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

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.

Study Overview

• Status: Completed
• Conditions: Effects of 2 Mu-opiates on Gastrointestinal Transit
• Intervention / Treatment: Drug: Tapentadol; Drug: Oxycodone; Drug: Placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: 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: Oxycontin; Oxecta; Roxicodone; Dazidox; ETH-Oxydose; Endocodone; Oxy IR; Oxyfast; Percolone
Placebo Comparator: Placebo; Placebo tid	Drug: Placebo; Subjects received placebo three times per day (tid) for 48 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Colonic Transit, Geometric Center at 24 Hours	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.	24 hours
Gastric Emptying Half-time (t1/2) at 24 Hours		24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Colonic Geometric Center at 8 and 48 Hours	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.	8 hours, 48 hours
Colonic Filling at 6 Hours	Percent of the radio-labeled meal that reached the colon at 6 hours, indirectly reflecting small bowel transit time.	6 hours
Ascending Colon Emptying (AC t1/2)	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.	Over the first 24 hours after ingestion of the radioisotopically labeled charcoal particles

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Center for Research Resources (NCRR)

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: May 20, 2011
• First Submitted That Met QC Criteria: December 22, 2011
• First Posted (Estimate): December 28, 2011

Study Record Updates

• Last Update Posted (Estimate): December 17, 2012
• Last Update Submitted That Met QC Criteria: December 13, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: nausea; colon; oxycodone; constipation; stomach; motility; small intestine; tapentadol; mu-opiate
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Adrenergic Uptake Inhibitors; Oxycodone; Tapentadol
• Other Study ID Numbers: 11-002334; UL1RR024150 (U.S. NIH Grant/Contract); Pharmacodynamic study (Other Identifier: Mayo Clinic)