Safety and Efficacy of Solithromycin in Adolescents and Children With Community-Acquired Bacterial Pneumonia

Study Overview
=================
Brief Summary
-----------------
This is a phase 2/3, randomized, open-label, active control, multi-center study to assess the safety and efficacy of solithromycin in children and adolescents with community-acquired bacterial pneumonia (CABP).

Detailed Description
-----------------
Subjects who meet all inclusion/exclusion criteria and sign the informed consent/assent were enrolled. Subjects were randomized to receive solithromycin or a comparator antibiotic, administered IV and/or by mouth (PO) based on weight and age. Subjects were treated daily for 5 to 7 days with oral solithromycin and 5 to 7 days with IV or IV-to-oral solithromycin. Subjects were treated for 5 to 10 days with comparator antibiotics. Subjects received safety and efficacy assessments during and after treatment.

Official Title
-----------------
A Phase 2/3, Randomized, Open-Label, Multi-center Study to Determine the Safety and Efficacy of Solithromycin in Adolescents and Children With Suspected or Confirmed Community-Acquired Bacterial Pneumonia

Conditions
-----------------
Community-acquired Bacterial Pneumonia

Intervention / Treatment
-----------------
* Drug: Solithromycin
* Drug: Standard of Care


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: History of and/or documented fever (rectal, ear, or oral temperature ≥38°C or axillary temperature ≥37.5°C) or hypothermia (rectal, ear, or oral temperature <35°C or axillary temperature <34.5°C) Chest radiograph infiltrates consistent with bacterial pneumonia (or pneumonia caused by atypical bacterial agents); if a subject is outpatient and starting on oral therapy, a radiograph is not required. Presence of at least 2 of the following signs or symptoms: Cough Difficulty breathing Production of purulent sputum Chest pain Grunting Hypotension Tachycardia, defined as follows: 2 months to <24 months: ≥160 beats/min 24 months to <10 years: ≥140 beats/min 10 years: ≥100 beats/min Tachypnea, defined as follows: 2 months to <12 months: ≥50 breaths/min 12 months to <5 years: ≥40 breaths/min 5 years: ≥20 breaths/min Physical exam consistent with pulmonary consolidation Presence of at least 1 of the following: Leukocytosis (≥12,000 white blood cells [WBC]/mm3) Leukopenia (<5000 WBC/mm3) ≥10% immature neutrophils (bands) regardless of total peripheral WBC Elevated inflammatory markers (C-reactive protein or procalcitonin) Oxygen saturation <97% on room air Organism consistent with a typical respiratory pathogen identified Exclusion Criteria: Ventilator-associated or hospital-acquired pneumonia >48 hours of systemic antibacterial therapy confirmed or suspected bacterial meningitis breast-feeding females positive pregnancy test

Ages Eligible for Study
-----------------
Minimum Age: 2 Months
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Solithromycin<br>Solithromycin will be administered orally, as capsules or as a suspension, or intravenously. Patients may receive intravenous therapy initially and switch to an oral formulation. Dosage is weight based and age based. | Drug: Solithromycin<br> <br> * Other names: CEM-101;|
| Active Comparator: Standard of Care<br>Comparators will be selected according to subject age and are consistent with current recommendations for treatment of CABP in children. These include intravenous ceftriaxone, ampicillin, and amoxicillin and oral amoxicillin and amoxicillin-clavulanic acid. Azithromycin or erythromycin may be added as well. | Drug: Standard of Care<br>* Age- and weight-based dosing as appropriate per sites standard of care.<br>* Other names: Erythromycin lactobionate;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overview of Adverse Events By Treatment Arm | Summary of subjects experiencing Treatment Emergent Adverse Events (TEAE) through Day 16 visit and Treatment Emergent Serious Adverse Events (TESAE) through Day 28 visit (28 days +/- 4 days after randomization) | Up to 28 days post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summary of Early Clinical Response | Early clinical response (ECR) was defined using the latest efficacy evaluation from Day 2 (if subject discharged prior to Day 2), Day3, or Day 4, and was defined as improvement in at least 1 presenting sign/symptom of CABP with no deterioration in any signs/symptoms of CABP and no requirement for an additional antibiotic. | During Treatment Days 3 to 4 | 
| Summary of Clinical Improvement | Clinical improvement was assessed using the latest efficacy evaluation conducted on last day of treatment (+48 hours), and was defined identically to the early clinical response. | Last day of Treatment (+48 hours) | 
| Summary of Clinical Cure | Clinical cure was assessed using the latest efficacy evaluation conducted on Day 16 (+/- 4 days) post-randomization, and was defined as resolution of all presenting signs/symptoms of CABP (excluding cough), no development of new signs/symptoms of CABP, and no requirement for an additional antibiotic. | Short-term follow-up at 16 days (+/- 4 days) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pneumonia, macrolide, pediatric