Efficacy, Tolerability, Safety, and Pharmacokinetic Study of DFN-15
Condition: Acute Pain
MeSH terms: Acute Pain
Study type: Interventional
Phase: Phase 2

Summary: 
      Efficacy, Tolerability, Safety and Pharmacokinetic Study of DFN-15 in Post-Surgical Dental
      Pain.
    

Detailed description: 
      This is a Phase 2, single-center, randomized, double blind, dose-ranging placebo-controlled,
      clinical study evaluating the efficacy, tolerability, safety, and the pharmacokinetic
      properties of a known drug (selective COX-2 inhibitor) administered as an alternative
      formulation/dosage form (DFN-15, a liquid oral formulation) in an accepted model of acute
      post-operative pain (acute pain following oral surgery for extraction of bilateral impacted
      mandibular third molar teeth in otherwise healthy subjects).120 female and male healthy
      subjects scheduled to undergo elective bilateral third molar extraction will be randomized,
      after they provide informed consent and are confirmed to meet all the study selection
      criteria, in a 1:1:1:1 ratio to receive a single oral dose of either DFN-15 Dose A DFN-15
      Dose B, DFN-15 Dose C or matching placebo.

      Subjects will undergo a screening procedure (within 28 days of the scheduled extraction of
      the impacted third molars) that will involve the collection of demographic information,
      height, weight and body mass index (BMI), urine pregnancy test (women of child-bearing
      potential,) medical and medicinal history, physical examination, dental examination, vital
      signs measurement (blood pressure, pulse rate, respiratory rate), clinical laboratory
      investigation (hematology,serology, coagulation parameters, serum chemistry and
      urinalysis),12-lead ECG and a panoramic x-ray to document the impacted mandibular third molar
      teeth. As a pre-requisite for randomization, subjects will be required to report "moderate"
      to "severe" baseline pain on the provided paper diary within 6 hours post-surgery (called the
      'Baseline' period) as characterized on a 4-point categorical pain intensity (PI) scale (0=
      none, 1= mild, 2= moderate, 3= severe), and a score of ≥5, on the 11-point Numerical Pain
      Rating Scale (NPRS) where 0 represents 'no pain' and 10 represents 'worst pain imaginable'.
      Eligible subjects will be randomized and will receive a single dose of the assigned study
      treatment. Subjects will be randomized and administered the study medication within 15
      minutes of meeting the post-operative inclusion criteria (baseline score).Subjects will be
      assessed at pre-specified time-points over an observation period of 8 hours from the time of
      randomization.

      Subjects with inadequately controlled pain symptoms may request rescue analgesic medication.
      Subjects will be encouraged to delay using the rescue medication if their pain is tolerable
      until 120 minutes post-dose of study medication. A subject who is administered rescue pain
      medication will continue completing pain assessments until 8 hours after treatment
      initiation. All randomized subjects will be provided with a paper diary to record pain
      assessments (Pain Intensity on 11-point NPRS scale, followed by Pain Relief using a 5-point
      categorical scale [where 0= no pain relief, 1= little pain relief, 2= some pain relief, 3= a
      lot of pain relief, 4= complete pain relief]) At study medication administration, two
      stopwatches will be started, to measure times to 'perceptible' and 'meaningful' pain-relief.
      Subjects will be instructed to stop the first stopwatch when they first perceive pain relief
      to occur (time to perceptible relief). Subjects will be instructed to stop the second
      stopwatch when they first experience meaningful pain relief (time to meaningful relief).
      Stopwatch times of perceptible relief and meaningful relief will be recorded using exact
      stopwatch time displayed.

      In addition, at 8 hours post-dose or within 5 minutes prior to first use of rescue medication
      (whichever is earlier), subjects will be asked to record within the provided patient diary:
      'Patient Rating of Treatment Satisfactoriness' using a 5-point verbal rating scale (0 =poor,
      1 =fair, 2 =good, 3=very good, 4 =excellent).

      Subjects will remain NPO (nothing by mouth), including water, from Check-in (i.e., at least 2
      hours before the administration of the dose of study medication to randomized subjects) until
      2 hours post-dose, on Day 1 (study day). After 2 hours post-dose, subjects may be permitted
      to consume water, or gelatin snacks. Subjects are prohibited from ingesting solid foods or
      carbonated beverages for at least 6 hours post-dose.

      12-lead ECG and Vital Signs were performed before surgery, at baseline and at periodic
      intervals post-dose until 8 hours .At discharge (8 hours post-randomization) from the
      clinical facility, all AEs reported for the subjects will be reviewed. A physical
      examination, including evaluation of the incision site for hematomas, and clinical laboratory
      evaluation (coagulation parameters and specific hematology, serum biochemistry and urinalysis
      parameters) will be conducted.

      All subjects will have blood drawn at specified time points (pre-dose and over the 8 hour
      observation period) for pharmacokinetic evaluation.

      Subjects will return to the research center 7 days (± 3 days) post-surgery for evaluation of
      their safety and well-being. Any AEs experienced post-surgery will be reviewed. A physical
      examination, of the subject will be performed, 12-lead ECG, and vital signs parameters will
      be repeated. Hematology, coagulation parameters, serum biochemistry and urinalysis parameters
      will be repeated only if there is a clinically significant abnormality or ongoing AE(s). Any
      changes to the prior and concomitant medication made after discharge will be reviewed and
      recorded.
    

Intervention name(s): DFN-15 (Celecoxib Oral Solution) 62.5 mg; DFN-15 (Celecoxib Oral Solution) 125 mg; DFN-15 (Celecoxib Oral Solution) 250 mg; Placebo
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Oral Solution; Oral Solution; Oral Solution; Oral Solution
Intervention MeSH terms: Celecoxib; Pharmaceutical Solutions
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment