A Dental Pain Study Comparing The Analgesic Efficacy Of Ibuprofen/Caffeine

A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY COMPARING THE ANALGESIC EFFICACY AND SAFETY OF A SINGLE ORAL DOSE OF A NOVEL FIXED-DOSE COMBINATION OF IBUPROFEN 400 MG WITH CAFFEINE 100 MG TO IBUPROFEN 400 MG AND TO PLACEBO IN THE TREATMENT OF POST-SURGICAL DENTAL PAIN IN OTHERWISE HEALTHY SUBJECTS

An efficacy study assessing analgesic effect of ibuprofen/caffeine in post-surgical dental pain.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: Placebo; Drug: Ibuprofen/Caffeine; Drug: Ibuprofen

Detailed Description

The purpose of this study is to assess the analgesic efficacy of a fixed dose combination of ibuprofen/caffeine compared to ibuprofen alone and also to placebo.

• Study Type: Interventional
• Enrollment (Actual): 374
• Phase: Phase 3

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 40 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females 16 years to 40 years of age (inclusive).
• Subjects who have undergone outpatient surgical extraction of 3 or more third molars, of which at least 2 must be a partial or complete bony mandibular impaction within 30 days of Screening and have met baseline pain criteria as described in this protocol
• Examined by the attending dentist or physician and medically cleared to participate in the study.

Exclusion Criteria:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, metabolic or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing) determined by the Investigator to place the subject at increased risk including the presence or history within 2 years of screening of the following medical conditions/disorders:

  • Bleeding disorder;
  • Gastrointestinal ulcer or gastrointestinal bleeding;
  • Paralytic ileus or other gastrointestinal obstructive disorders.
• Pregnant female subjects; breastfeeding female subjects; fertile male subjects and female subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception
• Hypersensitivity to ibuprofen, naproxen, aspirin, or any other NSAID, caffeine, or other component of the product.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo comparator	Drug: Placebo; Placebo treatment
Experimental: Ibuprofen/Caffeine; Ibuprofen 400 mg/ Caffeine 100 mg fixed-dose combination	Drug: Ibuprofen/Caffeine; Ibuprofen/Caffeine fixed-dose combination
Active Comparator: Ibuprofen; Ibuprofen 400 mg	Drug: Ibuprofen; Ibuprofen capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time Weighted Sum of Pain Relief Rating (PRR) and Pain Intensity Difference (PID) Scores From 0 to 8 Hours Post-dose (SPRID 0-8): Ibuprofen + Caffeine Versus Ibuprofen	SPRID 0-8: time-weighted sum of PRID scores from 0 to 8 hours. PRID: sum of PID and PRR at each post-dose time point. PRR score: at each post-dose time point participants answered to question "How much relief do you have from your starting pain?" on a 5-point scale: 0= none, 1= a little, 2= some, 3= a lot, 4= complete; higher scores = more relief from pain. Numerical pain severity rating (NPSR) scale: at baseline and each post-dose time point participants answered to question "How much pain do you have at this time?" on an 11-point scale: range from 0= no pain to 10= worst possible pain; higher scores = worse pain. PID score: NPSR score at baseline (0 hour) minus NPSR score at each post-dose time point; overall possible PID score range at a post-dose time point: -10 to 10, higher positive value = greater improvement. Overall possible SPRID 0-8 score range: -80 to 112, higher scores = more improvement in pain.	From 0 to 8 hours post-dose on Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time Weighted Sum of Pain Relief Rating and Pain Intensity Difference Scores From 0 to 2 (SPRID 0-2), 0 to 4 (SPRID 0-4), 0 to 6 (SPRID 0-6) and 0 to 8 Hours Post-dose (SPRID 0-8)	SPRID 0-2, SPRID 0-4, SPRID 0-6, SPRID 0-8: time-weighted sum of PRID scores from 0 to 2, 0 to 4, 0 to 6 and 0 to 8 hours respectively. PRID at each post-dose time point = PID + PRR. PRR score: at each post-dose time point participants answered to question "How much relief do you have from your starting pain?" on 5-point scale: 0=none, 1=a little, 2=some, 3=a lot, 4=complete; higher scores=more relief from pain. NPSR scale: at baseline and each post-dose time point participants answered to question "How much pain do you have at this time?" on 11-point scale: range from 0=no pain to 10=worst possible pain; higher scores=worse pain. PID score: NPSR score at baseline (0 hour) minus NPSR score at each post-dose time point; overall possible PID score range at a post-dose time point: -10 to 10, higher positive value=greater improvement. Score range for: SPRID 0-2= -20 to 28; SPRID 0-4= -40 to 56; SPRID 0-6= -60 to 84; SPRID 0-8= -80 to 112. Higher SPRID scores=more improvement in pain.	From 0 to 2, 0 to 4, 0 to 6 and 0 to 8 hours post-dose on Day 1
Time Weighted Sum of Pain Intensity Difference Scores From 0 to 2 Hours (SPID 0-2), 0 to 4 (SPID 0-4), 0 to 6 (SPID 0-6) and 0 to 8 Hours Post-dose (SPID 0-8)	SPID 0-2, SPID 0-4, SPID 0-6, SPID 0-8: time-weighted sum of PID scores from 0 to 2, 0 to 4, 0 to 6 and 0 to 8 hours post-dose respectively. NPSR scale: at baseline and each post-dose time point participants answered to question "How much pain do you have at this time?" on an 11-point scale: score range from 0 = no pain to 10 = worst possible pain; higher scores = worse pain. PID score: NPSR score at baseline (0 hour) minus NPSR score at each post-dose time point; overall possible PID score range at a post-dose time point: -10 to 10, higher positive value = greater improvement. Overall possible range: SPID 0-2 = -20 to 20; SPID 0-4 = -40 to 40; SPID 0-6 = -60 to 60; SPID 0-8 = -80 to 80. Higher SPID scores = more improvement in pain.	From 0 to 2, 0 to 4, 0 to 6 and 0 to 8 hours post-dose on Day 1
Time Weighted Sum of Pain Relief Rating Scores From 0 to 2 (TOTPAR 0-2), 0 to 4 (TOTPAR 0-4), 0 to 6 (TOTPAR 0-6) and 0 to 8 Hours Post-dose (TOTPAR 0-8)	TOTPAR 0-2, TOTPAR 0-4, TOTPAR 0-6, TOTPAR 0-8: time-weighted sum of PRR scores from 0 to 2, 0 to 4, 0 to 6 and 0 to 8 hours post-dose respectively. PRR score: at each post-dose time point participants answered to the question "How much relief do you have from your starting pain?" on a 5-point scale: 0= none, 1= a little, 2= some, 3= a lot, 4= complete; higher scores = more relief from pain. Overall possible range: TOTPAR 0-2 = 0 to 8; TOTPAR 0-4 = 0 to 16; TOTPAR 0-6 = 0 to 24; TOTPAR 0-8 = 0 to 32. Higher TOTPAR scores = more improvement in pain.	From 0 to 2, 0 to 4, 0 to 6 and 0 to 8 hours post-dose on Day 1
Sum of Pain Relief Rating and Pain Intensity Difference (PRID) Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose	PRID: sum of PID and PRR at each post-dose time point. PRR score: at each post-dose time point participants answered to a question "How much relief do you have from your starting pain?" on a 5-point scale: 0= none, 1= a little, 2= some, 3= a lot, 4= complete; higher scores = more relief from pain. NPSR scale: at baseline and each post-dose time point participants answered to a question "How much pain do you have at this time?" on an 11-point scale: range from 0= no pain to 10= worst possible pain; higher scores = worse pain. PID score: NPSR score at baseline (0 hour) minus NPSR score at each post-dose time point; overall possible PID score range at a post-dose time point: -10 to 10, higher positive value = greater improvement. At a single post-dose time point overall possible range for PRID score: -10 to 14, higher scores = more improvement in pain.	0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dose on Day 1
Pain Relief Rating Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose	PRR score: at each post-dose time point participants answered to a question "How much relief do you have from your starting pain?" on a 5-point scale: 0= none, 1= a little, 2= some, 3= a lot, 4= complete; higher scores = more relief from pain.	0.25, 0.5, 1, 1.5, 2, 3, 4 5, 6, 7, and 8 hours post-dose on Day 1
Pain Intensity Difference Scores at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 Hours Post-dose	NPSR scale: at baseline and each post-dose time point participants answered to a question "How much pain do you have at this time?" on an 11-point scale: range from 0= no pain to 10= worst possible pain; higher scores = worse pain. PID score: NPSR score at baseline (0 hour) minus NPSR score at each post-dose time point; overall possible PID score range at a single post-dose time point: -10 to 10, higher positive value = greater improvement in pain.	0.25, 0.5, 1, 1.5, 2, 3, 4 5, 6, 7, and 8 hours post-dose on Day 1
Time to Onset of Achieving Meaningful Relief	When the participants were administered study medication at time 0 hours they were given the 2 stopwatches: 1 stopwatch was labelled as "first perceptible relief" and another as "meaningful relief." Participants were instructed to stop the stopwatch labelled as "meaningful relief" at the moment when they first experienced meaningful relief, that is, when the relief from the pain was meaningful to them. The stopwatch remained active for 8 hours (until stopped by the participants, or until rescue medication was administered).	Up to 8 hours post-dose on Day 1
Time to Onset of First Perceptible Relief	When the participants were administered study medication at time 0 hours they were given the 2 stopwatches: 1 stopwatch was labelled as "first perceptible relief" and another as "meaningful relief." Participants were instructed to stop the stopwatch labelled as "first perceptible relief" at the moment when they first began to feel any pain relieving effect. It was when they first felt a little/noticeable pain relief. It did not mean that they felt completely better (though they might), but when they first felt any difference in pain that they had at present. The stopwatch remained active for 8 hours (until stopped by the participants, or until rescue medication was administered).	Up to 8 hours post-dose on Day 1
Time to Treatment Failure	Treatment failure was defined as time to first dose of rescue medication or study discontinuation of the participants due to lack of efficacy.	Up to 8 hours post dose on Day 1

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (AEs) by Severity	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pre-treatment state. AEs are classified according to severity in 3 categories as mild (did not interfere with participant's usual function), moderate (interfered to some extent with participant's usual function) and severe (interfered significantly with participant's usual function).	Screening up to Day 17 after the last dose of study drug (approximately maximum of 48 days)
Number of Participants With Treatment Emergent Treatment Related Adverse Events (AEs)	Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pre-treatment state. Relatedness of an AE to study drug was assessed by investigator.	Screening up to Day 17 after the last dose of study drug (approximately maximum of 48 days)
Number of Participants With Clinically Significant Vital Signs Abnormalities	Vital signs included: heart rate, blood pressure, respiratory rate, and temperature. Normal range for the vital signs were: systolic blood pressure 90 to 140 millimeter of mercury (mmHg), diastolic blood pressure 60 to 90 mmHg, heart rate 50 to 110 beats per minute, respiratory rate 12 to 22 breaths per minute, and oral temperature 97.0 to 99.6 Fahrenheit (F). Value for vital signs outside the normal range was consider as abnormal. Clinical significance of vital signs abnormalities was determined at the investigator's discretion.	Screening up to Day 17 after the last dose of study drug (approximately maximum of 48 days)
Number of Participants Who Used Concomitant Medications, and Rescue Medications	Rescue medication: participants who did not experience adequate relief after the 1 hour (post study drug dose) evaluation were given tramadol hydrochloride 50 to 100 mg orally or codeine sulfate 15 to 60 mg orally, based on the discretion of the Investigator, as rescue medication. If needed, 2 additional doses of rescue medications based on the discretion of the Investigator at the study center was given. Total maximum dose of tramadol was 300 mg and of codeine sulfate was 180 mg. Concomitant medication: medication received by participant other than study medication and rescue medication.	Day 1
Number of Participants Who Used Medications Prior to This Study	In this outcome measure number of participants who were using any type of medications, prior to start of the study were reported.	At Screening

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 (Actual): October 24, 2017
• Primary Completion (Actual): April 6, 2018
• Study Completion (Actual): April 6, 2018

Study Registration Dates

• First Submitted: August 8, 2016
• First Submitted That Met QC Criteria: August 8, 2016
• First Posted (Estimate): August 11, 2016

Study Record Updates

• Last Update Posted (Actual): April 8, 2019
• Last Update Submitted That Met QC Criteria: April 5, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: ibuprofen; third molar extraction; post-surgical dental pain; ibuprofen/caffeine
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Stomatognathic Diseases; Tooth Diseases; Facial Pain; Toothache; Physiological Effects of Drugs; Neurotransmitter Agents; 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; Purinergic Antagonists; Purinergic Agents; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; Ibuprofen; Caffeine
• Other Study ID Numbers: B3741002; MIG (Other Identifier: Alias Study Number); MIG II (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

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