Trial Outcomes & Findings for Safety and Efficacy of Solithromycin in Adolescents and Children With Community-Acquired Bacterial Pneumonia (NCT NCT02605122)

Last Updated: 2019-01-03

Results Overview

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)

Recruitment status

TERMINATED

Study phase

PHASE2/PHASE3

Target enrollment

97 participants

Primary outcome timeframe

Up to 28 days post-treatment

Results posted on

2019-01-03

Participant Flow

Subjects who met 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 received safety and efficacy assessments during and after treatment.

Participant milestones

Participant milestones
Measure	Solithromycin Solithromycin was dosed for 5-7 days. Orally, as capsules or as a suspension, or intravenously. Subjects could receive intravenous therapy initially and switch to an oral formulation.	Standard of Care Comparators were dosed according to age and were consistent with current recommendations for treatment of CABP in children per site standard of care.
Overall Study STARTED	73	24
Overall Study Received Study Drug	70	24
Overall Study COMPLETED	68	22
Overall Study NOT COMPLETED	5	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Solithromycin Solithromycin was dosed for 5-7 days. Orally, as capsules or as a suspension, or intravenously. Subjects could receive intravenous therapy initially and switch to an oral formulation.	Standard of Care Comparators were dosed according to age and were consistent with current recommendations for treatment of CABP in children per site standard of care.
Overall Study Withdrawal by Subject	4	1
Overall Study Lost to Follow-up	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Solithromycin n=70 Participants Solithromycin was dosed for 5-7 days.	Standard of Care n=24 Participants Comparators were does up to 10 days per site standard of care.	Total n=94 Participants Total of all reporting groups
Age, Categorical <=18 years	70 Participants n=5 Participants	24 Participants n=7 Participants	94 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	9.48 years STANDARD_DEVIATION 4.71 • n=5 Participants	9.65 years STANDARD_DEVIATION 4.95 • n=7 Participants	9.57 years STANDARD_DEVIATION 4.83 • n=5 Participants
Sex: Female, Male Female	30 Participants n=5 Participants	11 Participants n=7 Participants	41 Participants n=5 Participants
Sex: Female, Male Male	40 Participants n=5 Participants	13 Participants n=7 Participants	53 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	65 Participants n=5 Participants	21 Participants n=7 Participants	86 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	12 Participants n=5 Participants	4 Participants n=7 Participants	16 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	11 Participants n=5 Participants	2 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) White	47 Participants n=5 Participants	16 Participants n=7 Participants	63 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Hungary	19 participants n=5 Participants	4 participants n=7 Participants	23 participants n=5 Participants
Region of Enrollment United States	18 participants n=5 Participants	9 participants n=7 Participants	27 participants n=5 Participants
Region of Enrollment Philippines	12 participants n=5 Participants	4 participants n=7 Participants	16 participants n=5 Participants
Region of Enrollment Bulgaria	21 participants n=5 Participants	6 participants n=7 Participants	27 participants n=5 Participants
Region of Enrollment Spain	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 28 days post-treatment

Population: Treatment through Day 28 (28 days +/- 4days after randomization)

Outcome measures

Outcome measures
Measure	Solithromycin n=70 Participants Solithromycin was dosed for 5-7 days.	Standard of Care n=24 Participants Comparators were dosed up to 10 days per site standard of care.
Overview of Adverse Events By Treatment Arm TEAE	24 Participants	7 Participants
Overview of Adverse Events By Treatment Arm TESAE	1 Participants	1 Participants

SECONDARY outcome

Timeframe: During Treatment Days 3 to 4

Population: Not all subjects had the Early Clinical Improvement assessment performed.

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.

Outcome measures

Outcome measures
Measure	Solithromycin n=51 Participants Solithromycin was dosed for 5-7 days.	Standard of Care n=15 Participants Comparators were dosed up to 10 days per site standard of care.
Summary of Early Clinical Response	66.7 percentage of participants Interval 52.0 to 79.0	46.7 percentage of participants Interval 21.0 to 73.0

SECONDARY outcome

Timeframe: Last day of Treatment (+48 hours)

Population: Not all subjects had the Clinical Improvement assessment performed.

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.

Outcome measures

Outcome measures
Measure	Solithromycin n=62 Participants Solithromycin was dosed for 5-7 days.	Standard of Care n=21 Participants Comparators were dosed up to 10 days per site standard of care.
Summary of Clinical Improvement	64.5 percentage of participants Interval 51.0 to 76.0	81 percentage of participants Interval 58.0 to 95.0

SECONDARY outcome

Timeframe: Short-term follow-up at 16 days (+/- 4 days)

Population: Not all subjects had the Clinical cure assessment performed.

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.

Outcome measures

Outcome measures
Measure	Solithromycin n=60 Participants Solithromycin was dosed for 5-7 days.	Standard of Care n=19 Participants Comparators were dosed up to 10 days per site standard of care.
Summary of Clinical Cure	60.0 percentage of participants Interval 47.0 to 72.0	68.4 percentage of participants Interval 43.0 to 87.0

Adverse Events

Solithromycin

Serious events: 1 serious events

Other events: 24 other events

Deaths: 0 deaths

Standard of Care

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Solithromycin n=70 participants at risk Solithromycin was dosed for 5-7 days.	Standard of Care n=24 participants at risk Comparators were dosed up to 10 days per sites standard of care.
Infections and infestations Pneumonia	1.4% 1/70 • Number of events 1 • Up to 32 days	0.00% 0/24 • Up to 32 days
Infections and infestations Pneumonia Viral	0.00% 0/70 • Up to 32 days	4.2% 1/24 • Number of events 1 • Up to 32 days

Other adverse events

Other adverse events
Measure	Solithromycin n=70 participants at risk Solithromycin was dosed for 5-7 days.	Standard of Care n=24 participants at risk Comparators were dosed up to 10 days per sites standard of care.
Vascular disorders Phlebitis	7.1% 5/70 • Number of events 5 • Up to 32 days	0.00% 0/24 • Up to 32 days
Investigations Alanine Aminotransferase Increased	4.3% 3/70 • Number of events 3 • Up to 32 days	0.00% 0/24 • Up to 32 days
Investigations Hepatic Enzyme Increased	1.4% 1/70 • Number of events 1 • Up to 32 days	0.00% 0/24 • Up to 32 days
Investigations Oxygen Saturation Decreased	1.4% 1/70 • Number of events 1 • Up to 32 days	0.00% 0/24 • Up to 32 days
Investigations Transaminases Increased	1.4% 1/70 • Number of events 1 • Up to 32 days	0.00% 0/24 • Up to 32 days
Cardiac disorders Bradycardia	0.00% 0/70 • Up to 32 days	4.2% 1/24 • Number of events 1 • Up to 32 days
Blood and lymphatic system disorders Anaemia	1.4% 1/70 • Number of events 1 • Up to 32 days	0.00% 0/24 • Up to 32 days
Respiratory, thoracic and mediastinal disorders Nasal Congestion	0.00% 0/70 • Up to 32 days	4.2% 1/24 • Number of events 1 • Up to 32 days
Respiratory, thoracic and mediastinal disorders Epistaxis	1.4% 1/70 • Number of events 1 • Up to 32 days	0.00% 0/24 • Up to 32 days
Respiratory, thoracic and mediastinal disorders Rhinitis Allergic	1.4% 1/70 • Number of events 1 • Up to 32 days	0.00% 0/24 • Up to 32 days
Respiratory, thoracic and mediastinal disorders Tachypnoea	1.4% 1/70 • Number of events 1 • Up to 32 days	0.00% 0/24 • Up to 32 days
General disorders Fatigue	0.00% 0/70 • Up to 32 days	4.2% 1/24 • Number of events 1 • Up to 32 days
General disorders Infusion Site Pain	8.6% 6/70 • Number of events 6 • Up to 32 days	0.00% 0/24 • Up to 32 days
General disorders Infusion Site Pruritus	1.4% 1/70 • Number of events 1 • Up to 32 days	0.00% 0/24 • Up to 32 days
General disorders Infusion Site Urticaria	1.4% 1/70 • Number of events 1 • Up to 32 days	0.00% 0/24 • Up to 32 days
General disorders Injection Site Reaction	1.4% 1/70 • Number of events 1 • Up to 32 days	0.00% 0/24 • Up to 32 days
General disorders Oedema Peripheral	1.4% 1/70 • Number of events 1 • Up to 32 days	0.00% 0/24 • Up to 32 days
Gastrointestinal disorders Diarrhoea	1.4% 1/70 • Number of events 1 • Up to 32 days	16.7% 4/24 • Number of events 4 • Up to 32 days
Gastrointestinal disorders Abdominal Discomfort	1.4% 1/70 • Number of events 1 • Up to 32 days	0.00% 0/24 • Up to 32 days
Gastrointestinal disorders Vomiting	1.4% 1/70 • Number of events 1 • Up to 32 days	0.00% 0/24 • Up to 32 days
Skin and subcutaneous tissue disorders Pruritus	1.4% 1/70 • Number of events 1 • Up to 32 days	0.00% 0/24 • Up to 32 days
Skin and subcutaneous tissue disorders Rash	1.4% 1/70 • Number of events 1 • Up to 32 days	0.00% 0/24 • Up to 32 days
Skin and subcutaneous tissue disorders Rash Erythematous	1.4% 1/70 • Number of events 1 • Up to 32 days	0.00% 0/24 • Up to 32 days
Skin and subcutaneous tissue disorders Rash Maculo-Papular	1.4% 1/70 • Number of events 1 • Up to 32 days	0.00% 0/24 • Up to 32 days
Skin and subcutaneous tissue disorders Urticaria	1.4% 1/70 • Number of events 1 • Up to 32 days	0.00% 0/24 • Up to 32 days
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/70 • Up to 32 days	4.2% 1/24 • Number of events 1 • Up to 32 days
Metabolism and nutrition disorders Hyperglycaemia	1.4% 1/70 • Number of events 1 • Up to 32 days	0.00% 0/24 • Up to 32 days
Infections and infestations Bacteraemia	1.4% 1/70 • Number of events 1 • Up to 32 days	0.00% 0/24 • Up to 32 days
Infections and infestations Infectious Pleural Effusion	1.4% 1/70 • Number of events 1 • Up to 32 days	0.00% 0/24 • Up to 32 days

Additional Information

Melissa Allaband

Cempra Pharmeuticals, a wholly owned subsidary of Melinta Therapeutics, Inc.

Phone: 9199140822

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Study Site will not submit its results for independent publication until after a coordinated, multicenter Study publication has been submitted or one (1) year after the conclusion of the Study, whichever occurs first. Study Site and/or Investigator shall submit any proposed publication or presentation resulting from Study Site's performance of the Protocol to the Prime Recipient for review and comment at least forty-five (45) days prior to the date of submission.
Publication restrictions are in place

Restriction type: OTHER