Dental Pain, Pain, Postoperative
Conditions
Brief summary
To assess the safety, tolerability, analgesic, efficacy and pharmacokinetics of high dose acetaminophen relative to placebo and low dose acetaminophen relative to placebo over a 24 hour period in patient experiencing moderate to severe pain following the surgical removal of third molar.
Detailed description
This will be a randomized, double-blind, single-site, placebo-controlled, parallel-group study to assess similarities in safety, tolerability, efficacy, and pharmacokinetics of high dose acetaminophen given relative to placebo, and low dose acetaminophen given relative to placebo over a 24-hour period in patients experiencing moderate to severe postsurgical pain within 7 hours following surgical removal of 2 or more molars
Interventions
DRUGAcetaminophen
Acetaminophen is an analgesic and antipyretic
OTHERPlacebo
Saline
Sponsors
Nevakar, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double Blind, Placebo controlled
Intervention model description
High Dose Acetaminophen (APAP) versus Placebo, Low Dose APAP versus Placebo
Eligibility
Sex/Gender
ALL
Age
17 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Patients must be capable of reading, comprehending, and signing the informed consent/assent form; 2. Male and female patients between 17-55 years of age; 3. Body Mass Index (BMI) ≤35.0 kg/m2 4. Body weight of \>50 kg 5. Patients are American Society of Anaesthesiologists (ASA) Category I or II and are in good physical health as judged by a thorough history and physical examination; 6. Patients without infections in the area of the impacted teeth; 7. Patients must agree to refrain from ingesting any systemic or applying any topical analgesic medication for 3 days or 5 half-lives of the drug prior to and during the study; 8. No alcohol for a minimum of 24 hours prior to the surgery; 9. Female patients must be of non-child bearing potential, defined as postmenopausal for more than 1 year or surgically sterile (hysterectomy, tubal ligation/occlusion) or practicing an acceptable method of contraception (hormonal oral, patch, or implant, double barrier method, intrauterine device, vasectomized or same sex partner, or abstinence). Patients using hormonal birth control must have been on a stable dose of treatment for at least 30 days and received at least 1 cycle of treatment prior to randomization. At Screening and at the day of surgery, all females of childbearing potential must have a negative (serum at screening and urine on day of surgery 1) pregnancy test and not be breastfeeding; 10. Patients must have a negative urine drug screen for drugs of abuse at Screening and on the day of surgery. At the discretion of the Principal Investigator, a positive drug screen result may be permitted if the patient has been on a stable dose of an allowed medication for \>30 days; 11. Patients who are scheduled to undergo the surgical removal of up to 4 third molars of which at least two have to be mandibular molars with a difficulty rating of 4 or 5 and meeting the following criteria: * two full bony impactions * two partial bony impactions * one full bony impaction in combination with one partial bony impaction (see Appendix 1 for Impaction Difficulty Rating Scale); 12. Patients able to comprehend and follow the requirements of the study (including availability on scheduled visit dates) based upon the research site's judgment.
Exclusion criteria
1. Patients with a history of any significant medical condition that, in the opinion of the Principal Investigator or his designee, would place the patient at increased risk such as: hepatic, renal, endocrine, cardiac, neurological, psychiatric, gastrointestinal, pulmonary, hematologic, or metabolic disorders, including glaucoma, diabetes, emphysema, and chronic bronchitis; 2. Patients with a history of any type of malignancy within the past 5 years other than minor skin related cancers; 3. Patients with a history of alcohol or substance abuse in the past three years according to Diagnostic and Statistical Manual (DSM) V and who do not satisfy Inclusion Criteria 10 (including a positive urine drug screen test); 4. Patients with a known allergy or hypersensitivity to any local anesthetic drug, acetaminophen, ibuprofen, or other NSAIDS; 5. Patients who are taking any concomitant medications that might confound assessments of pain relief, such as psychotropic drugs, antidepressants, sedative hypnotics or any analgesics taken within three days or five times of their elimination half-lives, whichever is longer. Selective serotonin reuptake inhibitors (SSRIs) and selective noradrenaline reuptake inhibitors (SNRIs) are permitted if the patient has been on a stable dose for at least 30 days prior to screening; 6. Patients who have smoked or chewed tobacco-containing substances within 48 hours prior to the day of surgery; 7. Patients judged by the Principal Investigator to be unable or unwilling to comply with the requirements of the protocol; 8. Patients who have used an investigational drug within 30 days prior to the screening day or have previously participated in any Nevakar trial; 9. Patients who have donated blood within 3 months prior to the screening day; 10. Patients who are employees or relatives of employees of JBR Clinical Research or Nevakar, Inc. 11. Patients with liver function tests (ALT, AST) that are above the normal reference range. \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sum of Pain Intensity Difference From 0 to 24 Hours (SPID24) Based on the 11 Point Numeric Pain Rating Scale | Baseline (0.0) and 0.5, 0.75, 1, 1.25, 1.75, 2.25 3.25, 4.25, 5.25, 6.25, 7.25, 8.25, 9.25, 10.25, 11.25, 12.25 (± 5 min) and 14.25, 16.25, 18.25, 20.25, 22.25, and 24.25 (± 10 min) hours | Pain Intensity was self-reported over 24 hours, using a pain rating of 0-10 on the Numerical Rating Scale (NRS), with score between 0-10 (0= no pain; 10 = worst imaginable pain). Time weighted sum of pain intensity difference from 0 to 24 hours was reported. Pain Intensity (PI-NPRS) was collected at initiation of Dose 1 (T0) and post dose 0.5, 0.75, 1, 1.25, 1.75, 2.25 3.25, 4.25, 5.25, 6.25, 7.25, 8.25, 9.25, 10.25, 11.25, 12.25 (± 5 min) and 14.25, 16.25, 18.25, 20.25, 22.25, and 24.25 (± 10 min). SPID24 was include all nominal timepoints from T0 to T24.25 hours. SPID is calculated as Σ\[T(i) -T(i-1)\] x \[(PID(i-1) + PID(i))/2\], where T(0)=0, T(i) is the scheduled time, and PID(i) is the pain intensity difference (PID) score at time i. Pain intensity differences were calculated with respect to Baseline. A baseline assessment is defined as the last non-missing result prior to administration of the first dose of study medication. |
| Sum of Pain Relief From 0 to 24 Hours (TOTPAR24) Based on a 5-point Likert Scale. | Baseline (0.0) and 0.5, 0.75, 1, 1.25, 1.75, 2.25 3.25, 4.25, 5.25, 6.25, 7.25, 8.25, 9.25, 10.25, 11.25, 12.25 (± 5 min) and 14.25, 16.25, 18.25, 20.25, 22.25, and 24.25 (± 10 min) hours | Pain Relief Rating (PR) was scored on a 5-point scale (0=no-, 1=a little-, 2=some-, 3=a lot of-, and 4=complete- PR). PR was collected at initiation of Dose 1 (T0) and post dose 0.5, 0.75, 1, 1.25, 1.75, 2.25 3.25, 4.25, 5.25, 6.25, 7.25, 8.25, 9.25, 10.25, 11.25, 12.25 (± 5 min) and 14.25, 16.25, 18.25, 20.25, 22.25, and 24.25 (± 10 min) hours. TOTPAR24 is calculated as Sum (\[T(i) - T(i-1)\] x (PR(i-1) + PR(i)) / 2), where T(0)=0, T(i) is the actual time, and PR(i) is the pain relief score at time i. and calculated as Σ\[T(i) -T(i-1)\] x \[(PR(i-1) + PR(i))/2\], where T(0)=0, T(i) is the scheduled time, and PR(i) is the pain relief (PR) score at time i. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Perceptible Pain Relief Confirmed (FPR-C) After Dose 1 Administration Stratified by Baseline Pain Score of Moderate or Severe for the 3 Treatment Groups | 0 to 24 Hours | Upon initiation of the infusion of Dose 1, the participants were given stopwatch #1 and asked to press the stopwatch when they first perceived any pain relief (first perceptible pain relief \[FPR\]) ; a record of the time was noted in the participant record. If a participant does not record perceptible pain relief and prematurely discontinued from the study prior to 24 hours, then the participant was censored at time of drop out. If a participant does not record perceptible pain relief prior to taking rescue medication, the participant was censored at 24 hours |
| Time to Meaningful Perceptible Relief (MPR) Measure Stratified by Baseline Pain Score of Moderate or Severe for the 3 Treatment Groups | 0 to 24 Hours | Upon initiation of the infusion of Dose 1, the participants were given a second stopwatch and asked to press the stopwatch if and when they feel any meaningful perceptible relief; a record of the time was noted in the participant record. If a participant does not record perceptible pain relief and was prematurely discontinued from the study prior to 24 hours, then the participant was censored at time of drop out. If a participant does not record perceptible pain relief prior to taking rescue medication, the participant was censored at 24 hours. |
| Patient Global Evaluation of the Study Medication | 0 to 24 Hours | Patients Global Evaluation was assessed on a scale of 0 (Poor), 1 (Fair), 2 (Good), 3 (Very Good) and 4 (Excellent) at 24.25 hours post-dose 1 or at participant withdrawal (if applicable), whichever occurred first. Least squares mean of the score are reported. |
| Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | Baseline (0.0) and 0.5, 0.75, 1, 1.25, 1.75, 2.25 3.25, 4.25, 5.25, 6.25, 7.25, 8.25, 9.25, 10.25, 11.25, 12.25 (± 5 min) and 14.25, 16.25, 18.25, 20.25, 22.25, and 24.25 hours (± 10 min) | Pain Intensity was self-reported over 24 hours, using a pain rating of 0-10 on the Numerical Rating Scale (NRS), with score between 0-10 (0= no pain; 10 = worst imaginable pain). Pain intensity differences were calculated with respect to Baseline at each time point after Dose 1 administration. A baseline assessment was defined as the last non-missing result prior to administration of the first dose of study medication |
| Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 0 to 24 hours | Pain intensity is reported using the 11-point Numerical Rating Scale (NRS), with score between 0-10 (0= no pain; 10 = worst imaginable pain). |
| Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 0 to 24 hours | Pain Relief is reported on a 5-Point Categorical Pain Relief Assessment scale: 0 = No Pain Relief, 1 = A Little Pain Relief, 2 = Some Pain Relief, 3 = A Lot of Pain Relief, 4 = Complete Pain Relief. |
| Time to Treatment Failure | 0 to 24 Hours | Time to treatment failure is defined as time to first dose of rescue medication after Dose 1 or withdrawal from the study for any reason. If a participant does not take rescue medication or withdraw from the study prior to 24 hours, the participant was censored at 24 hours |
Other
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline to 24 Hours in Vital Signs (Systolic Blood Pressure) | 0 to 24 hours | Change from Baseline in systolic blood pressure is the value at 24 hours minus value at Baseline. Baseline was defined as the last non-missing result prior to administration of the first dose of study drug. Systolic blood pressure is obtained at screening, prior to surgery and at Hours 4, 8, 12, 16, 20 and 24 following initiation of dose (±10 min). |
| Mean Change From Baseline to 24 Hours in Vital Signs (Temperature) | 0 to 24 hours | Change from Baseline in temperature is the value at 24 hours minus value at Baseline. Baseline was defined as the last non-missing result prior to administration of the first dose of study drug. Temperature is obtained at screening, prior to surgery and at Hours 4, 8, 12, 16, 20 and 24 following initiation of dose (±10 min) |
| Mean Change From Baseline to 24 Hours in Vital Signs (Diastolic Blood Pressure) | 0 to 24 hours | Change from Baseline in diastolic blood pressure is the value at 24 hours minus value at Baseline. Baseline was defined as the last non-missing result prior to administration of the first dose of study drug. Diastolic blood pressure is obtained at screening, prior to surgery and at Hours 4, 8, 12, 16, 20 and 24 following initiation of dose (±10 min) |
| Mean Change From Baseline to 24 Hours in Vital Signs (Pulse Rate) | 0 to 24 hours | Change from Baseline in pulse rate is the value at 24 hours minus value at Baseline. Baseline was defined as the last non-missing result prior to administration of the first dose of study drug. Pulse rate is obtained at screening, prior to surgery and at Hours 4, 8, 12, 16, 20 and 24 following initiation of dose (±10 min) |
| Mean Change From Baseline to 24 Hours in Vital Signs (Respiratory Rate) | 0 to 24 hours | Change from Baseline in respiratory rate was the value at 24 hours minus value at Baseline. Baseline was defined as the last non-missing result prior to administration of the first dose of study drug. Respiratory rate was obtained at screening, prior to surgery and at Hours 4, 8, 12, 16, 20 and 24 following initiation of dose (±10 min) |
| Area Under the Plasma Concentration-Time Curve From Time of Administration to 24 Hours After Dosing (AUC 0-24h) | Pre-dose, and 0.25, 0.5, 0.75, 1.0, 2.0, 4.0, 6.25, 8.0, 8.25, 8.25, 12.0, 12.25, 16.0, 16.25, 18.0, 18.25, 24.25 hours post-dose | The Area Under the Plasma Concentration-Time Curve (AUC) is a measure of the plasma concentration of the drug over time. It is used to characterize drug absorption. The values for pharmacokinetic (PK) evaluable population-excluding participants with positive pre-dose concentrations have been populated. The samples were collected at 5 min prior to Dose 1, and at 0.25, 0.5, 0.75, 1.0, 2.0, 4.0, 6.25, 8.0, 8.25, 8.25, 12.0, 12.25, 16.0, 16.25, 18.0, 18.25, 24.25 hours post-dose 1. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) | Pre-dose, and 0.25, 0.5, 0.75, 1.0, 2.0, 4.0, 6.25, 8.0, 8.25, 8.25, 12.0, 12.25, 16.0, 16.25, 18.0, 18.25, 24.25 hours post-dose | The AUC(0-infinity) is area under the plasma concentration-time curve from time zero to infinite time. The samples were collected at 5 min prior to Dose 1, and at 0.25, 0.5, 0.75, 1.0, 2.0, 4.0, 6.25, 8.0, 8.25, 8.25, 12.0, 12.25, 16.0, 16.25, 18.0, 18.25, 24.25 hours post-dose 1. |
| Half-life | Pre-dose, and 0.25, 0.5, 0.75, 1.0, 2.0, 4.0, 6.25, 8.0, 8.25, 8.25, 12.0, 12.25, 16.0, 16.25, 18.0, 18.25, 24.25 hours post-dose | The half-life (t 1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. |
| Maximum Observed Plasma Concentration (Cmax) | Pre-dose, and 0.25, 0.5, 0.75, 1.0, 2.0, 4.0, 6.25, 8.0, 8.25, 8.25, 12.0, 12.25, 16.0, 16.25, 18.0, 18.25, 24.25 hours post-dose | The Plasma Concentration (Cmax) is defined as maximum observed concentration |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from April 2019 till July 2019 from the site
Pre-assignment details
A total of 226 participants were screened from Day-30 to Day 0 before getting randomized
Participants by arm
| Arm | Count |
|---|---|
| High Dose APAP Acetaminophen (APAP) administered post-operatively at a high dose | 44 |
| Low Dose APAP Acetaminophen (APAP) administered post-operatively at a low dose | 44 |
| Placebo Placebo given post-operatively | 22 |
| Total | 110 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | High Dose APAP | Low Dose APAP | Placebo |
|---|---|---|---|---|
| Age, Continuous | 18.9 years STANDARD_DEVIATION 2.23 | 18.7 years STANDARD_DEVIATION 2.06 | 18.8 years STANDARD_DEVIATION 2.31 | 19.3 years STANDARD_DEVIATION 2.42 |
| Body Mass Index | 24.61 kg/m^2 STANDARD_DEVIATION 4.13 | 24.45 kg/m^2 STANDARD_DEVIATION 4.124 | 24.33 kg/m^2 STANDARD_DEVIATION 3.762 | 25.49 kg/m^2 STANDARD_DEVIATION 4.869 |
| Categorical pain intensity score Mild (1) | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Categorical pain intensity score Moderate (2) | 35 Participants | 14 Participants | 11 Participants | 10 Participants |
| Categorical pain intensity score None (0) | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Categorical pain intensity score Severe (3) | 75 Participants | 30 Participants | 33 Participants | 12 Participants |
| NRS pain intensity 0 = No pain | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| NRS pain intensity 1 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| NRS pain intensity 10 = Worst imaginable pain | 4 Participants | 3 Participants | 1 Participants | 0 Participants |
| NRS pain intensity 2 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| NRS pain intensity 3 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| NRS pain intensity 4 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| NRS pain intensity 5 | 3 Participants | 1 Participants | 1 Participants | 1 Participants |
| NRS pain intensity 6 | 26 Participants | 11 Participants | 7 Participants | 8 Participants |
| NRS pain intensity 7 | 31 Participants | 13 Participants | 12 Participants | 6 Participants |
| NRS pain intensity 8 | 38 Participants | 13 Participants | 18 Participants | 7 Participants |
| NRS pain intensity 9 | 8 Participants | 3 Participants | 5 Participants | 0 Participants |
| Race/Ethnicity, Customized Ethinicity-Not Hispanic or Latino | 92 Participants | 35 Participants | 36 Participants | 21 Participants |
| Race/Ethnicity, Customized Ethnicity-Hispanic or Latino | 18 Participants | 9 Participants | 8 Participants | 1 Participants |
| Race/Ethnicity, Customized Race-Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race-Black or African American | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race- Native Hawaiian or Other Pacific Islander | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race-Others | 6 Participants | 2 Participants | 4 Participants | 0 Participants |
| Race/Ethnicity, Customized Race-White | 100 Participants | 39 Participants | 39 Participants | 22 Participants |
| Sex: Female, Male Female | 58 Participants | 25 Participants | 22 Participants | 11 Participants |
| Sex: Female, Male Male | 52 Participants | 19 Participants | 22 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 44 | 0 / 44 | 0 / 22 |
| other Total, other adverse events | 9 / 44 | 13 / 44 | 7 / 22 |
| serious Total, serious adverse events | 0 / 44 | 0 / 44 | 0 / 22 |
Outcome results
Primary
Sum of Pain Intensity Difference From 0 to 24 Hours (SPID24) Based on the 11 Point Numeric Pain Rating Scale
Pain Intensity was self-reported over 24 hours, using a pain rating of 0-10 on the Numerical Rating Scale (NRS), with score between 0-10 (0= no pain; 10 = worst imaginable pain). Time weighted sum of pain intensity difference from 0 to 24 hours was reported. Pain Intensity (PI-NPRS) was collected at initiation of Dose 1 (T0) and post dose 0.5, 0.75, 1, 1.25, 1.75, 2.25 3.25, 4.25, 5.25, 6.25, 7.25, 8.25, 9.25, 10.25, 11.25, 12.25 (± 5 min) and 14.25, 16.25, 18.25, 20.25, 22.25, and 24.25 (± 10 min). SPID24 was include all nominal timepoints from T0 to T24.25 hours. SPID is calculated as Σ\[T(i) -T(i-1)\] x \[(PID(i-1) + PID(i))/2\], where T(0)=0, T(i) is the scheduled time, and PID(i) is the pain intensity difference (PID) score at time i. Pain intensity differences were calculated with respect to Baseline. A baseline assessment is defined as the last non-missing result prior to administration of the first dose of study medication.
Time frame: Baseline (0.0) and 0.5, 0.75, 1, 1.25, 1.75, 2.25 3.25, 4.25, 5.25, 6.25, 7.25, 8.25, 9.25, 10.25, 11.25, 12.25 (± 5 min) and 14.25, 16.25, 18.25, 20.25, 22.25, and 24.25 (± 10 min) hours
Population: The Evaluable Population included all randomized participants who, as documented prior to the breaking of the study blind: (1) met all the inclusion and exclusion criteria and; (2) were administered Dose 1.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| High Dose APAP | Sum of Pain Intensity Difference From 0 to 24 Hours (SPID24) Based on the 11 Point Numeric Pain Rating Scale | -96.80 score on a scale | Standard Error 6.369 |
| Low Dose APAP | Sum of Pain Intensity Difference From 0 to 24 Hours (SPID24) Based on the 11 Point Numeric Pain Rating Scale | -100.69 score on a scale | Standard Error 6.333 |
| Placebo | Sum of Pain Intensity Difference From 0 to 24 Hours (SPID24) Based on the 11 Point Numeric Pain Rating Scale | -74.96 score on a scale | Standard Error 9.055 |
p-value: 0.0258ANCOVA
p-value: 0.0115ANCOVA
Primary
Sum of Pain Relief From 0 to 24 Hours (TOTPAR24) Based on a 5-point Likert Scale.
Pain Relief Rating (PR) was scored on a 5-point scale (0=no-, 1=a little-, 2=some-, 3=a lot of-, and 4=complete- PR). PR was collected at initiation of Dose 1 (T0) and post dose 0.5, 0.75, 1, 1.25, 1.75, 2.25 3.25, 4.25, 5.25, 6.25, 7.25, 8.25, 9.25, 10.25, 11.25, 12.25 (± 5 min) and 14.25, 16.25, 18.25, 20.25, 22.25, and 24.25 (± 10 min) hours. TOTPAR24 is calculated as Sum (\[T(i) - T(i-1)\] x (PR(i-1) + PR(i)) / 2), where T(0)=0, T(i) is the actual time, and PR(i) is the pain relief score at time i. and calculated as Σ\[T(i) -T(i-1)\] x \[(PR(i-1) + PR(i))/2\], where T(0)=0, T(i) is the scheduled time, and PR(i) is the pain relief (PR) score at time i.
Time frame: Baseline (0.0) and 0.5, 0.75, 1, 1.25, 1.75, 2.25 3.25, 4.25, 5.25, 6.25, 7.25, 8.25, 9.25, 10.25, 11.25, 12.25 (± 5 min) and 14.25, 16.25, 18.25, 20.25, 22.25, and 24.25 (± 10 min) hours
Population: The Evaluable Population included all randomized participants who, as documented prior to the breaking of the study blind: (1) met all the inclusion and exclusion criteria and; (2) were administered Dose 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose APAP | Sum of Pain Relief From 0 to 24 Hours (TOTPAR24) Based on a 5-point Likert Scale. | 55.82 score on a scale | Standard Error 3.024 |
| Low Dose APAP | Sum of Pain Relief From 0 to 24 Hours (TOTPAR24) Based on a 5-point Likert Scale. | 55.24 score on a scale | Standard Error 3.007 |
| Placebo | Sum of Pain Relief From 0 to 24 Hours (TOTPAR24) Based on a 5-point Likert Scale. | 43.11 score on a scale | Standard Error 4.3 |
p-value: 0.0087ANCOVA
p-value: 0.012ANCOVA
Secondary
Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration
Pain Intensity was self-reported over 24 hours, using a pain rating of 0-10 on the Numerical Rating Scale (NRS), with score between 0-10 (0= no pain; 10 = worst imaginable pain). Pain intensity differences were calculated with respect to Baseline at each time point after Dose 1 administration. A baseline assessment was defined as the last non-missing result prior to administration of the first dose of study medication
Time frame: Baseline (0.0) and 0.5, 0.75, 1, 1.25, 1.75, 2.25 3.25, 4.25, 5.25, 6.25, 7.25, 8.25, 9.25, 10.25, 11.25, 12.25 (± 5 min) and 14.25, 16.25, 18.25, 20.25, 22.25, and 24.25 hours (± 10 min)
Population: The Evaluable Population included all randomized participants who, as documented prior to the breaking of the study blind: (1) met all the inclusion and exclusion criteria and; (2) were administered Dose 1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 1 | -3.7 score on a scale | Standard Deviation 1.89 |
| High Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 18.25 | -4.4 score on a scale | Standard Deviation 2.34 |
| High Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 7.25 | -3.0 score on a scale | Standard Deviation 2.61 |
| High Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 0.75 | -3.3 score on a scale | Standard Deviation 1.88 |
| High Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 22.25 | -4.7 score on a scale | Standard Deviation 2.25 |
| High Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 1.75 | -3.9 score on a scale | Standard Deviation 1.97 |
| High Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 0.5 | -2.5 score on a scale | Standard Deviation 1.65 |
| High Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 9.25 | -4.5 score on a scale | Standard Deviation 2.89 |
| High Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 5.25 | -3.3 score on a scale | Standard Deviation 2.48 |
| High Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 8.25 | -3.8 score on a scale | Standard Deviation 2.72 |
| High Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 4.25 | -3.4 score on a scale | Standard Deviation 2.4 |
| High Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 10.25 | -4.6 score on a scale | Standard Deviation 2.71 |
| High Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 24.25 | -4.6 score on a scale | Standard Deviation 2.29 |
| High Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 20.25 | -4.7 score on a scale | Standard Deviation 2.04 |
| High Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 11.25 | -4.7 score on a scale | Standard Deviation 2.44 |
| High Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 2.25 | -3.8 score on a scale | Standard Deviation 2.16 |
| High Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 14.25 | -3.7 score on a scale | Standard Deviation 2.13 |
| High Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 12.25 | -4.9 score on a scale | Standard Deviation 1.85 |
| High Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 3.25 | -3.4 score on a scale | Standard Deviation 2.32 |
| High Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 1.25 | -3.9 score on a scale | Standard Deviation 2.02 |
| High Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 16.25 | -3.5 score on a scale | Standard Deviation 2.29 |
| High Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 6.25 | -3.2 score on a scale | Standard Deviation 2.48 |
| Low Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 1 | -3.8 score on a scale | Standard Deviation 2.12 |
| Low Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 1.75 | -3.7 score on a scale | Standard Deviation 2.45 |
| Low Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 8.25 | -4.4 score on a scale | Standard Deviation 2.29 |
| Low Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 10.25 | -5.0 score on a scale | Standard Deviation 1.98 |
| Low Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 11.25 | -4.5 score on a scale | Standard Deviation 1.99 |
| Low Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 12.25 | -4.5 score on a scale | Standard Deviation 2.31 |
| Low Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 16.25 | -4.4 score on a scale | Standard Deviation 2.08 |
| Low Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 20.25 | -4.9 score on a scale | Standard Deviation 2.37 |
| Low Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 22.25 | -5.0 score on a scale | Standard Deviation 2.35 |
| Low Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 24.25 | -5.1 score on a scale | Standard Deviation 2.42 |
| Low Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 6.25 | -3.5 score on a scale | Standard Deviation 2.49 |
| Low Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 3.25 | -3.0 score on a scale | Standard Deviation 2.39 |
| Low Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 4.25 | -2.9 score on a scale | Standard Deviation 2.32 |
| Low Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 5.25 | -2.8 score on a scale | Standard Deviation 2.39 |
| Low Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 7.25 | -4.1 score on a scale | Standard Deviation 2.34 |
| Low Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 0.5 | -3.1 score on a scale | Standard Deviation 2.01 |
| Low Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 0.75 | -3.5 score on a scale | Standard Deviation 2.1 |
| Low Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 1.25 | -4.0 score on a scale | Standard Deviation 2.29 |
| Low Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 2.25 | -3.6 score on a scale | Standard Deviation 2.44 |
| Low Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 9.25 | -4.7 score on a scale | Standard Deviation 2.18 |
| Low Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 14.25 | -5.0 score on a scale | Standard Deviation 2.42 |
| Low Dose APAP | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 18.25 | -4.5 score on a scale | Standard Deviation 2.27 |
| Placebo | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 0.5 | -0.7 score on a scale | Standard Deviation 1.28 |
| Placebo | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 20.25 | -3.6 score on a scale | Standard Deviation 2.24 |
| Placebo | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 14.25 | -2.9 score on a scale | Standard Deviation 1.97 |
| Placebo | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 0.75 | -0.8 score on a scale | Standard Deviation 1.4 |
| Placebo | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 16.25 | -2.9 score on a scale | Standard Deviation 1.97 |
| Placebo | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 1 | -0.8 score on a scale | Standard Deviation 1.44 |
| Placebo | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 12.25 | -2.7 score on a scale | Standard Deviation 2.27 |
| Placebo | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 1.75 | -0.7 score on a scale | Standard Deviation 1.59 |
| Placebo | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 1.25 | -0.7 score on a scale | Standard Deviation 1.52 |
| Placebo | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 18.25 | -3.5 score on a scale | Standard Deviation 1.97 |
| Placebo | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 2.25 | -0.7 score on a scale | Standard Deviation 1.67 |
| Placebo | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 5.25 | -2.4 score on a scale | Standard Deviation 2.59 |
| Placebo | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 3.25 | -0.9 score on a scale | Standard Deviation 1.95 |
| Placebo | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 6.25 | -3.7 score on a scale | Standard Deviation 2.32 |
| Placebo | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 8.25 | -3.7 score on a scale | Standard Deviation 2.36 |
| Placebo | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 4.25 | -0.9 score on a scale | Standard Deviation 1.97 |
| Placebo | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 24.25 | -4.3 score on a scale | Standard Deviation 1.86 |
| Placebo | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 10.25 | -3.4 score on a scale | Standard Deviation 2.22 |
| Placebo | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 11.25 | -3.3 score on a scale | Standard Deviation 2.28 |
| Placebo | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 7.25 | -4.2 score on a scale | Standard Deviation 1.99 |
| Placebo | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 22.25 | -3.9 score on a scale | Standard Deviation 2.19 |
| Placebo | Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration | 9.25 | -3.6 score on a scale | Standard Deviation 2.26 |
Secondary
Pain Intensity Rating at Different Timepoints After Dose 1 Administration
Pain intensity is reported using the 11-point Numerical Rating Scale (NRS), with score between 0-10 (0= no pain; 10 = worst imaginable pain).
Time frame: 0 to 24 hours
Population: The Evaluable Population included all randomized participants who, as documented prior to the breaking of the study blind: (1) met all the inclusion and exclusion criteria and; (2) were administered Dose 1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 12.25 | 2.5 score on a scale | Standard Deviation 1.83 |
| High Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 14.25 | 3.6 score on a scale | Standard Deviation 2.29 |
| High Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 16.25 | 3.8 score on a scale | Standard Deviation 2.55 |
| High Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 22.25 | 2.6 score on a scale | Standard Deviation 2.58 |
| High Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 11.25 | 2.7 score on a scale | Standard Deviation 2.27 |
| High Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 18.25 | 2.9 score on a scale | Standard Deviation 2.58 |
| High Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 20.25 | 2.7 score on a scale | Standard Deviation 2.28 |
| High Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 24.25 | 2.8 score on a scale | Standard Deviation 2.38 |
| High Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 0.75 | 4.0 score on a scale | Standard Deviation 2.12 |
| High Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 0.5 | 4.8 score on a scale | Standard Deviation 1.83 |
| High Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 1 | 3.6 score on a scale | Standard Deviation 1.98 |
| High Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 1.25 | 3.4 score on a scale | Standard Deviation 2.16 |
| High Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 1.75 | 3.5 score on a scale | Standard Deviation 2.24 |
| High Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 2.25 | 3.6 score on a scale | Standard Deviation 2.4 |
| High Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 3.25 | 3.9 score on a scale | Standard Deviation 2.53 |
| High Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 4.25 | 4.0 score on a scale | Standard Deviation 2.58 |
| High Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 5.25 | 4.0 score on a scale | Standard Deviation 2.48 |
| High Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 6.25 | 4.2 score on a scale | Standard Deviation 2.52 |
| High Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 7.25 | 4.3 score on a scale | Standard Deviation 2.46 |
| High Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 8.25 | 3.5 score on a scale | Standard Deviation 2.58 |
| High Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 9.25 | 2.9 score on a scale | Standard Deviation 2.71 |
| High Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 10.25 | 2.8 score on a scale | Standard Deviation 2.48 |
| Low Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 22.25 | 2.5 score on a scale | Standard Deviation 1.96 |
| Low Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 5.25 | 4.7 score on a scale | Standard Deviation 2.44 |
| Low Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 7.25 | 3.4 score on a scale | Standard Deviation 2.22 |
| Low Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 10.25 | 2.5 score on a scale | Standard Deviation 1.68 |
| Low Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 1 | 3.7 score on a scale | Standard Deviation 2.01 |
| Low Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 8.25 | 3.1 score on a scale | Standard Deviation 2.2 |
| Low Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 14.25 | 2.5 score on a scale | Standard Deviation 2.11 |
| Low Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 6.25 | 4.0 score on a scale | Standard Deviation 2.59 |
| Low Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 3.25 | 4.5 score on a scale | Standard Deviation 2.48 |
| Low Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 16.25 | 3.1 score on a scale | Standard Deviation 2.01 |
| Low Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 20.25 | 2.6 score on a scale | Standard Deviation 2.14 |
| Low Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 1.25 | 3.5 score on a scale | Standard Deviation 2.14 |
| Low Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 0.5 | 4.4 score on a scale | Standard Deviation 1.97 |
| Low Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 9.25 | 2.8 score on a scale | Standard Deviation 1.95 |
| Low Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 11.25 | 3.0 score on a scale | Standard Deviation 1.66 |
| Low Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 24.25 | 2.4 score on a scale | Standard Deviation 2.06 |
| Low Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 2.25 | 3.9 score on a scale | Standard Deviation 2.39 |
| Low Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 12.25 | 3.0 score on a scale | Standard Deviation 2.09 |
| Low Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 1.75 | 3.8 score on a scale | Standard Deviation 2.33 |
| Low Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 0.75 | 4.0 score on a scale | Standard Deviation 1.98 |
| Low Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 4.25 | 4.6 score on a scale | Standard Deviation 2.33 |
| Low Dose APAP | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 18.25 | 3.0 score on a scale | Standard Deviation 2.23 |
| Placebo | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 7.25 | 2.7 score on a scale | Standard Deviation 1.86 |
| Placebo | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 4.25 | 6.0 score on a scale | Standard Deviation 2.21 |
| Placebo | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 22.25 | 3.0 score on a scale | Standard Deviation 2.16 |
| Placebo | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 24.25 | 2.61 score on a scale | Standard Deviation 1.71 |
| Placebo | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 5.25 | 4.5 score on a scale | Standard Deviation 2.56 |
| Placebo | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 0.5 | 6.1 score on a scale | Standard Deviation 1.42 |
| Placebo | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 0.75 | 6.0 score on a scale | Standard Deviation 1.7 |
| Placebo | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 8.25 | 3.2 score on a scale | Standard Deviation 2.3 |
| Placebo | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 1 | 6.0 score on a scale | Standard Deviation 1.68 |
| Placebo | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 1.25 | 6.2 score on a scale | Standard Deviation 1.89 |
| Placebo | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 6.25 | 3.2 score on a scale | Standard Deviation 2.11 |
| Placebo | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 1.75 | 6.2 score on a scale | Standard Deviation 1.94 |
| Placebo | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 9.25 | 3.3 score on a scale | Standard Deviation 2.25 |
| Placebo | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 2.25 | 6.2 score on a scale | Standard Deviation 1.97 |
| Placebo | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 10.25 | 3.5 score on a scale | Standard Deviation 2.15 |
| Placebo | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 18.25 | 3.4 score on a scale | Standard Deviation 1.99 |
| Placebo | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 14.25 | 4.0 score on a scale | Standard Deviation 2.08 |
| Placebo | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 20.25 | 3.2 score on a scale | Standard Deviation 2.22 |
| Placebo | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 3.25 | 6.0 score on a scale | Standard Deviation 2.17 |
| Placebo | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 11.25 | 3.5 score on a scale | Standard Deviation 2.24 |
| Placebo | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 12.25 | 4.1 score on a scale | Standard Deviation 2.32 |
| Placebo | Pain Intensity Rating at Different Timepoints After Dose 1 Administration | 16.25 | 4.0 score on a scale | Standard Deviation 2.21 |
Secondary
Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration
Pain Relief is reported on a 5-Point Categorical Pain Relief Assessment scale: 0 = No Pain Relief, 1 = A Little Pain Relief, 2 = Some Pain Relief, 3 = A Lot of Pain Relief, 4 = Complete Pain Relief.
Time frame: 0 to 24 hours
Population: The Evaluable Population included all randomized participants who, as documented prior to the breaking of the study blind: (1) met all the inclusion and exclusion criteria and; (2) were administered Dose 1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 20.25 | 2.7 score on a scale | Standard Deviation 1 |
| High Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 10.25 | 2.6 score on a scale | Standard Deviation 1.1 |
| High Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 9.25 | 2.6 score on a scale | Standard Deviation 1.22 |
| High Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 4.25 | 2.0 score on a scale | Standard Deviation 1.21 |
| High Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 3.25 | 2.0 score on a scale | Standard Deviation 1.18 |
| High Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 8.25 | 2.2 score on a scale | Standard Deviation 1.15 |
| High Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 5.25 | 1.9 score on a scale | Standard Deviation 1.2 |
| High Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 6.25 | 1.9 score on a scale | Standard Deviation 1.23 |
| High Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 24.25 | 2.5 score on a scale | Standard Deviation 1.12 |
| High Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 7.25 | 1.8 score on a scale | Standard Deviation 1.21 |
| High Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 22.25 | 2.7 score on a scale | Standard Deviation 1.11 |
| High Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 18.25 | 2.5 score on a scale | Standard Deviation 1.1 |
| High Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 16.25 | 2.1 score on a scale | Standard Deviation 1.14 |
| High Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 14.25 | 2.1 score on a scale | Standard Deviation 1 |
| High Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 0.5 | 1.7 score on a scale | Standard Deviation 0.95 |
| High Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 0.75 | 2.0 score on a scale | Standard Deviation 1.02 |
| High Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 2.25 | 2.2 score on a scale | Standard Deviation 1.09 |
| High Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 12.25 | 2.7 score on a scale | Standard Deviation 0.83 |
| High Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 1 | 2.1 score on a scale | Standard Deviation 0.93 |
| High Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 1.75 | 2.3 score on a scale | Standard Deviation 0.97 |
| High Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 11.25 | 2.7 score on a scale | Standard Deviation 0.97 |
| High Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 1.25 | 2.3 score on a scale | Standard Deviation 0.97 |
| Low Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 14.25 | 2.6 score on a scale | Standard Deviation 1.04 |
| Low Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 1.75 | 2.0 score on a scale | Standard Deviation 1.07 |
| Low Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 2.25 | 2.0 score on a scale | Standard Deviation 1.05 |
| Low Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 3.25 | 1.7 score on a scale | Standard Deviation 1.12 |
| Low Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 5.25 | 1.5 score on a scale | Standard Deviation 1.21 |
| Low Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 0.75 | 2.0 score on a scale | Standard Deviation 0.98 |
| Low Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 1 | 2.2 score on a scale | Standard Deviation 0.96 |
| Low Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 1.25 | 2.2 score on a scale | Standard Deviation 0.99 |
| Low Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 4.25 | 1.6 score on a scale | Standard Deviation 1.12 |
| Low Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 6.25 | 1.9 score on a scale | Standard Deviation 1.15 |
| Low Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 7.25 | 2.2 score on a scale | Standard Deviation 1.03 |
| Low Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 8.25 | 2.4 score on a scale | Standard Deviation 1.06 |
| Low Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 9.25 | 2.5 score on a scale | Standard Deviation 0.93 |
| Low Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 10.25 | 2.7 score on a scale | Standard Deviation 0.8 |
| Low Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 11.25 | 2.5 score on a scale | Standard Deviation 0.87 |
| Low Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 12.25 | 2.4 score on a scale | Standard Deviation 1.04 |
| Low Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 0.5 | 1.8 score on a scale | Standard Deviation 0.94 |
| Low Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 16.25 | 2.3 score on a scale | Standard Deviation 1.06 |
| Low Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 18.25 | 2.4 score on a scale | Standard Deviation 1.02 |
| Low Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 20.25 | 2.6 score on a scale | Standard Deviation 0.95 |
| Low Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 22.25 | 2.6 score on a scale | Standard Deviation 0.94 |
| Low Dose APAP | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 24.25 | 2.7 score on a scale | Standard Deviation 0.99 |
| Placebo | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 1 | 0.6 score on a scale | Standard Deviation 0.85 |
| Placebo | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 0.5 | 0.6 score on a scale | Standard Deviation 0.85 |
| Placebo | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 11.25 | 2.0 score on a scale | Standard Deviation 1.31 |
| Placebo | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 0.75 | 0.6 score on a scale | Standard Deviation 0.85 |
| Placebo | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 20.25 | 2.2 score on a scale | Standard Deviation 1.18 |
| Placebo | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 1.75 | 0.6 score on a scale | Standard Deviation 0.9 |
| Placebo | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 14.25 | 1.8 score on a scale | Standard Deviation 1.11 |
| Placebo | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 12.25 | 1.6 score on a scale | Standard Deviation 1.33 |
| Placebo | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 24.25 | 2.5 score on a scale | Standard Deviation 0.91 |
| Placebo | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 16.25 | 1.8 score on a scale | Standard Deviation 1.14 |
| Placebo | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 6.25 | 2.1 score on a scale | Standard Deviation 1.25 |
| Placebo | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 5.25 | 1.5 score on a scale | Standard Deviation 1.44 |
| Placebo | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 7.25 | 2.5 score on a scale | Standard Deviation 1.1 |
| Placebo | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 4.25 | 0.7 score on a scale | Standard Deviation 1.08 |
| Placebo | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 22.25 | 2.3 score on a scale | Standard Deviation 1.09 |
| Placebo | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 8.25 | 2.2 score on a scale | Standard Deviation 1.27 |
| Placebo | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 3.25 | 0.8 score on a scale | Standard Deviation 1.15 |
| Placebo | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 18.25 | 2.1 score on a scale | Standard Deviation 1.17 |
| Placebo | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 9.25 | 2.1 score on a scale | Standard Deviation 1.19 |
| Placebo | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 1.25 | 0.6 score on a scale | Standard Deviation 0.85 |
| Placebo | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 2.25 | 0.6 score on a scale | Standard Deviation 0.9 |
| Placebo | Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration | 10.25 | 2.0 score on a scale | Standard Deviation 1.2 |
Secondary
Patient Global Evaluation of the Study Medication
Patients Global Evaluation was assessed on a scale of 0 (Poor), 1 (Fair), 2 (Good), 3 (Very Good) and 4 (Excellent) at 24.25 hours post-dose 1 or at participant withdrawal (if applicable), whichever occurred first. Least squares mean of the score are reported.
Time frame: 0 to 24 Hours
Population: The Evaluable Population included all randomized participants who, as documented prior to the breaking of the study blind: (1) met all the inclusion and exclusion criteria and; (2) were administered Dose 1.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| High Dose APAP | Patient Global Evaluation of the Study Medication | 2.8 score on a scale | Standard Error 0.16 |
| Low Dose APAP | Patient Global Evaluation of the Study Medication | 2.7 score on a scale | Standard Error 0.15 |
| Placebo | Patient Global Evaluation of the Study Medication | 2.3 score on a scale | Standard Error 0.22 |
Secondary
Time to Meaningful Perceptible Relief (MPR) Measure Stratified by Baseline Pain Score of Moderate or Severe for the 3 Treatment Groups
Upon initiation of the infusion of Dose 1, the participants were given a second stopwatch and asked to press the stopwatch if and when they feel any meaningful perceptible relief; a record of the time was noted in the participant record. If a participant does not record perceptible pain relief and was prematurely discontinued from the study prior to 24 hours, then the participant was censored at time of drop out. If a participant does not record perceptible pain relief prior to taking rescue medication, the participant was censored at 24 hours.
Time frame: 0 to 24 Hours
Population: The Evaluable Population included all randomized participants who, as documented prior to the breaking of the study blind: (1) met all the inclusion and exclusion criteria and; (2) were administered Dose 1.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| High Dose APAP | Time to Meaningful Perceptible Relief (MPR) Measure Stratified by Baseline Pain Score of Moderate or Severe for the 3 Treatment Groups | Median time to MPR (hours)- for moderate baseline categorical pain intensity score | 0.660 hours |
| High Dose APAP | Time to Meaningful Perceptible Relief (MPR) Measure Stratified by Baseline Pain Score of Moderate or Severe for the 3 Treatment Groups | Median time to MPR (hours)- for severe baseline categorical pain intensity score | 0.680 hours |
| Low Dose APAP | Time to Meaningful Perceptible Relief (MPR) Measure Stratified by Baseline Pain Score of Moderate or Severe for the 3 Treatment Groups | Median time to MPR (hours)- for moderate baseline categorical pain intensity score | 0.310 hours |
| Low Dose APAP | Time to Meaningful Perceptible Relief (MPR) Measure Stratified by Baseline Pain Score of Moderate or Severe for the 3 Treatment Groups | Median time to MPR (hours)- for severe baseline categorical pain intensity score | 0.870 hours |
| Placebo | Time to Meaningful Perceptible Relief (MPR) Measure Stratified by Baseline Pain Score of Moderate or Severe for the 3 Treatment Groups | Median time to MPR (hours)- for moderate baseline categorical pain intensity score | NA hours |
| Placebo | Time to Meaningful Perceptible Relief (MPR) Measure Stratified by Baseline Pain Score of Moderate or Severe for the 3 Treatment Groups | Median time to MPR (hours)- for severe baseline categorical pain intensity score | NA hours |
Secondary
Time to Perceptible Pain Relief Confirmed (FPR-C) After Dose 1 Administration Stratified by Baseline Pain Score of Moderate or Severe for the 3 Treatment Groups
Upon initiation of the infusion of Dose 1, the participants were given stopwatch #1 and asked to press the stopwatch when they first perceived any pain relief (first perceptible pain relief \[FPR\]) ; a record of the time was noted in the participant record. If a participant does not record perceptible pain relief and prematurely discontinued from the study prior to 24 hours, then the participant was censored at time of drop out. If a participant does not record perceptible pain relief prior to taking rescue medication, the participant was censored at 24 hours
Time frame: 0 to 24 Hours
Population: The Evaluable Population included all randomized participants who, as documented prior to the breaking of the study blind: (1) met all the inclusion and exclusion criteria and; (2) were administered Dose 1.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| High Dose APAP | Time to Perceptible Pain Relief Confirmed (FPR-C) After Dose 1 Administration Stratified by Baseline Pain Score of Moderate or Severe for the 3 Treatment Groups | Median time to FPR-C (hours)- for moderate baseline categorical pain intensity score | 0.215 hours |
| High Dose APAP | Time to Perceptible Pain Relief Confirmed (FPR-C) After Dose 1 Administration Stratified by Baseline Pain Score of Moderate or Severe for the 3 Treatment Groups | Median time to FPR-C (hours)- for severe baseline categorical pain intensity score | 0.160 hours |
| Low Dose APAP | Time to Perceptible Pain Relief Confirmed (FPR-C) After Dose 1 Administration Stratified by Baseline Pain Score of Moderate or Severe for the 3 Treatment Groups | Median time to FPR-C (hours)- for moderate baseline categorical pain intensity score | 0.160 hours |
| Low Dose APAP | Time to Perceptible Pain Relief Confirmed (FPR-C) After Dose 1 Administration Stratified by Baseline Pain Score of Moderate or Severe for the 3 Treatment Groups | Median time to FPR-C (hours)- for severe baseline categorical pain intensity score | 0.220 hours |
| Placebo | Time to Perceptible Pain Relief Confirmed (FPR-C) After Dose 1 Administration Stratified by Baseline Pain Score of Moderate or Severe for the 3 Treatment Groups | Median time to FPR-C (hours)- for moderate baseline categorical pain intensity score | 0.595 hours |
| Placebo | Time to Perceptible Pain Relief Confirmed (FPR-C) After Dose 1 Administration Stratified by Baseline Pain Score of Moderate or Severe for the 3 Treatment Groups | Median time to FPR-C (hours)- for severe baseline categorical pain intensity score | 0.890 hours |
Secondary
Time to Treatment Failure
Time to treatment failure is defined as time to first dose of rescue medication after Dose 1 or withdrawal from the study for any reason. If a participant does not take rescue medication or withdraw from the study prior to 24 hours, the participant was censored at 24 hours
Time frame: 0 to 24 Hours
Population: The Evaluable Population included all randomized participant who, as documented prior to the breaking of the study blind: (1) met all the inclusion and exclusion criteria and; (2) were administered Dose 1.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| High Dose APAP | Time to Treatment Failure | Median time to treatment failure- for moderate baseline categorical pain intensity score | NA hours |
| High Dose APAP | Time to Treatment Failure | Median time to treatment failure for severe baseline categorical pain intensity score | NA hours |
| Low Dose APAP | Time to Treatment Failure | Median time to treatment failure- for moderate baseline categorical pain intensity score | NA hours |
| Low Dose APAP | Time to Treatment Failure | Median time to treatment failure for severe baseline categorical pain intensity score | NA hours |
| Placebo | Time to Treatment Failure | Median time to treatment failure- for moderate baseline categorical pain intensity score | 3.680 hours |
| Placebo | Time to Treatment Failure | Median time to treatment failure for severe baseline categorical pain intensity score | 1.335 hours |
Other Pre-specified
Area Under the Plasma Concentration-Time Curve From Time of Administration to 24 Hours After Dosing (AUC 0-24h)
The Area Under the Plasma Concentration-Time Curve (AUC) is a measure of the plasma concentration of the drug over time. It is used to characterize drug absorption. The values for pharmacokinetic (PK) evaluable population-excluding participants with positive pre-dose concentrations have been populated. The samples were collected at 5 min prior to Dose 1, and at 0.25, 0.5, 0.75, 1.0, 2.0, 4.0, 6.25, 8.0, 8.25, 8.25, 12.0, 12.25, 16.0, 16.25, 18.0, 18.25, 24.25 hours post-dose 1.
Time frame: Pre-dose, and 0.25, 0.5, 0.75, 1.0, 2.0, 4.0, 6.25, 8.0, 8.25, 8.25, 12.0, 12.25, 16.0, 16.25, 18.0, 18.25, 24.25 hours post-dose
Population: The PK Evaluable Population included all randomized participants who, as documented prior to the breaking of the study blind: (1) met all the inclusion and exclusion criteria and; (2) were administered Dose 1 resulting in an adequate number of quantifiable concentrations to calculate PK parameters.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| High Dose APAP | Area Under the Plasma Concentration-Time Curve From Time of Administration to 24 Hours After Dosing (AUC 0-24h) | 236326.3081 microgram*hour/milliliter | Standard Error 1.06026 |
| Low Dose APAP | Area Under the Plasma Concentration-Time Curve From Time of Administration to 24 Hours After Dosing (AUC 0-24h) | 231104.0073 microgram*hour/milliliter | Standard Error 1.05427 |
Other Pre-specified
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity])
The AUC(0-infinity) is area under the plasma concentration-time curve from time zero to infinite time. The samples were collected at 5 min prior to Dose 1, and at 0.25, 0.5, 0.75, 1.0, 2.0, 4.0, 6.25, 8.0, 8.25, 8.25, 12.0, 12.25, 16.0, 16.25, 18.0, 18.25, 24.25 hours post-dose 1.
Time frame: Pre-dose, and 0.25, 0.5, 0.75, 1.0, 2.0, 4.0, 6.25, 8.0, 8.25, 8.25, 12.0, 12.25, 16.0, 16.25, 18.0, 18.25, 24.25 hours post-dose
Population: The PK Evaluable Population included all randomized participants who, as documented prior to the breaking of the study blind: (1) met all the inclusion and exclusion criteria and; (2) were administered Dose 1 resulting in an adequate number of quantifiable concentrations to calculate PK parameters
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| High Dose APAP | Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) | 75925.2553 hour*nanogram per milliliter | Geometric Coefficient of Variation 22.405 |
| Low Dose APAP | Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) | 55018.1382 hour*nanogram per milliliter | Geometric Coefficient of Variation 27.089 |
Other Pre-specified
Half-life
The half-life (t 1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration.
Time frame: Pre-dose, and 0.25, 0.5, 0.75, 1.0, 2.0, 4.0, 6.25, 8.0, 8.25, 8.25, 12.0, 12.25, 16.0, 16.25, 18.0, 18.25, 24.25 hours post-dose
Population: The PK Evaluable Population included all randomized participants who, as documented prior to the breaking of the study blind: (1) met all the inclusion and exclusion criteria and; (2) were administered Dose 1 resulting in an adequate number of quantifiable concentrations to calculate PK parameters
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose APAP | Half-life | 2.565 hours | Standard Deviation 0.5774 |
| Low Dose APAP | Half-life | 2.360 hours | Standard Deviation 0.4134 |
Other Pre-specified
Maximum Observed Plasma Concentration (Cmax)
The Plasma Concentration (Cmax) is defined as maximum observed concentration
Time frame: Pre-dose, and 0.25, 0.5, 0.75, 1.0, 2.0, 4.0, 6.25, 8.0, 8.25, 8.25, 12.0, 12.25, 16.0, 16.25, 18.0, 18.25, 24.25 hours post-dose
Population: The PK Evaluable Population included all randomized participants who, as documented prior to the breaking of the study blind: (1) met all the inclusion and exclusion criteria and; (2) were administered Dose 1 resulting in an adequate number of quantifiable concentrations to calculate PK parameters
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| High Dose APAP | Maximum Observed Plasma Concentration (Cmax) | 39531.4 nanogram per milliliter (ng/ml) | Geometric Coefficient of Variation 26 |
| Low Dose APAP | Maximum Observed Plasma Concentration (Cmax) | 28495.6 nanogram per milliliter (ng/ml) | Geometric Coefficient of Variation 30 |
Other Pre-specified
Mean Change From Baseline to 24 Hours in Vital Signs (Diastolic Blood Pressure)
Change from Baseline in diastolic blood pressure is the value at 24 hours minus value at Baseline. Baseline was defined as the last non-missing result prior to administration of the first dose of study drug. Diastolic blood pressure is obtained at screening, prior to surgery and at Hours 4, 8, 12, 16, 20 and 24 following initiation of dose (±10 min)
Time frame: 0 to 24 hours
Population: The Safety Population included all randomized participants who received the study medication. This population was used for all safety summaries.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose APAP | Mean Change From Baseline to 24 Hours in Vital Signs (Diastolic Blood Pressure) | -0.2 mm Hg | Standard Deviation 8.82 |
| Low Dose APAP | Mean Change From Baseline to 24 Hours in Vital Signs (Diastolic Blood Pressure) | 2.3 mm Hg | Standard Deviation 9.56 |
| Placebo | Mean Change From Baseline to 24 Hours in Vital Signs (Diastolic Blood Pressure) | 5.2 mm Hg | Standard Deviation 11.08 |
Other Pre-specified
Mean Change From Baseline to 24 Hours in Vital Signs (Pulse Rate)
Change from Baseline in pulse rate is the value at 24 hours minus value at Baseline. Baseline was defined as the last non-missing result prior to administration of the first dose of study drug. Pulse rate is obtained at screening, prior to surgery and at Hours 4, 8, 12, 16, 20 and 24 following initiation of dose (±10 min)
Time frame: 0 to 24 hours
Population: The Safety Population included all randomized participants who received the study medication. This population was used for all safety summaries.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose APAP | Mean Change From Baseline to 24 Hours in Vital Signs (Pulse Rate) | 5.0 beats/minute | Standard Deviation 11.85 |
| Low Dose APAP | Mean Change From Baseline to 24 Hours in Vital Signs (Pulse Rate) | 4.2 beats/minute | Standard Deviation 11.58 |
| Placebo | Mean Change From Baseline to 24 Hours in Vital Signs (Pulse Rate) | 5.7 beats/minute | Standard Deviation 11.17 |
Other Pre-specified
Mean Change From Baseline to 24 Hours in Vital Signs (Respiratory Rate)
Change from Baseline in respiratory rate was the value at 24 hours minus value at Baseline. Baseline was defined as the last non-missing result prior to administration of the first dose of study drug. Respiratory rate was obtained at screening, prior to surgery and at Hours 4, 8, 12, 16, 20 and 24 following initiation of dose (±10 min)
Time frame: 0 to 24 hours
Population: The Safety Population included all randomized participants who received the study medication. This population was used for all safety summaries.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose APAP | Mean Change From Baseline to 24 Hours in Vital Signs (Respiratory Rate) | 0.3 breaths/minute | Standard Deviation 3.39 |
| Low Dose APAP | Mean Change From Baseline to 24 Hours in Vital Signs (Respiratory Rate) | -0.6 breaths/minute | Standard Deviation 4.12 |
| Placebo | Mean Change From Baseline to 24 Hours in Vital Signs (Respiratory Rate) | -1.3 breaths/minute | Standard Deviation 3.68 |
Other Pre-specified
Mean Change From Baseline to 24 Hours in Vital Signs (Systolic Blood Pressure)
Change from Baseline in systolic blood pressure is the value at 24 hours minus value at Baseline. Baseline was defined as the last non-missing result prior to administration of the first dose of study drug. Systolic blood pressure is obtained at screening, prior to surgery and at Hours 4, 8, 12, 16, 20 and 24 following initiation of dose (±10 min).
Time frame: 0 to 24 hours
Population: The Safety Population included all randomized participants who received the study medication. This population was used for all safety summaries.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose APAP | Mean Change From Baseline to 24 Hours in Vital Signs (Systolic Blood Pressure) | 1.6 mm Hg | Standard Deviation 10.78 |
| Low Dose APAP | Mean Change From Baseline to 24 Hours in Vital Signs (Systolic Blood Pressure) | 1.0 mm Hg | Standard Deviation 11.39 |
| Placebo | Mean Change From Baseline to 24 Hours in Vital Signs (Systolic Blood Pressure) | 9.2 mm Hg | Standard Deviation 10.99 |
Other Pre-specified
Mean Change From Baseline to 24 Hours in Vital Signs (Temperature)
Change from Baseline in temperature is the value at 24 hours minus value at Baseline. Baseline was defined as the last non-missing result prior to administration of the first dose of study drug. Temperature is obtained at screening, prior to surgery and at Hours 4, 8, 12, 16, 20 and 24 following initiation of dose (±10 min)
Time frame: 0 to 24 hours
Population: The Safety Population included all randomized participants who received the study medication. This population was used for all safety summaries.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose APAP | Mean Change From Baseline to 24 Hours in Vital Signs (Temperature) | 0.12 degrees Celsius | Standard Deviation 0.336 |
| Low Dose APAP | Mean Change From Baseline to 24 Hours in Vital Signs (Temperature) | 0.21 degrees Celsius | Standard Deviation 0.275 |
| Placebo | Mean Change From Baseline to 24 Hours in Vital Signs (Temperature) | 0.06 degrees Celsius | Standard Deviation 0.347 |