A Dental Pain Study to Test the Effectiveness of a New Pain Reliever Medicine

A Randomized, Double-blind, Placebo- and Active-controlled Trial to Investigate the Single-dose Efficacy, Safety, and Pharmacokinetics of 250 and 1000 mg JNJ-10450232 in Postoperative Dental Pain

To assess the safety and effectiveness one dose of a new pain reliever medicine (JNJ-10450232 at either the 250 or 1000 mg strength) compared with placebo (sugar pill) or acetaminophen 1000 mg after surgical removal of third molars. The primary endpoint will evaluate pain relief effectiveness up to 6 hours after administration of the study drug.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: JNJ-10450232 / Not yet marketed; Drug: acetaminophen / Tylenol

Detailed Description

This is a single-center, randomized, double-blind, placebo- and active-controlled, parallel group study to evaluate the efficacy, safety and pharmacokinetic profile of JNJ-10450232, administered as a single dose in capsules (250 or 1000 mg), over a 24 hour period after molar extractions. Subjects will stay at the research center for ~24 hours after administration of study drug. Healthy male subjects, ages 18 to 45 years inclusive, will be screened by medical history, vital signs, an electrocardiogram (ECG), and clinical laboratory tests. Eligible subjects will return to the clinic on the day of surgery and complete baseline vital signs and clinical laboratory tests. They will undergo dental extraction of a minimum of three third-molars and, if qualified, will be randomly assigned to one of four study treatments for pain.

• Study Type: Interventional
• Enrollment (Actual): 269
• 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: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Subjects aged 18-45 years
• At least moderate dental pain assessed by a categorical scale pain intensity scale and a score of at least 5 on the 11-point (0-10) pain intensity numerical rating scale (PI-NRS) following surgical removal of three third-molars

Exclusion Criteria:

• Subjects who are not otherwise healthy
• Test positive for the urine drug screen
• Taking prohibited medications will not be allowed to participate in this study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: JNJ-10450232 / Not yet marketed; Subjects who meet the randomization criteria at baseline within 4.5 hours after dental surgery will be assigned to one of four treatment groups stratified by pharmacokinetic blood sampling schedule and by baseline pain intensity level.
Experimental: JNJ-10450232 250 mg	Drug: JNJ-10450232 / Not yet marketed; Subjects who meet the randomization criteria at baseline within 4.5 hours after dental surgery will be assigned to one of four treatment groups stratified by pharmacokinetic blood sampling schedule and by baseline pain intensity level.
Experimental: JNJ-10450232 1000 mg	Drug: JNJ-10450232 / Not yet marketed; Subjects who meet the randomization criteria at baseline within 4.5 hours after dental surgery will be assigned to one of four treatment groups stratified by pharmacokinetic blood sampling schedule and by baseline pain intensity level.
Active Comparator: Acetaminophen 1000 mg	Drug: acetaminophen / Tylenol; Subjects who meet the randomization criteria at baseline within 4.5 hours after dental surgery will be assigned to one of four treatment groups stratified by pharmacokinetic blood sampling schedule and by baseline pain intensity level.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analgesic Efficacy From 0 to 6 Hours After the Dose Using the Time-weighted Sum of Pain Intensity Difference (SPID 0-6)	Time-weighted sum of pain intensity difference by first multiplying each pain intensity difference (PID) score by the time from the previous time point, and adding them together for each scheduled time point within 0-6 hours. Time points included 15 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, and 6 hours. The minimum SPID 0-6 was -30 and the maximum SPID 0-6 was 60, where higher is better. Pain intensity is the amount of pain experienced on a scale of 1-10 (where 1=no pain and 10=very severe pain).	6 Hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Intensity Difference From Baseline (PID) Scores at 15 Minutes Post Dose	Pain intensity is the amount of pain experienced on a scale of 1-10 (where 1=no pain and 10=very severe pain). The PID will be derived by subtracting the pain intensity from the baseline pain intensity.	Baseline to 15 minutes post dose
Pain Intensity Difference From Baseline (PID) Scores at 30 Minutes Post Dose	Pain intensity is the amount of pain experienced on a scale of 1-10 (where 1=no pain and 10=very severe pain). The PID will be derived by subtracting the pain intensity from the baseline pain intensity.	Baseline to 30 minutes post dose
Pain Intensity Difference From Baseline (PID) Scores at 45 Minutes Post Dose	Pain intensity is the amount of pain experienced on a scale of 1-10 (where 1=no pain and 10=very severe pain). The PID will be derived by subtracting the pain intensity from the baseline pain intensity.	Baseline to 45 minutes post dose
Pain Intensity Difference From Baseline (PID) Scores at 1 Hour Post Dose	Pain intensity is the amount of pain experienced on a scale of 1-10 (where 1=no pain and 10=very severe pain). The PID will be derived by subtracting the pain intensity from the baseline pain intensity.	Baseline to 1 hour post dose
Pain Intensity Difference From Baseline (PID) Scores at 1.5 Hours Post Dose	Pain intensity is the amount of pain experienced on a scale of 1-10 (where 1=no pain and 10=very severe pain). The PID will be derived by subtracting the pain intensity from the baseline pain intensity.	Baseline to 1.5 hours post dose
Pain Intensity Difference From Baseline (PID) Scores at 2 Hours Post Dose	Pain intensity is the amount of pain experienced on a scale of 1-10 (where 1=no pain and 10=very severe pain). The PID will be derived by subtracting the pain intensity from the baseline pain intensity.	Baseline to 2 hours post dose
Pain Intensity Difference From Baseline (PID) Scores at 3 Hours Post Dose	Pain intensity is the amount of pain experienced on a scale of 1-10 (where 1=no pain and 10=very severe pain). The PID will be derived by subtracting the pain intensity from the baseline pain intensity.	Baseline to 3 hours post dose
Pain Intensity Difference From Baseline (PID) Scores at 4 Hours Post Dose	Pain intensity is the amount of pain experienced on a scale of 1-10 (where 1=no pain and 10=very severe pain). The PID will be derived by subtracting the pain intensity from the baseline pain intensity.	Baseline to 4 hours post dose
Pain Intensity Difference From Baseline (PID) Scores at 5 Hours Post Dose	Pain intensity is the amount of pain experienced on a scale of 1-10 (where 1=no pain and 10=very severe pain). The PID will be derived by subtracting the pain intensity from the baseline pain intensity.	Baseline to 5 hours post dose
Pain Intensity Difference From Baseline (PID) Scores at 6 Hours Post Dose	Pain intensity is the amount of pain experienced on a scale of 1-10 (where 1=no pain and 10=very severe pain). The PID will be derived by subtracting the pain intensity from the baseline pain intensity.	Baseline to 6 hours post dose
Pain Intensity Difference From Baseline (PID) Scores at 7 Hours Post Dose	Pain intensity is the amount of pain experienced on a scale of 1-10 (where 1=no pain and 10=very severe pain). The PID will be derived by subtracting the pain intensity from the baseline pain intensity.	Baseline to 7 hours post dose
Pain Intensity Difference From Baseline (PID) Scores at 8 Hours Post Dose	Pain intensity is the amount of pain experienced on a scale of 1-10 (where 1=no pain and 10=very severe pain). The PID will be derived by subtracting the pain intensity from the baseline pain intensity.	Baseline to 8 hours post dose
Pain Intensity Difference From Baseline (PID) Scores at 9 Hours Post Dose	Pain intensity is the amount of pain experienced on a scale of 1-10 (where 1=no pain and 10=very severe pain). The PID will be derived by subtracting the pain intensity from the baseline pain intensity.	Baseline to 9 hours post dose
Pain Intensity Difference From Baseline (PID) Scores at 10 Hours Post Dose	Pain intensity is the amount of pain experienced on a scale of 1-10 (where 1=no pain and 10=very severe pain). The PID will be derived by subtracting the pain intensity from the baseline pain intensity.	Baseline to 10 hours post dose
Pain Intensity Difference From Baseline (PID) Scores at 11 Hours Post Dose	Pain intensity is the amount of pain experienced on a scale of 1-10 (where 1=no pain and 10=very severe pain). The PID will be derived by subtracting the pain intensity from the baseline pain intensity.	Baseline to 11 hours post dose
Pain Intensity Difference From Baseline (PID) Scores at 12 Hours Post Dose	Pain intensity is the amount of pain experienced on a scale of 1-10 (where 1=no pain and 10=very severe pain). The PID will be derived by subtracting the pain intensity from the baseline pain intensity.	Baseline to 12 hours post dose
Pain Intensity Difference From Baseline (PID) Scores at 16 Hours Post Dose	Pain intensity is the amount of pain experienced on a scale of 1-10 (where 1=no pain and 10=very severe pain). The PID will be derived by subtracting the pain intensity from the baseline pain intensity.	Baseline to 16 hours post dose
Pain Intensity Difference From Baseline (PID) Scores at 24 Hours Post Dose	Pain intensity is the amount of pain experienced on a scale of 1-10 (where 1=no pain and 10=very severe pain). The PID will be derived by subtracting the pain intensity from the baseline pain intensity.	Baseline to 24 hours post dose
Pain Relief (PAR) Scores at 15 Minutes Post Dose	Pain relief is the amount of pain relief on a scale of 1-10 (where 1=no relief and 10=complete relief).	15 minutes post dose
Pain Relief (PAR) Scores at 30 Minutes Post Dose	Pain relief is the amount of pain relief on a scale of 1-10 (where 1=no relief and 10=complete relief).	30 minutes post dose
Pain Relief (PAR) Scores at 45 Minutes Post Dose	Pain relief is the amount of pain relief on a scale of 1-10 (where 1=no relief and 10=complete relief).	45 minutes post dose
Pain Relief (PAR) Scores at 1 Hour Post Dose	Pain relief is the amount of pain relief on a scale of 1-10 (where 1=no relief and 10=complete relief).	1 hour post dose
Pain Relief (PAR) Scores at 1.5 Hours Post Dose	Pain relief is the amount of pain relief on a scale of 1-10 (where 1=no relief and 10=complete relief).	1.5 hours post dose
Pain Relief (PAR) Scores at 2 Hours Post Dose	Pain relief is the amount of pain relief on a scale of 1-10 (where 1=no relief and 10=complete relief).	2 hours post dose
Pain Relief (PAR) Scores at 3 Hours Post Dose	Pain relief is the amount of pain relief on a scale of 1-10 (where 1=no relief and 10=complete relief).	3 hours post dose
Pain Relief (PAR) Scores at 4 Hours Post Dose	Pain relief is the amount of pain relief on a scale of 1-10 (where 1=no relief and 10=complete relief).	4 hours post dose
Pain Relief (PAR) Scores at 5 Hours Post Dose	Pain relief is the amount of pain relief on a scale of 1-10 (where 1=no relief and 10=complete relief).	5 hours post dose
Pain Relief (PAR) Scores at 6 Hours Post Dose	Pain relief is the amount of pain relief on a scale of 1-10 (where 1=no relief and 10=complete relief).	6 hours post dose
Pain Relief (PAR) Scores at 7 Hours Post Dose	Pain relief is the amount of pain relief on a scale of 1-10 (where 1=no relief and 10=complete relief).	7 hours post dose
Pain Relief (PAR) Scores at 8 Hours Post Dose	Pain relief is the amount of pain relief on a scale of 1-10 (where 1=no relief and 10=complete relief).	8 hours post dose
Pain Relief (PAR) Scores at 9 Hours Post Dose	Pain relief is the amount of pain relief on a scale of 1-10 (where 1=no relief and 10=complete relief).	9 hours post dose
Pain Relief (PAR) Scores at 10 Hours Post Dose	Pain relief is the amount of pain relief on a scale of 1-10 (where 1=no relief and 10=complete relief).	10 hours post dose
Pain Relief (PAR) Scores at 11 Hours Post Dose	Pain relief is the amount of pain relief on a scale of 1-10 (where 1=no relief and 10=complete relief).	11 hours post dose
Pain Relief (PAR) Scores at 12 Hours Post Dose	Pain relief is the amount of pain relief on a scale of 1-10 (where 1=no relief and 10=complete relief).	12 hours post dose
Pain Relief (PAR) Scores at 16 Hours Post Dose	Pain relief is the amount of pain relief on a scale of 1-10 (where 1=no relief and 10=complete relief).	16 hours post dose
Pain Relief (PAR) Scores at 24 Hours Post Dose	Pain relief is the amount of pain relief on a scale of 1-10 (where 1=no relief and 10=complete relief).	24 hours post dose
Duration of Pain Relief After Dosing (Time to Rescue Medication)	Time (minutes) to rescue medication was measured as the elapsed time from when the investigational product was given until the time rescue medication was given.	Completed at time of the first rescue medication (hours post dose), estimated up through Day 2
Subject Global Evaluation	How the subject would rate the study medication as a pain-reliever on a scale of 0-4 (where 0=poor and 4=excellent).	Completed at hour 12 or at time of the first rescue medication (hours post dose).

Collaborators and Investigators

• Sponsor: McNeil Consumer Healthcare Division of McNEIL-PPC, Inc.
• Investigators: Study Director: Cathy Gelotte, Ph.D., McNeil Consumer Healthcare Division of McNEIL-PPC, Inc.

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: July 22, 2014
• First Submitted That Met QC Criteria: August 1, 2014
• First Posted (Estimate): August 5, 2014

Study Record Updates

• Last Update Posted (Estimate): February 3, 2017
• Last Update Submitted That Met QC Criteria: December 10, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: dental pain; post-surgical dental pain
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Stomatognathic Diseases; Tooth Diseases; Facial Pain; Toothache; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Acetaminophen
• Other Study ID Numbers: CO-131230135611-CTPA