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

This study has been terminated.
(See termination reason in detailed description.)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01512160
First received: August 30, 2011
Last updated: May 23, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Post-surgical Dental Pain
Drug: PF-04531083
Other: Placebo
Drug: Ibuprofen
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Total Pain Relief (TOTPAR) Score From 0 to 6 Hours [ Time Frame: 0 to 6 hours ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of Participants With Peak Pain Relief (PPR) [ Time Frame: 0 to 24 hours ] [ Designated as safety issue: No ]
    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).

  • Time-specific Pain Relief (PR) Score [ Time Frame: 0, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 6, 8, 24 hours, prior to rescue medication (RM) ] [ Designated as safety issue: No ]
    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.

  • Time-specific Pain Intensity Difference (PID) Score [ Time Frame: 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 6, 8, 24 hours, prior to RM ] [ Designated as safety issue: No ]
    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.

  • Summed Pain Intensity Difference (SPID) Score at 6 Hours and 24 Hours [ Time Frame: 0 to 6, 0 to 24 hours ] [ Designated as safety issue: No ]
    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.

  • Total Pain Relief (TOTPAR) Score From 0 to 24 Hours [ Time Frame: 0 to 24 hours ] [ Designated as safety issue: No ]
    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.

  • Time to Onset of First Perceptible Pain Relief (PR) [ Time Frame: 0 to 24 hours ] [ Designated as safety issue: No ]
    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.

  • Time to Onset of First Meaningful Pain Relief (PR) [ Time Frame: 0 to 24 hours ] [ Designated as safety issue: No ]
    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.

  • Time to First Use of Rescue Medication [ Time Frame: 1.5 to 24 hours ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Rescue Medication [ Time Frame: 0 to 24 hours ] [ Designated as safety issue: No ]
    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.

  • Participant Global Evaluation of Study Medication [ Time Frame: 6, 24 hours, prior to RM ] [ Designated as safety issue: No ]
    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.

  • Participant Satisfaction Questionnaire [ Time Frame: 6, 24 hours, prior to RM ] [ Designated as safety issue: No ]
    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.

  • Maximum Observed Plasma Concentration (Cmax) of PF-04531083 [ Time Frame: 0 (pre-dose), 1, 2, 4, 6, 24 hours post-dose ] [ Designated as safety issue: No ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04531083 [ Time Frame: 0 (pre-dose), 1, 2, 4, 6, 24 hours post-dose ] [ Designated as safety issue: No ]
  • Area Under the Curve From Time Zero to 6 Hour [AUC (0-6)] of PF-04531083 [ Time Frame: 0 (pre-dose), 1, 2, 4, 6 hours post-dose ] [ Designated as safety issue: No ]
    AUC (0-6)= Area under the plasma concentration versus time curve from time zero (pre-dose) to 6 hours post-dose concentration.

  • Area Under the Curve From Time Zero to 24 Hour [AUC (0-24)] of PF-04531083 [ Time Frame: 0 (pre-dose), 1, 2, 4, 6, 24 hours post-dose ] [ Designated as safety issue: No ]
    AUC (0-24)= Area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours post-dose concentration.

  • Maximum Observed Plasma Concentration (Cmax) of Ibuprofen [ Time Frame: 0 (pre-dose), 1, 2, 4, 6, 24 hours post-dose ] [ Designated as safety issue: No ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ibuprofen [ Time Frame: 0 (pre-dose), 1, 2, 4, 6, 24 hours post-dose ] [ Designated as safety issue: No ]
  • Area Under the Curve From Time Zero to 6 Hour [AUC (0-6)] of Ibuprofen [ Time Frame: 0 (pre-dose), 1, 2, 4, 6 hours post-dose ] [ Designated as safety issue: No ]
    AUC (0-6)= Area under the plasma concentration versus time curve from time zero (pre-dose) to 6 hours post-dose concentration.

  • Area Under the Curve From Time Zero to 24 Hour [AUC (0-24)] of Ibuprofen [ Time Frame: 0 (pre-dose), 1, 2, 4, 6, 24 hours post-dose ] [ Designated as safety issue: No ]
    AUC (0-24)= Area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours post-dose concentration.

  • Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Day 10-14 (Follow-up) ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Clinically Significant Laboratory Test Abnormality [ Time Frame: Baseline up to Day 10-14 (Follow-up) ] [ Designated as safety issue: Yes ]
    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.

  • Supine Systolic and Diastolic Blood Pressure (BP) [ Time Frame: Screening, Day 0, 1 (pre-dose), 2, 10-14 (Follow-up) ] [ Designated as safety issue: Yes ]
    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.

  • 12-Lead Electrocardiogram (ECG) Parameters (PR, QRS, QT, QTcF Intervals) [ Time Frame: Screening, Day 1, 2, 10-14 (Follow-up) ] [ Designated as safety issue: Yes ]
    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).

  • 12-Lead Electrocardiogram (ECG) Parameter (Heart Rate) [ Time Frame: Screening, Day 1, 2, 10-14 (Follow-up) ] [ Designated as safety issue: Yes ]
    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.

  • Supine Pulse Rate [ Time Frame: Screening, Day 0, 1 (pre-dose), 2, 10-14 (Follow-up) ] [ Designated as safety issue: Yes ]
    Supine pulse rate was measured in the brachial/radial artery for at least 30 seconds.


Enrollment: 90
Study Start Date: October 2011
Study Completion Date: May 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PF-04531083 2000 mg Drug: PF-04531083
2000 mg oral solution
Other: Placebo
Placebo tablets for Ibuprofen
Experimental: PF-04531083 1000 mg Drug: PF-04531083
1000 mg oral solution
Other: Placebo
Placebo tablets for Ibuprofen
Active Comparator: Ibuprofen 400 mg Drug: Ibuprofen
2 x 200 mg tablets
Other: Placebo
Placebo solution for PF-04531083
Placebo Comparator: Placebo Other: Placebo
Placebo solution for PF-04531083
Other: Placebo
Placebo tablets for Ibuprofen

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01512160

Locations
United States, Texas
Pfizer Investigational Site
Austin, Texas, United States, 78744
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01512160     History of Changes
Other Study ID Numbers: B1351010
Study First Received: August 30, 2011
Results First Received: March 14, 2013
Last Updated: May 23, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Post-surgical dental pain

Additional relevant MeSH terms:
Toothache
Tooth Diseases
Stomatognathic Diseases
Facial Pain
Pain
Signs and Symptoms
Ibuprofen
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 28, 2014