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

Ortho-McNeil Janssen Scientific Affairs, LLC382 enrolled

Overview

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.

This is a double-blind (neither the patient nor the study doctor knows the name of the assigned study drug during the study), randomized (study drug selected by chance like flipping a coin), active-comparator (patient will get active drug and there is no inactive drug), outpatient study to evaluate efficacy and how well a patient tolerates multiple doses of tapentadol immediate release (IR) versus oxycodone IR for short-term moderate to severe post-operative pain after arthroscopic (a surgical technique whereby a doctor inserts a tube-like instrument into a joint to visually inspect and repair tissues) shoulder surgery. About 370 patients will be enrolled to either receive tapentadol IR or oxycodone IR until approximately 150 patients in each treatment group are enrolled. After obtaining informed consent, patients will have screening visit procedures to determine study eligibility. Visit 1 (screening) may begin up to 21 days prior to surgery. Pre-operative assessments (e.g., physical examinations, clinical laboratory assessments) will be conducted as part of routine procedures. Patients will have a urine drug test and women who are able to have children will have a urine pregnancy test performed as part of screening prior to the study. Height and weight will be taken and a sleep questionnaire will also be completed at screening. Study staff will conduct pre-operative teaching regarding post-operative pain including: the pain intensity assessment for the study (11-point numeric rating scale where 0=no pain and 10=pain as bad as you can imagine); descriptions of mild, moderate and severe pain; instructions for dosing with study medication; and completing the study diary. Eligible patients will be post-operative men and women who have undergone elective outpatient arthroscopic shoulder surgery. Patients must have received a regional interscalene (within the scalene muscles) nerve block as the primary anesthetic (numbing medication) during the procedure and do not require intravenous (through a vein) patient-controlled analgesia post-operatively. Patients who are expected to have moderate to severe acute post-operative pain from shoulder surgery and who are appropriate candidates for outpatient pain management with an oral opioid (narcotic) pain medication will be eligible. In addition, appropriate patients are expected to require oral opioid pain medication post-operatively. Patients who continue to meet all study criteria post-operatively will be assigned to a study drug group prior to PACU discharge (PACU is considered Visit 2) and will be sent home with study medication. All patients will be prescribed a standard regimen of cold pack application to the surgical shoulder. Patients will be instructed to take the first dose of study medication as their first oral pain medication when they have at least "moderate" pain (prior to discharge or at home). Patients will be reminded about instructions on post-operative pain that were discussed during the pre-operative screening visit. Patients will also be instructed to complete a diary assessment of their current pain intensity before taking the first dose of study medication. Day 1 will be the calendar day when the patient takes the first dose of study medication. Starting on Day 1, patients will be instructed to complete assessments in paper diaries each morning and evening related to pain intensity, pain relief, and occurrences of vomiting. All patients will be contacted by telephone by a member of the study staff on the day following surgery. The staff will verify that the first dose of study medication was taken and the baseline pain intensity assessment was recorded. All patients will receive a second telephone call from the study staff on Day 3. During this telephone call, site personnel will inquire about the patient's overall status and will reinforce diary compliance. If the study staff determines it is necessary, the patient will be required to return to the study site for an unscheduled visit. Patients may take up to 2 pills (any form) of acetaminophen for pain other than post-operative shoulder pain (e.g., headache, back pain) once per day only for up to a total of 2 days during the study. Patients who take up to 325 mg/day aspirin as prevention for a heart condition will be permitted to enter the study and continue on study medication provided they are on a stable dose for at least 1 month prior to study entry and plan to continue the same dose during the study. Patients who complete the study will return to the study site for a final visit (Visit 3) on Day 7. Patients who discontinue early for any reason (i.e., lack of efficacy, adverse events, patient's choice) should contact the study staff before taking supplemental pain medication and schedule his/her final visit. Patients will complete a final assessment of pain intensity and pain relief. In addition, all patients will complete a sleep questionnaire, a Patient Global Impression of Change and an assessment of satisfaction with treatment. The study doctor will complete a Clinician Global Impression of Change and will record any medical resource utilization noted in the office charts (e.g., unplanned calls from the subject, unscheduled office visits, emergency room visits). Vital signs will be obtained and study medication will be collected and counted. Patients will have adverse events assessed and any changes in concomitant medications (other medications taken at the same time as the study medication) recorded. All patients will have post-study medication prescribed at the study doctor's discretion. A patient may elect to take supplemental pain medication to treat their post-operative shoulder pain at any time during the study; however, patients who take supplemental pain medication will be considered discontinued from the study. Patients will be assigned by chance equally (1:1) in a blinded (neither the patient or study doctor knows) fashion to get tapentadol immediate release (IR) 50 or 100 mg vs oxycodone IR 5 or 10 mg, every 4-6 hours as needed. Treatment is up to 7 days starting on Day 1 with one capsule of study medication. A "re-dose" is permitted and may be administered as soon as one hour after the first dose only. For subsequent doses, patients may take one or two capsules every 4 to 6 hours as needed.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

382

Conditions

Postoperative Pain

Interventions

Tapentadol IRDRUG

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

Oxycodone IRDRUG

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Summary and Analysis of Sum of Pain Intensity Difference (SPID) (With Imputation) Over 3 Days (72 Hours)

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.

Time frame: 3 Days (72 hours)

Secondary Outcomes

Summary of Kaplan-Meier Estimates for Time to Achieve 50% Reduction in Pain Intensity From Baseline

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.

Time frame: 7 Days

Summary of Kaplan-Meier Estimates for Time to Achieve 30% Reduction in Pain Intensity From Baseline

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.

Time frame: 7 Days

Summary of 30% Responder Rate (With Imputation) on Day 3

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.

Data from ClinicalTrials.gov

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Summary of 30% Responder Rate (With Imputation) on Day 7

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.

Time frame: Day 7

Summary of 50% Responder Rate (With Imputation) on Day 3

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.

Time frame: Day 3

Summary of 50% Responder Rate (With Imputation) on Day 7

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.

Time frame: Day 7

Summary and Analysis of Sum of Pain Intensity Difference (SPID) (With Imputation) Over 2 Days (48 Hours)

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.

Time frame: 2 Days (48 hours)

Summary and Analysis of Sum of Pain Intensity Difference (SPID) (With Imputation) Over 7 Days

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.

Time frame: 7 Days

Summary and Analysis of Total Pain Relief (TOTPAR) (With Imputation) Over 2 Days (48 Hours)

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.

Time frame: 2 Days (48 hours)

Summary and Analysis of Total Pain Relief (TOTPAR) (With Imputation) Over 3 Days (72hours)

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.

Time frame: 3 Days (72hours)

Summary and Analysis of Total Pain Relief (TOTPAR) (With Imputation) Over 7 Days

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.

Time frame: 7 Days

Summary and Analysis of the Sum of Total Pain Relief and Sum of Pain Intensity Difference (SPRID) (With Imputation) Over 2 Days (48 Hours)

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.

Time frame: 2 Days (48 hours)

Summary and Analysis of the Sum of Total Pain Relief and Sum of Pain Intensity Difference (SPRID) (With Imputation) Over 3 Days (72 Hours)

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.

Time frame: 3 Days (72hours)

Summary and Analysis of the Sum of Total Pain Relief and Sum of Pain Intensity Difference (SPRID) (With Imputation) Over 7 Days

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.

Time frame: 7 Days

Subject Satisfaction With Treatment

Treatment satisfaction was measured using a 7-point scale where 1 = very satisfied and 7 = very dissatisfied

Time frame: 7 Days

Patient Global Impression of Change (PGIC) at End of Study

Patient Global Impression of Change (PGIC) was defined as the 7-point numeric scale, where 1=very much improved to 7=very much worse.

Time frame: 7 Days

Clinician Global Impression of Change (CGIC) at End of Study

Clinician Global Impression of Change (CGIC) was defined as the 7-point numeric scale, where 1=very much improved to 7=very much worse.

Time frame: 7 Days

Summary of Medical Resource Utilization - Number of Calls by the Subject to Study Site Personnel

Information associated with contacts with a healthcare professional was collected by the investigator and study staff for all subjects throughout the study.

Time frame: 7 Days

Summary of Medical Resource Utilization - Number of Other Types of Contacts With Healthcare Professionals

Information associated with contacts with a healthcare professional was collected by the investigator and study staff for all subjects throughout the study.

Time frame: 7 Days

Sleep Quality: Trouble Falling Asleep? - Shift of Measurement From Baseline to End of Study (Tapentadol IR)

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).