A Study of Acetaminophen for Post Surgical Dental Pain

NCT04018612 | Completed Phase 2 Results FDA Drug

• 1 other identifier: CP-NVK009-0002
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

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.

Conditions

Pain, Postoperative; Dental Pain

Outcome Measures

Primary Outcomes (2)

• 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.

  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

• 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.

  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 (7)

• 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

• 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

• Patient Global Evaluation of the Study Medication

  0 to 24 Hours

• 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 Rating at Different Timepoints After Dose 1 Administration

  0 to 24 hours

Other Outcomes (9)

• Mean Change From Baseline to 24 Hours in Vital Signs (Systolic Blood Pressure)

  0 to 24 hours

• Mean Change From Baseline to 24 Hours in Vital Signs (Diastolic Blood Pressure)

  0 to 24 hours

• Mean Change From Baseline to 24 Hours in Vital Signs (Temperature)

  0 to 24 hours

Study Arms (3)

High Dose Acetaminophen

ACTIVE COMPARATOR

High Dose Acetaminophen Post Op

Drug: Acetaminophen

Low Dose Acetaminophen

ACTIVE COMPARATOR

Low Dose Acetaminophen Post Op

Drug: Acetaminophen

Placebo

PLACEBO COMPARATOR

Placebo Post Op

Other: Placebo

Interventions

Acetaminophen DRUG

Acetaminophen is an analgesic and antipyretic

Also known as: APAP

High Dose Acetaminophen; Low Dose Acetaminophen

Placebo OTHER

Saline

Placebo

Eligibility Criteria

• Age: 17 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must be capable of reading, comprehending, and signing the informed consent/assent form;
• Male and female patients between 17-55 years of age;
• Body Mass Index (BMI) ≤35.0 kg/m2
• Body weight of \>50 kg
• 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;
• Patients without infections in the area of the impacted teeth;
• 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;
• No alcohol for a minimum of 24 hours prior to the surgery;
• 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;
• 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;
• 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);
• Patients able to comprehend and follow the requirements of the study (including availability on scheduled visit dates) based upon the research site's judgment.

You may not qualify if:

• 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;
• Patients with a history of any type of malignancy within the past 5 years other than minor skin related cancers;
• Patients with a known allergy or hypersensitivity to any local anesthetic drug, acetaminophen, ibuprofen, or other NSAIDS;
• 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;
• Patients who have smoked or chewed tobacco-containing substances within 48 hours prior to the day of surgery;
• Patients judged by the Principal Investigator to be unable or unwilling to comply with the requirements of the protocol;
• Patients who have used an investigational drug within 30 days prior to the screening day or have previously participated in any Nevakar trial;
• Patients who have donated blood within 3 months prior to the screening day;
• Patients who are employees or relatives of employees of JBR Clinical Research or Nevakar, Inc.
• Patients with liver function tests (ALT, AST) that are above the normal reference range.

Sponsors & Collaborators

• Nevakar, Inc.: lead

Study Sites (1)

JBR

Salt Lake City, Utah, 84107, United States

Location

MeSH Terms

Conditions

Pain, Postoperative; Toothache

Interventions

Acetaminophen

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Tooth Diseases; Stomatognathic Diseases; Facial Pain

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Results Point of Contact

• Title: Eric Lang, MD
• Organization: Nevakar, Inc.

Clinicaltrials@nevakar.com

(908) 367-7400

Study Officials

• Eric Lang, MD

  Nevakar, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double Blind, Placebo controlled
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: High Dose Acetaminophen (APAP) versus Placebo, Low Dose APAP versus Placebo

Study Record Dates

• First Submitted: July 8, 2019
• First Posted: July 12, 2019
• Study Start: April 25, 2019
• Primary Completion: July 26, 2019
• Study Completion: August 15, 2019
• Last Updated: March 29, 2022
• Results First Posted: March 29, 2022

Record last verified: 2022-03

Locations

US (1)