Dose-Response Study of MR-107A-01 in The Treatment of Post-Surgical Dental Pain

A Randomized, Double Blind, Placebo-Controlled, Parallel Group, Dose-Response Study of MR-107A-01 in The Treatment of Post-Surgical Dental Pain

MR-107A-01 is being studied to investigate its efficacy, safety, and dose-response after dental surgery.

Study Overview

• Status: Completed
• Conditions: Pain; Postoperative Pain; Pain, Acute
• Intervention / Treatment: Drug: Placebo; Drug: MR-107A-01

• Study Type: Interventional
• Enrollment (Actual): 114
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Research Facility 101

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males and females ≥18 years of age.
2. Requirement for dental surgery for extraction of ≥2 x third molars, at least 1 of which involves partial or complete mandibular bony impaction.
3. Pain Intensity (PI) using a Numeric Pain Rating Scale (NPRS) ≥5 during the 5 hours following the end of surgery.
4. 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:

1. Previously dosed with MR-107A-01.
2. Subject with known hypersensitivity to nonsteroidal antiinflammatory drugs (NSAIDs).
3. Active GI bleeding or a history of peptic ulcer disease, active inflammatory bowel disease, e.g., Crohn's Disease or ulcerative colitis, bleeding disorders that may affect coagulation.
4. Use of any investigational drug within 28 days, or 5 half-lives, prior to screening whichever is longer.
5. Use of medications with the potential to interact with MR-107A-01.
6. 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, would make the subject inappropriate for entry into this study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MR-107A-01 15 mg once in a 24-hour period; Oral tablet one day of dosing	Drug: MR-107A-01; Oral tablet
Experimental: MR-107A-01 10 mg once in a 24-hour period; Oral tablet one day of dosing	Drug: MR-107A-01; Oral tablet
Experimental: MR-107A-01 15 mg twice in a 24-hour period; Oral tablet one day of dosing	Drug: MR-107A-01; Oral tablet
Experimental: MR-107A-01 10 mg twice in a 24-hour period; Oral tablet one day of dosing	Drug: MR-107A-01; Oral tablet
Placebo Comparator: Placebo twice in a 24-hour period; Placebo tablet one day of dosing	Drug: Placebo; Oral tablet

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 17 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 Numeric Pain Rating Scale Utilizing 2-hour Windowed Last Observation Carried Forward (W2LOCF)	10 point scale, where 0 is no pain and 10 is the worst pain imaginable; 2-hour windowed last observation carried forward (W2LOCF) utilizes "pain right now" just prior to rescue medication use and censors subsequent pain intensity values for 2 hours when calculating SPIDs	24 hours after the first dose
Total Pain Relief	Pain relief was assessed by participants using a 5 point scale, where 0 = none, 1 = slight, 2 = moderate, 3 = good or a lot, and 4 = complete. Pain relief was measured 17 times within 24 hours after the first study medication dose, and immediately before any rescue medication and/or at the time of early termination. Two-hour windowed last observation carried forward approach was used whereby the pain relief score obtained before a given rescue medication was carried forward to replace the pain relief scores collected at each observation timepoint within 2 hours following the rescue dose. Total pain relief (TOTPAR) had Areas Under the Curve (AUCs) calculated for each time point. The range for 24 hours post dose TOTPAR AUC was 0 to 96. Higher positive values indicate a better outcome with larger pain improvements.	24 hours after the first dose
Pain Relief: Number and Percentage of Subjects With Perceptible and Meaningful Pain Relief	The time to onset of first perceptible relief was defined as the post dose time at which the subject first begins to feel pain relief. The time to meaningful pain relief was defined as the post dose time at which the subject begins to feel meaningful pain relief. The assessments of perceptible and meaningful pain relief were ceased when rescue medication was taken.	24 hours after the first dose
Patient's Global Assessment of Pain Control	5 point 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 after the first dose
Rescue Medication Use	Number of rescue medication doses	24 hours after the first dose

Collaborators and Investigators

• Sponsor: Mylan Inc.
• Investigators: Study Director: Susanne Vogt, MEDA Pharma GmbH & Co. KG (A Viatris Company)

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2020
• Primary Completion (Actual): December 15, 2020
• Study Completion (Actual): December 22, 2020

Study Registration Dates

• First Submitted: September 21, 2020
• First Submitted That Met QC Criteria: September 25, 2020
• First Posted (Actual): October 1, 2020

Study Record Updates

• Last Update Posted (Actual): August 8, 2022
• Last Update Submitted That Met QC Criteria: July 12, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Stomatognathic Diseases; Tooth Diseases; Facial Pain; Acute Pain; Toothache
• Other Study ID Numbers: MECC-TBZ-2001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No