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

Phase 2

Terminated

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Solithromycin	Solithromycin	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.
Standard of Care	Standard of Care	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.

Primary Outcome Measures

Name	Time	Method
Overview of Adverse Events By Treatment Arm	Up to 28 days post-treatment	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)

Secondary Outcome Measures

Name	Time	Method
Summary of Clinical Cure	Short-term follow-up at 16 days (+/- 4 days)	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.
Summary of Early Clinical Response	During Treatment Days 3 to 4	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.
Summary of Clinical Improvement	Last day of Treatment (+48 hours)	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.