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

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

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).

Study Overview

• Status: Terminated
• Conditions: Community-acquired Bacterial Pneumonia
• Intervention / Treatment: Drug: Solithromycin; Drug: Standard of Care

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.

• Study Type: Interventional
• Enrollment (Actual): 97
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Pleven, Bulgaria, 5800
  • Plovdiv, Bulgaria, 4000
  • Ruse, Bulgaria, 7002
  • Sofia, Bulgaria, 1233
  • Sofia, Bulgaria, 1431
  • Sofia, Bulgaria, 1407
  • Vratsa, Bulgaria, 3001
• Hungary
  • Budapest, Hungary, 1125
  • Budapest, Hungary, 1083
  • Budapest, Hungary, 1097
  • Budapest, Hungary, 1089
  • Cegléd, Hungary, 2700
  • Debrecen, Hungary, 4031
  • Gyor, Hungary, 9024
  • Gyula, Hungary, 5700
  • Mosdós, Hungary, 7257
  • Nagykanizsa, Hungary, 8800
  • Nyiregyhaza, Hungary, 4400
  • Szeged, Hungary, 6720
  • Szekesfehervar, Hungary, 8000
  • Torokbalint, Hungary, 2045
  • Veszprém, Hungary, 8200
• Philippines
  • Caloocan City, Philippines, 1400
  • Cebu City, Philippines, 6000
  • Davao City, Philippines, 8000
  • Iloilo, Philippines, 5000
  • Manila, Philippines, 1000
  • Muntinlupa, Philippines, 1781
  • Quezon City, Philippines, 1100
  • Quezon City, Philippines, 1104
• Spain
  • Barcelona, Spain, 08035
  • Barcelona, Spain, 08916
  • Madrid, Spain, 28046
  • Barcelona
    • Esplugues de Llobregat, Barcelona, Spain, 08950
  • Guipuzcoa
    • San Sebastian, Guipuzcoa, Spain, 20014
• United Kingdom
  • London, United Kingdom, SW17 0RE
  • London, United Kingdom, N18 1QX
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
  • California
    • Los Angeles, California, United States, 90095
    • Sacramento, California, United States, 95817
    • San Diego, California, United States, 92123
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
  • Florida
    • Tampa, Florida, United States, 33606
  • Kentucky
    • Louisville, Kentucky, United States, 40202
  • Nebraska
    • Omaha, Nebraska, United States, 68198-2162
  • Nevada
    • Las Vegas, Nevada, United States, 89102
  • North Carolina
    • Durham, North Carolina, United States, 27710
    • Greenville, North Carolina, United States, 27834
  • Ohio
    • Toledo, Ohio, United States, 43606
  • Oregon
    • Portland, Oregon, United States, 97239
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
  • Tennessee
    • Memphis, Tennessee, United States, 38105
  • Texas
    • Amarillo, Texas, United States, 79106
    • Houston, Texas, United States, 77030
    • Splendora, Texas, United States, 77372
  • Virginia
    • Charlottesville, Virginia, United States, 22905
    • Richmond, Virginia, United States, 29298
    • Roanoke, Virginia, United States, 24013

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Solithromycin; Other Names: CEM-101
Active Comparator: 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.	Drug: Standard of Care; Age- and weight-based dosing as appropriate per sites standard of care.; Other Names: Erythromycin; ampicillin; amoxicillin; Azithromycin; ceftriaxone; amoxicillin-clavulanic acid; 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)

Collaborators and Investigators

• Sponsor: Melinta Therapeutics, Inc.
• Collaborators: Biomedical Advanced Research and Development Authority
• Investigators: Principal Investigator: Michael Cohen-Wolkowiez, MD, PhD, Duke Clinical Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Actual): March 21, 2018
• Study Completion (Actual): March 21, 2018

Study Registration Dates

• First Submitted: November 10, 2015
• First Submitted That Met QC Criteria: November 13, 2015
• First Posted (Estimate): November 16, 2015

Study Record Updates

• Last Update Posted (Actual): January 3, 2019
• Last Update Submitted That Met QC Criteria: December 12, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: pediatric; pneumonia; macrolide
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Pneumonia; Pneumonia, Bacterial; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Bacterial Agents; Protein Synthesis Inhibitors; beta-Lactamase Inhibitors; Ceftriaxone; Erythromycin; Erythromycin Estolate; Erythromycin Ethylsuccinate; Erythromycin stearate; Ampicillin; Amoxicillin; Azithromycin; Clavulanic Acid; Clavulanic Acids; Amoxicillin-Potassium Clavulanate Combination; Solithromycin; Erythromycin lactobionate
• Other Study ID Numbers: CE01-203

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No