Efficacy and Safety of Ibuprofen and Caffeine in Dental Pain

Pain, Postoperative Clinical Trial

Official title:

A Single-centre, Double-blind, Randomised, Two-stage, Parallel-group Study to Assess the Efficacy and Safety of the Fixed Dose Combination of Ibuprofen 400 mg and Caffeine 100 mg Versus Ibuprofen 400 mg, Caffeine 100 mg and Placebo in Patients With Postoperative Dental Pain

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01929031
• Other study ID #: 1335.1
• Status: Completed
• Phase: Phase 3
• First received: August 22, 2013
• Last updated: April 2, 2014
• Start date: August 2013
• Est. completion date: March 2014

Study information

• Verified date: April 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to compare the efficacy of a combination product containing ibuprofen 400 mg and caffeine 100 mg versus either ingredient alone as well as placebo for the treatment of post-surgical dental pain over an eight-hour period followed by a single dose of study medication (study stage 1). A secondary objective is to evaluate efficacy of multiple doses of the combination in comparison to ibuprofen alone over a 5-day post-surgical period (study stage 2).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 561
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

Inclusion criteria:

• Males and females 18 to 55 years of age;

• Outpatients scheduled to undergo surgical extraction of 3-4 impacted third molar(s), with a minimum of two mandibular extractions. The two mandibular third molars may be partial bony impactions or full bony impactions (as long as the trauma rating is not severe and the surgeons do not feel the subject will have extreme post-surgical pain) OR there may be a combination of one full bony impaction with the second mandibular being a soft tissue impaction or partial bony impaction. Maxillary third molars (or supernumerary teeth) of any type can be extracted;

• Use of only the following preoperative medication(s)/ anesthetic(s): topical benzocaine, short-acting local anesthetic (mepivacaine or lidocaine) with or without vasoconstrictor and/or nitrous oxide;

• Reliable, cooperative, and of adequate intelligence to record the requested information on the analgesic questionnaire form;

• Examined by the attending oral surgeon or physician and medically cleared to participate in the study;

• Scheduled to undergo a qualifying surgical procedure;

• In good general health, with a BMI of 30 or less, and have no contraindications to any of the study medications or anesthetic drugs;

• Subjects have at least a categorical pain score of moderate and a numerical rating scale (NRS) score of 5 or greater within 4.5 hours from the time of the last suture.

Exclusion criteria:

• Presence of a serious medical condition (e.g., poorly controlled hypertension, poorly controlled diabetes, significantly impaired cardiac, renal or hepatic function, hyper- or hypothyroidism);

• Use of a prescription or non-prescription drug with which the administration of ibuprofen or any other non steroidal anti inflammatory or caffeine is contraindicated;

• Acute local infection at the time of surgery that could confound the post-surgical evaluation;

• Females who are pregnant, lactating, of child-bearing potential, or post-menopausal for less than 2 years and not using a medically approved method of contraception (i.e., oral, transdermal, intravaginal or implanted contraceptives, intrauterine device, diaphragm, condom, abstinence, or surgical sterility), or females who test positive on a urine-based pregnancy test;

• Presence or history (within 2 years of enrollment) of bleeding disorder(s) or peptic ulcer disease;

• History of alcoholism or substance abuse within the last year, or is currently abusing alcohol or other mood-altering drugs (e.g., cannabis). Subjects who are taking central nervous sytem or other psychotropic drugs (including St. Johns Wort, or any other nutritional supplement known to have psychotropic effects) may be enrolled if they have been on stable doses of medication for at least 2 months, will maintain this dose throughout the study, and their condition is judged by the Principal Investigator to be well-controlled;

• Habituation to analgesic drugs or caffeine (i.e., routine use of oral analgesics 5 or more times per week or ingestion of 4 or more caffeine-containing drinks daily); use of "high energy" drinks more than once per week;

• Use of any type of systemic corticosteroid within the past 30 days or a history of current or previous use of anabolic steroids;

• History of allergic reaction (e.g., asthma, rhinitis, swelling, shock, or hives) to acetaminophen, ibuprofen, naproxen, aspirin, celecoxib, or any other non steroidal anti inflammatory or caffeine;

• Prior use of any type of analgesic or non steroidal anti inflammatory within 5 half-lives of that drug before surgery, except for pre-anesthetic medication and anesthesia for the procedure;

• Ingestion of any caffeine-containing beverages, chocolate, or alcohol 6 hours or less before surgery;

• Has impaired liver function, e.g., serum Alanine transaminase, aspartate aminotransferase, alkaline phosphatase, or Gamma-glutamyltransferase greater than 2.5 times the upper limit of normal, or blood urea nitrogen, creatinine, or bilirubin greater than 1.5 times the upper limit of normal without a known benign explanation;

• Has known history of a positive HIV antibody test or known HIV infection;

• Has a known history of Hepatitis B or C;

• Has a clinically significant abnormal electrocardiogram (ECG) at screening as determined by the Investigator:

• Has taken an investigational product within the past 30 days;

• Has previously been entered into this study;

• The subject is a member of the study site staff either directly involved with the study, an employee of the Sponsor, or a relative of study site personnel directly involved with the study or Sponsor.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pain, Postoperative
• Tooth Diseases

Intervention

Drug:
• Ibuprofen and caffeine
FDC tablet, single dose at stage 1 and multiple doses at stage 2
• ibuprofen + caffeine
FDC tablet, multiple doses at stage 2
• placebo
single dose at stage 1
• caffeine
tablet, single dose at stage 1
• ibuprofen
tablet, multiple doses at stage 2
• ibuprofen
tablet, single dose at stage 1
• placebo
tablet, single dose at stage 1
• caffeine
tablet, single dose at stage 1
• ibuprofen
tablet, multiple doses at stage 2¿
• Ibuprofen and caffeine
FDC tablet, multiple doses at stage 2¿ 1 and multiple doses at stage 2

Locations

Country	Name	City	State
United States	1335.1.202 Boehringer Ingelheim Investigational Site	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time-weighted sum of pain relief (PAR) and pain intensity difference (PID) from 0 to 8 hours (SPRID0-8h)		8 hours	No
Secondary	Time-weighted sum of PAR and PID from 0 to 2 hours (SPRID0-2h)		2 hours	No
Secondary	Duration of Pain relief		defined by the time to first dose of rescue medication or second dose of study medication, what ever is first in 8 hrs	No
Secondary	Time to meaningful pain relief		defined by the time to first dose of rescue medication or second dose of study medication, what ever is first in 8 hrs	No