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

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT01500317
• Collaborator: National Center for Research Resources (NCRR) (NIH)
• Enrollment: 38
• Location: 1
• Arms: 3
• Duration (Months): 7
• Patients Per Site Per Month: 5.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Effects of 2 Mu-opiates on Gastrointestinal Transit	Drug: Tapentadol; Drug: Oxycodone; Drug: Placebo	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 38 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Supportive Care
• Official Title: Comparison of the Effects of Tapentadol and Oxycodone on Gastrointestinal and Colonic Transit in Humans
• Study Start Date: May 1, 2011
• Actual Primary Completion Date: Oct 1, 2011
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

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: 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.

Outcome Measures

Primary Outcome Measures

1. Colonic Transit, Geometric Center at 24 Hours [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.

2. Gastric Emptying Half-time (t1/2) at 24 Hours [24 hours]

Secondary Outcome Measures

1. Colonic Geometric Center at 8 and 48 Hours [8 hours, 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.

2. Colonic Filling at 6 Hours [6 hours]

   Percent of the radio-labeled meal that reached the colon at 6 hours, indirectly reflecting small bowel transit time.

3. Ascending Colon Emptying (AC t1/2) [Over the first 24 hours after ingestion of the radioisotopically labeled charcoal particles]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

1. Female subjects who are pregnant or breast feeding.

2. 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.

3. Subjects who are considered by the investigator to be alcoholics not in remission or known substance abusers.

4. Subjects who have participated in another clinical study within the past 30 days

5. 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

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic
• National Center for Research Resources (NCRR)

Investigators

• Principal Investigator: Michael Camilleri, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Michael Camilleri, MD, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT01500317
• Other Study ID Numbers: 11-002334; Pharmacodynamic study; UL1RR024150
• First Posted: Dec 28, 2011
• Last Update Posted: Dec 17, 2012
• Last Verified: Dec 1, 2012

• Keywords provided by Michael Camilleri, MD, Mayo Clinic: tapentadol; oxycodone; mu-opiate; stomach; small intestine; colon; motility; nausea; constipation
• Additional relevant MeSH terms: Oxycodone; Tapentadol

Study Results

Participant Flow

Arm/Group Title	Tapentadol	Oxycodone	Placebo
Arm/Group Description	75 mg tapentadol tid	5 mg oxycodone tid	Placebo tid
Period Title: Overall Study
STARTED	13	12	13
COMPLETED	10	10	13
NOT COMPLETED	3	2	0

Baseline Characteristics

Arm/Group Title	Tapentadol	Oxycodone	Placebo	Total
Arm/Group Description	75 mg tapentadol tid	5 mg oxycodone tid	Placebo tid	Total of all reporting groups
Overall Participants	13	12	13	38
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.99 (7.82)	33.26 (12.94)	39.48 (12)	35.98 (11.11)
Sex: Female, Male (Count of Participants)
Female	9 69.2%	9 75%	10 76.9%	28 73.7%
Male	4 30.8%	3 25%	3 23.1%	10 26.3%
Region of Enrollment (participants) [Number]
United States	13 100%	12 100%	13 100%	38 100%
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	26.27 (4.88)	27.36 (6.11)	25.16 (4.88)	26.23 (5.23)

Outcome Measures

1. Primary Outcome

Title	Colonic Transit, Geometric Center at 24 Hours
Description	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.
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tapentadol	Oxycodone	Placebo
Arm/Group Description	75 mg tapentadol tid	5 mg oxycodone tid	Placebo tid
Measure Participants	13	12	13
Mean (Standard Deviation) [units on a scale]	2.06 (0.67)	2.07 (0.6)	2.17 (0.739)

2. Secondary Outcome

Title	Colonic Geometric Center at 8 and 48 Hours
Description	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.
Time Frame	8 hours, 48 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tapentadol	Oxycodone	Placebo
Arm/Group Description	75 mg tapentadol tid	5 mg oxycodone tid	Placebo tid
Measure Participants	13	12	13
Colonic geometric center at 8 hr	0.78 (0.589)	0.75 (0.54)	0.79 (0.98)
Colonic geometric center at 48 hr	3.59 (1.16)	3.51 (0.82)	3.742 (0.83)

3. Primary Outcome

Title	Gastric Emptying Half-time (t1/2) at 24 Hours
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tapentadol	Oxycodone	Placebo
Arm/Group Description	75 mg tapentadol tid	5 mg oxycodone tid	Placebo tid
Measure Participants	13	12	13
Mean (Standard Deviation) [minutes]	159.2 (46.45)	155.2 (38.44)	124.7 (39.08)

4. Secondary Outcome

Title	Colonic Filling at 6 Hours
Description	Percent of the radio-labeled meal that reached the colon at 6 hours, indirectly reflecting small bowel transit time.
Time Frame	6 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tapentadol	Oxycodone	Placebo
Arm/Group Description	75 mg tapentadol tid	5 mg oxycodone tid	Placebo tid
Measure Participants	13	12	13
Mean (Standard Deviation) [percentage of radio-labeled meal]	35.55 (32.3)	38.6 (19.5)	65.54 (26.1)

5. Secondary Outcome

Title	Ascending Colon Emptying (AC t1/2)
Description	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.
Time Frame	Over the first 24 hours after ingestion of the radioisotopically labeled charcoal particles

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tapentadol	Oxycodone	Placebo
Arm/Group Description	75 mg tapentadol tid	5 mg oxycodone tid	Placebo tid
Measure Participants	13	12	13
Mean (Standard Deviation) [hours]	21.92 (9.89)	19.3 (6.27)	17.88 (6.21)

Adverse Events

Time Frame	Adverse events were recorded during visits, and participants were contacted 5-7 days following the last dose of study medication to determine if any adverse events had occurred.
Arm/Group Title	Tapentadol		Oxycodone		Placebo
Arm/Group Description	75 mg tapentadol tid		5 mg oxycodone tid		Placebo tid
All Cause Mortality
	Tapentadol		Oxycodone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Tapentadol		Oxycodone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/12 (0%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	Tapentadol		Oxycodone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/13 (76.9%)		4/12 (33.3%)		1/13 (7.7%)
Gastrointestinal disorders
Nausea	5/13 (38.5%)	5	4/12 (33.3%)	4	0/13 (0%)	0
Vomiting	3/13 (23.1%)	3	1/12 (8.3%)	1	0/13 (0%)	0
Nervous system disorders
Headache	1/13 (7.7%)	1	0/12 (0%)	0	1/13 (7.7%)	1
Dizziness	5/13 (38.5%)	5	0/12 (0%)	0	0/13 (0%)	0
Light-headed	2/13 (15.4%)	2	0/12 (0%)	0	0/13 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.