Tramadol/Diclofenac Fixed-dose Combination Phase III Trial in Acute Pain After Third Molar Extraction
Condition: Acute Pain
MeSH terms: Acute Pain
Intervention: Tramadol/Diclofenac 50/50; Tramadol/Diclofenac 25/25; Tramadol 50; Diclofenac 50
Intervention description: Each dose comprised 1 fixed-dose combination tablet and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.; Each dose comprised 1 fixed-dose combination tablet and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.; Each dose comprised 1 capsule containing 50 mg tramadol hydrochloride and 3 placebo tablets matching the other active treatment groups. Doses were taken 8 hours apart.; Each dose comprised 1 tablet containing 50 mg diclofenac sodium and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.
Intervention MeSH terms: Diclofenac; Tramadol
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: This study used double-blind and double-dummy methods to guarantee the blinding of all personnel involved in the study. Participants, investigators, and all persons involved in the conduct, data management, and analysis of the study were fully blinded to the participant's treatment.
Enrollment: 1151.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Wisdom tooth removal; Dental pain

Summary:

      This study evaluated a new drug fixed-dose combination tablet (FDC) called
      tramadol/diclofenac at two different strengths (fixed doses of 25 milligrams [mg] of tramadol
      and of diclofenac or of 50 mg each). Tramadol and diclofenac each relieve pain, but they do
      so by different mechanisms. They were used alone as comparator drug in this study. Both are
      marketed drugs and are standard treatment for acute pain, including wisdom tooth removal.
    

Eligibility criteria:

        Inclusion Criteria:

          1. The participant has read the informed consent form, has understood the relevant
             aspects of the clinical study, and grants his/her authorization to participate by
             signing the informed consent form prior to the inclusion in the clinical study and the
             performance of any procedure.

          2. Male and female participants above 18 years up to 60 years.

          3. Female participants of childbearing potential must be practicing an acceptable method
             of birth control and must have a negative urine pregnancy test at enrollment with
             confirmation at the Allocation Visit.

          4. Participants are in good health, i.e., the medical record, vital signs, physical
             examination, and laboratory parameter assessments do not show any abnormal deviations
             impeding the participation in the clinical study.

          5. Participants requiring extraction of 3 or more third molars with 2 mandibular impacted
             third molars.

          6. Clinical and radiological diagnosis of impacted lower third molars.

          7. Class I and Class II molars according to Pell and Gregory's classification (Gay Escoda
             et al. 2004).

          8. Participants must be able to swallow the IMPs.

        Exclusion Criteria at Enrollment:

          1. Findings in the medical record, vital signs, and/or physical examination demonstrating
             abnormal conditions of participant's general state of health preventing his/her
             participation in the clinical study according to the investigator's opinion.

          2. Participant unable to speak, read, or write in Spanish language.

          3. Clinical laboratory parameters exceed the pre-defined alert ranges (i.e., 1 standard
             deviation above or below the upper/lower limit of the normal ranges).

          4. Known hypersensitivity to the IMPs, the anesthetic to be used during surgery, or to
             the rescue medication (ibuprofen, ketorolac).

          5. Known alcohol or drug abuse in the last 6 months or any history of seizures. Alcohol
             abuse is defined as the consumption of more than 3 ounces (about 90 milliliters) of
             liquor or spirits or 18 ounces (about 530 milliliters) of beer per day, for 5
             consecutive days during the 6-month period. Drug abuse is defined as the use of any
             recreational drug for 5 consecutive days during the 6 month period.

          6. Participants who take analgesic medication for chronic pain, monoamine oxidase
             inhibitors, tricyclic antidepressants, neuroleptics, or other drugs that reduce the
             seizure threshold within 4 weeks of enrollment.

          7. Pregnant or lactating women.

          8. Participants who received systemic corticosteroids or opioid analgesics less than 2
             weeks before surgery.

          9. Participants with molars linked to the mandibular canal.

         10. Participants requiring immediate dental procedures other than third and fourth molars
             extraction,

             Exclusion Criteria at the Allocation Visit:

         11. Participant received a long-acting non-steroidal anti-inflammatory drug within 24
             hours or 5 times the elimination half-life of that drug prior to surgery, whatever the
             longer.

         12. Participant received any analgesic medication other than short-acting pre-operative or
             intra-operative anesthetic agents within 24 hours before taking IMPs.

         13. Participant received more than 300 mg of lidocaine in total.

         14. Participant received any analgesic medication other than the IMPs immediately after
             the oral surgical procedure was completed.

         15. Baseline pain intensity of the participant after oral surgical procedure remains below
             5 points on the 11-point NRS.