therapy for gram-positive infections
10. History of seizures, with the exception of well-documented febrile seizure of childhood; peripheral neuropathy
11. History of rhabdomyolysis (with the exception of muscle injury due to trauma)
12. Sickle cell anemia
13. Subjects in whom clinical assessments of AHO (e.g., localized pain, point tenderness, localized warmth, localized swelling, induration, difficulty bearing weight, motion restriction and/or loss of function) may not be possible (e.g., due to a surgical procedure resulting in non-removable cast or splint placement) during the first several days post randomization
14. Any condition (e.g., cystic fibrosis, current septic shock) that would make the subject, in the opinion of the Investigator, unsuitable for the study (e.g., would place a subject at risk or compromise the quality of the data), or evidence of immediately life-threatening disease, progressively fatal disease, or life expectancy of 6 months or less
15. Creatinine clearance (CrCl) < 50 mL/min/1.73 m2 as calculated using the updated Schwartz bedside” formula:
CrCl (mL/min/1.73 m2) = 0.413 × height (length) (cm) / serum creatinine (mg/dL)
16. Evidence of significant hepatic, hematologic, or immunologic dysfunction as defined by the following:
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 times the upper limit of normal (× ULN) or bilirubin level > 2 × ULN
• Neutropenia (< 500 neutrophils/mm3)
• Thrombocytopenia (< 50,000 platelets/mm3)
• If human immunodeficiency virus (HIV) positive, CD4 count < 200 cells/mm3 at the last measurement, history of AIDS-defining illness within the last year, or at risk for HIV if child is < 18 months of age
• Bone marrow or solid organ recipients who have had an episode of graft versus host disease or acute rejection episode, respectively, within the last 6 months; and/or bone marrow ablative therapy, including bone marrow transplantation, within the last 12 months
• Diagnosis of any primary immunod

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified