Clinical trial NCT01500317: Comparison of the Effects of Tapentadol and Oxycodone on Gastrointestinal and Colonic Transit in Humans
Official title: Comparison of the Effects of Tapentadol and Oxycodone on Gastrointestinal and Colonic Transit in Humans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Effects of 2 Mu-opiates on Gastrointestinal Transit
Keywords: tapentadol
oxycodone
mu-opiate
stomach
small intestine
colon
motility
nausea
constipation
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Center for Research Resources (NCRR)
First posted: 2011-12-28
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief 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.

Detailed description: Single center, parallel group, randomized controlled trial of tapentadol, oxycodone and placebo effects on gastrointestinal and colonic transit in healthy human volunteers

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)

Primary outcomes:
measure: Colonic Transit, Geometric Center at 24 Hours
timeFrame: 24 hours
measure: Gastric Emptying Half-time (t1/2) at 24 Hours
timeFrame: 24 hours
Secondary outcomes:
measure: Colonic Geometric Center at 8 and 48 Hours
timeFrame: 8 hours, 48 hours
measure: Colonic Filling at 6 Hours
timeFrame: 6 hours
measure: Ascending Colon Emptying (AC t1/2)
timeFrame: Over the first 24 hours after ingestion of the radioisotopically labeled charcoal particles
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Michael Camilleri, MD
role: PRINCIPAL_INVESTIGATOR
References: