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The purpose of this study is to evaluate the efficacy and safety of MDT-10013 in men and women 18 to 80 years of age who are undergoing bunionectomy. The primary objective is to determine the analgesic efficacy of MDT-10013 compared with standard of care in the treatment of acute postoperative pain after subjects undergo bunionectomy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MDT-10013 | Experimental | Subjects will receive MDT-10013. |
|
| Standard of Care | Active Comparator | Subjects will receive standard of care. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MDT-10013 | Drug |
| ||
| Standard of care for pain |
| Measure | Description | Time Frame |
|---|---|---|
| Summed Pain Intensity Over 1- 48hrs (SPI-48) From Cohort 1 to 3 | Summed pain intensity is a time-weighted average pain score in numeric rating scale (NRS) over 1 to 48hrs (SPI-48). Summed pain intensity is calculated as area under the curve, using the trapezoidal rule to bridge adjacent time points. Specifically, NRS scores for two adjacent time points are averaged and then multiplied by the time span between points (in hours). The theoretical range for SPI-48 is 0 to 470, with lower scores indicative of less pain over this time period (i.e., lower scores are consistent with better analgesia). Time 0 was defined as the time the capsule was closed. | over 1 to 48hrs |
| Summed Pain Intensity Over 1- 48hrs (SPI-48)--Sensitivity Analysis Using Last Observation Carried Forward (LOCF) | Similar to SPI-48, the theoretical range for this LOCF adjustment for rescue medication is 0-470, with lower scores indicative of less pain over this time period (i.e., lower scores are consistent with better analgesia). The calculation is identical to SPI-48 in terms of area-under the curve using the trapezoidal rule. However, the NRS score at the final assessment prior to rescue is carried forward through 48 hours, replacing the raw NRS scores post-rescue for each patient as applicable. | over 1 to 48hrs |
| Integrated Summed Pain Intensity Over 1- 48hrs (SPI-48) and Total Opioid Intake in First 48hrs --Sensitivity Analysis Using Silverman Method | This sensitivity analysis is an integrated assessment of summed pain intensity over 1 to 48hrs (SPI-48) and total opioid intake (ME0-48) in first 48hrs. Briefly, subjects were ranked according to SPI-48 regardless of the treatment received (including Standard of Care, SOC). The mean of all the ranks for this variable was calculated. Then, the percent difference for each individual rank from the pooled mean rank was computed. This process was repeated for total opioid intake in the first 48hrs (ME0-48). The integrated endpoint for each subject was the sum of the rank order percent differences for SPI-48 and ME0-48. The theoretical minimum and maximum on the integrated endpoint are -197% and +197% in this study. Lower scores are better, indicative of less pain and/or less opioid intake. |
| Measure | Description | Time Frame |
|---|---|---|
| Summed Pain Intensity Scores Over 1- 24hrs (SPI-24), 1- 72hrs (SPI-72) and 1- 96hrs (SPI-96) | The theoretical range for SPI-24, SPI-72, and SPI-96 is 0 to 230, 0-710, and 0-960, respectively, with lower scores indicative of less pain over this time period (i.e., lower scores are consistent with better analgesia). Summed pain intensity is calculated as area under the curve, using the trapezoidal rule to bridge adjacent time points. Specifically, NRS scores for two adjacent time points are averaged and then multiplied by the time span between points (in hours). |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetic (PK) Parameters of MDT-10013: Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-t) | Blood samples were taken for pharmacokinetic parameters of MDT-10013 determinations before surgery on Day 0; at 1, 2, 4, 6, 8, 12, 24, 48, 72, and 96 hours after Time 0 (96-hour sample for Cohort 4 only); and on Days 7 to 10 after Time 0. Time 0 was defined as the time the capsule was closed. Actual sampling times after T0 (to 1/1000th of an hour) were used to calculate PK parameters. |
Inclusion Criteria:
Is male or female aged 18 to 80 years.
Has a body mass index from 18 kg/m2 to 40 kg/m2.
Is scheduled to undergo primary, unilateral, first metatarsal bunionectomy (osteotomy and internal fixation) with no additional collateral procedures.
Is classified by American Society of Anesthesiologists Physical Status Classification System as Class I or II.
Must meet the following criteria if female:
Has read, understood, and signed the informed consent prior to study entry.
Is mentally competent, reliable, and cooperative to undergo all visits and procedures scheduled in the study protocol and to record the required information.
Has medical history, physical examination, vital signs, laboratory tests, and 12-lead electrocardiograms (ECGs) that are normal or without clinically relevant abnormalities as per investigator's judgment.
Exclusion Criteria:
Is a female who is pregnant or breastfeeding.
Is not indicated for surgery because of an inflammatory process or risk of infection or delayed wound healing (e.g., autoimmune disorder).
Has a history of allergy or hypersensitivity to the components in the investigational product or to the opioid medication (oxycodone).
Before surgery, has current orthostatic hypotension (defined as systolic blood pressure decrease of at least 20 mm Hg or a diastolic blood pressure decrease of at least 10 mm Hg or an increase in heart rate by 20 beats per minute within 3 minutes of sitting up or standing).
Has severe asthma, defined as requiring frequent or ongoing treatment to control symptoms. Exercise-induced asthma or mild asthma not requiring ongoing treatment may not be exclusionary at the discretion of the investigator.
Has a current gastrointestinal disorder associated with bleeding, a history of such a disorder, or gastrointestinal inflammatory diseases as Crohn's disease or ulcerative colitis.
Has any clinically significant cardiovascular condition as evidenced by physical examination, medical history, and/or baseline ECG.
Has evidence of bradycardia as shown by heart rate of <50 beats per minute via screening ECG.
Has a known infection with human immunodeficiency virus, hepatitis B virus, or hepatitis C virus.
Has a chronic pain condition that may interfere with the subject's assessment of pain postoperatively, as determined by the investigator.
Has any poorly controlled or serious medical conditions, psychiatric illnesses, or clinically significant laboratory values that, in the opinion of the investigator, could compromise the safety of the subject or the scientific integrity of the study (e.g., uncontrolled hypertension, autoimmune disease, or clinically relevant symptoms of thyroid dysfunction).
Has presence or history of local or systemic malignant disease in the past 5 years (history of basal cell carcinoma will be allowed).
Has impaired renal function (creatinine >1.5 times upper limit of normal).
Has chronic impairment liver function (aspartate aminotransferase or alanine aminotransferase >3 times upper limit of normal).
Has insulin-dependent diabetes or uncontrolled diabetes mellitus (glycosylated hemoglobin >7%).
Has leukopenia (<3500 leukocytes/μL).
Has current treatment with any of the following medications:
Has chronic use of opioids (including tramadol), defined as use 20 out of the last 30 days before study screening.
Has a history of or current diagnosis of epilepsy.
Has a known or suspected history of drug or alcohol abuse (as determined by the investigator).
Is judged by the investigator not to be a suitable candidate for study treatment and pain relief medication on the basis of medical history, concomitant medication, and concurrent systemic disease.
Is not stabilized on the following medications for at least 8 weeks prior to dosing: selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).
Is unable to refrain from taking nonsteroidal anti inflammatory drugs (NSAIDs) or opioids within the 24-hour period prior to surgery.
Has participated in any other clinical trial in the 4 weeks prior to Screening.
Experiences any surgical complication that, in the opinion of the investigator, precludes implantation of MDT-10013.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Phoenix | Arizona | 85027 | United States | ||
| Research Site |
Not provided
The study was planned to enroll 3 sequential cohorts, the 4th cohort was added after data review from Cohort 1-3. In each cohort, 48 subjects were randomized in a 3:1 ratio (investigational vs. control). The investigational subjects were implanted MDT-10013 strips in surgical wound while control subjects received standard of care for pain control.
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| ID | Title | Description |
|---|---|---|
| FG000 | 1 MDT-10013 Strip (In Cohort 1) | For the investigational subjects of Cohort 1, one MDT-10013 strip was sutured to the exterior of the capsule wall. |
| FG001 | 2 MDT-10013 Strips (In Cohort 2) | For the investigational subjects of Cohort 2, one MDT-10013 strip was sutured to the exterior of the capsule and 1 strip was sutured to the interior capsule wall. |
| FG002 | 3 MDT-10013 Strips (In Cohort 3) | For the investigational subjects of Cohort 3, one MDT-10013 strip was sutured to the exterior of the capsule and 2 strips were sutured to the interior capsule wall. |
| FG003 | 2 MDT-10013 Strips (In Cohort 4) | For the investigational subjects of Cohort 4, two strips were sutured to the interior capsule wall. |
| FG004 | Control (In Cohort 1-4) | Control subjects in Cohort 1 to 4 received standard of care (no strip) for pain control. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 1 MDT-10013 Strip (In Cohort 1) | For the investigational subjects of Cohort 1, one MDT-10013 strip was sutured to the exterior of the capsule wall. |
| BG001 | 2 MDT-10013 Strips (In Cohort 2) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Summed Pain Intensity Over 1- 48hrs (SPI-48) From Cohort 1 to 3 | Summed pain intensity is a time-weighted average pain score in numeric rating scale (NRS) over 1 to 48hrs (SPI-48). Summed pain intensity is calculated as area under the curve, using the trapezoidal rule to bridge adjacent time points. Specifically, NRS scores for two adjacent time points are averaged and then multiplied by the time span between points (in hours). The theoretical range for SPI-48 is 0 to 470, with lower scores indicative of less pain over this time period (i.e., lower scores are consistent with better analgesia). Time 0 was defined as the time the capsule was closed. | The primary efficacy analysis was based on the Full Analysis dataset of Cohort 1 to 3. Full Analysis dataset included Safety population (i.e., all subjects who received at least 1 MDT-10013 strip or completed surgery in a standard-of-care group based on the actual treatment a subject received) having at least 1 postoperative pain assessment. | Posted | Mean | Standard Deviation | units on a scale | over 1 to 48hrs |
|
up to 3 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 1 MDT-10013 Strip (In Cohort 1) | For the investigational subjects of Cohort 1, one MDT-10013 strip was sutured to the exterior of the capsule wall. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bradycardia | Cardiac disorders | MedDRA version 16.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Affairs | Medtronic Spine and Biologics | 1800-876-3133 | 6068 | msbkclinicalresearch@medtronic.com |
Not provided
| ID | Term |
|---|---|
| D010149 | Pain, Postoperative |
| ID | Term |
|---|---|
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010146 | Pain |
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| ID | Term |
|---|---|
| D059039 | Standard of Care |
| ID | Term |
|---|---|
| D019984 | Quality Indicators, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
| D017530 | Health Care Quality, Access, and Evaluation |
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|
| over 1 to 48hrs |
| Summed Pain Intensity Over 1- 48hrs (SPI-48)--Sensitivity Analysis Using Windowed Worst Observation Carried Forward (WOCF) | Similar to SPI-48, the theoretical range for this WOCF adjustment for rescue medication is 0-470, with lower scores indicative of less pain over this time period (i.e., lower scores are consistent with better analgesia). The calculation is identical in terms of area-under the curve using the trapezoidal rule. However, the NRS score at the final assessment prior to each instance of rescue medication is carried forward through for a window based on the approximate half-life of the drug, replacing the raw NRS scores post-rescue for each patient until the end of the pharmacological activity window, at which point calculations revert to raw NRS as applicable. Note that WOCF SPI-48 may include multiple adjustment windows for each patient, depending on the number or rescue events and the active life of the medication selected. | over 1 to 48hrs |
| over 1 to 24hrs, 1 to 72hrs, and 1 to 96hrs |
| Total Use of Opioid Analgesia Over 0 to 24hrs, 0 to 48hrs, 0 to 72hrs, and 0 to 96hrs. | Total use of opioid analgesia over 0 to 24hrs, 0 to 48hrs, 0 to 72hrs, and 0 to 96hrs. The analgesia administered was converted to a morphine equivalent by using a standard conversion table. | over 0 to 24hrs, 0 to 48hrs, 0 to 72hrs, and 0 to 96hrs |
| Time to First Use of Opioid Analgesia | up to 96hrs |
| Subject's Satisfaction With Study Treatment | Subject's satisfaction with study treatment as measured by a 5-point categorical scale where 0 = poor, 1 = fair, 2 = good, 3 = very good, and 4 = excellent | up to 72hrs |
| up to 10 days |
| Pharmacokinetic (PK) Parameters of MDT-10013: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-∞) | Blood samples were taken for pharmacokinetic parameters of MDT-10013 determinations before surgery on Day 0; at 1, 2, 4, 6, 8, 12, 24, 48, 72, and 96 hours after Time 0 (96-hour sample for Cohort 4 only); and on Days 7 to 10 after Time 0. Time 0 was defined as the time the capsule was closed. Actual sampling times after T0 (to 1/1000th of an hour) were used to calculate PK parameters. | up to 10 days |
| Pharmacokinetic (PK) Parameters of MDT-10013: Maximum Observed Plasma Concentration (Cmax) | Blood samples were taken for pharmacokinetic parameters of MDT-10013 determinations before surgery on Day 0; at 1, 2, 4, 6, 8, 12, 24, 48, 72, and 96 hours after Time 0 (96-hour sample for Cohort 4 only); and on Days 7 to 10 after Time 0. Time 0 was defined as the time the capsule was closed. Actual sampling times after T0 (to 1/1000th of an hour) were used to calculate PK parameters. | up to 10 days |
| Pharmacokinetic (PK) Parameters of MDT-10013: Time to Maximum Plasma Concentration Observed (Tmax) | Blood samples were taken for pharmacokinetic parameters of MDT-10013 determinations before surgery on Day 0; at 1, 2, 4, 6, 8, 12, 24, 48, 72, and 96 hours after Time 0 (96-hour sample for Cohort 4 only); and on Days 7 to 10 after Time 0. Time 0 was defined as the time the capsule was closed. Actual sampling times after T0 (to 1/1000th of an hour) were used to calculate PK parameters. | up to 10 days |
| Pharmacokinetic (PK) Parameters of MDT-10013: Lag Time Before First Measurable Drug Concentration (Tlag) | Blood samples were taken for pharmacokinetic parameters of MDT-10013 determinations before surgery on Day 0; at 1, 2, 4, 6, 8, 12, 24, 48, 72, and 96 hours after Time 0 (96-hour sample for Cohort 4 only); and on Days 7 to 10 after Time 0. Time 0 was defined as the time the capsule was closed. Actual sampling times after T0 (to 1/1000th of an hour) were used to calculate PK parameters. | up to 10 days |
| Pharmacokinetic (PK) Parameters of MDT-10013: Terminal Plasma Half-life (t½) | Blood samples were taken for pharmacokinetic parameters of MDT-10013 determinations before surgery on Day 0; at 1, 2, 4, 6, 8, 12, 24, 48, 72, and 96 hours after Time 0 (96-hour sample for Cohort 4 only); and on Days 7 to 10 after Time 0. Time 0 was defined as the time the capsule was closed. | up to 10 days |
| Pharmacokinetic (PK) Parameters of MDT-10013: Terminal Phase Rate Constant (λz) | Blood samples were taken for pharmacokinetic parameters of MDT-10013 determinations before surgery on Day 0; at 1, 2, 4, 6, 8, 12, 24, 48, 72, and 96 hours after Time 0 (96-hour sample for Cohort 4 only); and on Days 7 to 10 after Time 0. Time 0 was defined as the time the capsule was closed. | up to 10 days |
| Summed Pain Intensity Scores (Exploratory Analysis) | The theoretical range for SPI-24, SPI-48, SPI-72, and SPI-96 is 0 to 230, 0-470, 0-710, and 0-960, respectively, with lower scores indicative of less pain over this time period (i.e., lower scores are consistent with better analgesia). Summed pain intensity is calculated as area under the curve, using the trapezoidal rule to bridge adjacent time points. Specifically, NRS scores for two adjacent time points are averaged and then multiplied by the time span between points (in hours). | over 1 to 24hr, 1 to 48 hrs, 1 to 72hrs, and 1 to 96hrs |
| Total Use of Opioid Analgesia (Exploratory Analysis). | over 0 to 24hrs, 0 to 48hrs, 0 to 72hrs, and 0 to 96hrs |
| Time to First Use of Opioid Analgesia (Exploratory Analysis) | up to 96hrs |
| Subject's Satisfaction With Study Treatment (Exploratory Analysis) | Subject's satisfaction with study treatment as measured by a 5-point categorical scale where 0 = poor, 1 = fair, 2 = good, 3 = very good, and 4 = excellent | up to 72hrs |
| Austin |
| Texas |
| 78705 |
| United States |
| Withdrawal by Subject |
|
For the investigational subjects of Cohort 2, one MDT-10013 strip was sutured to the exterior of the capsule and 1 strip was sutured to the interior capsule wall.
| BG002 | 3 MDT-10013 Strips (In Cohort 3) | For the investigational subjects of Cohort 3, one MDT-10013 strip was sutured to the exterior of the capsule and 2 strips were sutured to the interior capsule wall. |
| BG003 | 2 MDT-10013 Strips (In Cohort 4) | For the investigational subjects of Cohort 4, two MDT-10013 strips were sutured to the interior capsule wall. |
| BG004 | Control (In Cohort 1 to 4) | Control subjects in Cohort 1 to 4 received standard of care for pain control. |
| BG005 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Weight | Mean | Standard Deviation | lbs |
|
| Height | Mean | Standard Deviation | cm |
|
| BMI | Mean | Standard Deviation | kg/m^2 |
|
| OG000 |
| 1 MDT-10013 Strip (In Cohort 1) |
For the investigational subjects of Cohort 1, one MDT-10013 strip was sutured to the exterior of the capsule wall. |
| OG001 | 2 MDT-10013 Strips (In Cohort 2) | For the investigational subjects of Cohort 2, one MDT-10013 strip was sutured to the exterior of the capsule and 1 strip was sutured to the interior capsule wall. |
| OG002 | 3 MDT-10013 Strips (In Cohort 3) | For the investigational subjects of Cohort 3, one MDT-10013 strip was sutured to the exterior of the capsule and 2 strips were sutured to the interior capsule wall. |
| OG003 | Control (In Cohort 1-3) | Control subjects in Cohort 1 to 3 received standard of care for pain control. |
|
|
| Primary | Summed Pain Intensity Over 1- 48hrs (SPI-48)--Sensitivity Analysis Using Last Observation Carried Forward (LOCF) | Similar to SPI-48, the theoretical range for this LOCF adjustment for rescue medication is 0-470, with lower scores indicative of less pain over this time period (i.e., lower scores are consistent with better analgesia). The calculation is identical to SPI-48 in terms of area-under the curve using the trapezoidal rule. However, the NRS score at the final assessment prior to rescue is carried forward through 48 hours, replacing the raw NRS scores post-rescue for each patient as applicable. | The primary efficacy analysis was based on the Full Analysis dataset of Cohort 1 to 3. Full Analysis dataset included Safety population (i.e., all subjects who received at least 1 MDT-10013 strip or completed surgery in a standard-of-care group based on the actual treatment a subject received) having at least 1 postoperative pain assessment. | Posted | Mean | Standard Deviation | units on a scale | over 1 to 48hrs |
|
|
|
| Primary | Integrated Summed Pain Intensity Over 1- 48hrs (SPI-48) and Total Opioid Intake in First 48hrs --Sensitivity Analysis Using Silverman Method | This sensitivity analysis is an integrated assessment of summed pain intensity over 1 to 48hrs (SPI-48) and total opioid intake (ME0-48) in first 48hrs. Briefly, subjects were ranked according to SPI-48 regardless of the treatment received (including Standard of Care, SOC). The mean of all the ranks for this variable was calculated. Then, the percent difference for each individual rank from the pooled mean rank was computed. This process was repeated for total opioid intake in the first 48hrs (ME0-48). The integrated endpoint for each subject was the sum of the rank order percent differences for SPI-48 and ME0-48. The theoretical minimum and maximum on the integrated endpoint are -197% and +197% in this study. Lower scores are better, indicative of less pain and/or less opioid intake. | The primary efficacy analysis was based on the Full Analysis dataset of Cohort 1 to 3. Full Analysis dataset included Safety population (i.e., all subjects who received at least 1 MDT-10013 strip or completed surgery in a standard-of-care group based on the actual treatment a subject received) having at least 1 postoperative pain assessment. | Posted | Mean | Standard Deviation | percent difference | over 1 to 48hrs |
|
|
|
| Primary | Summed Pain Intensity Over 1- 48hrs (SPI-48)--Sensitivity Analysis Using Windowed Worst Observation Carried Forward (WOCF) | Similar to SPI-48, the theoretical range for this WOCF adjustment for rescue medication is 0-470, with lower scores indicative of less pain over this time period (i.e., lower scores are consistent with better analgesia). The calculation is identical in terms of area-under the curve using the trapezoidal rule. However, the NRS score at the final assessment prior to each instance of rescue medication is carried forward through for a window based on the approximate half-life of the drug, replacing the raw NRS scores post-rescue for each patient until the end of the pharmacological activity window, at which point calculations revert to raw NRS as applicable. Note that WOCF SPI-48 may include multiple adjustment windows for each patient, depending on the number or rescue events and the active life of the medication selected. | The primary efficacy analysis was based on the Full Analysis dataset of Cohort 1 to 3. Full Analysis dataset included Safety population (i.e., all subjects who received at least 1 MDT-10013 strip or completed surgery in a standard-of-care group based on the actual treatment a subject received) having at least 1 postoperative pain assessment. | Posted | Mean | Standard Deviation | units on a scale | over 1 to 48hrs |
|
|
|
| Secondary | Summed Pain Intensity Scores Over 1- 24hrs (SPI-24), 1- 72hrs (SPI-72) and 1- 96hrs (SPI-96) | The theoretical range for SPI-24, SPI-72, and SPI-96 is 0 to 230, 0-710, and 0-960, respectively, with lower scores indicative of less pain over this time period (i.e., lower scores are consistent with better analgesia). Summed pain intensity is calculated as area under the curve, using the trapezoidal rule to bridge adjacent time points. Specifically, NRS scores for two adjacent time points are averaged and then multiplied by the time span between points (in hours). | The primary efficacy analysis was based on the Full Analysis dataset of Cohort 1 to 3. Full Analysis dataset included Safety population (i.e., all subjects who received at least 1 MDT-10013 strip or completed surgery in a standard-of-care group based on the actual treatment a subject received) having at least 1 postoperative pain assessment. | Posted | Mean | Standard Deviation | units on a scale | over 1 to 24hrs, 1 to 72hrs, and 1 to 96hrs |
|
|
|
| Secondary | Total Use of Opioid Analgesia Over 0 to 24hrs, 0 to 48hrs, 0 to 72hrs, and 0 to 96hrs. | Total use of opioid analgesia over 0 to 24hrs, 0 to 48hrs, 0 to 72hrs, and 0 to 96hrs. The analgesia administered was converted to a morphine equivalent by using a standard conversion table. | The primary efficacy analysis was based on the Full Analysis dataset of Cohort 1 to 3. Full Analysis dataset included Safety population (i.e., all subjects who received at least 1 MDT-10013 strip or completed surgery in a standard-of-care group based on the actual treatment a subject received) having at least 1 postoperative pain assessment. | Posted | Mean | Standard Deviation | morphine mg equivalent | over 0 to 24hrs, 0 to 48hrs, 0 to 72hrs, and 0 to 96hrs |
|
|
|
| Secondary | Time to First Use of Opioid Analgesia | The primary efficacy analysis was based on the Full Analysis dataset of Cohort 1 to 3. Full Analysis dataset included Safety population (i.e., all subjects who received at least 1 MDT-10013 strip or completed surgery in a standard-of-care group based on the actual treatment a subject received) having at least 1 postoperative pain assessment. | Posted | Median | 95% Confidence Interval | hours | up to 96hrs |
|
|
|
| Secondary | Subject's Satisfaction With Study Treatment | Subject's satisfaction with study treatment as measured by a 5-point categorical scale where 0 = poor, 1 = fair, 2 = good, 3 = very good, and 4 = excellent | The primary efficacy analysis was based on the Full Analysis dataset of Cohort 1 to 3. Full Analysis dataset included Safety population (i.e., all subjects who received at least 1 MDT-10013 strip or completed surgery in a standard-of-care group based on the actual treatment a subject received) having at least 1 postoperative pain assessment. | Posted | Count of Participants | Participants | up to 72hrs |
|
|
|
| Other Pre-specified | Pharmacokinetic (PK) Parameters of MDT-10013: Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-t) | Blood samples were taken for pharmacokinetic parameters of MDT-10013 determinations before surgery on Day 0; at 1, 2, 4, 6, 8, 12, 24, 48, 72, and 96 hours after Time 0 (96-hour sample for Cohort 4 only); and on Days 7 to 10 after Time 0. Time 0 was defined as the time the capsule was closed. Actual sampling times after T0 (to 1/1000th of an hour) were used to calculate PK parameters. | PK analysis population consisted of all subjects who had PK samples analyzed. | Posted | Mean | Standard Deviation | h*pg/mL | up to 10 days |
|
|
|
| Other Pre-specified | Pharmacokinetic (PK) Parameters of MDT-10013: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-∞) | Blood samples were taken for pharmacokinetic parameters of MDT-10013 determinations before surgery on Day 0; at 1, 2, 4, 6, 8, 12, 24, 48, 72, and 96 hours after Time 0 (96-hour sample for Cohort 4 only); and on Days 7 to 10 after Time 0. Time 0 was defined as the time the capsule was closed. Actual sampling times after T0 (to 1/1000th of an hour) were used to calculate PK parameters. | PK analysis population consisted of all subjects who had PK samples analyzed. | Posted | Mean | Standard Deviation | h*pg/mL | up to 10 days |
|
|
|
| Other Pre-specified | Pharmacokinetic (PK) Parameters of MDT-10013: Maximum Observed Plasma Concentration (Cmax) | Blood samples were taken for pharmacokinetic parameters of MDT-10013 determinations before surgery on Day 0; at 1, 2, 4, 6, 8, 12, 24, 48, 72, and 96 hours after Time 0 (96-hour sample for Cohort 4 only); and on Days 7 to 10 after Time 0. Time 0 was defined as the time the capsule was closed. Actual sampling times after T0 (to 1/1000th of an hour) were used to calculate PK parameters. | PK analysis population consisted of all subjects who had PK samples analyzed. | Posted | Mean | Standard Deviation | pg/mL | up to 10 days |
|
|
|
| Other Pre-specified | Pharmacokinetic (PK) Parameters of MDT-10013: Time to Maximum Plasma Concentration Observed (Tmax) | Blood samples were taken for pharmacokinetic parameters of MDT-10013 determinations before surgery on Day 0; at 1, 2, 4, 6, 8, 12, 24, 48, 72, and 96 hours after Time 0 (96-hour sample for Cohort 4 only); and on Days 7 to 10 after Time 0. Time 0 was defined as the time the capsule was closed. Actual sampling times after T0 (to 1/1000th of an hour) were used to calculate PK parameters. | PK analysis population consisted of all subjects who had PK samples analyzed. | Posted | Median | Full Range | hrs | up to 10 days |
|
|
|
| Other Pre-specified | Pharmacokinetic (PK) Parameters of MDT-10013: Lag Time Before First Measurable Drug Concentration (Tlag) | Blood samples were taken for pharmacokinetic parameters of MDT-10013 determinations before surgery on Day 0; at 1, 2, 4, 6, 8, 12, 24, 48, 72, and 96 hours after Time 0 (96-hour sample for Cohort 4 only); and on Days 7 to 10 after Time 0. Time 0 was defined as the time the capsule was closed. Actual sampling times after T0 (to 1/1000th of an hour) were used to calculate PK parameters. | PK analysis population consisted of all subjects who had PK samples analyzed. | Posted | Median | Full Range | hrs | up to 10 days |
|
|
|
| Other Pre-specified | Pharmacokinetic (PK) Parameters of MDT-10013: Terminal Plasma Half-life (t½) | Blood samples were taken for pharmacokinetic parameters of MDT-10013 determinations before surgery on Day 0; at 1, 2, 4, 6, 8, 12, 24, 48, 72, and 96 hours after Time 0 (96-hour sample for Cohort 4 only); and on Days 7 to 10 after Time 0. Time 0 was defined as the time the capsule was closed. | PK analysis population consisted of all subjects who had PK samples analyzed. | Posted | Mean | Standard Deviation | hrs | up to 10 days |
|
|
|
| Other Pre-specified | Pharmacokinetic (PK) Parameters of MDT-10013: Terminal Phase Rate Constant (λz) | Blood samples were taken for pharmacokinetic parameters of MDT-10013 determinations before surgery on Day 0; at 1, 2, 4, 6, 8, 12, 24, 48, 72, and 96 hours after Time 0 (96-hour sample for Cohort 4 only); and on Days 7 to 10 after Time 0. Time 0 was defined as the time the capsule was closed. | PK analysis population consisted of all subjects who had PK samples analyzed. | Posted | Mean | Standard Deviation | /hr | up to 10 days |
|
|
|
| Other Pre-specified | Summed Pain Intensity Scores (Exploratory Analysis) | The theoretical range for SPI-24, SPI-48, SPI-72, and SPI-96 is 0 to 230, 0-470, 0-710, and 0-960, respectively, with lower scores indicative of less pain over this time period (i.e., lower scores are consistent with better analgesia). Summed pain intensity is calculated as area under the curve, using the trapezoidal rule to bridge adjacent time points. Specifically, NRS scores for two adjacent time points are averaged and then multiplied by the time span between points (in hours). | The efficacy analyses of Cohort 1 to 4 were considered for exploratory analyses. | Posted | Mean | Standard Deviation | units on a scale | over 1 to 24hr, 1 to 48 hrs, 1 to 72hrs, and 1 to 96hrs |
|
|
|
| Other Pre-specified | Total Use of Opioid Analgesia (Exploratory Analysis). | The efficacy analyses of Cohort 1 to 4 were considered for exploratory analyses. | Posted | Mean | Standard Deviation | morphine mg equivalent | over 0 to 24hrs, 0 to 48hrs, 0 to 72hrs, and 0 to 96hrs |
|
|
|
| Other Pre-specified | Time to First Use of Opioid Analgesia (Exploratory Analysis) | The efficacy analyses of Cohort 1 to 4 were considered for exploratory analyses. | Posted | Median | 95% Confidence Interval | hours | up to 96hrs |
|
|
|
| Other Pre-specified | Subject's Satisfaction With Study Treatment (Exploratory Analysis) | Subject's satisfaction with study treatment as measured by a 5-point categorical scale where 0 = poor, 1 = fair, 2 = good, 3 = very good, and 4 = excellent | The efficacy analyses of Cohort 1 to 4 were considered for exploratory analyses. | Posted | Count of Participants | Participants | up to 72hrs |
|
|
|
| 0 |
| 36 |
| 0 |
| 36 |
| 28 |
| 36 |
| EG001 | 2 MDT-10013 Strips (In Cohort 2) | For the investigational subjects of Cohort 2, one MDT-10013 strip was sutured to the exterior of the capsule and 1 strip was sutured to the interior capsule wall. | 0 | 36 | 0 | 36 | 34 | 36 |
| EG002 | 3 MDT-10013 Strips (In Cohort 3) | For the investigational subjects of Cohort 3, one MDT-10013 strip was sutured to the exterior of the capsule and 2 strips were sutured to the interior capsule wall. | 0 | 36 | 0 | 36 | 30 | 36 |
| EG003 | 2 MDT-10013 Strips (In Cohort 4) | For the investigational subjects of Cohort 4, two strips were sutured to the interior capsule wall. | 0 | 36 | 0 | 36 | 24 | 36 |
| EG004 | Control (In Cohort 1 to 4) | Control subjects in Cohort 1 to 4 received standard of care (no strip) for pain control. | 0 | 48 | 0 | 48 | 38 | 48 |
| Tinnitus | Ear and labyrinth disorders | MedDRA version 16.0 | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA version 16.0 | Systematic Assessment |
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| Ocular hyperaemia | Eye disorders | MedDRA version 16.0 | Systematic Assessment |
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| Abdominal discomfort | Gastrointestinal disorders | MedDRA version 16.0 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA version 16.0 | Systematic Assessment |
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| Aphthous stomatitis | Gastrointestinal disorders | MedDRA version 16.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA version 16.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA version 16.0 | Systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | MedDRA version 16.0 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA version 16.0 | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA version 16.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA version 16.0 | Systematic Assessment |
|
| Paraesthesia oral | Gastrointestinal disorders | MedDRA version 16.0 | Systematic Assessment |
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| Rectal haemorrhage | Gastrointestinal disorders | MedDRA version 16.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA version 16.0 | Systematic Assessment |
|
| Chills | General disorders | MedDRA version 16.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA version 16.0 | Systematic Assessment |
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| Feeling hot | General disorders | MedDRA version 16.0 | Systematic Assessment |
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| Granuloma | General disorders | MedDRA version 16.0 | Systematic Assessment |
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| Hypothermia | General disorders | MedDRA version 16.0 | Systematic Assessment |
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| Impaired healing | General disorders | MedDRA version 16.0 | Systematic Assessment |
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| Infusion site bruising | General disorders | MedDRA version 16.0 | Systematic Assessment |
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| Infusion site haematoma | General disorders | MedDRA version 16.0 | Systematic Assessment |
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| Infusion site pain | General disorders | MedDRA version 16.0 | Systematic Assessment |
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| Infusion site phlebitis | General disorders | MedDRA version 16.0 | Systematic Assessment |
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| Infusion site pruritus | General disorders | MedDRA version 16.0 | Systematic Assessment |
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| Mucosal dryness | General disorders | MedDRA version 16.0 | Systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA version 16.0 | Systematic Assessment |
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| Pain | General disorders | MedDRA version 16.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA version 16.0 | Systematic Assessment |
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| Allergy to animal | Immune system disorders | MedDRA version 16.0 | Systematic Assessment |
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| Drug hypersensitivity | Immune system disorders | MedDRA version 16.0 | Systematic Assessment |
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| Seasonal allergy | Immune system disorders | MedDRA version 16.0 | Systematic Assessment |
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| Cellulitis | Infections and infestations | MedDRA version 16.0 | Systematic Assessment |
|
| Clostridium difficile colitis | Infections and infestations | MedDRA version 16.0 | Systematic Assessment |
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| Gastroenteritis viral | Infections and infestations | MedDRA version 16.0 | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA version 16.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA version 16.0 | Systematic Assessment |
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| Post procedural cellulitis | Infections and infestations | MedDRA version 16.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA version 16.0 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA version 16.0 | Systematic Assessment |
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| Viral infection | Infections and infestations | MedDRA version 16.0 | Systematic Assessment |
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| Viral upper respiratory tract infection | Infections and infestations | MedDRA version 16.0 | Systematic Assessment |
|
| Vulvovaginal mycotic infection | Infections and infestations | MedDRA version 16.0 | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA version 16.0 | Systematic Assessment |
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| Eschar | Injury, poisoning and procedural complications | MedDRA version 16.0 | Systematic Assessment |
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| Foot fracture | Injury, poisoning and procedural complications | MedDRA version 16.0 | Systematic Assessment |
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| Incision site haemorrhage | Injury, poisoning and procedural complications | MedDRA version 16.0 | Systematic Assessment |
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| Incision site pain | Injury, poisoning and procedural complications | MedDRA version 16.0 | Systematic Assessment |
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| Laceration | Injury, poisoning and procedural complications | MedDRA version 16.0 | Systematic Assessment |
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| Muscle strain | Injury, poisoning and procedural complications | MedDRA version 16.0 | Systematic Assessment |
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| Post procedural complication | Injury, poisoning and procedural complications | MedDRA version 16.0 | Systematic Assessment |
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| Post procedural haemorrhage | Injury, poisoning and procedural complications | MedDRA version 16.0 | Systematic Assessment |
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| Post procedural oedema | Injury, poisoning and procedural complications | MedDRA version 16.0 | Systematic Assessment |
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| Procedural pain | Injury, poisoning and procedural complications | MedDRA version 16.0 | Systematic Assessment |
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| Stress fracture | Injury, poisoning and procedural complications | MedDRA version 16.0 | Systematic Assessment |
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| Thermal burn | Injury, poisoning and procedural complications | MedDRA version 16.0 | Systematic Assessment |
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| Wound dehiscence | Injury, poisoning and procedural complications | MedDRA version 16.0 | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA version 16.0 | Systematic Assessment |
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| Body temperature increased | Investigations | MedDRA version 16.0 | Systematic Assessment |
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| Liver function test abnormal | Investigations | MedDRA version 16.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA version 16.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 16.0 | Systematic Assessment |
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| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA version 16.0 | Systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA version 16.0 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA version 16.0 | Systematic Assessment |
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| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA version 16.0 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA version 16.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA version 16.0 | Systematic Assessment |
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| Dizziness postural | Nervous system disorders | MedDRA version 16.0 | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA version 16.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA version 16.0 | Systematic Assessment |
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| Hyperaesthesia | Nervous system disorders | MedDRA version 16.0 | Systematic Assessment |
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| Lethargy | Nervous system disorders | MedDRA version 16.0 | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA version 16.0 | Systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA version 16.0 | Systematic Assessment |
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| Sinus headache | Nervous system disorders | MedDRA version 16.0 | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA version 16.0 | Systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA version 16.0 | Systematic Assessment |
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| Tremor | Nervous system disorders | MedDRA version 16.0 | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA version 16.0 | Systematic Assessment |
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| Dysuria | Renal and urinary disorders | MedDRA version 16.0 | Systematic Assessment |
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| Glycosuria | Renal and urinary disorders | MedDRA version 16.0 | Systematic Assessment |
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| Haematuria | Renal and urinary disorders | MedDRA version 16.0 | Systematic Assessment |
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| Pollakiuria | Renal and urinary disorders | MedDRA version 16.0 | Systematic Assessment |
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| Urinary tract disorder | Renal and urinary disorders | MedDRA version 16.0 | Systematic Assessment |
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| Breast cyst | Reproductive system and breast disorders | MedDRA version 16.0 | Systematic Assessment |
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| Breast pain | Reproductive system and breast disorders | MedDRA version 16.0 | Systematic Assessment |
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| Menopausal symptoms | Reproductive system and breast disorders | MedDRA version 16.0 | Systematic Assessment |
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| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA version 16.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 16.0 | Systematic Assessment |
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| Dry throat | Respiratory, thoracic and mediastinal disorders | MedDRA version 16.0 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA version 16.0 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA version 16.0 | Systematic Assessment |
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| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA version 16.0 | Systematic Assessment |
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| Erythema | Skin and subcutaneous tissue disorders | MedDRA version 16.0 | Systematic Assessment |
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| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA version 16.0 | Systematic Assessment |
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| Ingrowing nail | Skin and subcutaneous tissue disorders | MedDRA version 16.0 | Systematic Assessment |
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| Papule | Skin and subcutaneous tissue disorders | MedDRA version 16.0 | Systematic Assessment |
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| Petechiae | Skin and subcutaneous tissue disorders | MedDRA version 16.0 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA version 16.0 | Systematic Assessment |
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| Pruritus generalised | Skin and subcutaneous tissue disorders | MedDRA version 16.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA version 16.0 | Systematic Assessment |
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| Rash papular | Skin and subcutaneous tissue disorders | MedDRA version 16.0 | Systematic Assessment |
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| Skin irritation | Skin and subcutaneous tissue disorders | MedDRA version 16.0 | Systematic Assessment |
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| Urticaria | Skin and subcutaneous tissue disorders | MedDRA version 16.0 | Systematic Assessment |
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| Hot flush | Vascular disorders | MedDRA version 16.0 | Systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA version 16.0 | Systematic Assessment |
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| Orthostatic hypotension | Vascular disorders | MedDRA version 16.0 | Systematic Assessment |
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| Phlebitis | Vascular disorders | MedDRA version 16.0 | Systematic Assessment |
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Not provided
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| SPI-72 |
|
| SPI-96 |
|
| Total opioid analgesia use over 0 to 48 hrs |
|
| Total opioid analgesia use over 0 to 72 hrs |
|
| Total opioid analgesia use over 0 to 96 hrs |
|
| Fair |
|
| Good |
|
| Very good |
|
| Excellent |
|
| SPI-48 |
|
| SPI-72 |
|
| SPI-96 |
|
| Total opioid analgesia use over 0 to 48 hrs |
|
| Total opioid analgesia use over 0 to 72 hrs |
|
| Total opioid analgesia use over 0 to 96 hrs |
|
| Fair |
|
| Good |
|
| Very good |
|
| Excellent |
|