Trial Outcomes & Findings for Safety and Pharmacokinetic Study of Intravenous Ibuprofen in Pediatric Patients (NCT NCT02583399)

NCT ID: NCT02583399

Last Updated: 2020-11-20

Results Overview

This outcome measurement was to the determine the area under the plot of plasma concentrations of drug against time after drug administration. Pharmacokinetic samples were collected immediately following the first dose, the utilizing sparse sampling techniques, samples were collected at 30 minutes, 1 hour, 2 hours and 4 hours.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 30 participants
• Primary outcome timeframe: 4 hours
• Results posted on: 2020-11-20

Participant Flow

Enrollment occurred between 08-Aug2017 and 21-Feb2019. Subject were recruited were hospitalized pediatric subjects, aged birth (greater than 37 weeks gestational age) to less than six months of age, with a clinical indication of pain and fever.

Participant milestones

Measure	Ibuprofen Ibuprofen, 10 mg/kg Ibuprofen: Ibuprofen, 10 mg/kg
Overall Study STARTED	30
Overall Study COMPLETED	24
Overall Study NOT COMPLETED	6

Reasons for withdrawal

Measure	Ibuprofen Ibuprofen, 10 mg/kg Ibuprofen: Ibuprofen, 10 mg/kg
Overall Study Able to be discharged	3
Overall Study Wanted to use a restricted medication	3

Baseline Characteristics

Safety and Pharmacokinetic Study of Intravenous Ibuprofen in Pediatric Patients

Baseline characteristics by cohort

Measure	Ibuprofen n=24 Participants Ibuprofen, 10 mg/kg Ibuprofen: Ibuprofen, 10 mg/kg
Age, Continuous	127.7 days STANDARD_DEVIATION 33.77 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	3 Participants n=5 Participants
Race/Ethnicity, Customized White	17 Participants n=5 Participants
Race/Ethnicity, Customized Other	4 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic/Latino	5 Participants n=5 Participants
Race/Ethnicity, Customized Non-Hispanic/Non-Latino	19 Participants n=5 Participants
Weight	6 kilograms STANDARD_DEVIATION 1.45 • n=5 Participants

PRIMARY outcome

Timeframe: 4 hours

This outcome measurement was to the determine the area under the plot of plasma concentrations of drug against time after drug administration. Pharmacokinetic samples were collected immediately following the first dose, the utilizing sparse sampling techniques, samples were collected at 30 minutes, 1 hour, 2 hours and 4 hours.

Outcome measures

Measure	Ibuprofen n=24 Participants Ibuprofen, 10 mg/kg Ibuprofen: Ibuprofen, 10 mg/kg
Area Under the Curve (AUC) 0-4 Hours of a Single Dose of Intravenous Ibuprofen (IVIb) Administered Over 5-7 Minutes.	75.74 mcg*hr/mL Standard Error 4.09

PRIMARY outcome

Timeframe: 4 hours

This outcome measurement was to measure the maximal or peak measured serum concentration (Cmax) of a single dose of intravenous ibuprofen (IVIb) after its administration. Pharmacokinetic samples were collected immediately following the first dose, the utilizing sparse sampling techniques, samples were collected at 30 minutes, 1 hour, 2 hours and 4 hours.

Outcome measures

Measure	Ibuprofen n=24 Participants Ibuprofen, 10 mg/kg Ibuprofen: Ibuprofen, 10 mg/kg
Maximum Observed Plasma Concentration (Cmax) of a Single Dose of Intravenous Ibuprofen (IVIb) Administered Over 5-7 Minutes.	56.28 microgram/milliliter Standard Error 2.77

PRIMARY outcome

Timeframe: 4 hours

Population: Analysis were performed using sparse sampling concentration. Phoenix WinNonlin treats the sparse data as a special case of plasma concentration data. The NCA sparse methodology calculates PK parameters based on the mean profile for all the subjects in the dataset. Consequently, standard deviation can only be calculated based on observed data (AUC0-t and Cmax) but not on derived data (Tmax, T½ el.)

This outcome measurement was to determine the half-life or the period of time required for the concentration or amount of drug in the body to be reduced to exactly one-half of a given concentration or amount. Pharmacokinetic samples were collected immediately following the first dose, the utilizing sparse sampling techniques, samples were collected at 30 minutes, 1 hour, 2 hours and 4 hours.

Outcome measures

Measure	Ibuprofen n=24 Participants Ibuprofen, 10 mg/kg Ibuprofen: Ibuprofen, 10 mg/kg
Elimination Half Life (T 1/2) of a Single Dose of Intravenous Ibuprofen (IVIb) Administered Over 5-7 Minutes.	1.30 hours

PRIMARY outcome

Timeframe: 4 hours

Population: Analysis were performed using sparse sampling concentration. Phoenix WinNonlin treats the sparse data as a special case of plasma concentration data. The NCA sparse methodology calculates PK parameters based on the mean profile for all the subjects in the dataset. Consequently, standard deviation can only be calculated based on observed data (AUC0-t and Cmax) but not on derived data (Tmax, T½ el.)

This outcome measurement was to determine the time to maximum concentration (Tmax) of a single dose of intravenous ibuprofen (IVIb) after its administration. Pharmacokinetic samples were collected immediately following the first dose, the utilizing sparse sampling techniques, samples were collected at 30 minutes, 1 hour, 2 hours and 4 hours.

Outcome measures

Measure	Ibuprofen n=24 Participants Ibuprofen, 10 mg/kg Ibuprofen: Ibuprofen, 10 mg/kg
Time to Maximum Concentration (Tmax) of a Single Dose of Intravenous Ibuprofen (IVIb) Administered Over 5-7 Minutes.	10 minutes

Adverse Events

Ibuprofen

Serious events: 1 serious events

Other events: 7 other events

Deaths: 8 deaths

Serious adverse events

Measure	Ibuprofen n=24 participants at risk Ibuprofen, 10 mg/kg Ibuprofen: Ibuprofen, 10 mg/kg
Cardiac disorders Pericardial effusion	4.2% 1/24 • Number of events 1 • Adverse events were assessed during the treatment period beginning with the start of the study drug administration through study hour 72 or until discharge, whichever occurs first.
Cardiac disorders Chylothorax	4.2% 1/24 • Number of events 2 • Adverse events were assessed during the treatment period beginning with the start of the study drug administration through study hour 72 or until discharge, whichever occurs first.

Other adverse events

Measure	Ibuprofen n=24 participants at risk Ibuprofen, 10 mg/kg Ibuprofen: Ibuprofen, 10 mg/kg
Eye disorders Eye discharge	4.2% 1/24 • Number of events 1 • Adverse events were assessed during the treatment period beginning with the start of the study drug administration through study hour 72 or until discharge, whichever occurs first.
Gastrointestinal disorders Constipation	8.3% 2/24 • Number of events 2 • Adverse events were assessed during the treatment period beginning with the start of the study drug administration through study hour 72 or until discharge, whichever occurs first.
Injury, poisoning and procedural complications Post-procedural fever	4.2% 1/24 • Number of events 1 • Adverse events were assessed during the treatment period beginning with the start of the study drug administration through study hour 72 or until discharge, whichever occurs first.
Investigations White blood cells increased	4.2% 1/24 • Number of events 1 • Adverse events were assessed during the treatment period beginning with the start of the study drug administration through study hour 72 or until discharge, whichever occurs first.
Metabolism and nutrition disorders Hypokalemia	4.2% 1/24 • Number of events 1 • Adverse events were assessed during the treatment period beginning with the start of the study drug administration through study hour 72 or until discharge, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Atelectasis	4.2% 1/24 • Number of events 1 • Adverse events were assessed during the treatment period beginning with the start of the study drug administration through study hour 72 or until discharge, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Chylothorax	4.2% 1/24 • Number of events 1 • Adverse events were assessed during the treatment period beginning with the start of the study drug administration through study hour 72 or until discharge, whichever occurs first.
Respiratory, thoracic and mediastinal disorders Pleural effusion	4.2% 1/24 • Number of events 1 • Adverse events were assessed during the treatment period beginning with the start of the study drug administration through study hour 72 or until discharge, whichever occurs first.
Vascular disorders Peripherial artery thrombosis	4.2% 1/24 • Number of events 1 • Adverse events were assessed during the treatment period beginning with the start of the study drug administration through study hour 72 or until discharge, whichever occurs first.

Additional Information

Sr. Manager, Clinical Operations

Cumberland Pharmaceuticals Inc.

Phone: 615-255-0068

Email: bkaelin@cumberlandpharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place