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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Pain, Postoperative Pain

Intervention / Treatment
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* Drug: Tramadol Hydrochloride
* Drug: Acetaminophen
* Drug: Placebo
* Drug: Tramadol plus Acetaminophen


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tramadol plus Acetaminophen and Placebo<br>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<br>* Two oral tablets or capsules of matching Placebo will be administered once along with Tramadol Hydrochloride and/or acetaminophen.<br>Drug: Tramadol plus Acetaminophen<br>* 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.<br>* Other names: JNS013;|
| Experimental: Tramadol and Placebo<br>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: Tramadol Hydrochloride<br>* Tramadol hydrochloride two oral capsules will be administered once as 75 milligram (mg).<br>Drug: Placebo<br>* Two oral tablets or capsules of matching Placebo will be administered once along with Tramadol Hydrochloride and/or acetaminophen.<br>|
| Experimental: Acetaminophen and Placebo<br>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: Acetaminophen<br>* Acetaminophen two oral capsules will be administered once as 650 mg.<br>Drug: Placebo<br>* Two oral tablets or capsules of matching Placebo will be administered once along with Tramadol Hydrochloride and/or acetaminophen.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, Tooth extraction, Oral surgery, Postoperative pain, JNS013, Tramadol hydrochloride, Acetaminophen