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

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

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.

Study Overview

• Status: Completed
• Conditions: Hallux Valgus
• Intervention / Treatment: Drug: Tapentadol IR 50 mg; Drug: Tapentadol IR 75 mg; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 353
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of
  • Chungcheongbuk-Do, Korea, Republic of
  • Gwangju, Korea, Republic of
  • Gyeonggi-Do, Korea, Republic of
  • Pusan, Korea, Republic of
  • Seoul, Korea, Republic of
  • Ulsan, Korea, Republic of

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; 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.
Experimental: Tapentadol IR 50 mg	Drug: Tapentadol IR 50 mg; 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.
Experimental: Tapentadol IR 75 mg	Drug: Tapentadol IR 75 mg; 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.

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
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
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
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

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Publications and helpful links

General Publications

• Lee YK, Ko JS, Rhim HY, Lee EJ, Karcher K, Li H, Shapiro D, Lee HS. Acute postoperative pain relief with immediate-release tapentadol: randomized, double-blind, placebo-controlled study conducted in South Korea. Curr Med Res Opin. 2014 Dec;30(12):2561-70. doi: 10.1185/03007995.2014.954665. Epub 2014 Aug 27.

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: January 19, 2012
• First Submitted That Met QC Criteria: January 19, 2012
• First Posted (Estimate): January 24, 2012

Study Record Updates

• Last Update Posted (Estimate): April 28, 2014
• Last Update Submitted That Met QC Criteria: March 28, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: Acute pain; Tapentadol; Hallux Valgus; Bunionectomy; Bunion; Tapentadol IR
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Musculoskeletal Diseases; Foot Deformities; Acute Pain; Hallux Valgus; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Adrenergic Uptake Inhibitors; Tapentadol
• Other Study ID Numbers: CR100459; R331333PAI3030 (Other Identifier: Janssen Research & Development, LLC)