Safety and Efficacy of Tapentadol Immediate Release (IR) and Oxycodone IR for Treatment of Acute Post-op Pain Following Elective Arthroscopic (Surgery Using a Thin Flexible Scope) Shoulder Surgery - Full Text View

Sponsor:	Ortho-McNeil Janssen Scientific Affairs, LLC
Collaborator:	Grünenthal GmbH
Information provided by:	Ortho-McNeil Janssen Scientific Affairs, LLC
ClinicalTrials.gov Identifier:	NCT00814580

Purpose

The purpose of this study is to evaluate how tapentadol immediate release (IR) and oxycodone IR treat moderate to severe post-operative pain after elective arthroscopic shoulder surgery.

Condition	Intervention	Phase
Postoperative Pain	Drug: Tapentadol IR Drug: Oxycodone IR	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Randomized, Double-Blind, Multi-Center, Parallel-Group Study of Tapentadol Immediate Release (IR) Versus Oxycodone IR for the Treatment of Subjects With Acute Post-Operative Pain Following Elective Arthroscopic Shoulder Surgery

Resource links provided by NLM:

Drug Information available for: Oxycodone Tapentadol Oxycodone hydrochloride

U.S. FDA Resources

Further study details as provided by Ortho-McNeil Janssen Scientific Affairs, LLC:

Primary Outcome Measures:

Summary and Analysis of Sum of Pain Intensity Difference (SPID) (With Imputation) Over 3 Days (72 Hours) [ Time Frame: 3 Days (72 hours) ] [ Designated as safety issue: No ]
Pain Intensity (PI) was assessed on 11-point numerical rating scale from 0=no pain to 10=pain as bad as you can imagine. Pain Intensity Difference (PID) was the difference between baseline PI (prior to the first dose) and current PI at assessment. SPID72 was calculated as the time-weighted Sum of PID scores over 72 hours. The range of SPID72 is from -720 to 720. The higher value in SPID indicates greater pain relief.

Secondary Outcome Measures:

Summary of Kaplan-Meier Estimates for Time to Achieve 50% Reduction in Pain Intensity From Baseline [ Time Frame: 7 Days ] [ Designated as safety issue: No ]
From date of first administration of study medication to time to achieve adequate 50% reduction in pain intensity from baseline score. Censored observations included subjects who completed or discontinued from the study without a 50% reduction in pain intensity from baseline score. If a subject discontinued due to lack of efficacy (including rescue medication), the subject was censored on Day 7, 12 PM.
Summary of Kaplan-Meier Estimates for Time to Achieve 30% Reduction in Pain Intensity From Baseline [ Time Frame: 7 Days ] [ Designated as safety issue: No ]
From date of first administration of study medication to time to achieve adequate 30% reduction in pain intensity from baseline score. Censored observations included subjects who completed or discontinued from the study without a 30% reduction in pain intensity from baseline score. If a subject discontinued due to lack of efficacy (including rescue medication), the subject was censored on Day 7, 12 PM.
Summary of 30% Responder Rate (With Imputation) on Day 3 [ Time Frame: Day 3 ] [ Designated as safety issue: No ]
The 30% responder rate was defined as the proportion of participants with a value of percentage change greater than or equal to the 30% from baseline in pain intensity at Day 3 (average of Day 3 PM and Day 4 AM). If a subject has only the Day 3 PM value or Day 4 AM value, then response rate will be based on the non-missing value. If a subject withdraws or uses rescue medication before Day 3 PM then Baseline Observation Carried Forward (BOCF) will be imputed. Last Observation Carried Forward (LOCF) may be used if no value afterward.
Summary of 30% Responder Rate (With Imputation) on Day 7 [ Time Frame: Day 7 ] [ Designated as safety issue: No ]
The 30% responder rate was defined as the proportion of participants with a value of percentage change greater than or equal to the 30% from baseline in pain intensity at Day 7 (average of Day 6 PM and Day 7 AM). If a subject has only the Day 6 PM value or Day 7 AM value, then response rate will be based on the non-missing value. If a subject withdraws or uses rescue medication before Day 6 PM then BOCF will be imputed. LOCF may be used if no value afterward.
Summary of 50% Responder Rate (With Imputation) on Day 3 [ Time Frame: Day 3 ] [ Designated as safety issue: No ]
The 50% responder rate was defined as the proportion of participants with a value of percentage change greater than or equal to the 50% from baseline in pain intensity at Day 3 (average of Day 3 PM and Day 4 AM). If a subject has only the Day 3 PM value or Day 4 AM value, then response rate will be based on the non-missing value. If a subject withdraws or uses rescue medication before Day 3 PM then BOCF will be imputed. LOCF may be used if no value afterward.
Summary of 50% Responder Rate (With Imputation) on Day 7 [ Time Frame: Day 7 ] [ Designated as safety issue: No ]
The 50% responder rate was defined as the proportion of participants with a value of percentage change greater than or equal to the 50% from baseline in pain intensity at Day 7 (average of Day 6 PM and Day 7 AM). If a subject has only the Day 6 PM value or Day 7 AM value, then response rate will be based on the non-missing value. If a subject withdraws or uses rescue medication before Day 6 PM then BOCF will be imputed. LOCF may be used if no value afterward.
Summary and Analysis of Sum of Pain Intensity Difference (SPID) (With Imputation) Over 2 Days (48 Hours) [ Time Frame: 2 Days (48 hours) ] [ Designated as safety issue: No ]
Pain Intensity (PI) was assessed on 11-point numerical rating scale from 0=no pain to 10=pain as bad as you can imagine. Pain Intensity Difference (PID) was the difference between baseline PI (prior to the first dose) and current PI at assessment. SPID48 was calculated as the time-weighted Sum of PID scores over 48 hours. The range of SPID48 is from -480 to 480. The higher value in SPID indicates greater pain relief.
Summary and Analysis of Sum of Pain Intensity Difference (SPID) (With Imputation) Over 7 Days [ Time Frame: 7 Days ] [ Designated as safety issue: No ]
Pain Intensity (PI) was assessed on 11-point numerical rating scale from 0=no pain to 10=pain as bad as you can imagine. Pain Intensity Difference (PID) was the difference between baseline PI (prior to the first dose) and current PI at assessment. SPID over 7 Days was calculated as the time-weighted Sum of PID scores up to Day 7, 8 AM. The range is from -1440 to 1440. The higher value in SPID indicates greater pain relief.
Summary and Analysis of Total Pain Relief (TOTPAR) (With Imputation) Over 2 Days (48 Hours) [ Time Frame: 2 Days (48 hours) ] [ Designated as safety issue: No ]
Pain Relief was defined as a 5-point categorical scale of 0-4 (0=none, 1=A little, 2=Some, 3=A lot, 4=Complete). Total Pain Relief (TOTPAR) was calculated as the time-weighted sum over all pain relief up to hour 48. The range of TOTPAR over 2 days is from 0 to 192. A higher value in TOTPAR indicated greater pain relief.
Summary and Analysis of Total Pain Relief (TOTPAR) (With Imputation) Over 3 Days (72hours) [ Time Frame: 3 Days (72hours) ] [ Designated as safety issue: No ]
Pain Relief was defined as a 5-point categorical scale of 0-4 (0=none, 1=A little, 2=Some, 3=A lot, 4=Complete). Total Pain Relief (TOTPAR) was calculated as the time-weighted sum over all pain relief up to hour 72. The range of TOTPAR over 3 days is from 0 to 288. A higher value in TOTPAR indicated greater pain relief.
Summary and Analysis of Total Pain Relief (TOTPAR) (With Imputation) Over 7 Days [ Time Frame: 7 Days ] [ Designated as safety issue: No ]
Pain Relief was defined as a 5-point categorical scale of 0-4 (0=none, 1=A little, 2=Some, 3=A lot, 4=Complete). Total Pain Relief (TOTPAR) was calculated as the time-weighted sum over all pain relief up to Day 7, 8 AM. The range of TOTPAR over 7 days is from 0 to 576. A higher value in TOTPAR indicated greater pain relief.
Summary and Analysis of the Sum of Total Pain Relief and Sum of Pain Intensity Difference (SPRID) (With Imputation) Over 2 Days (48 Hours) [ Time Frame: 2 Days (48 hours) ] [ Designated as safety issue: No ]
The Sum of Total Pain Relief and Sum of Pain Intensity Difference (SPRID) was derived from Sum of TOTPAR and SPID. The range of SPRID over 2 days is from -480 to 672. A higher value in SPRID indicated greater pain relief.
Summary and Analysis of the Sum of Total Pain Relief and Sum of Pain Intensity Difference (SPRID) (With Imputation) Over 3 Days (72 Hours) [ Time Frame: 3 Days (72hours) ] [ Designated as safety issue: No ]
The Sum of Total Pain Relief and Sum of Pain Intensity Difference (SPRID) was derived from Sum of TOTPAR and SPID. The range of SPRID over 3 days is from -720 to 1008. A higher value in SPRID indicated greater pain relief.
Summary and Analysis of the Sum of Total Pain Relief and Sum of Pain Intensity Difference (SPRID) (With Imputation) Over 7 Days [ Time Frame: 7 Days ] [ Designated as safety issue: No ]
The Sum of Total Pain Relief and Sum of Pain Intensity Difference (SPRID) was derived from Sum of TOTPAR and SPID. The range of SPRID over 7 days is from -1440 to 2016. A higher value in SPRID indicated greater pain relief.
Subject Satisfaction With Treatment [ Time Frame: 7 Days ] [ Designated as safety issue: No ]
Treatment satisfaction was measured using a 7-point scale where 1 = very satisfied and 7 = very dissatisfied
Patient Global Impression of Change (PGIC) at End of Study [ Time Frame: 7 Days ] [ Designated as safety issue: No ]
Patient Global Impression of Change (PGIC) was defined as the 7-point numeric scale, where 1=very much improved to 7=very much worse.
Clinician Global Impression of Change (CGIC) at End of Study [ Time Frame: 7 Days ] [ Designated as safety issue: No ]
Clinician Global Impression of Change (CGIC) was defined as the 7-point numeric scale, where 1=very much improved to 7=very much worse.
Summary of Medical Resource Utilization - Number of Calls by the Subject to Study Site Personnel [ Time Frame: 7 Days ] [ Designated as safety issue: No ]
Information associated with contacts with a healthcare professional was collected by the investigator and study staff for all subjects throughout the study.
Summary of Medical Resource Utilization - Number of Other Types of Contacts With Healthcare Professionals [ Time Frame: 7 Days ] [ Designated as safety issue: No ]
Information associated with contacts with a healthcare professional was collected by the investigator and study staff for all subjects throughout the study.
Sleep Quality: Trouble Falling Asleep? - Shift of Measurement From Baseline to End of Study (Tapentadol IR) [ Time Frame: Baseline and 7 Days ] [ Designated as safety issue: No ]
Over the past 7 days patients reported "trouble falling asleep" by using a 4-category scale (not at all, 1 to 2 days, 3 to 5 days, 6 to 7 days) at baseline and the final study visit (Day 7).
Sleep Quality: Trouble Falling Asleep? - Shift of Measurement From Baseline to End of Study (Oxycodone IR) [ Time Frame: Baseline and 7 Days ] [ Designated as safety issue: No ]
Over the past 7 days patients reported "trouble falling asleep" by using a 4-category scale (not at all, 1 to 2 days, 3 to 5 days, 6 to 7 days) at baseline and the final study visit (Day 7).
Sleep Quality: Wake up Several Times During Night? - Shift of Measurement From Baseline to End of Study (Tapentadol IR) [ Time Frame: Baseline and 7 Days ] [ Designated as safety issue: No ]
Over the past 7 days patients reported "Wake up several times during night" by using a 4-category scale (not at all, 1 to 2 days, 3 to 5 days, 6 to 7 days) at baseline and the final study visit (Day 7).
Sleep Quality: Wake up Several Times During Night? - Shift of Measurement From Baseline to End of Study (Oxycodone IR) [ Time Frame: Baseline and 7 Days ] [ Designated as safety issue: No ]
Over the past 7 days patients reported "Wake up several times during night" by using a 4-category scale (not at all, 1 to 2 days, 3 to 5 days, 6 to 7 days) at baseline and the final study visit (Day 7).
Sleep Quality: Trouble Staying Asleep? - Shift of Measurement From Baseline to End of Study (Tapentadol IR) [ Time Frame: Baseline and 7 Days ] [ Designated as safety issue: No ]
Over the past 7 days patients reported "Trouble staying asleep" by using a 4-category scale (not at all, 1 to 2 days, 3 to 5 days, 6 to 7 days) at baseline and the final study visit (Day 7).
Sleep Quality: Trouble Staying Asleep? - Shift of Measurement From Baseline to End of Study (Oxycodone IR) [ Time Frame: Baseline and 7 Days ] [ Designated as safety issue: No ]
Over the past 7 days patients reported "Trouble staying asleep" by using a 4-category scale (not at all, 1 to 2 days, 3 to 5 days, 6 to 7 days) at baseline and the final study visit (Day 7).
Sleep Quality: Pain Interferes With Sleep? - Shift of Measurement From Baseline to End of Study (Tapentadol IR) [ Time Frame: Baseline and 7 Days ] [ Designated as safety issue: No ]
Over the past 7 days patients reported "Pain interferes with sleep" by using a 4-category scale (not at all, 1 to 2 days, 3 to 5 days, 6 to 7 days) at baseline and the final study visit (Day 7).
Sleep Quality: Pain Interferes With Sleep? - Shift of Measurement From Baseline to End of Study (Oxycodone IR) [ Time Frame: Baseline and 7 Days ] [ Designated as safety issue: No ]
Over the past 7 days patients reported "Pain interferes with sleep" by using a 4-category scale (not at all, 1 to 2 days, 3 to 5 days, 6 to 7 days) at baseline and the final study visit (Day 7).
Sleep Quality: Wake up Feeling Tired and Worn Out? - Shift of Measurement From Baseline to End of Study (Tapentadol IR) [ Time Frame: Baseline and 7 Days ] [ Designated as safety issue: No ]
Over the past 7 days patients reported "Wake up feeling tired and worn out" by using a 4-category scale (not at all, 1 to 2 days, 3 to 5 days, 6 to 7 days) at baseline and the final study visit (Day 7).
Sleep Quality: Wake up Feeling Tired and Worn Out? - Shift of Measurement From Baseline to End of Study (Oxycodone IR) [ Time Frame: Baseline and 7 Days ] [ Designated as safety issue: No ]
Over the past 7 days patients reported "Wake up feeling tired and worn out" by using a 4-category scale (not at all, 1 to 2 days, 3 to 5 days, 6 to 7 days) at baseline and the final study visit (Day 7).
Sleep Quality: Feeling Alert During Daytime Hours? - Shift of Measurement From Baseline to End of Study (Tapentadol IR) [ Time Frame: Baseline and 7 Days ] [ Designated as safety issue: No ]
Over the past 7 days patients reported "Feeling alert during daytime hours" by using a 4-category scale (not at all, 1 to 2 days, 3 to 5 days, 6 to 7 days) at baseline and the final study visit (Day 7).
Sleep Quality: Feeling Alert During Daytime Hours? - Shift of Measurement From Baseline to End of Study (Oxycodone IR) [ Time Frame: Baseline and 7 Days ] [ Designated as safety issue: No ]
Over the past 7 days patients reported "Feeling alert during daytime hours" by using a 4-category scale (not at all, 1 to 2 days, 3 to 5 days, 6 to 7 days) at baseline and the final study visit (Day 7).
Sleep Quality: Feeling Well Rested? - Shift of Measurement From Baseline to End of Study (Tapentadol IR) [ Time Frame: Baseline and 7 Days ] [ Designated as safety issue: No ]
Over the past 7 days patients reported "Feeling well rested" by using a 4-category scale (not at all, 1 to 2 days, 3 to 5 days, 6 to 7 days) at baseline and the final study visit (Day 7).
Sleep Quality: Feeling Well Rested? - Shift of Measurement From Baseline to End of Study (Oxycodone IR) [ Time Frame: Baseline and 7 Days ] [ Designated as safety issue: No ]
Over the past 7 days patients reported "Feeling well rested" by using a 4-category scale (not at all, 1 to 2 days, 3 to 5 days, 6 to 7 days) at baseline and the final study visit (Day 7).

Enrollment:	382
Study Start Date:	December 2008
Study Completion Date:	March 2010
Primary Completion Date:	March 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 001 Tapentadol IR First dose: one 50 mg capsule (a re-dose of 50 mg is permitted as soon as one hour after the first dose on Day 1 if needed) Subsequent doses: one or two capsules (50 mg or 100 mg) every 4 to 6 hours as needed	Drug: Tapentadol IR First dose: one 50 mg capsule (a re-dose of 50 mg is permitted as soon as one hour after the first dose on Day 1, if needed) Subsequent doses: one or two capsules (50 mg or 100 mg) every 4 to 6 hours as needed
Active Comparator: 002 Oxycodone IR First dose: one 5 mg capsule (a re-dose of 5 mg is permitted as soon as one hour after the first dose on Day 1 if needed Subsequent doses: one or two capsules (5 mg or 10 mg) every 4 to 6 hours as needed	Drug: Oxycodone IR First dose: one 5 mg capsule (a re-dose of 5 mg is permitted as soon as one hour after the first dose on Day 1, if needed Subsequent doses: one or two capsules (5 mg or 10 mg) every 4 to 6 hours as needed

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Healthy on the basis of medical history and vital signs and meeting the American Society of Anesthesiology (ASA) physical status I, II, or III
completed screening procedures and have undergone one of the following elective outpatient arthroscopic surgical procedures: rotator cuff repair, labral tear repair, Bankart repair
an arthroscopic mini-open rotator cuff repair
(an arthroscopic distal clavicle resection performed in conjunction with a rotator cuff, labral tear or Bankart repair is also permitted)
received anesthesia administered to the shoulder by interscalene nerve block
receive study medication as the first oral analgesic medication following the orthopedic surgical procedure and expected to have moderate to severe pain requiring oral opioids for at least 3 days after surgery.

Exclusion Criteria:

Patients whose post-operative pain would require non opioid analgesia as standard of care
received a non-allowed procedure
received intraoperative or post-operative anesthesia and/or analgesic medications which are expected to provide post-operative analgesia for >24 hours after discharge from the PACU (recovery room)
received intraoperatively >200 mg fentanyl or the morphine equivalent of another opioid (for the total procedure) or potent inhaled anesthesia (e.g., sevoflurane, isoflurane)
received IV PCA analgesia (intravenous pump the patient controls) in the PACU or a PACU stay >8 hours
expected to require inpatient treatment in a hospital or rehabilitation unit post operatively
anticipate any surgical procedure(s) within 7 days after the initial shoulder surgery
have significant nausea and/or vomiting at the time of randomization (patients may receive an anti-emetic prior to or during surgery)
received any of the following: long-acting or controlled-release opioids within 1-month prior to randomization
immediate release CII opioid formulations (e.g., Opana IR, Percocet, Percodan, oxycodone IR, Dilaudid) for >5 days total within 1 month before, and within 24 hours of, randomization
intra-articular (within a joint) or systemic steroids (except inhalers and topical steroids), within 1 month before randomization (exception, patients on a stable dose of chronic steroids for a minimum of 3 months, for a condition other than the shoulder pain)
use of non-steroidal anti-inflammatory drugs (NSAIDs) within 24-hours of randomization
have taken any CIII opioid formulation (e.g., Tylenol with Codeine) >3 days/week in the 1-month prior to randomization
treated with anticonvulsants, monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), neuroleptics, or serotonin norepinephrine reuptake inhibitors (SNRIs) within 2 weeks before randomization
positive urine drug screen (cocaine, methadone, amphetamines, cannabinoids, opiates, benzodiazepines, barbiturates, and oxycodone)
have an active systemic or local infection
significant co-existing autoimmune inflammatory conditions
history of seizure disorder or epilepsy
presence of any of the following: mild or moderate traumatic brain injury, stroke, transient ischemic attack, or brain neoplasm within 1 year of screening
severe traumatic brain injury, episode(s) of unconsciousness of more than 24 hours duration, or post-traumatic amnesia of more than 24 hours duration within 15 years of screening
known history of alcohol or drug abuse in the study doctor's judgment based on medical history
known or suspected to be opioid tolerant or dependent
known history of laboratory values reflecting severe kidney disease, known history of moderately or severely impaired liver function
history of allergy to, or hypersensitivity to tapentadol, oxycodone, or other components of the medication
history (within the past 6 months) of a major psychiatric disorder
history of suicidal ideation or suicidal attempts within the past 2 years
currently involved in litigation regarding their shoulder injury, have a disability claim or patients who are receiving Worker's Compensation due to their shoulder injury or are being evaluated to receive disability or Worker's Compensation

Responsible Party:	Vice President, Medical Affairs Internal Medicine, Ortho-McNeil Janssen Scientific Affairs, LLC
ClinicalTrials.gov Identifier:	NCT00814580 History of Changes
Other Study ID Numbers:	CR015040, R331333PAI3022, KF5503/49
Study First Received:	December 23, 2008
Results First Received:	March 10, 2011
Last Updated:	December 5, 2011
Health Authority:	United States: Food and Drug Administration