Clinical trial NCT04018612: A Study of Acetaminophen for Post Surgical Dental Pain
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pain, Postoperative
Dental Pain
Lead sponsor: Nevakar, Inc.
Sponsor class: INDUSTRY
First posted: 2019-07-12
Enrollment: 110
Sex: ALL
Minimum age (years): 17
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: High Dose Acetaminophen (APAP) versus Placebo, Low Dose APAP versus Placebo
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

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Primary outcomes:
measure: Sum of Pain Intensity Difference From 0 to 24 Hours (SPID24) Based on the 11 Point Numeric Pain Rating Scale
timeFrame: 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
measure: Sum of Pain Relief From 0 to 24 Hours (TOTPAR24) Based on a 5-point Likert Scale.
timeFrame: 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
Secondary outcomes:
measure: 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
timeFrame: 0 to 24 Hours
measure: Time to Meaningful Perceptible Relief (MPR) Measure Stratified by Baseline Pain Score of Moderate or Severe for the 3 Treatment Groups
timeFrame: 0 to 24 Hours
measure: Patient Global Evaluation of the Study Medication
timeFrame: 0 to 24 Hours
measure: Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration
timeFrame: 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)
measure: Pain Intensity Rating at Different Timepoints After Dose 1 Administration
timeFrame: 0 to 24 hours
measure: Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration
timeFrame: 0 to 24 hours
measure: Time to Treatment Failure
timeFrame: 0 to 24 Hours
Other outcomes:
measure: Mean Change From Baseline to 24 Hours in Vital Signs (Systolic Blood Pressure)
timeFrame: 0 to 24 hours
measure: Mean Change From Baseline to 24 Hours in Vital Signs (Diastolic Blood Pressure)
timeFrame: 0 to 24 hours
measure: Mean Change From Baseline to 24 Hours in Vital Signs (Temperature)
timeFrame: 0 to 24 hours
measure: Mean Change From Baseline to 24 Hours in Vital Signs (Pulse Rate)
timeFrame: 0 to 24 hours
measure: Mean Change From Baseline to 24 Hours in Vital Signs (Respiratory Rate)
timeFrame: 0 to 24 hours
measure: Area Under the Plasma Concentration-Time Curve From Time of Administration to 24 Hours After Dosing (AUC 0-24h)
timeFrame: 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
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity])
timeFrame: 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
measure: Half-life
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 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
Locations:
city: Salt Lake City
country: United States
facility: JBR
state: Utah
Study officials:
affiliation: Nevakar, Inc.
name: Eric Lang, MD
role: STUDY_DIRECTOR
References: