Efficacy and Safety of Ibuprofen and Caffeine in Dental Pain

NCT01929031 | Completed Phase 3 Results

• 1 other identifier: 1335.1
• Study Type: interventional
• Target: 562
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Pain, Postoperative; Tooth Diseases

Outcome Measures

Primary Outcomes (1)

• Time-weighted Sum of Pain Relief (PAR) and Pain Intensity Difference (PID) From 0 to 8 Hours (SPRID0-8h)

  SPRID0-8h: Time-weighted sum of PAR and PID from 0 to 8 hours, score range: -40 (worst) to 112 (best). PI was assessed on a 0-10 numerical pain rating scale (NPRS), where 0=no pain and 10=worst possible pain, pre-dose and at 0.25,0.5,0.75,1,1.5,2,3,4,5, 6,7 and 8 hours; PAR was assessed on a 5-point verbal rating scale (VRS) (0=none to 4=complete) at the same post-dose time points. Time-weights were equal to the elapsed time (hour) between the time point of interest and the preceding time point. All PAR and pain intensity (PI) assessments completed after the patient had taken rescue medication or the second dose of study medication, whichever was first, until hour 8 were considered missing. Last observation carried forward (LOCF) was used with the last completed PI/PAR assessments prior to first rescue/second study medication, whichever was first, to impute missing values up to 8 hours.

  0 to 8 hours

Secondary Outcomes (3)

• Time-weighted Sum of Pain Relief (PAR) and Pain Intensity Difference (PID) From 0 to 2 Hours (SPRID0-2h)

  0 to 2 hours

• Duration of Pain Relief

  8 hours

• Time to Meaningful Pain Relief

  8 hours

Study Arms (6)

Caffeine-Ibuprofen

OTHER

Study Stage 1: One Caffeine 100 mg tablet after dental surgery; Arm Type: Active Comparator - Study Stage 2: Subsequent to Stage 1, every 6-8 hours one ibuprofen 400 mg tablet, while awake, over 5 days; Arm Type: Active Comparator

Drug: ibuprofen; Drug: caffeine

Placebo-Ibuprofen/Caffeine

OTHER

Study Stage 1: One Placebo tablet after dental surgery Arm Type: Placebo Comparator - Study Stage 2: Subsequent to Stage 1, every 6-8 hours one Ibuprofen 400 mg/Caffeine tablet, while awake, over 5 days; Arm Type: Experimental

Drug: ibuprofen + caffeine; Drug: placebo

Ibuprofen/Caffeine-Ibuprofen/Caffeine

OTHER

Study Stage 1: One Ibuprofen 400 mg/Caffeine 100 mg tablet after dental surgery: Arm Type Experimental - Study Stage 2: Subsequent to Stage 1, every 6-8 hours one Ibuprofen 400 mg/Caffeine 100 mg tablet, while awake, over 5 days; Arm Type Experimental

Drug: ibuprofen + caffeine

Ibuprofen-Ibuprofen

OTHER

Study Stage 1: One Ibuprofen 400 mg tablet after dental surgery; Arm Type Active Comparator - Study Stage 2: Subsequent to stage 1, every 6-8 hours one Ibuprofen 400 mg tablet, while awake, over 5 days; Arm type; Active Comparator

Drug: ibuprofen

Caffeine-Ibuprofen/Caffeine

OTHER

Study Stage 1: One Caffeine 100 mg tablet after dental surgery. Arm Type; Active Comparator - Study Stage 2: Subsequent to Stage 1, every 6-8 hours one Ibuprofen 400mg/Caffeine 100 mg tablet, while awake, over 5 days; Arm Type: Experimental

Drug: caffeine; Drug: ibuprofen + caffeine

Placebo-Ibuprofen

OTHER

Study Stage 1: One Placebo tablet after dental surgery Arm Type: Placebo Comparator - Study Stage 2: Subsequent to Stage 1, every 6-8 hours one Ibuprofen 400 mg tablet, while awake over 5 days; Arm Type: Active Comparator

Drug: placebo; Drug: ibuprofen

Interventions

ibuprofen + caffeine DRUG

FDC tablet

Placebo-Ibuprofen/Caffeine

ibuprofen DRUG

tablet.

Ibuprofen-Ibuprofen

caffeine DRUG

tablet

Caffeine-Ibuprofen/Caffeine

placebo DRUG

tablet

Placebo-Ibuprofen

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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 system 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:

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

1335.1.202 Boehringer Ingelheim Investigational Site

Salt Lake City, Utah, United States

Location

Related Publications (2)

• Forderreuther S, Lampert A, Hitier S, Lange R, Weiser T. The Impact of Baseline Pain Intensity on the Analgesic Efficacy of Ibuprofen/Caffeine in Patients with Acute Postoperative Dental Pain: Post Hoc Subgroup Analysis of a Randomised Controlled Trial. Adv Ther. 2020 Jun;37(6):2976-2987. doi: 10.1007/s12325-020-01297-y. Epub 2020 Apr 24.

  PMID: 32333328 DERIVED

• Weiser T, Richter E, Hegewisch A, Muse DD, Lange R. Efficacy and safety of a fixed-dose combination of ibuprofen and caffeine in the management of moderate to severe dental pain after third molar extraction. Eur J Pain. 2018 Jan;22(1):28-38. doi: 10.1002/ejp.1068. Epub 2017 Aug 14.

  PMID: 28805281 DERIVED

MeSH Terms

Conditions

Pain, Postoperative; Tooth Diseases

Interventions

Ibuprofen; Caffeine

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim Pharmaceuticals

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2013
• First Posted: August 27, 2013
• Study Start: August 1, 2013
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: November 16, 2016
• Results First Posted: November 16, 2016

Record last verified: 2016-09

Locations

US (1)