Efficacy Of Pf-04531083 In Treating Post-Surgical Dental Pain

A Randomized, Double-Blind Third Party Open, Double-Dummy, Parallel Group, Placebo Controlled Study Assessing The Efficacy Of Single Doses Of Pf-04531083 For The Treatment Of Post-Surgical Dental Pain Using Ibuprofen 400 Mg As A Positive Control

The purpose of this study is to evaluate the overall pain relief of a single dose of PF-04531083 against placebo following third molar extraction.

Study Overview

• Status: Terminated
• Conditions: Post-surgical Dental Pain
• Intervention / Treatment: Drug: PF-04531083; Other: Placebo; Drug: PF-04531083; Other: Placebo; Drug: Ibuprofen

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Oral surgical procedure having removed 2 third molars (unilateral).
• Pre-dose pain intensity score (100 mm Visual Analog Scale [VAS]) >50 mm within 5 hours of oral surgery.
• Pre-dose pain intensity score of moderate or within 5 hours of oral surgery.

Exclusion Criteria:

• Presence or history of any significant hepatic, renal, endocrine, cardiovascular, neurological (including subjects with a history of frequent moderate to severe headaches or subjects with episodic migraines more than twice per month), psychiatric, gastrointestinal, pulmonary, hematologic, or metabolic disorder.
• Prior use of any type of analgesic or NSAID within five half-lives of that drug or less before taking the first dose of study medication, except for anesthesia for the procedure.
• Recent history of chronic analgesic or tranquilizer dependency.
• Active dental infection at the time of surgery.
• Any significant oral surgery complication at the time of surgery or in the immediate postoperative period or dental surgery lasting > 30 minutes.
• Subjects who are smokers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Other: Placebo; Placebo tablets for Ibuprofen; Other: Placebo; Placebo solution for PF-04531083
EXPERIMENTAL: PF-04531083 2000 mg	Drug: PF-04531083; 2000 mg oral solution; Other: Placebo; Placebo tablets for Ibuprofen; Drug: PF-04531083; 1000 mg oral solution; Other: Placebo; Placebo solution for PF-04531083
EXPERIMENTAL: PF-04531083 1000 mg	Drug: PF-04531083; 2000 mg oral solution; Other: Placebo; Placebo tablets for Ibuprofen; Drug: PF-04531083; 1000 mg oral solution; Other: Placebo; Placebo solution for PF-04531083
ACTIVE_COMPARATOR: Ibuprofen 400 mg	Other: Placebo; Placebo tablets for Ibuprofen; Other: Placebo; Placebo solution for PF-04531083; Drug: Ibuprofen; 2 x 200 mg tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Pain Relief (TOTPAR) Score From 0 to 6 Hours	TOTPAR [6] was defined as the area under the pain relief (PR) curve through the first 6 hours after dosing. Area under the curve (AUC) was calculated using the trapezoid rule with PR was assumed to be 0 at time=0. PR assessed on a 5-point categorical scale; 0 (none), 1 (a little), 2 (some), 3 (a lot) and 4 (complete), at 15, 30, 45, minutes and at different time points during the study up to 6 hours post-dose. Total score range for TOTPAR [6]: 0 (worst) - 24 (best), higher value of TOTPAR indicated greater degree of PR.	0 to 6 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Peak Pain Relief (PPR)	PPR was defined as the highest PR score achieved at any time point during the evaluation period, prior to rescue medication. PR was assessed on a 5-point categorical scale; 0 (none), 1 (a little), 2 (some), 3 (a lot) and 4 (complete).	0 to 24 hours
Time-specific Pain Relief (PR) Score	PR was assessed on a 5-point categorical scale; 0 (none), 1 (a little), 2 (some), 3 (a lot) and 4 (complete) at each relevant time points.	0, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 6, 8, 24 hours, prior to rescue medication (RM)
Time-specific Pain Intensity Difference (PID) Score	Pain intensity was assessed on a categorical scale ranging from 0 (none), 1 (mild), 2 (moderate) and 3 (severe). PID was calculated as pain intensity at baseline minus pain intensity at the respective post-baseline visit.	15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 6, 8, 24 hours, prior to RM
Summed Pain Intensity Difference (SPID) Score at 6 Hours and 24 Hours	Pain intensity was assessed on a categorical scale ranging from 0 (none), 1 (mild), 2 (moderate) and 3 (severe). PID was calculated as pain intensity at baseline minus pain intensity at the respective post-baseline visit. The SPID at 6 and 24 hours was derived by calculating the area under the PID effect curve through the first 6 or 24 hours post-dose respectively. The AUC was calculated using the trapezoid rule. Total score range: -6 (worst) to 18 (best) for SPID 0-6, and -24 (worst) to 72 (best) for SPID 0-24. Higher value of SPID indicated greater degree of pain relief.	0 to 6, 0 to 24 hours
Total Pain Relief (TOTPAR) Score From 0 to 24 Hours	TOTPAR [24] was defined as the area under the pain relief (PR) curve through the 24 hours after dosing. Area under the curve (AUC) was calculated using the trapezoid rule with PR assumed to be 0 at time=0. PR was assessed on a 5-point categorical scale; 0 (none), 1 (a little), 2 (some), 3 (a lot) and 4 (complete), at 15, 30, 45, minutes and at different time points during the study up to 24 hours post-dose. Total score range for TOTPAR [24]: 0 (worst) - 96 (best), higher value of TOTPAR indicated greater degree of PR.	0 to 24 hours
Time to Onset of First Perceptible Pain Relief (PR)	Participants evaluated the time to first perceptible relief by stopping a stopwatch labeled 'first perceptible relief' at the moment they first began to experience any relief.	0 to 24 hours
Time to Onset of First Meaningful Pain Relief (PR)	Participants evaluated the time to first meaningful relief by stopping a second stopwatch labeled 'meaningful relief' at the moment they first began to experience meaningful relief.	0 to 24 hours
Time to First Use of Rescue Medication	Time to first use of rescue medication (2 tablets of acetaminophen 500 mg as starting dose) was calculated by subtracting time of first administration of study medication from the rescue medication administration time.	1.5 to 24 hours
Number of Participants With Rescue Medication	Participants who did not experience adequate pain relief after 90 minutes post-dose of study medication had received 2 tablets of acetaminophen 500 mg as rescue medication.	0 to 24 hours
Participant Global Evaluation of Study Medication	Participant rated the study medication that they received during the study, at both the 6 hour and 24 hour observations or at time of rescue medication, whichever occurs first, by answering the following question on 6-point categorical scale: how would you rate the study medication you received for pain? 5=excellent, 4=very good, 3=good, 2=fair and 1=poor.	6, 24 hours, prior to RM
Participant Satisfaction Questionnaire	Participant's response to 2 questions about "how satisfied or dissatisfied they were with the study medication for PR and overall performance (OP)" was obtained on a 5 point categorical scale, 1=very dissatisfied, 2=somewhat dissatisfied, 3=neither satisfied nor dissatisfied, 4=somewhat satisfied and 5=very satisfied.	6, 24 hours, prior to RM
Maximum Observed Plasma Concentration (Cmax) of PF-04531083		0 (pre-dose), 1, 2, 4, 6, 24 hours post-dose
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04531083		0 (pre-dose), 1, 2, 4, 6, 24 hours post-dose
Area Under the Curve From Time Zero to 6 Hour [AUC (0-6)] of PF-04531083	AUC (0-6)= Area under the plasma concentration versus time curve from time zero (pre-dose) to 6 hours post-dose concentration.	0 (pre-dose), 1, 2, 4, 6 hours post-dose
Area Under the Curve From Time Zero to 24 Hour [AUC (0-24)] of PF-04531083	AUC (0-24)= Area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours post-dose concentration.	0 (pre-dose), 1, 2, 4, 6, 24 hours post-dose
Maximum Observed Plasma Concentration (Cmax) of Ibuprofen		0 (pre-dose), 1, 2, 4, 6, 24 hours post-dose
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ibuprofen		0 (pre-dose), 1, 2, 4, 6, 24 hours post-dose
Area Under the Curve From Time Zero to 6 Hour [AUC (0-6)] of Ibuprofen	AUC (0-6)= Area under the plasma concentration versus time curve from time zero (pre-dose) to 6 hours post-dose concentration.	0 (pre-dose), 1, 2, 4, 6 hours post-dose
Area Under the Curve From Time Zero to 24 Hour [AUC (0-24)] of Ibuprofen	AUC (0-24)= Area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours post-dose concentration.	0 (pre-dose), 1, 2, 4, 6, 24 hours post-dose
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial/prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Day 10 to 14.	Baseline up to Day 10-14 (Follow-up)
Number of Participants With Clinically Significant Laboratory Test Abnormality	Hematology (hemoglobin, hematocrit, red blood cell count, platelets, leukocytes, total neutrophils, eosinophils, basophils, lymphocytes, monocytes); liver function (total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, albumin, total protein); renal function (creatinine, blood urea nitrogen, uric acid, sodium, potassium, chloride, bicarbonate, calcium); urinalysis (urine pH, glucose, ketones, protein, blood, nitrite, leukocyte esterase), and clinical chemistry (glucose) were performed.	Baseline up to Day 10-14 (Follow-up)
Supine Systolic and Diastolic Blood Pressure (BP)	Supine systolic and diastolic BP was measured after the participant has been rested in the supine position for at least 5 minutes with the participant's arm supported at the level of the heart, and recorded to the nearest millimeters of mercury (mmHg). The same arm and position and same size BP cuff was used throughout the study.	Screening, Day 0, 1 (pre-dose), 2, 10-14 (Follow-up)
12-Lead Electrocardiogram (ECG) Parameters (PR, QRS, QT, QTcF Intervals)	Standard 12-lead ECG was performed after the participant has rested quietly for at least 10 minutes in a supine position. ECG intervals included PR interval (time between the onset of atrial depolarization and the onset of ventricular depolarization), QRS interval (represented ventricular depolarization) and QT interval (time corresponding to the beginning of depolarization to repolarization of the ventricles) corrected using Fridericia's formula (QTcF = QT divided by cube root of RR interval).	Screening, Day 1, 2, 10-14 (Follow-up)
12-Lead Electrocardiogram (ECG) Parameter (Heart Rate)	Standard 12-lead ECG was performed after the participant has rested quietly for at least 10 minutes in a supine position. The time interval between consecutive heart beats (RR interval) was used to calculate heart rate.	Screening, Day 1, 2, 10-14 (Follow-up)
Supine Pulse Rate	Supine pulse rate was measured in the brachial/radial artery for at least 30 seconds.	Screening, Day 0, 1 (pre-dose), 2, 10-14 (Follow-up)

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (ACTUAL): March 1, 2012
• Study Completion (ACTUAL): May 1, 2012

Study Registration Dates

• First Submitted: August 30, 2011
• First Submitted That Met QC Criteria: January 13, 2012
• First Posted (ESTIMATE): January 19, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): June 28, 2013
• Last Update Submitted That Met QC Criteria: May 23, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: Post-surgical dental pain
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Stomatognathic Diseases; Tooth Diseases; Facial Pain; Toothache; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ibuprofen
• Other Study ID Numbers: B1351010