Dental Pain Study of Analgesics in Patients Undergoing Molar Removal (NVK009-0001)

Randomized, Double-blind, Parallel Group, Single-center, Placebo-controlled Study to Evaluate Efficacy and Safety of Analgesic Combo in Prevention and Treatment of Post-surgical Dental Pain in Healthy Subjects

• Accessing the efficacy and safety of pregabalin when used alone and in combo with acetaminophen in a dental pain model.
• To test whether pre-operative dose of pregabalin increases the time to significant post-operative pain (NRS ≥ 5), and hence time to first analgesia consumed post-operatively.

Study Overview

• Status: Completed
• Conditions: Dental Pain
• Intervention / Treatment: Drug: Pre-Op Placebo 1; Drug: Post-Op Placebo 1; Drug: Post-Op Placebo 2; Drug: Post-Op acetaminophen; Drug: Post-Op pregabalin; Drug: Pre-Op pregabalin

Detailed Description

This is a 5 arm randomized, double-blind, parallel group, single-center, placebo-controlled study to evaluate the efficacy and safety of pregabalin-acetaminophen combination in the prevention and treatment of post-surgical dental pain in healthy patients.

Subjects in every treatment arm will receive a dose 60 min prior to surgery. It is not required to receive a post-operative dose if patient does not feel pain at a scale of NRS≥ 5. Dose 2 will be given post-surgically when patients report at least moderate pain on the categorical scale and a score of ≥5 on 0-10 PI-NRS. Subsequent to dose 2, patients can request rescue analgesic at any time.

• Study Type: Interventional
• Enrollment (Actual): 115
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Jean Brown Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 55 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients who are scheduled to undergo the surgical removal of up to 4 third molars of which at least 2 have to be mandibular molars with a difficulty rating of 4 or 5.
• Patient must have a negative urine drug screen for drugs of abuse (including tobacco) at screening and at the day of surgery.
• No alcohol for a minimum of 1 day prior to the surgery.

Exclusion Criteria:

• Patients should not be experiencing oral infections or symptoms of concomitant illness at the time of a scheduled surgery.
• Patients with a history of any type of malignancy within the past 5 years other than minor skin related cancers.
• Patients who currently have or have had a history of uncontrolled hypertension.
• Patients with a known allergy or hypersensitivity to any local anesthetic drug, NSAIDs, gabapentin or pregabalin;.
• Patients with conditions that affect the absorption, metabolism, or passage of drugs out of the body (e.g., sprue, celiac disease, crohn's disease, etc.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; Pre-op Placebo 1; Post-op Placebo 1; Post-op Placebo 2	Drug: Pre-Op Placebo 1; Placebo 1 will be administered 60 min prior to surgery.; Other Names: pre-op placebo; Drug: Post-Op Placebo 1; Placebo 1 will be administered post-operatively.; Drug: Post-Op Placebo 2; Placebo 2 will be administered post-operatively.
Experimental: Group B; Pre-op Placebo 1; Post-op Placebo 2; Post-op acetaminophen.	Drug: Pre-Op Placebo 1; Placebo 1 will be administered 60 min prior to surgery.; Other Names: pre-op placebo; Drug: Post-Op Placebo 1; Placebo 1 will be administered post-operatively.; Drug: Post-Op acetaminophen; Acetaminophen will be administered Post-operatively.
Experimental: Group C; Pre-op Placebo 1; Post-op pregabalin; Post-op Placebo 2.	Drug: Pre-Op Placebo 1; Placebo 1 will be administered 60 min prior to surgery.; Other Names: pre-op placebo; Drug: Post-Op Placebo 2; Placebo 2 will be administered post-operatively.; Drug: Post-Op pregabalin; Post-op pregabalin will be administered Post-operatively.
Experimental: Group D; Pre-op Placebo 1; Post-op pregabalin Post-op acetaminophen.	Drug: Pre-Op Placebo 1; Placebo 1 will be administered 60 min prior to surgery.; Other Names: pre-op placebo; Drug: Post-Op acetaminophen; Acetaminophen will be administered Post-operatively.; Drug: Post-Op pregabalin; Post-op pregabalin will be administered Post-operatively.
Experimental: Group E; Pre-op pregabalin; Post-op Placebo 1; Post-op acetaminophen.	Drug: Post-Op Placebo 1; Placebo 1 will be administered post-operatively.; Drug: Post-Op acetaminophen; Acetaminophen will be administered Post-operatively.; Drug: Pre-Op pregabalin; Pre-op pregabalin will be administered 60 min prior to surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sum Pain Intensity Difference Scores	Beginning post-surgery (at initiation of Dose 2), 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 = pain as bad as can be). Time weighted sum pain intensity difference scores are reported over 0 to 24 hours. Last observation carried forward method was used.	0.5, 0.75, 1, 1.25, 1.75, 2.25 hours (± 5 min) and 3.25, 4.25, 5.25, 6.25, 8.25, 10.25, 12.25, 24 hours (± 10 min)
Total Pain Relief Measure	Beginning post-surgery (at initiation of Dose 2), Pain Relief 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 = pain as bad as can be). Time-weighted sum pain total pain relief scores over 24 hours is reported Last observation carried forward method was used.	0.5, 0.75, 1, 1.25, 1.75, 2.25 hours (± 5 min) and 3.25, 4.25, 5.25, 6.25, 8.25, 10.25, 12.25, 24 hours (± 10 min)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Differing Patient Global Evaluation Scores	Patient global evaluation was self-reported at time of first rescue or at 12.25 hours post-surgery, whichever was first, using a 0-4 categorical rating scale of: (0) poor, (1) fair, (2) good, (3) very good, and (4) excellent. The number of participants with differing patient global evaluation scores were reported.	Upto 12.25 hours
Cumulative Number of Participants With Onset of First Perceptible Relief (FPR) Confirmed at 24 Hours After Dose 2	Beginning post-surgery (at initiation of Dose 2), participants were given a stopwatch and asked to press the stopwatch if and when they feel first perceptible relief; a record of the time was noted in the participants record. Cumulative number of participants with onset of FPR confirmed after dose 2 and was recorded from 0.25 hour till 24 hours after administration of dose 2.	0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0 and 24 hours
Cumulative Number of Participants With Onset of Meaning Pain Relief (MPR) Confirmed at 24 Hours After Dose 2	Beginning post-surgery (at initiation of Dose 2), participants were given a stopwatch and asked to press the stopwatch if and when they feel first perceptible relief; a record of the time was noted in the participants record. Cumulative number of participants with onset of MPR confirmed after dose 2 and was recorded from 0.25 hour till 24 hours after administration of dose 2.	0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0 and 24 hours

Collaborators and Investigators

• Sponsor: Nevakar, Inc.
• Investigators: Study Director: Kenneth Somberg, MD, Nevakar, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2018
• Primary Completion (Actual): September 20, 2018
• Study Completion (Actual): September 20, 2018

Study Registration Dates

• First Submitted: July 18, 2018
• First Submitted That Met QC Criteria: August 27, 2018
• First Posted (Actual): August 29, 2018

Study Record Updates

• Last Update Posted (Actual): November 23, 2021
• Last Update Submitted That Met QC Criteria: October 25, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Stomatognathic Diseases; Tooth Diseases; Facial Pain; Toothache; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Acetaminophen; Pregabalin
• Other Study ID Numbers: CP-NVK009-0001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No