A Comparative Study of JNS013 in Participants With Post-Tooth-Extraction Pain

A Double-Blind Comparative Study of JNS013 in Patients With Post-Tooth-Extraction Pain

The purpose of this study is to evaluate the efficacy and safety of JNS013 with single oral dose administration in participants with pain after tooth-extraction of mandibular impacted wisdom tooth.

Study Overview

• Status: Completed
• Conditions: Pain; Postoperative Pain
• Intervention / Treatment: Drug: Placebo; Drug: Tramadol plus Acetaminophen; Drug: Tramadol Hydrochloride; Drug: Acetaminophen

Detailed Description

This is a multi-center (conducted in more than one center), double-blind (neither Physician nor participant knows the name of the assigned drug), randomized (study drug assigned by chance), parallel-group (each group of participant will be treated at the same time) and comparative study in participants having pain intensity of at least 50.0 millimeter (mm) (on visual analog scale, score ranging from 0 mm [no pain] to 100 mm [worst possible pain]), following extraction of an impacted mandibular wisdom tooth. The study consists of 3 parts: Pre-observation (7 days before study commences on Day 1); Treatment (Day 1, consists of single oral dosing of either tramadol plus acetaminophen and placebo; or tramadol and placebo; or acetaminophen and placebo) and Follow-up (Day 2 and 8). All the eligible participants will be randomly assigned to 1 of the 3 study treatments. Efficacy of the participants will primarily be evaluated through total pain relief, which will be evaluated on numerical rating scale. Participants' safety will be monitored throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 328
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Isehara, Japan
  • Kitakyushu, Japan
  • Kumamoto, Japan
  • Ohta-Ku, Japan
  • Osaka, Japan
  • Sapporo, Japan
  • Shimotsuga, Japan
  • Shimotsuke, Japan
  • Tokyo, Japan
  • Yokohama, Japan
  • Yokohama N/A, Japan
  • Yokosuka, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 74 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants planned to receive a tooth extraction of one mandibular impacted wisdom tooth
• Participants who require bone removal and separation of the crown at tooth extraction
• Participants whose intensity of pain associated with tooth extraction within 2 hours after tooth extraction is greater than or equal to 50.0 millimeter on the visual analog scale (VAS)
• Participants who did not undergo general anesthesia or sedation at tooth extraction
• Participants without an abnormality (including laboratory test values) corresponding to Grade 3 in the "Criteria for severity classification of adverse drug reactions" during the pretreatment observation period

Exclusion Criteria:

• Participants with conditions for which tramadol is contraindicated
• Participants with conditions for which acetaminophen is contraindicated
• Participants with history of convulsions or the possibility of convulsive seizures
• Pregnant participants or those who may be pregnant, lactating mothers, and those who wish pregnancy during the study period
• Participants with concurrent, previous, or possible alcohol dependence, drug dependence or narcotic addiction

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Tramadol plus Acetaminophen and Placebo; Tramadol hydrochloride and acetaminophen combination tablet will be administered as single oral dosing of two tablets at a dose of 75 and 650 milligram respectively, along with two oral capsules of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed greater than or equal to (>=) 50.0 millimeter (mm) on the Visual Analog Scale (VAS), score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Drug: Placebo; Two oral tablets or capsules of matching Placebo will be administered once along with Tramadol Hydrochloride and/or acetaminophen.; Drug: Tramadol plus Acetaminophen; Tramadol hydrochloride and acetaminophen combination tablet will be administered as single oral dosing of two tablets at a dose of 75 and 650 milligram respectively.; Other Names: JNS013
EXPERIMENTAL: Tramadol and Placebo; Tramadol hydrochloride will be administered as single oral dosing of two capsules once at a dose of 75 milligram, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed >= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Drug: Placebo; Two oral tablets or capsules of matching Placebo will be administered once along with Tramadol Hydrochloride and/or acetaminophen.; Drug: Tramadol Hydrochloride; Tramadol hydrochloride two oral capsules will be administered once as 75 milligram (mg).
EXPERIMENTAL: Acetaminophen and Placebo; Acetaminophen will be administered as single oral dosing of two capsules once at a dose of 650 milligram, along with two oral tablets of matching placebo, within 30 minutes after the intensity of pain associated with tooth extraction showed >= 50.0 mm on the VAS, score ranging from 0 mm (no pain) to 100 mm (worst possible pain).	Drug: Placebo; Two oral tablets or capsules of matching Placebo will be administered once along with Tramadol Hydrochloride and/or acetaminophen.; Drug: Acetaminophen; Acetaminophen two oral capsules will be administered once as 650 mg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Pain Relief Based on Numerical Rating Scale (NRS) Score	Total pain relief was evaluated using numerical rating scale score ranging from 0 to 32, wherein 0 indicates no treatment response and 32 indicates the most improved. Higher score indicates treatment response.	8 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Pain Relief Based on Numerical Rating Scale (NRS) Score Every 4 Hours up to 8 Hours	Total pain relief was evaluated using numerical rating scale score ranging from 0 to 32, wherein 0 indicates no treatment response and 32 indicates the most improved. Higher score indicates treatment response.	Baseline up to 8 hours post-administration of study treatment
Sum of Pain Intensity Difference (SPID)	Pain Intensity (PI) was assessed using numerical rating scale score ranging from 0 to 32, wherein 0 indicates no treatment response and 32 indicates the most improved. Scores were measured at Baseline (that is, 0 hours after tooth extraction) and 8 hours post-administration of study treatments.Pain intensity difference (PID) was calculated (that is, for 0-8 hours, time point [8 hour] score minus baseline [0 hour] score).	Baseline up to 8 hours post-administration of study treatment
Sum of Pain Relief Combined With Pain Intensity Difference (SPRID)	The SPRID is the sum of pain relief scores combined with pain intensity difference, score ranging from from (-) 24 (the worst) through 56 (the most improved). Higher score indicates treatment response. Pain Intensity (PI) and Pain relief (PAR) were assessed using numerical rating scale score ranging from 0 to 32, wherein 0 indicates no treatment response and 32 indicates the most improved. Scores were measured at Baseline (that is, 0 hours after tooth extraction) and at 8 hours post-administration of study treatments. Pain intensity difference (PID) was calculated (that is, for 0-8 hours, time point [8 hour] score minus baseline [0 hour] score).	Baseline up to 8 hours post-administration of study treatment
Change From Baseline in Visual Analog Scale (VAS) Score at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment	Pain was assessed by using Visual Analogue Scale (VAS) score ranges from 0 millimeter (mm)=no pain to 100 mm=worst possible pain. An increase in score from Baseline represented disease progression and decrease represented treatment response.	0.5, 1, 2, 3, 4, 5, 6, 7 and 8 hours post-administration of study treatment
Mean Change Over Time for Pain Intensity Difference (PID) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-Administration of Study Treatment	The PID is defined as difference between current pain intensity (PI) and Baseline PI, PI was assessed using numerical rating scale score ranging from 0 to 32, wherein 0 indicates no treatment response and 32 indicates the most improved. Higher score indicates treatment response. Mean change from Baseline (that is, 0 hours after tooth extraction) at specified end time points were evaluated.	0.5, 1, 2, 3, 4, 5, 6, 7 and 8 hours post-administration of study treatment
Mean Change Over Time for Pain Relief (PAR) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment	Pain Relief (PAR) was assessed using numerical rating scale score ranging from 0 to 32, wherein 0 indicates no treatment response and 32 indicates the most improved. Higher score indicates treatment response. Mean change from Baseline (that is, 0 hours after tooth extraction) at specified end time points were evaluated.	0.5, 1, 2, 3, 4, 5, 6, 7 and 8 hours post-administration of study treatment
Mean Change Over Time for Pain Relief Combined With Pain Intensity Difference (PRID) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment	Pain Relief combined with pain Intensity Difference (PRID) represented pain relief scores combined with Pain Intensity difference (PID) scores. PRID score ranges from -3 (the worst) through +7 (the most improved). Higher score indicates treatment response. Mean change from Baseline (that is, 0 hours after tooth extraction) at specified end time points were evaluated.	0.5, 1, 2, 3, 4, 5, 6, 7 and 8 hours post-administration of study treatment
Time to Reach the Onset of Drug Efficacy and Time to Recurrence of Pain After the Onset of Drug Efficacy	Time to reach the onset of drug efficacy (TOE) means time took by participants for the onset of relief from pain after tooth-extraction and time to recurrence of pain (TOR) after the onset of drug efficacy (that is, duration of drug efficacy) were assessed after study drug treatment.	Baseline up to 8 hours post-administration of study treatment
Percentage of Participants With Categorical Score for Patient Impressions	Percentage of participants with patient impressions were assessed on categories, that are: worked well; worked; worked a little; and didn't work.	Baseline up to 8 hours post-administration of study treatment
Number of Participants Treated With a Relief Analgesic	Participants who were treated with a relief analgesic were assessed. Analgesics are the compounds capable of relieving pain without the loss of consciousness.	Baseline up to 8 hours post-administration of study treatment
Percentage of Participants With Treatment Response Based on Evaluation Criteria for Efficacy of Analgesics in Post-Tooth-Extraction Pain	Percentage of participants were assessed with treatment response based on "evaluation criteria for efficacy of analgesics in post-tooth-extraction pain" for the efficacy of analgesics used to treat pain following tooth extraction. Participants were assessed as "very effective, effective, somewhat effective and ineffective" for the following categories: Pain suppression (PS), speed of pain relief (SPR), duration of pain relief (DPR), general effectiveness (GE). Participants judged the treatment as "extremely useful, useful, not useful & could not be assessed" for overall evaluation (OE).	Baseline up to 8 hours post-administration of study treatment

Collaborators and Investigators

• Sponsor: Janssen Pharmaceutical K.K.

Publications and helpful links

Helpful Links

• A confirmatory study of JNS013 in patients with post-tooth-extraction pain

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (ACTUAL): September 1, 2008
• Study Completion (ACTUAL): September 1, 2008

Study Registration Dates

• First Submitted: August 14, 2008
• First Submitted That Met QC Criteria: August 15, 2008
• First Posted (ESTIMATE): August 18, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): March 31, 2016
• Last Update Submitted That Met QC Criteria: March 29, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Pain; Postoperative pain; Acetaminophen; Tooth extraction; Tramadol hydrochloride; Oral surgery; JNS013
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Analgesics, Opioid; Narcotics; Acetaminophen; Tramadol
• Other Study ID Numbers: CR015109; JNS013-JPN-03