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

• Sponsor: Mylan Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04571515
• Collaborator: (none)
• Enrollment: 114
• Location: 1
• Arms: 5
• Actual Duration (Months): 2.8
• Patients Per Site Per Month: 41.3

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Pain; Postoperative Pain; Pain, Acute	Drug: MR-107A-01; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 114 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double Blind, Placebo-Controlled, Parallel Group, Dose-Response Study of MR-107A-01 in The Treatment of Post-Surgical Dental Pain
• Actual Study Start Date: Sep 29, 2020
• Actual Primary Completion Date: Dec 15, 2020
• Actual Study Completion Date: Dec 22, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Overall Summed Pain Intensity Difference (SPID) [24 hours after the first dose]

   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.

Secondary Outcome Measures

1. Pain Intensity Using a Numeric Pain Rating Scale Utilizing 2-hour Windowed Last Observation Carried Forward (W2LOCF) [24 hours after the first dose]

   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

2. Total Pain Relief [24 hours after the first dose]

   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.

3. Pain Relief: Number and Percentage of Subjects With Perceptible and Meaningful Pain Relief [24 hours after the first dose]

   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.

4. Patient's Global Assessment of Pain Control [24 hours after the first dose]

   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

5. Rescue Medication Use [24 hours after the first dose]

   Number of rescue medication doses

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Facility 101	Salt Lake City	Utah	United States	84107

Sponsors and Collaborators

• Mylan Inc.

Investigators

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

Study Documents (Full-Text)

• Study Protocol - Sep 15, 2020
• Statistical Analysis Plan - Feb 5, 2021

More Information

Publications

None provided.

• Responsible Party: Mylan Inc.
• ClinicalTrials.gov Identifier: NCT04571515
• Other Study ID Numbers: MECC-TBZ-2001
• First Posted: Oct 1, 2020
• Last Update Posted: Aug 8, 2022
• Last Verified: Jul 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Toothache; Acute Pain

Study Results

Participant Flow

Arm/Group Title	MR-107A-01 10 mg Once in a 24-hour Period	MR-107A-01 15 mg Once in a 24-hour Period	MR-107A-01 10 mg Twice in a 24-hour Period	MR-107A-01 15 mg Twice in a 24-hour Period	Placebo Twice in a 24-hour Period
Arm/Group Description	Oral tablet one day of dosing MR-107A-01: Oral tablet	Oral tablet one day of dosing MR-107A-01: Oral tablet	Oral tablet one day of dosing MR-107A-01: Oral tablet	Oral tablet one day of dosing MR-107A-01: Oral tablet	Placebo tablet one day of dosing Placebo: Oral tablet
Period Title: Overall Study
STARTED	22	24	23	23	22
COMPLETED	21	24	23	23	19
NOT COMPLETED	1	0	0	0	3

Baseline Characteristics

Arm/Group Title	MR-107A-01 10 mg Once in a 24-hour Period	MR-107A-01 15 mg Once in a 24-hour Period	MR-107A-01 10 mg Twice in a 24-hour Period	MR-107A-01 15 mg Twice in a 24-hour Period	Placebo Twice in a 24-hour Period	Total
Arm/Group Description	Oral tablet one day of dosing MR-107A-01: Oral tablet	Oral tablet one day of dosing MR-107A-01: Oral tablet	Oral tablet one day of dosing MR-107A-01: Oral tablet	Oral tablet one day of dosing MR-107A-01: Oral tablet	Placebo tablet one day of dosing Placebo: Oral tablet	Total of all reporting groups
Overall Participants	21	24	23	23	21	112
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	20.1 (2.17)	19.2 (1.46)	19.8 (2.37)	19.4 (2.39)	20.1 (2.41)	19.7 (2.17)
Sex: Female, Male (Count of Participants)
Female	11 52.4%	18 75%	11 47.8%	12 52.2%	8 38.1%	60 53.6%
Male	10 47.6%	6 25%	12 52.2%	11 47.8%	13 61.9%	52 46.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 9.5%	5 20.8%	6 26.1%	7 30.4%	3 14.3%	23 20.5%
Not Hispanic or Latino	19 90.5%	19 79.2%	17 73.9%	16 69.6%	18 85.7%	89 79.5%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	2 9.5%	2 1.8%
Native Hawaiian or Other Pacific Islander	1 4.8%	0 0%	1 4.3%	0 0%	2 9.5%	4 3.6%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
White	20 95.2%	24 100%	20 87%	23 100%	17 81%	104 92.9%
More than one race	0 0%	0 0%	1 4.3%	0 0%	0 0%	1 0.9%
Unknown or Not Reported	0 0%	0 0%	1 4.3%	0 0%	0 0%	1 0.9%

Outcome Measures

1. Primary Outcome

Title	Overall Summed Pain Intensity Difference (SPID)
Description	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.
Time Frame	24 hours after the first dose

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat Analysis Set

Arm/Group Title	MR-107A-01 10 mg Once in a 24-hour Period	MR-107A-01 15 mg Once in a 24-hour Period	MR-107A-01 10 mg Twice in a 24-hour Period	MR-107A-01 15 mg Twice in a 24-hour Period	Placebo Twice in a 24-hour Period
Arm/Group Description	Oral tablet one day of dosing MR-107A-01: Oral tablet	Oral tablet one day of dosing MR-107A-01: Oral tablet	Oral tablet one day of dosing MR-107A-01: Oral tablet	Oral tablet one day of dosing MR-107A-01: Oral tablet	Placebo tablet one day of dosing Placebo: Oral tablet
Measure Participants	21	24	23	23	21
Mean (Standard Deviation) [score on a scale * hours]	109.5 (32.82)	111.8 (40.37)	108.8 (33.85)	108.6 (40.20)	80.0 (39.78)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MR-107A-01 10 mg Once in a 24-hour Period, Placebo Twice in a 24-hour Period
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Emax
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	28.3
	Confidence Interval	(2-Sided) 95%; 9.9 to 46.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 9.25
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MR-107A-01 15 mg Once in a 24-hour Period, Placebo Twice in a 24-hour Period
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Emax
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	29.6
	Confidence Interval	(2-Sided) 95%; 13.8 to 45.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.94
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MR-107A-01 10 mg Twice in a 24-hour Period, Placebo Twice in a 24-hour Period
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Emax
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	30.3
	Confidence Interval	(2-Sided) 95%; 14.4 to 46.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 8.04
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	MR-107A-01 15 mg Twice in a 24-hour Period, Placebo Twice in a 24-hour Period
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Emax
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	31.1
	Confidence Interval	(2-Sided) 95%; 13.5 to 48.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 8.87
	Estimation Comments

2. Secondary Outcome

Title	Pain Intensity Using a Numeric Pain Rating Scale Utilizing 2-hour Windowed Last Observation Carried Forward (W2LOCF)
Description	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
Time Frame	24 hours after the first dose

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat

Arm/Group Title	MR-107A-01 10 mg Once in a 24-hour Period	MR-107A-01 15 mg Once in a 24-hour Period	MR-107A-01 10 mg Twice in a 24-hour Period	MR-107A-01 15 mg Twice in a 24-hour Period	Placebo Twice in a 24-hour Period
Arm/Group Description	Oral tablet one day of dosing MR-107A-01: Oral tablet	Oral tablet one day of dosing MR-107A-01: Oral tablet	Oral tablet one day of dosing MR-107A-01: Oral tablet	Oral tablet one day of dosing MR-107A-01: Oral tablet	Placebo tablet one day of dosing Placebo: Oral tablet
Measure Participants	21	24	23	22	21
Mean (Standard Deviation) [score on a scale]	2.5 (1.86)	2.1 (1.60)	1.5 (1.34)	2.3 (1.98)	2.5 (2.39)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MR-107A-01 10 mg Once in a 24-hour Period, Placebo Twice in a 24-hour Period
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -1.4 to 1.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.62
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MR-107A-01 15 mg Once in a 24-hour Period, Placebo Twice in a 24-hour Period
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.5 to 0.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.60
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MR-107A-01 10 mg Twice in a 24-hour Period, Placebo Twice in a 24-hour Period
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.8 to 0.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.61
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	MR-107A-01 15 mg Twice in a 24-hour Period, Placebo Twice in a 24-hour Period
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -1.1 to 1.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.61
	Estimation Comments

3. Secondary Outcome

Title	Total Pain Relief
Description	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.
Time Frame	24 hours after the first dose

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat Analysis Set

Arm/Group Title	MR-107A-01 10 mg Once in a 24-hour Period	MR-107A-01 15 mg Once in a 24-hour Period	MR-107A-01 10 mg Twice in a 24-hour Period	MR-107A-01 15 mg Twice in a 24-hour Period	Placebo Twice in a 24-hour Period
Arm/Group Description	Oral tablet one day of dosing MR-107A-01: Oral tablet	Oral tablet one day of dosing MR-107A-01: Oral tablet	Oral tablet one day of dosing MR-107A-01: Oral tablet	Oral tablet one day of dosing MR-107A-01: Oral tablet	Placebo tablet one day of dosing Placebo: Oral tablet
Measure Participants	21	24	23	23	21
Mean (Standard Deviation) [score on a scale * hours]	55.5 (12.31)	57.3 (11.29)	60.2 (13.48)	56.6 (16.82)	41.2 (17.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MR-107A-01 10 mg Once in a 24-hour Period, Placebo Twice in a 24-hour Period
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Emax
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	15.2
	Confidence Interval	(2-Sided) 95%; 7.3 to 23.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.99
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MR-107A-01 15 mg Once in a 24-hour Period, Placebo Twice in a 24-hour Period
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Emax
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	16.1
	Confidence Interval	(2-Sided) 95%; 9.3 to 22.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.43
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MR-107A-01 10 mg Twice in a 24-hour Period, Placebo Twice in a 24-hour Period
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Emax
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	16.5
	Confidence Interval	(2-Sided) 95%; 9.7 to 23.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.47
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	MR-107A-01 15 mg Twice in a 24-hour Period, Placebo Twice in a 24-hour Period
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Emax
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	17.1
	Confidence Interval	(2-Sided) 95%; 9.4 to 24.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.84
	Estimation Comments

4. Secondary Outcome

Title	Pain Relief: Number and Percentage of Subjects With Perceptible and Meaningful Pain Relief
Description	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.
Time Frame	24 hours after the first dose

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat Analysis Set

Arm/Group Title	MR-107A-01 10 mg Once in a 24-hour Period	MR-107A-01 15 mg Once in a 24-hour Period	MR-107A-01 10 mg Twice in a 24-hour Period	MR-107A-01 15 mg Twice in a 24-hour Period	Placebo Twice in a 24-hour Period
Arm/Group Description	Oral tablet one day of dosing MR-107A-01: Oral tablet	Oral tablet one day of dosing MR-107A-01: Oral tablet	Oral tablet one day of dosing MR-107A-01: Oral tablet	Oral tablet one day of dosing MR-107A-01: Oral tablet	Placebo tablet one day of dosing Placebo: Oral tablet
Measure Participants	21	24	23	23	21
Perceptible Pain Relief	15 71.4%	22 91.7%	16 69.6%	19 82.6%	10 47.6%
Meaningful Pain Relief	10 47.6%	17 70.8%	13 56.5%	15 65.2%	3 14.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MR-107A-01 10 mg Once in a 24-hour Period, Placebo Twice in a 24-hour Period
	Comments	Time to Perceptible Pain Relief Subjects are censored at 24 hours if they do not report relief.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.208
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MR-107A-01 15 mg Once in a 24-hour Period, Placebo Twice in a 24-hour Period
	Comments	Time to Perceptible Pain Relief Subjects are censored at 24 hours if they do not report relief.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MR-107A-01 10 mg Twice in a 24-hour Period, Placebo Twice in a 24-hour Period
	Comments	Time to Perceptible Pain Relief Subjects are censored at 24 hours if they do not report relief.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.192
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	MR-107A-01 15 mg Twice in a 24-hour Period, Placebo Twice in a 24-hour Period
	Comments	Time to Perceptible Pain Relief Subjects are censored at 24 hours if they do not report relief.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.067
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	MR-107A-01 10 mg Once in a 24-hour Period, Placebo Twice in a 24-hour Period
	Comments	Time to Meaningful Pain Relief Subjects are censored at 24 hours if they do not report relief.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.059
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	MR-107A-01 15 mg Once in a 24-hour Period, Placebo Twice in a 24-hour Period
	Comments	Time to Meaningful Pain Relief Subjects are censored at 24 hours if they do not report relief.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	MR-107A-01 10 mg Twice in a 24-hour Period, Placebo Twice in a 24-hour Period
	Comments	Time to Meaningful Pain Relief Subjects are censored at 24 hours if they do not report relief.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.017
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	MR-107A-01 15 mg Twice in a 24-hour Period, Placebo Twice in a 24-hour Period
	Comments	Time to Meaningful Pain Relief Subjects are censored at 24 hours if they do not report relief.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Log Rank
	Comments

5. Secondary Outcome

Title	Patient's Global Assessment of Pain Control
Description	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
Time Frame	24 hours after the first dose

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat Analysis Set

Arm/Group Title	MR-107A-01 10 mg Once in a 24-hour Period	MR-107A-01 15 mg Once in a 24-hour Period	MR-107A-01 10 mg Twice in a 24-hour Period	MR-107A-01 15 mg Twice in a 24-hour Period	Placebo Twice in a 24-hour Period
Arm/Group Description	Oral tablet one day of dosing MR-107A-01: Oral tablet	Oral tablet one day of dosing MR-107A-01: Oral tablet	Oral tablet one day of dosing MR-107A-01: Oral tablet	Oral tablet one day of dosing MR-107A-01: Oral tablet	Placebo tablet one day of dosing Placebo: Oral tablet
Measure Participants	21	24	23	23	21
Responders	14 66.7%	16 66.7%	18 78.3%	13 56.5%	7 33.3%
Non-responders	7 33.3%	8 33.3%	5 21.7%	10 43.5%	14 66.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MR-107A-01 10 mg Once in a 24-hour Period, Placebo Twice in a 24-hour Period
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.051
	Comments
	Method	Regression, Logistic
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MR-107A-01 15 mg Once in a 24-hour Period, Placebo Twice in a 24-hour Period
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.035
	Comments
	Method	Regression, Logistic
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MR-107A-01 10 mg Twice in a 24-hour Period, Placebo Twice in a 24-hour Period
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.016
	Comments
	Method	Regression, Logistic
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	MR-107A-01 15 mg Twice in a 24-hour Period, Placebo Twice in a 24-hour Period
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.180
	Comments
	Method	Regression, Logistic
	Comments

6. Secondary Outcome

Title	Rescue Medication Use
Description	Number of rescue medication doses
Time Frame	24 hours after the first dose

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat

Arm/Group Title	MR-107A-01 10 mg Once in a 24-hour Period	MR-107A-01 15 mg Once in a 24-hour Period	MR-107A-01 10 mg Twice in a 24-hour Period	MR-107A-01 15 mg Twice in a 24-hour Period	Placebo Twice in a 24-hour Period
Arm/Group Description	Oral tablet one day of dosing MR-107A-01: Oral tablet	Oral tablet one day of dosing MR-107A-01: Oral tablet	Oral tablet one day of dosing MR-107A-01: Oral tablet	Oral tablet one day of dosing MR-107A-01: Oral tablet	Placebo tablet one day of dosing Placebo: Oral tablet
Measure Participants	21	24	23	23	21
Mean (Standard Deviation) [Medication doses]	0.8 (1.03)	0.8 (0.92)	0.7 (0.70)	0.7 (1.14)	1.8 (1.58)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MR-107A-01 10 mg Once in a 24-hour Period, Placebo Twice in a 24-hour Period
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.022
	Comments
	Method	Wilcoxon Rank Sum
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MR-107A-01 15 mg Once in a 24-hour Period, Placebo Twice in a 24-hour Period
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.028
	Comments
	Method	Wilcoxon Rank Sum
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MR-107A-01 10 mg Twice in a 24-hour Period, Placebo Twice in a 24-hour Period
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	Wilcoxon Rank Sum
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	MR-107A-01 15 mg Twice in a 24-hour Period, Placebo Twice in a 24-hour Period
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	Wilcoxon Rank Sum
	Comments

Adverse Events

Time Frame	Study period reporting of Adverse Events was up to 7 days post first dose. Subjects were reminded that AEs should be reported to the study staff up to 30 days after the last dose of study medication.
Adverse Event Reporting Description	An adverse event is any untoward medical occurrence in a patient/ clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory/ physical findings, symptom, or disease (new/ exacerbated) temporally associated with the use of a medicinal product whether or not considered related to the medicinal product.
Arm/Group Title	MR-107A-01 10 mg Once in a 24-hour Period		MR-107A-01 15 mg Once in a 24-hour Period		MR-107A-01 10 mg Twice in a 24-hour Period		MR-107A-01 15 mg Twice in a 24-hour Period		Placebo Twice in a 24-hour Period
Arm/Group Description	Oral tablet one day of dosing MR-107A-01: Oral tablet		Oral tablet one day of dosing MR-107A-01: Oral tablet		Oral tablet one day of dosing MR-107A-01: Oral tablet		Oral tablet one day of dosing MR-107A-01: Oral tablet		Placebo tablet one day of dosing Placebo: Oral tablet
All Cause Mortality
	MR-107A-01 10 mg Once in a 24-hour Period		MR-107A-01 15 mg Once in a 24-hour Period		MR-107A-01 10 mg Twice in a 24-hour Period		MR-107A-01 15 mg Twice in a 24-hour Period		Placebo Twice in a 24-hour Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/24 (0%)		0/23 (0%)		0/23 (0%)		0/21 (0%)
Serious Adverse Events
	MR-107A-01 10 mg Once in a 24-hour Period		MR-107A-01 15 mg Once in a 24-hour Period		MR-107A-01 10 mg Twice in a 24-hour Period		MR-107A-01 15 mg Twice in a 24-hour Period		Placebo Twice in a 24-hour Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/24 (0%)		0/23 (0%)		0/23 (0%)		0/21 (0%)
Other (Not Including Serious) Adverse Events
	MR-107A-01 10 mg Once in a 24-hour Period		MR-107A-01 15 mg Once in a 24-hour Period		MR-107A-01 10 mg Twice in a 24-hour Period		MR-107A-01 15 mg Twice in a 24-hour Period		Placebo Twice in a 24-hour Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/21 (19%)		6/24 (25%)		6/23 (26.1%)		0/23 (0%)		2/21 (9.5%)
Gastrointestinal disorders
Nausea	0/21 (0%)		3/24 (12.5%)		3/23 (13%)		0/23 (0%)		1/21 (4.8%)
Nervous system disorders
Headache	3/21 (14.3%)		3/24 (12.5%)		1/23 (4.3%)		0/23 (0%)		1/21 (4.8%)
Dizziness	1/21 (4.8%)		0/24 (0%)		2/23 (8.7%)		0/23 (0%)		0/21 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.