A Study of Acetaminophen for Post Surgical Dental Pain

Sponsor
Nevakar, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT04018612
Collaborator
(none)
110
1
3
3.7
29.9

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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

Study Design

Study Type:
Interventional
Actual Enrollment :
110 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
High Dose Acetaminophen (APAP) versus Placebo, Low Dose APAP versus PlaceboHigh Dose Acetaminophen (APAP) versus Placebo, Low Dose APAP versus Placebo
Masking:
Double (Participant, Investigator)
Masking Description:
Double Blind, Placebo controlled
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blind, Multi-Dose, Single-Site, Placebo- and Active-Controlled, Efficacy, Tolerability, Safety and Pharmacokinetic Study of Two Different Dosing Regimens of Acetaminophen in Post-Surgical Dental Pain.
Actual Study Start Date :
Apr 25, 2019
Actual Primary Completion Date :
Jul 26, 2019
Actual Study Completion Date :
Aug 15, 2019

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: High Dose Acetaminophen

High Dose Acetaminophen Post Op

Drug: Acetaminophen
Acetaminophen is an analgesic and antipyretic
Other Names:
  • APAP
  • Active Comparator: Low Dose Acetaminophen

    Low Dose Acetaminophen Post Op

    Drug: Acetaminophen
    Acetaminophen is an analgesic and antipyretic
    Other Names:
  • APAP
  • Placebo Comparator: Placebo

    Placebo Post Op

    Other: Placebo
    Saline

    Outcome Measures

    Primary Outcome Measures

    1. 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.

    2. 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 Outcome Measures

    1. 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

    2. 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.

    3. 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.

    4. 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

    5. 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).

    6. 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.

    7. 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 Outcome Measures

    1. 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).

    2. 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)

    3. 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)

    4. 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)

    5. 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)

    6. 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.

    7. 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.

    8. 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.

    9. 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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    17 Years to 55 Years
    Sexes Eligible for Study:
    All
    Accepts 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);

    1. 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 JBR Salt Lake City Utah United States 84107

    Sponsors and Collaborators

    • Nevakar, Inc.

    Investigators

    • Study Director: Eric Lang, MD, Nevakar, Inc.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Nevakar, Inc.
    ClinicalTrials.gov Identifier:
    NCT04018612
    Other Study ID Numbers:
    • CP-NVK009-0002
    First Posted:
    Jul 12, 2019
    Last Update Posted:
    Mar 29, 2022
    Last Verified:
    Mar 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details Participants were recruited from April 2019 till July 2019 from the site
    Pre-assignment Detail A total of 226 participants were screened from Day-30 to Day 0 before getting randomized
    Arm/Group Title High Dose APAP Low Dose APAP Placebo
    Arm/Group Description Acetaminophen (APAP) administered post-operatively at a high dose Acetaminophen (APAP) administered post-operatively at a low dose Placebo given post-operatively
    Period Title: Overall Study
    STARTED 44 44 22
    COMPLETED 43 44 21
    NOT COMPLETED 1 0 1

    Baseline Characteristics

    Arm/Group Title High Dose APAP Low Dose APAP Placebo Total
    Arm/Group Description Acetaminophen (APAP) administered post-operatively at a high dose Acetaminophen (APAP) administered post-operatively at a low dose Placebo given post-operatively Total of all reporting groups
    Overall Participants 44 44 22 110
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    18.7
    (2.06)
    18.8
    (2.31)
    19.3
    (2.42)
    18.9
    (2.23)
    Sex: Female, Male (Count of Participants)
    Female
    25
    56.8%
    22
    50%
    11
    50%
    58
    52.7%
    Male
    19
    43.2%
    22
    50%
    11
    50%
    52
    47.3%
    Race/Ethnicity, Customized (Count of Participants)
    Race-Asian
    1
    2.3%
    0
    0%
    0
    0%
    1
    0.9%
    Race-White
    39
    88.6%
    39
    88.6%
    22
    100%
    100
    90.9%
    Race-Others
    2
    4.5%
    4
    9.1%
    0
    0%
    6
    5.5%
    Race-Black or African American
    1
    2.3%
    0
    0%
    0
    0%
    1
    0.9%
    Race- Native Hawaiian or Other Pacific Islander
    1
    2.3%
    1
    2.3%
    0
    0%
    2
    1.8%
    Ethnicity-Hispanic or Latino
    9
    20.5%
    8
    18.2%
    1
    4.5%
    18
    16.4%
    Ethinicity-Not Hispanic or Latino
    35
    79.5%
    36
    81.8%
    21
    95.5%
    92
    83.6%
    Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m^2]
    24.45
    (4.124)
    24.33
    (3.762)
    25.49
    (4.869)
    24.61
    (4.130)
    Categorical pain intensity score (Count of Participants)
    None (0)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Mild (1)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Moderate (2)
    14
    31.8%
    11
    25%
    10
    45.5%
    35
    31.8%
    Severe (3)
    30
    68.2%
    33
    75%
    12
    54.5%
    75
    68.2%
    NRS pain intensity (Count of Participants)
    0 = No pain
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    4
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    5
    1
    2.3%
    1
    2.3%
    1
    4.5%
    3
    2.7%
    6
    11
    25%
    7
    15.9%
    8
    36.4%
    26
    23.6%
    7
    13
    29.5%
    12
    27.3%
    6
    27.3%
    31
    28.2%
    8
    13
    29.5%
    18
    40.9%
    7
    31.8%
    38
    34.5%
    9
    3
    6.8%
    5
    11.4%
    0
    0%
    8
    7.3%
    10 = Worst imaginable pain
    3
    6.8%
    1
    2.3%
    0
    0%
    4
    3.6%

    Outcome Measures

    1. Primary Outcome
    Title Sum of Pain Intensity Difference From 0 to 24 Hours (SPID24) Based on the 11 Point Numeric Pain Rating Scale
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title High Dose APAP Low Dose APAP Placebo
    Arm/Group Description Acetaminophen (APAP) administered post-operatively at a high dose Acetaminophen (APAP) administered post-operatively at a low dose Placebo given post-operatively
    Measure Participants 43 44 22
    Least Squares Mean (Standard Error) [score on a scale]
    -96.80
    (6.369)
    -100.69
    (6.333)
    -74.96
    (9.055)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection High Dose APAP, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0258
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -21.84
    Confidence Interval (1-Sided) 90%
    to -7.53
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 11.091
    Estimation Comments SPID24 was analyzed using ANCOVA model with treatment group as a fixed effect and baseline (BL) Pain Intensity-Numerical Pain Relief Scale (PI-NPRS) as a covariate. The lower limit of one-sided 90% confidence interval (CI) was -∞
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Low Dose APAP, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0115
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -25.74
    Confidence Interval (1-Sided) 90%
    to -11.35
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 11.154
    Estimation Comments SPID24 was analyzed using an analysis of covariance (ANCOVA) model with treatment group as a fixed effect and baseline PI-NPRS as a covariate. The lower limit of one-sided 90% CI was -∞
    2. Primary Outcome
    Title Sum of Pain Relief From 0 to 24 Hours (TOTPAR24) Based on a 5-point Likert Scale.
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title High Dose APAP Low Dose APAP Placebo
    Arm/Group Description Acetaminophen (APAP) administered post-operatively at a high dose Acetaminophen (APAP) administered post-operatively at a low dose Placebo given post-operatively
    Measure Participants 43 44 22
    Mean (Standard Error) [score on a scale]
    55.82
    (3.024)
    55.24
    (3.007)
    43.11
    (4.300)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection High Dose APAP, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0087
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 12.72
    Confidence Interval (1-Sided) 90%
    5.92 to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.267
    Estimation Comments TOTPAR24 was analyzed using an ANCOVA model with treatment group as a fixed effect and baseline PI-NPRS as a covariate. The upper limit of one-sided 90% CI was +∞
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Low Dose APAP, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0120
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 12.14
    Confidence Interval (1-Sided) 90%
    5.31 to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.297
    Estimation Comments TOTPAR24 was analyzed using an ANCOVA model with treatment group as a fixed effect and baseline PI-NPRS as a covariate. The upper limit of one-sided 90% CI was +∞
    3. Secondary Outcome
    Title 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
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title High Dose APAP Low Dose APAP Placebo
    Arm/Group Description Acetaminophen (APAP) administered post-operatively at a high dose Acetaminophen (APAP) administered post-operatively at a low dose Placebo given post-operatively
    Measure Participants 43 44 21
    Median time to FPR-C (hours)- for moderate baseline categorical pain intensity score
    0.215
    0.160
    0.595
    Median time to FPR-C (hours)- for severe baseline categorical pain intensity score
    0.160
    0.220
    0.890
    4. Secondary Outcome
    Title Time to Meaningful Perceptible Relief (MPR) Measure Stratified by Baseline Pain Score of Moderate or Severe for the 3 Treatment Groups
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title High Dose APAP Low Dose APAP Placebo
    Arm/Group Description Acetaminophen (APAP) administered post-operatively at a high dose Acetaminophen (APAP) administered post-operatively at a low dose Placebo given post-operatively
    Measure Participants 43 44 21
    Median time to MPR (hours)- for moderate baseline categorical pain intensity score
    0.660
    0.310
    NA
    Median time to MPR (hours)- for severe baseline categorical pain intensity score
    0.680
    0.870
    NA
    5. Secondary Outcome
    Title Patient Global Evaluation of the Study Medication
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title High Dose APAP Low Dose APAP Placebo
    Arm/Group Description Acetaminophen (APAP) administered post-operatively at a high dose Acetaminophen (APAP) administered post-operatively at a low dose Placebo given post-operatively
    Measure Participants 42 44 21
    Least Squares Mean (Standard Error) [score on a scale]
    2.8
    (0.16)
    2.7
    (0.15)
    2.3
    (0.22)
    6. Secondary Outcome
    Title Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title High Dose APAP Low Dose APAP Placebo
    Arm/Group Description Acetaminophen (APAP) administered post-operatively at a high dose Acetaminophen (APAP) administered post-operatively at a low dose Placebo given post-operatively
    Measure Participants 43 44 22
    0.5
    -2.5
    (1.65)
    -3.1
    (2.01)
    -0.7
    (1.28)
    0.75
    -3.3
    (1.88)
    -3.5
    (2.10)
    -0.8
    (1.40)
    1
    -3.7
    (1.89)
    -3.8
    (2.12)
    -0.8
    (1.44)
    1.25
    -3.9
    (2.02)
    -4.0
    (2.29)
    -0.7
    (1.52)
    1.75
    -3.9
    (1.97)
    -3.7
    (2.45)
    -0.7
    (1.59)
    2.25
    -3.8
    (2.16)
    -3.6
    (2.44)
    -0.7
    (1.67)
    3.25
    -3.4
    (2.32)
    -3.0
    (2.39)
    -0.9
    (1.95)
    4.25
    -3.4
    (2.40)
    -2.9
    (2.32)
    -0.9
    (1.97)
    5.25
    -3.3
    (2.48)
    -2.8
    (2.39)
    -2.4
    (2.59)
    6.25
    -3.2
    (2.48)
    -3.5
    (2.49)
    -3.7
    (2.32)
    7.25
    -3.0
    (2.61)
    -4.1
    (2.34)
    -4.2
    (1.99)
    8.25
    -3.8
    (2.72)
    -4.4
    (2.29)
    -3.7
    (2.36)
    9.25
    -4.5
    (2.89)
    -4.7
    (2.18)
    -3.6
    (2.26)
    10.25
    -4.6
    (2.71)
    -5.0
    (1.98)
    -3.4
    (2.22)
    11.25
    -4.7
    (2.44)
    -4.5
    (1.99)
    -3.3
    (2.28)
    12.25
    -4.9
    (1.85)
    -4.5
    (2.31)
    -2.7
    (2.27)
    14.25
    -3.7
    (2.13)
    -5.0
    (2.42)
    -2.9
    (1.97)
    16.25
    -3.5
    (2.29)
    -4.4
    (2.08)
    -2.9
    (1.97)
    18.25
    -4.4
    (2.34)
    -4.5
    (2.27)
    -3.5
    (1.97)
    20.25
    -4.7
    (2.04)
    -4.9
    (2.37)
    -3.6
    (2.24)
    22.25
    -4.7
    (2.25)
    -5.0
    (2.35)
    -3.9
    (2.19)
    24.25
    -4.6
    (2.29)
    -5.1
    (2.42)
    -4.3
    (1.86)
    7. Secondary Outcome
    Title Pain Intensity Rating at Different Timepoints After Dose 1 Administration
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title High Dose APAP Low Dose APAP Placebo
    Arm/Group Description Acetaminophen (APAP) administered post-operatively at a high dose Acetaminophen (APAP) administered post-operatively at a low dose Placebo given post-operatively
    Measure Participants 43 44 22
    0.5
    4.8
    (1.83)
    4.4
    (1.97)
    6.1
    (1.42)
    0.75
    4.0
    (2.12)
    4.0
    (1.98)
    6.0
    (1.70)
    1
    3.6
    (1.98)
    3.7
    (2.01)
    6.0
    (1.68)
    1.25
    3.4
    (2.16)
    3.5
    (2.14)
    6.2
    (1.89)
    1.75
    3.5
    (2.24)
    3.8
    (2.33)
    6.2
    (1.94)
    2.25
    3.6
    (2.40)
    3.9
    (2.39)
    6.2
    (1.97)
    3.25
    3.9
    (2.53)
    4.5
    (2.48)
    6.0
    (2.17)
    4.25
    4.0
    (2.58)
    4.6
    (2.33)
    6.0
    (2.21)
    5.25
    4.0
    (2.48)
    4.7
    (2.44)
    4.5
    (2.56)
    6.25
    4.2
    (2.52)
    4.0
    (2.59)
    3.2
    (2.11)
    7.25
    4.3
    (2.46)
    3.4
    (2.22)
    2.7
    (1.86)
    8.25
    3.5
    (2.58)
    3.1
    (2.20)
    3.2
    (2.30)
    9.25
    2.9
    (2.71)
    2.8
    (1.95)
    3.3
    (2.25)
    10.25
    2.8
    (2.48)
    2.5
    (1.68)
    3.5
    (2.15)
    11.25
    2.7
    (2.27)
    3.0
    (1.66)
    3.5
    (2.24)
    12.25
    2.5
    (1.83)
    3.0
    (2.09)
    4.1
    (2.32)
    14.25
    3.6
    (2.29)
    2.5
    (2.11)
    4.0
    (2.08)
    16.25
    3.8
    (2.55)
    3.1
    (2.01)
    4.0
    (2.21)
    18.25
    2.9
    (2.58)
    3.0
    (2.23)
    3.4
    (1.99)
    20.25
    2.7
    (2.28)
    2.6
    (2.14)
    3.2
    (2.22)
    22.25
    2.6
    (2.58)
    2.5
    (1.96)
    3.0
    (2.16)
    24.25
    2.8
    (2.38)
    2.4
    (2.06)
    2.61
    (1.71)
    8. Secondary Outcome
    Title Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title High Dose APAP Low Dose APAP Placebo
    Arm/Group Description Acetaminophen (APAP) administered post-operatively at a high dose Acetaminophen (APAP) administered post-operatively at a low dose Placebo given post-operatively
    Measure Participants 43 44 22
    0.5
    1.7
    (0.95)
    1.8
    (0.94)
    0.6
    (0.85)
    0.75
    2.0
    (1.02)
    2.0
    (0.98)
    0.6
    (0.85)
    1
    2.1
    (0.93)
    2.2
    (0.96)
    0.6
    (0.85)
    1.25
    2.3
    (0.97)
    2.2
    (0.99)
    0.6
    (0.85)
    1.75
    2.3
    (0.97)
    2.0
    (1.07)
    0.6
    (0.90)
    2.25
    2.2
    (1.09)
    2.0
    (1.05)
    0.6
    (0.90)
    3.25
    2.0
    (1.18)
    1.7
    (1.12)
    0.8
    (1.15)
    4.25
    2.0
    (1.21)
    1.6
    (1.12)
    0.7
    (1.08)
    5.25
    1.9
    (1.20)
    1.5
    (1.21)
    1.5
    (1.44)
    6.25
    1.9
    (1.23)
    1.9
    (1.15)
    2.1
    (1.25)
    7.25
    1.8
    (1.21)
    2.2
    (1.03)
    2.5
    (1.10)
    8.25
    2.2
    (1.15)
    2.4
    (1.06)
    2.2
    (1.27)
    9.25
    2.6
    (1.22)
    2.5
    (0.93)
    2.1
    (1.19)
    10.25
    2.6
    (1.10)
    2.7
    (0.80)
    2.0
    (1.20)
    11.25
    2.7
    (0.97)
    2.5
    (0.87)
    2.0
    (1.31)
    12.25
    2.7
    (0.83)
    2.4
    (1.04)
    1.6
    (1.33)
    14.25
    2.1
    (1.00)
    2.6
    (1.04)
    1.8
    (1.11)
    16.25
    2.1
    (1.14)
    2.3
    (1.06)
    1.8
    (1.14)
    18.25
    2.5
    (1.10)
    2.4
    (1.02)
    2.1
    (1.17)
    20.25
    2.7
    (1.00)
    2.6
    (0.95)
    2.2
    (1.18)
    22.25
    2.7
    (1.11)
    2.6
    (0.94)
    2.3
    (1.09)
    24.25
    2.5
    (1.12)
    2.7
    (0.99)
    2.5
    (0.91)
    9. Secondary Outcome
    Title Time to Treatment Failure
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title High Dose APAP Low Dose APAP Placebo
    Arm/Group Description Acetaminophen (APAP) administered post-operatively at a high dose Acetaminophen (APAP) administered post-operatively at a low dose Placebo given post-operatively
    Measure Participants 43 44 21
    Median time to treatment failure- for moderate baseline categorical pain intensity score
    NA
    NA
    3.680
    Median time to treatment failure for severe baseline categorical pain intensity score
    NA
    NA
    1.335
    10. Other Pre-specified Outcome
    Title Mean Change From Baseline to 24 Hours in Vital Signs (Systolic Blood Pressure)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    The Safety Population included all randomized participants who received the study medication. This population was used for all safety summaries.
    Arm/Group Title High Dose APAP Low Dose APAP Placebo
    Arm/Group Description Acetaminophen (APAP) administered post-operatively at a high dose Acetaminophen (APAP) administered post-operatively at a low dose Placebo given post-operatively
    Measure Participants 43 44 21
    Mean (Standard Deviation) [mm Hg]
    1.6
    (10.78)
    1.0
    (11.39)
    9.2
    (10.99)
    11. Other Pre-specified Outcome
    Title Mean Change From Baseline to 24 Hours in Vital Signs (Diastolic Blood Pressure)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    The Safety Population included all randomized participants who received the study medication. This population was used for all safety summaries.
    Arm/Group Title High Dose APAP Low Dose APAP Placebo
    Arm/Group Description Acetaminophen (APAP) administered post-operatively at a high dose Acetaminophen (APAP) administered post-operatively at a low dose Placebo given post-operatively
    Measure Participants 43 44 21
    Mean (Standard Deviation) [mm Hg]
    -0.2
    (8.82)
    2.3
    (9.56)
    5.2
    (11.08)
    12. Other Pre-specified Outcome
    Title Mean Change From Baseline to 24 Hours in Vital Signs (Temperature)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    The Safety Population included all randomized participants who received the study medication. This population was used for all safety summaries.
    Arm/Group Title High Dose APAP Low Dose APAP Placebo
    Arm/Group Description Acetaminophen (APAP) administered post-operatively at a high dose Acetaminophen (APAP) administered post-operatively at a low dose Placebo given post-operatively
    Measure Participants 43 44 21
    Mean (Standard Deviation) [degrees Celsius]
    0.12
    (0.336)
    0.21
    (0.275)
    0.06
    (0.347)
    13. Other Pre-specified Outcome
    Title Mean Change From Baseline to 24 Hours in Vital Signs (Pulse Rate)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    The Safety Population included all randomized participants who received the study medication. This population was used for all safety summaries.
    Arm/Group Title High Dose APAP Low Dose APAP Placebo
    Arm/Group Description Acetaminophen (APAP) administered post-operatively at a high dose Acetaminophen (APAP) administered post-operatively at a low dose Placebo given post-operatively
    Measure Participants 43 44 21
    Mean (Standard Deviation) [beats/minute]
    5.0
    (11.85)
    4.2
    (11.58)
    5.7
    (11.17)
    14. Other Pre-specified Outcome
    Title Mean Change From Baseline to 24 Hours in Vital Signs (Respiratory Rate)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    The Safety Population included all randomized participants who received the study medication. This population was used for all safety summaries.
    Arm/Group Title High Dose APAP Low Dose APAP Placebo
    Arm/Group Description Acetaminophen (APAP) administered post-operatively at a high dose Acetaminophen (APAP) administered post-operatively at a low dose Placebo given post-operatively
    Measure Participants 43 43 21
    Mean (Standard Deviation) [breaths/minute]
    0.3
    (3.39)
    -0.6
    (4.12)
    -1.3
    (3.68)
    15. Other Pre-specified Outcome
    Title Area Under the Plasma Concentration-Time Curve From Time of Administration to 24 Hours After Dosing (AUC 0-24h)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title High Dose APAP Low Dose APAP
    Arm/Group Description Acetaminophen (APAP) administered post-operatively at a high dose Acetaminophen (APAP) administered post-operatively at a low dose
    Measure Participants 31 38
    Least Squares Mean (Standard Error) [microgram*hour/milliliter]
    236326.3081
    (1.06026)
    231104.0073
    (1.05427)
    16. Other Pre-specified Outcome
    Title Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity])
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title High Dose APAP Low Dose APAP
    Arm/Group Description Acetaminophen (APAP) administered post-operatively at a high dose Acetaminophen (APAP) administered post-operatively at a low dose
    Measure Participants 42 43
    Geometric Mean (Geometric Coefficient of Variation) [hour*nanogram per milliliter]
    75925.2553
    (22.405)
    55018.1382
    (27.089)
    17. Other Pre-specified Outcome
    Title Half-life
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title High Dose APAP Low Dose APAP
    Arm/Group Description Acetaminophen (APAP) administered post-operatively at a high dose Acetaminophen (APAP) administered post-operatively at a low dose
    Measure Participants 42 43
    Mean (Standard Deviation) [hours]
    2.565
    (0.5774)
    2.360
    (0.4134)
    18. Other Pre-specified Outcome
    Title Maximum Observed Plasma Concentration (Cmax)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title High Dose APAP Low Dose APAP
    Arm/Group Description Acetaminophen (APAP) administered post-operatively at a high dose Acetaminophen (APAP) administered post-operatively at a low dose
    Measure Participants 31 39
    Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter (ng/ml)]
    39531.4
    (26)
    28495.6
    (30)

    Adverse Events

    Time Frame Up to 7 days (± 2 days)
    Adverse Event Reporting Description An adverse event (AE) is defined as any untoward medical occurrence and does not necessarily have to have causal relationship with the study medication. An AE can therefore be an unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease, which is a change from baseline and is temporally associated with the use of the study medication, whether or not it is considered related to the study medication.
    Arm/Group Title High Dose APAP Low Dose APAP Placebo
    Arm/Group Description Acetaminophen (APAP) administered post-operatively at a high dose Acetaminophen (APAP) administered post-operatively at a low dose Placebo given post-operatively
    All Cause Mortality
    High Dose APAP Low Dose APAP Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/44 (0%) 0/44 (0%) 0/22 (0%)
    Serious Adverse Events
    High Dose APAP Low Dose APAP Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/44 (0%) 0/44 (0%) 0/22 (0%)
    Other (Not Including Serious) Adverse Events
    High Dose APAP Low Dose APAP Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 9/44 (20.5%) 13/44 (29.5%) 7/22 (31.8%)
    Cardiac disorders
    Tachycardia 0/44 (0%) 0 1/44 (2.3%) 1 0/22 (0%) 0
    Gastrointestinal disorders
    Hypoaesthesia oral 0/44 (0%) 0 1/44 (2.3%) 1 0/22 (0%) 0
    Nausea 1/44 (2.3%) 1 1/44 (2.3%) 1 1/22 (4.5%) 1
    General disorders
    Infusion site extravasation 1/44 (2.3%) 1 0/44 (0%) 0 0/22 (0%) 0
    Infusion site haematoma 1/44 (2.3%) 1 0/44 (0%) 0 0/22 (0%) 0
    Pyrexia 1/44 (2.3%) 1 1/44 (2.3%) 1 0/22 (0%) 0
    Hepatobiliary disorders
    Hyperbilirubinaemia 7/44 (15.9%) 7 8/44 (18.2%) 8 6/22 (27.3%) 6
    Infections and infestations
    Postoperative wound infection 0/44 (0%) 0 1/44 (2.3%) 1 0/22 (0%) 0
    Injury, poisoning and procedural complications
    Arthropod bite 0/44 (0%) 0 1/44 (2.3%) 1 0/22 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/44 (0%) 0 1/44 (2.3%) 1 0/22 (0%) 0
    Nervous system disorders
    Dizziness 0/44 (0%) 0 0/44 (0%) 0 1/22 (4.5%) 1
    Headache 0/44 (0%) 0 0/44 (0%) 0 1/22 (4.5%) 1
    Respiratory, thoracic and mediastinal disorders
    Rhinorrhoea 0/44 (0%) 0 1/44 (2.3%) 1 0/22 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Eric Lang, MD
    Organization Nevakar, Inc.
    Phone (908) 367-7400
    Email Clinicaltrials@nevakar.com
    Responsible Party:
    Nevakar, Inc.
    ClinicalTrials.gov Identifier:
    NCT04018612
    Other Study ID Numbers:
    • CP-NVK009-0002
    First Posted:
    Jul 12, 2019
    Last Update Posted:
    Mar 29, 2022
    Last Verified:
    Mar 1, 2022