Acute Pain, Pain, Post Operative Pain
Conditions
Brief summary
MR-107A-02 is being studied to investigate its efficacy, safety and dose-response after dental surgery.
Interventions
DRUGMR-107A-02
MR-107A-02 oral tablet
DRUGPlacebo
Placebo oral tablet
Sponsors
Mylan Specialty, LP
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
double blind, placebo controlled
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Males and females ≥18 years of age. 2. Requirement for dental surgery for extraction of ≥2 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 in the eligibility assessment as well as in the baseline assessment immediately pre-dosing. 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-02. 2. Subject with known hypersensitivity to nonsteroidal anti-inflammatory 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,or bleeding disorders that may affect coagulation. 4. Moderate or severe hypertension, prior stroke or transient ischemic attack. 5. Use of any investigational drug within 28 days, or 5 half-lives, prior to consent whichever is longer. 6. Use of medications with the potential to interact with MR-107A-02. 7. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Intensity Using a Number Pain Rating Scale Utilizing 6-hour Windowed Last Observation Carried Forward (W6LOCF) | 24 hours after first dose | 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 |
| Time to Perceptible Pain Relief. | 24 hours after first dose | 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. |
| Time to Meaningful Pain Relief | 24 hours after first dose | 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 |
| Patient's Global Assessment of Pain Control | 24 hours | 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. |
| Rescue Medication Use | 24 hours after first dose | Percentage of subjects using rescue medication from 0-24 hours |
Countries
United States
Participant flow
Recruitment details
111 subjects were enrolled / randomized but only 110 subjects were treated.
Participants by arm
| Arm | Count |
|---|---|
| MR-107A-02 1.25 mg Twice in a 24 Hour Period Oral tablet, one day of dosing
MR-107A-02: MR-107A-02 oral tablet | 28 |
| MR-107A-02 5 mg Twice in a 24 Hour Period Oral tablet, one day of dosing
MR-107A-02: MR-107A-02 oral tablet | 28 |
| MR-107A-02 15 mg Twice in a 24 Hour Period Oral tablet, one day of dosing
MR-107A-02: MR-107A-02 oral tablet | 27 |
| Placebo Twice in a 24 Hour Period Oral tablet, one day of dosing
Placebo: Placebo oral tablet | 27 |
| Total | 110 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Excluded as exclusion criteria was met. | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | MR-107A-02 1.25 mg Twice in a 24 Hour Period | MR-107A-02 5 mg Twice in a 24 Hour Period | MR-107A-02 15 mg Twice in a 24 Hour Period | Placebo Twice in a 24 Hour Period |
|---|---|---|---|---|---|
| Age, Continuous | 19 years STANDARD_DEVIATION 1.53 | 18.9 years STANDARD_DEVIATION 1.45 | 19 years STANDARD_DEVIATION 1.52 | 19.3 years STANDARD_DEVIATION 1.94 | 18.7 years STANDARD_DEVIATION 1.13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 2 Participants | 4 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 98 Participants | 26 Participants | 24 Participants | 25 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 110 participants | 28 participants | 28 participants | 27 participants | 27 participants |
| Sex: Female, Male Female | 63 Participants | 17 Participants | 16 Participants | 16 Participants | 14 Participants |
| Sex: Female, Male Male | 47 Participants | 11 Participants | 12 Participants | 11 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 28 | 0 / 27 | 0 / 27 |
| other Total, other adverse events | 3 / 28 | 7 / 28 | 8 / 27 | 8 / 27 |
| serious Total, serious adverse events | 0 / 28 | 0 / 28 | 0 / 27 | 0 / 27 |
Outcome results
Primary
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.
Time frame: 24 hours after the first dose
Population: Modified Intent-to-treat Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MR-107A-02 1.25 mg Twice in a 24 Hour Period | Overall Summed Pain Intensity Difference (SPID) | 74.5 score on a scale x hours | Standard Deviation 46.49 |
| MR-107A-02 5 mg Twice in a 24 Hour Period | Overall Summed Pain Intensity Difference (SPID) | 82.4 score on a scale x hours | Standard Deviation 37.78 |
| MR-107A-02 15 mg Twice in a 24 Hour Period | Overall Summed Pain Intensity Difference (SPID) | 96.8 score on a scale x hours | Standard Deviation 35.31 |
| Placebo Twice in a 24 Hour Period | Overall Summed Pain Intensity Difference (SPID) | 50.5 score on a scale x hours | Standard Deviation 37.26 |
p-value: <0.00195% CI: [14.4, 55]Emax
p-value: 0.12395% CI: [-5.2, 42.7]Emax
p-value: <0.00195% CI: [23.9, 61.7]Emax
Secondary
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
Time frame: 24 hours after first dose
Population: Modified Intent-to-treat Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MR-107A-02 1.25 mg Twice in a 24 Hour Period | Pain Intensity Using a Number Pain Rating Scale Utilizing 6-hour Windowed Last Observation Carried Forward (W6LOCF) | 2.5 score on a scale | Standard Deviation 1.88 |
| MR-107A-02 5 mg Twice in a 24 Hour Period | Pain Intensity Using a Number Pain Rating Scale Utilizing 6-hour Windowed Last Observation Carried Forward (W6LOCF) | 3.1 score on a scale | Standard Deviation 2.32 |
| MR-107A-02 15 mg Twice in a 24 Hour Period | Pain Intensity Using a Number Pain Rating Scale Utilizing 6-hour Windowed Last Observation Carried Forward (W6LOCF) | 2.4 score on a scale | Standard Deviation 1.72 |
| Placebo Twice in a 24 Hour Period | Pain Intensity Using a Number Pain Rating Scale Utilizing 6-hour Windowed Last Observation Carried Forward (W6LOCF) | 3.5 score on a scale | Standard Deviation 2.29 |
95% CI: [-2, 0.2]
95% CI: [-1.8, 0.4]
95% CI: [-1.9, 0.3]
Secondary
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.
Time frame: 24 hours
Population: Subjects reporting a PGA score of 2 (good) or better defined as a responder
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MR-107A-02 1.25 mg Twice in a 24 Hour Period | Patient's Global Assessment of Pain Control | 60.7 percentage of PGA responders |
| MR-107A-02 5 mg Twice in a 24 Hour Period | Patient's Global Assessment of Pain Control | 67.9 percentage of PGA responders |
| MR-107A-02 15 mg Twice in a 24 Hour Period | Patient's Global Assessment of Pain Control | 85.2 percentage of PGA responders |
| Placebo Twice in a 24 Hour Period | Patient's Global Assessment of Pain Control | 33.3 percentage of PGA responders |
p-value: 0.04295% CI: [2, 52.7]Chi-squared
p-value: 0.0195% CI: [9.7, 59.3]Chi-squared
p-value: <0.00195% CI: [29.6, 74.1]Chi-squared
Secondary
Rescue Medication Use
Percentage of subjects using rescue medication from 0-24 hours
Time frame: 24 hours after first dose
Population: Rescue Medication Used within 24h
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MR-107A-02 1.25 mg Twice in a 24 Hour Period | Rescue Medication Use | 42.9 percentage of participants |
| MR-107A-02 5 mg Twice in a 24 Hour Period | Rescue Medication Use | 57.1 percentage of participants |
| MR-107A-02 15 mg Twice in a 24 Hour Period | Rescue Medication Use | 29.6 percentage of participants |
| Placebo Twice in a 24 Hour Period | Rescue Medication Use | 74.1 percentage of participants |
p-value: 0.01995% CI: [-55.9, -6.5]Chi-squared
p-value: 0.18795% CI: [-41.6, 7.8]Chi-squared
p-value: 0.00195% CI: [-68.3, 20.6]Chi-squared
Secondary
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
Time frame: 24 hours after first dose
Population: Modified Intent-to-treat Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MR-107A-02 1.25 mg Twice in a 24 Hour Period | Time to Meaningful Pain Relief | 4.5 hours |
| MR-107A-02 5 mg Twice in a 24 Hour Period | Time to Meaningful Pain Relief | 5.0 hours |
| MR-107A-02 15 mg Twice in a 24 Hour Period | Time to Meaningful Pain Relief | 1.5 hours |
| Placebo Twice in a 24 Hour Period | Time to Meaningful Pain Relief | 3.9 hours |
p-value: 0.411Log Rank
p-value: 0.383Log Rank
p-value: <0.001Log Rank
Secondary
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.
Time frame: 24 hours after first dose
Population: Modified Intent-to-treat Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MR-107A-02 1.25 mg Twice in a 24 Hour Period | Time to Perceptible Pain Relief. | 0.9 hours |
| MR-107A-02 5 mg Twice in a 24 Hour Period | Time to Perceptible Pain Relief. | 0.7 hours |
| MR-107A-02 15 mg Twice in a 24 Hour Period | Time to Perceptible Pain Relief. | 0.6 hours |
| Placebo Twice in a 24 Hour Period | Time to Perceptible Pain Relief. | NA hours |
p-value: 0.036Log Rank
p-value: 0.006Log Rank
p-value: <0.001Log Rank