Comparison of the Effects of Tapentadol and Oxycodone on Gastrointestinal and Colonic Transit in Humans (tap-oxy)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Michael Camilleri, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01500317
First received: May 20, 2011
Last updated: December 13, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Effects of 2 Mu-opiates on Gastrointestinal Transit
Drug: Tapentadol
Drug: Oxycodone
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Supportive Care
Official Title: Comparison of the Effects of Tapentadol and Oxycodone on Gastrointestinal and Colonic Transit in Humans

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Colonic Transit, Geometric Center at 24 Hours [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule. Anterior and posterior gamma images are taken hourly. The geometric center (GC) is the weighted average of counts in the different colonic regions. The scale ranges from 1 to 5; a high GC implies faster colonic transit, a GC of 1 implies all isotope is in the ascending colon, and a GC of 5 implies all isotope is in the stool.

  • Gastric Emptying Half-time (t1/2) at 24 Hours [ Time Frame: 24 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Colonic Geometric Center at 8 and 48 Hours [ Time Frame: 8 hours, 48 hours ] [ Designated as safety issue: No ]
    The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule. Anterior and posterior gamma images are taken hourly. The geometric center (GC) is the weighted average of counts in the different colonic regions. The scale ranges from 1 to 5; a high GC implies faster colonic transit, a GC of 1 implies all isotope is in the ascending colon, and a GC of 5 implies all isotope is in the stool.

  • Colonic Filling at 6 Hours [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
    Percent of the radio-labeled meal that reached the colon at 6 hours, indirectly reflecting small bowel transit time.

  • Ascending Colon Emptying (AC t1/2) [ Time Frame: Over the first 24 hours after ingestion of the radioisotopically labeled charcoal particles ] [ Designated as safety issue: No ]
    Ascending colon emptying t1/2 will be estimated by power exponential analysis of the proportionate emptying over time of counts from the colon. The primary data for this analysis will be the proportion of decay and depth-corrected counts in the ascending colon on the hourly scans on the first day of transit measurement and the 24 hour data.


Enrollment: 38
Study Start Date: May 2011
Study Completion Date: December 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Tapentadol
75 mg tapentadol tid
Drug: Tapentadol
Subjects received tapentadol immediate release formulation, 75 mg three times per day (tid) for 48 hours.
Other Name: Tapentadol brand name: Nucynta
Active Comparator: Oxycodone
5 mg oxycodone tid
Drug: Oxycodone
Subjects received oxycodone immediate release formulation, 5 mg three times per day (tid) for 48 hours.
Other Names:
  • Dazidox
  • ETH-Oxydose
  • Endocodone
  • Oxecta
  • Oxy IR
  • Oxycontin
  • Oxyfast
  • Percolone
  • Roxicodone
Placebo Comparator: Placebo
Placebo tid
Drug: Placebo
Subjects received placebo three times per day (tid) for 48 hours.

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01500317

Locations
United States, Minnesota
Mayo Clinic in Rochester
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Michael Camilleri, MD Mayo Clinic
  More Information

No publications provided

Responsible Party: Michael Camilleri, MD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01500317     History of Changes
Other Study ID Numbers: 11-002334, Pharmacodynamic study, UL1RR024150
Study First Received: May 20, 2011
Results First Received: November 8, 2012
Last Updated: December 13, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Mayo Clinic:
tapentadol
oxycodone
mu-opiate
stomach
small intestine
colon
motility
nausea
constipation

Additional relevant MeSH terms:
Oxycodone
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 21, 2014