Study of MR-107A-02 in the Treatment of Post Surgical Dental Pain.

Study Overview
=================
Brief Summary
-----------------
MR-107A-02 is being studied to investigate its efficacy, safety and dose-response after dental surgery.

Official Title
-----------------
A Randomized, Double Blind, Placebo Controlled, Parallel Group, Dose Response Study of MR-107A-02 in the Treatment of Post Surgical Dental Pain.

Conditions
-----------------
Acute Pain, Post Operative Pain, Pain

Intervention / Treatment
-----------------
* Drug: MR-107A-02
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males and females ≥18 years of age. Requirement for dental surgery for extraction of ≥2 third molars, at least 1 of which involves partial or complete mandibular bony impaction. Pain Intensity (PI) using a Numeric Pain Rating Scale (NPRS) ≥5 during the 5 hours following the end of surgery in the eligibility assessment as well as in the baseline assessment immediately pre-dosing. Rating of moderate or severe pain on a 4-point categorical pain rating scale (i.e., none, mild, moderate, severe) during the 5 hours following the end of surgery. Exclusion Criteria: Previously dosed with MR-107A-02. Subject with known hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs). Active GI bleeding or a history of peptic ulcer disease, active inflammatory bowel disease, e.g., Crohn's Disease or ulcerative colitis,or bleeding disorders that may affect coagulation. Moderate or severe hypertension, prior stroke or transient ischemic attack. Use of any investigational drug within 28 days, or 5 half-lives, prior to consent whichever is longer. Use of medications with the potential to interact with MR-107A-02. Other acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator.

Ages Eligible for Study
-----------------
Minimum Age: 18 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: MR-107A-02 1.25 mg twice in a 24 hour period<br>Oral tablet, one day of dosing | Drug: MR-107A-02<br>* MR-107A-02 oral tablet<br>|
| Experimental: MR-107A-02 5 mg twice in a 24 hour period<br>Oral tablet, one day of dosing | Drug: MR-107A-02<br>* MR-107A-02 oral tablet<br>|
| Experimental: MR-107A-02 15 mg twice in a 24 hour period<br>Oral tablet, one day of dosing | Drug: MR-107A-02<br>* MR-107A-02 oral tablet<br>|
| Placebo Comparator: Placebo twice in a 24 hour period<br>Oral tablet, one day of dosing | Drug: Placebo<br>* Placebo oral tablet<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Summed Pain Intensity Difference (SPID) | Participants assessed Pain Intensity (PI) using a 0-10 numeric pain rating scale (NPRS) where 0 is no pain and 10 is worst pain imaginable. PI was assessed 18 times within 24 hours after the first study dose, and immediately before any rescue medication and/or at early termination. The participant's baseline PI was subtracted from the timepoint PI, to derive a Pain Intensity Difference (PID) for each timepoint. Overall Summed Pain Intensity Difference (SPID) measures pain intensity change relative to baseline over the 24 hour period after dosing, and corresponds to the Area Under the Curve (AUC) of the PID. In this study, higher positive Overall SPID indicates better pain improvement. Overall SPID could range from -120 to 240. Two hour windowed last observation carried forward was used as applicable where PI score obtained before a rescue medication replaced PI score for each timepoint within 2 hours following rescue dose. | 24 hours after the first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Intensity Using a Number Pain Rating Scale Utilizing 6-hour Windowed Last Observation Carried Forward (W6LOCF) | 10 point scale, where 0 is no pain and 10 is the worst pain imaginable; 6-hour windowed last observation carried forward (W6LOCF) utilizes pain right now just prior to rescue medication use and censors subsequent pain intensity values for 6 hours when calculating SPIDs | 24 hours after first dose | 
| Time to Perceptible Pain Relief. | Measured by double stopwatch technique. The time to onset of first perceptible relief (time that the first watch is stopped) is defined as the postdose time at which the subject first begins to feel pain relief at their estimation. | 24 hours after first dose | 
| Time to Meaningful Pain Relief | Measured by double stopwatch technique The time to meaningful pain relief (time that the second watch is stopped) is defined as the postdose time at which the subject begins to feel meaningful pain relief at their estimation | 24 hours after first dose | 
| Patient's Global Assessment of Pain Control | 5 point PGA (Patient's Global Assessment) of pain control scale, where 0 is poor, 1 is fair, 2 is good, 3 is very good, and 4 is excellent Responder = 2 is good, 3 is very good, and 4 is excellent Non-responder = 1 is fair, 0 is poor, and missing values. | 24 hours | 
| Rescue Medication Use | Percentage of subjects using rescue medication from 0-24 hours | 24 hours after first dose |