Comparison of the Effects of Tapentadol and Oxycodone on Gastrointestinal and Colonic Transit in Humans

NCT01500317 | Completed Phase 4 Results

• 3 other identifiers: 11-002334Pharmacodynamic studyUL1RR024150
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

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.

Conditions

Effects of 2 Mu-opiates on Gastrointestinal Transit

Keywords

tapentadol; oxycodone; mu-opiate; stomach; small intestine; colon; motility; nausea; constipation

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Colonic Geometric Center at 8 and 48 Hours

  8 hours, 48 hours

• Colonic Filling at 6 Hours

  6 hours

• Ascending Colon Emptying (AC t1/2)

  Over the first 24 hours after ingestion of the radioisotopically labeled charcoal particles

Study Arms (3)

Tapentadol

ACTIVE COMPARATOR

75 mg tapentadol tid

Drug: Tapentadol

Oxycodone

ACTIVE COMPARATOR

5 mg oxycodone tid

Drug: Oxycodone

Placebo

PLACEBO COMPARATOR

Placebo tid

Drug: Placebo

Interventions

Tapentadol DRUG

Subjects received tapentadol immediate release formulation, 75 mg three times per day (tid) for 48 hours.

Also known as: Tapentadol brand name: Nucynta

Tapentadol

Oxycodone DRUG

Subjects received oxycodone immediate release formulation, 5 mg three times per day (tid) for 48 hours.

Also known as: Dazidox, ETH-Oxydose, Endocodone, Oxecta, Oxy IR, Oxycontin, Oxyfast, Percolone, Roxicodone

Oxycodone

Placebo DRUG

Subjects received placebo three times per day (tid) for 48 hours.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and non-pregnant, non-breastfeeding females
• years old

You may not qualify if:

• Use of any mu-opioid agent in the last 3 months
• 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.
• 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.
• Female subjects who are pregnant or breast feeding.
• 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.
• Subjects who are considered by the investigator to be alcoholics not in remission or known substance abusers.
• Subjects who have participated in another clinical study within the past 30 days
• 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)

Sponsors & Collaborators

• Mayo Clinic: lead
• National Center for Research Resources (NCRR): collaborator

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Nausea; Constipation

Interventions

Tapentadol; Oxycodone

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Codeine; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Michael Camilleri
• Organization: Mayo Clinic

camilleri.michael@mayo.edu

507-284-6218

Study Officials

• Michael Camilleri, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: May 20, 2011
• First Posted: December 28, 2011
• Study Start: May 1, 2011
• Primary Completion: October 1, 2011
• Study Completion: December 1, 2011
• Last Updated: December 17, 2012
• Results First Posted: December 17, 2012

Record last verified: 2012-12

Locations

US (1)