Ibuprofen Liquid Capsules 2 x 200 mg Efficacy and PK/PD Study in Surgical Removal of Impacted Third Molars
Condition: Tooth, Impacted; Tooth Diseases; Stomatognathic Diseases
MeSH terms: Tooth, Impacted; Tooth Diseases; Stomatognathic Diseases
Study type: Interventional
Phase: Phase 3

Summary: 
      This is a single centre, three-arm randomised, double-blind, double-dummy, parallel group,
      single-dose, active and placebo-controlled efficacy and pharmacokinetics/ pharmacodynamics
      study to evaluate the efficacy and safety of 2 x 200 mg Ibuprofen Liquid Capsules in subjects
      with post-operative dental pain.
    

Detailed description: 
      Eligible subjects will complete all screening procedures within 28 days before the surgery
      and randomisation.

      At Screening, subjects will provide written informed consent to participate in the study
      before any protocol specified procedures or assessments are completed. On Day 1, subjects who
      continue to be eligible for study participation after completing screening procedures and
      assessments will undergo extraction of 2 or more third molars. At least 1 of the third molars
      must be a fully or partially bone impacted mandibular molar.

      All subjects will receive local anaesthesia (2% lidocaine with 1:100,000 epinephrine).
      Nitrous oxide will be allowed at the discretion of the investigator. Subjects who experience
      moderate to severe pain intensity (a score of ≥ 5 on a numeric rating scale [NRS] from 0-10
      where 0 = no pain, 10 = worst pain ever) within 6 hours after surgery and who continue to
      meet all study entry criteria will be randomised in a 3:3:1 ratio to receive a single dose of
      2×200 mg Ibuprofen Liquid Capsules, 2×200 mg ibuprofen tablets, or placebo. The randomisation
      will be stratified by baseline pain category (moderate or severe) using a categorical scale
      based on the NRS score that includes the categories of none (0), mild (1-4), moderate (5-7),
      and severe (8-10).

      Subjects will re-assess their baseline pain intensity using the NRS immediately before
      receiving study drug (pre-dose, Time 0) and their pain intensity (NRS) and pain relief (5
      point categorical scale) at the following time points (pre-dose, 10, 20, 30 and 45 minutes,
      and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10 and 12 hours after Time 0; and immediately before each
      dose of rescue medication, if any. For assessments less than 1 hour apart a window of +/-2
      min is allowable whilst for assessments at least 1 hour apart a +/-5 min window is allowable.

      The double stopwatch method will be used to record the time to perceptible pain relief and
      time to meaningful pain relief during the 8 hours following the first dose or until subject
      takes rescue medication. Subjects will complete a global evaluation of study drug and
      satisfaction with pain relied assessment 12 hours (+/- 5 minutes) after Time 0 or immediately
      before the first dose of rescue medication (whichever occurs first). Vital signs will be
      recorded after the subject has been in a sitting position for 3 minutes at the following
      times: before surgery, within 30 minutes before Time 0, 12 hours after Time 0, immediately
      before the first dose of rescue medication(if required) and at the follow-up visit. Adverse
      events (AEs) will be monitored and recorded from the time of signing of the informed consent
      form (ICF) until the Follow up Visit (or Early Termination Visit). During the 12 hours
      following Time 0, subjects will complete efficacy and safety assessments. Subjects will
      remain at the study site overnight and will be discharged on Day 2.

      Paracetamol / acetaminophen (1000 mg) will be permitted as the initial rescue medication.
      Subjects will be encouraged to wait at least 60 minutes after receiving study drug before
      taking rescue medication. If acetaminophen rescue medication is not effective in relieving
      the subject's pain, 5 mg oxycodone rescue medication may be administered at the discretion of
      the investigator.

      Subjects are not permitted to take any concomitant medications that might confound
      assessments of pain relief, such as psychotropic drugs, antidepressants, sedative-hypnotics
      (other than those permitted for conscious sedation), or other analgesics taken within five
      times of their elimination half-lives (other than those used at the surgery).

      Other restrictions include the following: alcohol use is prohibited from 24 hours before
      surgery until discharge on Day 2; Food will be restricted from midnight before surgery until
      4 hour after surgery; during this time, water may be permitted up to 2 hours prior to surgery
      and a single drink of 8 fluid ounces of water with their treatment, water will not be
      permitted until 1 hour post dose. Vaccinations should not have been administered 7 days prior
      to surgery, subjects should avoid strenuous physical activity from 72 hours prior to dosing,
      and will not be permitted to smoke or use nicotine containing products for the duration of
      their involvement in the study.

      A subset of 70 subjects will be randomly selected from the study population to take part in a
      Pharmacokinetic sub study. Blood samples will be collected at 10, 15, 20, 30 and 45 minutes
      and 1, 1.25, 1.5, 2, 3, 4, 5, 6, 7, 8, 10 and 12 hours post dose.

      Upon discharge from the study site, subjects may be prescribed pain medication for use at
      home according to the standard practice of the study site. On Day 8 (± 2 days), subjects will
      return to the study site for an abbreviated confirmatory physical assessment and AE
      assessments.
    

Intervention name(s): Ibuprofen 200Mg Oral Cap; Ibuprofen 200Mg Oral Tablet; Placebo Liquid Capsule; Placebo Tablets
Intervention type(s): Drug; Drug; Other; Other
Intervention description(s): 2 x 200mg Liquid Capsules once in 12 hours; 2 x 200mg Tablets once in 12 hours; 2 x Liquid Capsules once in 12 hours; 2 x Tablets once in 12 hours
Other intervention name(s): Test Product; 200mg Ibuprofen Liquid Capsule; Nurofen 200mg Ibuprofen Liquid Capsule; Reference Product; 200mg Ibuprofen Tablet; Nurofen 200mg Ibuprofen Tablet
Intervention MeSH terms: Ibuprofen
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The dental pain model used in this study is a robust and well established postsurgical pain model that produces pain that is predictable in its character, duration, and intensity. The model is widely accepted and has a proven record of assay sensitivity (i.e. separating active drugs from each other, as well as from placebo). The model is frequently used to evaluate NSAID type analgesics. Results from dental pain studies are accepted by the US Food and Drug Administration (FDA) and European authorities and have been widely extrapolated to other general pain conditions.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Ibuprofen; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non Narcotic; Analgesics