A Study of Tapentadol Immediate-Release in the Treatment of Patients With Acute Pain From Bunionectomy

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to demonstrate the efficacy of at least 1 dose of tapentadol IR 50 mg and/or 75 mg versus placebo using the sum of pain intensity difference at 48 hours (SPID48) to measure analgesic effect in Korean patients with acute pain following bunionectomy.

Detailed Description
-----------------
This is a randomized (study drug assigned by chance like flipping a coin), double-blind (neither physician nor patient knows the name of the assigned drug), placebo-controlled, parallel-group, multicenter study to evaluate the efficacy and safety of tapentadol immediate-release (IR) 50 mg and 75 mg in patients who are undergoing bunionectomy (a surgical procedure to remove a bunion). This study was designed to be a similar study to the pivotal global study of PAI-3003/KF32 in order to bridge the results from the global studies and to show similarity in effect of tapentadol between Korean and Caucasian population which will allow extrapolation of the foreign clinical data of tapentadol into Korea. The study will be divided into screening period, surgical period, qualification period, and a double-blind treatment period. The study length, including the screening period, will be up to a maximum duration of 32 days. Eligible patients will be randomly assigned to 1 of 3 treatment groups (tapentadol IR 50 mg, tapentadol IR 75 mg or placebo) in a 1:1:1 ratio. Efficacy and safety assessments will be performed during the study.

Official Title
-----------------
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Evaluate the Efficacy and Safety of Tapentadol Immediate-Release Formulation in the Treatment of Acute Pain From Bunionectomy; Bridging Study for Korea

Conditions
-----------------
Hallux Valgus

Intervention / Treatment
-----------------
* Drug: Tapentadol IR 50 mg
* Drug: Tapentadol IR 75 mg
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients who are undergoing primary unilateral first metatarsal bunionectomy that includes a distal Chevron osteotomy only with or without the Akin procedure Healthy or medically stable on the basis of clinical laboratory tests performed at screening. If results are outside the normal reference ranges, the patient may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study Women must be postmenopausal, surgically sterile, abstinent, or practicing or agree to practice an effective method of birth control if they are sexually active before entry and throughout the study. Women of childbearing potential must have a negative serum β human chorionic gonadotropin pregnancy test at screening and a negative urine pregnancy test before surgery If a male and sexually active, agrees to use an approved method of birth control to prevent pregnancy in his female partner and not to donate sperm from the day of first study drug intake until 3 months after the day of last study drug intake. To qualify for entry into the double-blind treatment period, the following criteria must be met: Qualifying baseline pain intensity (PI) must be rated as greater than or equal to 4 on an 11-point (0 to10) PI numerical rating scale (NRS), recorded within 30 minutes before randomization Qualifying PI must occur no earlier than 10 hours after the first surgical incision Qualifying baseline PI must occur within 9 hours after termination of the systemic analgesia during the postoperative surgical period Exclusion Criteria: History of seizure disorder or epilepsy suggested by the presence of mild or moderate traumatic brain injury, stroke, transient ischemic attack, or brain neoplasm within 1 year of screening, and/or severe traumatic brain injury, episode(s) of unconsciousness of more than 24 hours duration, or posttraumatic amnesia of more than 24 hours duration within 15 years of screening History of malignancy within the past 2 years before the start of the study Evidence of active infections that may spread to other areas of the body or a history of human immunodeficiency virus 1 or 2 Clinical laboratory values reflecting severe renal insufficiency Moderately or severely impaired hepatic function, or patients with abnormal alanine aminotransaminase or aspartate aminotransferase Clinical laboratory values outside acceptable limits for surgery in the opinion of the investigator A clinically significant disease that in the investigator's opinion may affect efficacy or safety assessments Treated with anticonvulsants, monoamine oxidase inhibitors, tricyclic antidepressants, neuroleptics, or serotonin norepinephrine reuptake inhibitor within 2 weeks before randomization Systemic steroid therapy, excluding inhalers or topical steroids, within the 4 weeks before screening Women who plan to become pregnant during the study, or who are breast feeding

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tapentadol IR 50 mg<br> | Drug: Tapentadol IR 50 mg<br>* Type= exact number, unit= mg, number= 50, form= tablet, route= oral use. Tapentadol IR will be administered as a single oral dose once every 4 to 6 hours (patients may take their next dose as early as 4 hours, but no later than 6 hours, after the previous dose), for a period of 72 hours.<br>|
| Experimental: Tapentadol IR 75 mg<br> | Drug: Tapentadol IR 75 mg<br>* Type= exact number, unit= mg, number= 75, form= tablet, route= oral use. Tapentadol IR will be administered as a single oral dose once every 4 to 6 hours (patients may take their next dose as early as 4 hours, but no later than 6 hours, after the previous dose), for a period of 72 hours.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Form= tablet, route= oral use. Placebo tablets will be administered as a single oral dose every 4 to 6 hours, for a period of 72 hours.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sum of Pain Intensity Differences (SPID) Over 48 Hours | Pain Intensity (PI) was assessed on an 11-point numerical rating scale from 0=no pain to 10=pain as bad as you can imagine. PID was the difference between baseline PI (prior to the first dose) and current PI at assessment. SPID was calculated as the time-weighted Sum of PID scores over 48 hours. Total score ranges from -480 (worst) to 480 (best) for SPID48. A higher value of SPID indicates greater pain relief. | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Reduction in Pain Intensity From Baseline at 12, 24, 48, and 72 Hours | Pain intensity was assessed on a 11-point numerical rating scale from 0=no pain to 10=pain as bad as you can imagine. Participants with no assessment at the given time point, who used an analgesic medication prior to the time point, or who had worse pain intensity at the time point compared to baseline were assigned a percent reduction of 0 percent. | Baseline (Day 1) and 12, 24, 48, and 72 hours | 
| Response Rate for 30 Percent or Greater Reduction in Pain Intensity at 12, 24, 48, and 72 Hours | Response rate was defined as the percentage of participants with a 30 percent or greater reduction in pain intensity from baseline to 12, 24, 48, and 72 hours. Pain intensity was assessed on a 11-point numerical rating scale from 0=no pain to 10=pain as bad as you can imagine. Participants with no assessment at the given time point, who used an analgesic medication prior to the time point, or who had worse pain intensity at the time point compared to baseline were assigned a percent reduction of 0 percent. | 12, 24, 48, and 72 hours | 
| Response Rate for 50 Percent or Greater Reduction in Pain Intensity at 12, 24, 48, and 72 Hours | Response rate was defined as the percentage of participants with a 50 percent or greater reduction in pain intensity from baseline to 12, 24, 48, and 72 hours. Pain intensity was assessed on a 11-point numerical rating scale from 0=no pain to 10=pain as bad as you can imagine. Participants with no assessment at the given time point, who used an analgesic medication prior to the time point, or who had worse pain intensity at the time point compared to baseline were assigned a percent reduction of 0 percent. | 12, 24, 48, and 72 hours | 
| Sum of Pain Intensity Differences (SPID) Over 12, 24, and 72 Hours | Pain Intensity (PI) was assessed on an 11-point numerical rating scale from 0=no pain to 10=pain as bad as you can imagine. PID was the difference between baseline PI (prior to the first dose) and current PI at assessment. SPID was calculated as the time-weighted Sum of PID scores over 12, 24, and 72 hours. Total score ranges from -120 (worst) to 120 (best) for SPID12, -240 (worst) to 240 (best) for SPID24, -720 (worst) to 720 (best) for SPID72. A higher value of SPID indicates greater pain relief. | 12, 24, and 72 hours | 
| Total Pain Relief (TOTPAR) Over 12, 24, 48, and 72 Hours | Participants rated pain relief rated on 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 of pain relief scores up to Hour 12, 24, 48, and 72 hours. Total score ranges from 0 (worst) to 48 (best) for TOTPAR12, 0 (worst) to 96 (best) for TOTPAR24, 0 (worst) to 192 (best) for TOTPAR48, and 0 (worst) to 288 (best) for TOTPAR72. A higher value of TOTPAR indicated greater pain relief. | 12, 24, 48, and 72 hours | 
| Time to First Rescue Medication Use | Rescue medication was defined as any analgesic medication used for participants discontinued due to lack of efficacy (including those started at time of discontinuation) or analgesic medication used during the double-blind period for completed participants. | Up to 48 hours | 
| Sum of Pain Relief and Pain Intensity Differences (SPRID) Over 12, 24, 48, and 72 Hours | Participants rated pain relief rated on 5-point categorical scale of 0-4 (0=none, 1=A little, 2=Some, 3=A lot, 4=Complete). Pain Intensity (PI) was assessed on an 11-point numerical rating scale from 0=no pain to 10=pain as bad as you can imagine. PID was the difference between baseline PI (prior to the first dose) and current PI at assessment. PRID is the sum of pain relief and PID at the same assessment time. SPRID was calculated as the time-weighted Sum of PRID scores over 12, 24, 48, and 72 hours. Total score ranges from -120 (worst) to 168 (best) for SPRID12, -240 (worst) to 336 (best) for SPRID24, -480 (worst) to 672 (best) for SPRID48, and -720 (worst) to 1008 (best) for SPRID72. A higher value of SPRID indicates greater pain relief. | 12, 24, 48, and 72 hours | 
| Patient Global Impression of Change (PGI-C) Score at 72 Hours | The PGI-C is a 7-point scale that requires the patients to assess how much their illness has improved or worsened relative to a baseline state at the beginning of the intervention. The response options are: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; and 7=very much worse. Higher scores indicate worsening. | Baseline (Day 1) and 72 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hallux Valgus, Bunionectomy, Bunion, Acute pain, Tapentadol, Tapentadol IR