Pain, Postoperative
Conditions
Brief summary
The purposes of this study are to evaluate the safety and tolerability and to model the single-dose pharmacokinetic profile of diclofenac capsules low dose and high dose in children ages 6 to \<17 years experiencing mild to moderate acute postoperative pain.
Interventions
DRUGDiclofenac Capsules low dose
DRUGDiclofenac Capsules high dose
Sponsors
Iroko Pharmaceuticals, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
* Body weight ≥18 kilograms. * Mild to moderate acute pain requiring treatment with analgesic medication. * Willing to have blood samples taken for PK sampling using an indwelling catheter. * Must be able to swallow capsules and can tolerate oral medication. * For females: is not of reproductive potential (defined as premenarchal) or is practicing an acceptable method of birth control
Exclusion criteria
* Severe acute pain * Chronic analgesic or glucocorticoid use for any condition within 6 months before dosing with study drug. * Emergency surgery * History of allergic reaction, hypersensitivity, or clinically significant intolerance to diclofenac, aspirin, codeine, acetaminophen, or any NSAID * History of peptic ulcer disease or a GI event (eg, perforation, obstruction, or bleed) within 6 months before screening * Current use of any medication that may cause a clinically significant drug interaction when co-administered with diclofenac * Current use of any medication that might affect the pharmacokinetics of diclofenac * History of bleeding disorders . * Developmental delay or behavioral problems that would make it difficult to assess pain. * Impaired liver function * Clinically significant renal or cardiovascular disease * Any medical condition that compromises ability to swallow, absorb, metabolize, or excrete the study drug * Previously received any investigational product or device within 30 days before Screening or scheduled to receive an investigational device or another investigational drug (other than that in this study) during the course of this study. * Previous participation in this clinical study or currently taking diclofenac.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Concentration of Diclofenac | 0-6 hours after first dose of diclofenac | The estimated typical value for clearance (tvCl) following a single diclofenac dose based on population pharmacokinetic (PopPK) modeling using sparse plasma concentration data in pediatric subjects. |
Secondary
| Measure | Time frame |
|---|---|
| Safety of Diclofenac Capsules Low Dose and High Dose as Assessed by the Incidence of Adverse Events From Baseline to Day 3 or Early Termination | Baseline to Day 3/Early Termination |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Diclofenac Capsules Low Dose Diclofenac Capsules low dose three times daily for up to three days
Diclofenac Capsules low dose | 15 |
| Diclofenac Capsules High Dose Diclofenac Capsules high dose three times daily for up to three days
Diclofenac Capsules high dose | 15 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Diclofenac Capsules Low Dose | Diclofenac Capsules High Dose | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 15 Participants | 15 Participants | 30 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 9.0 years STANDARD_DEVIATION 1.69 | 14.1 years STANDARD_DEVIATION 1.51 | 11.6 years STANDARD_DEVIATION 3.05 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 15 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 9 Participants | 11 Participants | 20 Participants |
| Sex: Female, Male Female | 11 Participants | 6 Participants | 17 Participants |
| Sex: Female, Male Male | 4 Participants | 9 Participants | 13 Participants |
| Weight | 40.20 kg STANDARD_DEVIATION 16.628 | 74.44 kg STANDARD_DEVIATION 18.974 | 57.34 kg STANDARD_DEVIATION 24.693 |
| Weight Group >/=18 to <35 kg | 7 Participants | 0 Participants | 7 Participants |
| Weight Group >/=35 kg | 8 Participants | 15 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 7 / 15 | 7 / 15 |
| serious Total, serious adverse events | 1 / 15 | 0 / 15 |
Outcome results
Primary
Plasma Concentration of Diclofenac
The estimated typical value for clearance (tvCl) following a single diclofenac dose based on population pharmacokinetic (PopPK) modeling using sparse plasma concentration data in pediatric subjects.
Time frame: 0-6 hours after first dose of diclofenac
Population: Pharmacokinetic (PK) population. Defined as all subjects who received at least one dose of study drug and had at least one quantifiable plasma diclofenac concentration after dosing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diclofenac Capsules Low Dose | Plasma Concentration of Diclofenac | 29647.9 mL/hr | Standard Error 3710.526 |
| Diclofenac Capsules High Dose | Plasma Concentration of Diclofenac | 35131.0 mL/hr | Standard Error 5660.83 |
Secondary
Safety of Diclofenac Capsules Low Dose and High Dose as Assessed by the Incidence of Adverse Events From Baseline to Day 3 or Early Termination
Time frame: Baseline to Day 3/Early Termination