Comparison of the Effects of Tapentadol and Oxycodone on Gastrointestinal and Colonic Transit in Humans
Condition: Effects of 2 Mu-opiates on Gastrointestinal Transit
Intervention: Tapentadol; Oxycodone; Placebo
Intervention description: Subjects received tapentadol immediate release formulation, 75 mg three times per day (tid) for 48 hours.; Subjects received oxycodone immediate release formulation, 5 mg three times per day (tid) for 48 hours.; Subjects received placebo three times per day (tid) for 48 hours.
Intervention MeSH terms: Oxycodone; Tapentadol
Phase: Phase 4
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 38.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: tapentadol; oxycodone; mu-opiate; stomach; small intestine; colon; motility; nausea; constipation

Summary:

      Tapentadol is FDA approved for the treatment of moderate to severe acute pain. Due to the
      dual mechanism of action as an opioid agonist and norepinephrine reuptake inhibitor, there is
      potential for off label use in chronic pain.

      Tapentadol is a new molecular entity that is structurally similar to tramadol. Tapentadol is
      a centrally-acting analgesic with a dual mode of action as an agonist at the mu-opioid
      receptor and as a norepinephrine reuptake inhibitor. These two actions are synergistic in
      pain relief. While its action reflects aspects of tramadol and morphine, its ability to
      control pain is more on the order of hydrocodone and oxycodone.

      Its dual mode of action provides analgesia at similar levels of more potent narcotic
      analgesics such as hydrocodone, oxycodone, and meperidine with a more tolerable side effect
      profile. Clinical studies showed that tapentadol effectively relieves moderate to severe pain
      in various pain care settings. In addition, it was reported to be associated with
      significantly fewer treatment discontinuations due to a significantly lower incidence of
      gastrointestinal-related adverse events compared with equivalent doses of oxycodone. The
      combination of these reduced treatment discontinuation rates and tapentadol efficacy for the
      relief of moderate to severe nociceptive and neuropathic pain may offer an improvement in
      pain therapy by increasing patient compliance with their treatment regimen.
    

Eligibility criteria:

        Healthy volunteers Inclusion criteria

          1. Males and non-pregnant, non-breastfeeding females

          2. 18-65 years old

        Exclusion criteria

          1. Use of any mu-opioid agent in the last 3 months

          2. Structural or metabolic diseases/conditions that affect the gastrointestinal system,
             or functional gastrointestinal disorders. For screening the shortened screening
             version of the Bowel Disease Questionnaire (Appendix) will be used to exclude subjects
             with dyspepsia, irritable bowel syndrome or significant gastrointestinal symptoms. Of
             19 questions, participants have to have three or less positives to be eligible to
             participate.

          3. Unable to withdraw medications 48 hours prior to the study :

               -  Alter GI transit including laxatives, magnesium or aluminum-containing antacids,
                  prokinetics, erythromycin, narcotics, anticholinergics, tricyclic
                  antidepressants, selective serotonin re-uptake inhibitors (SSRIs) and newer
                  antidepressants.

               -  Analgesic drugs including opiates, nonsteroidal anti-inflammatory drugs (NSAIDs),
                  COX 2 inhibitors

               -  SSRI NOTE: Low stable doses of thyroid replacement, estrogen replacement, low
                  dose aspirin for cardioprotection and birth control pills or depot injections are
                  permissible.

          4. Female subjects who are pregnant or breast feeding.

          5. Clinical evidence (including physical exam, ECG, hemoglobin level and review of the
             medical history) of significant cardiovascular, respiratory, renal, hepatic,
             gastrointestinal, hematological, neurological, psychiatric, or other disease that
             interfere with the objectives of the study.

          6. Subjects who are considered by the investigator to be alcoholics not in remission or
             known substance abusers.

          7. Subjects who have participated in another clinical study within the past 30 days

          8. History of porphyria, renal (creatinine > 1.5mg/dL) or significant liver impairment
             (transaminases, alkaline phosphatase of gamma-glutamyl transpeptidase (GGT) >2 times
             upper limit of normal)