Efficacy of 300 mg Ibuprofen Prolonged-Release Tablets for the Treatment of Pain After Surgical Removal of Impacted Third Molars

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

280 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-04-29

Study Completion Date

2020-02-28

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This is a single centre, randomised, double-blind, double-dummy, parallel group, multiple-dose, active and placebo-controlled efficacy study to evaluate the efficacy and safety of 2×300mg ibuprofen Prolonged Release (PR) tablets in subjects with postoperative dental pain.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Ibuprofen Liquid Capsules 2 x 200 mg Efficacy and PK/PD Study in Surgical Removal of Impacted Third Molars

NCT05484401

Tooth, Impacted Tooth Diseases Stomatognathic Diseases

COMPLETED PHASE3

Efficacy of Ibuprofen Chronotherapy in Healing After Surgical Extraction of the Mandibular Third Molar

NCT03789058

Operation Site Inflammation Pain, Postoperative Teeth, Impacted

UNKNOWN PHASE2/PHASE3

Ibuprofen Extended-Release Dental Pain Study

NCT00707057

Pain Post-Operative Pain Third Molar Extraction

COMPLETED PHASE3

A Study of Ibuprofen (IBU) 250mg/APAP 500mg In The Treatment Of Post-Surgical Dental Pain

NCT02837952

Pain

COMPLETED PHASE3

Study Evaluating A Novel Ibuprofen Formulation In The Treatment Of Dental Pain

NCT01216163

Pain

COMPLETED PHASE3

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

This is a single centre, randomised, double-blind, double-dummy, parallel group, multiple-dose, active and placebo controlled efficacy study to evaluate the efficacy and safety of ibuprofen 2 × 300 mg ibuprofen PR tablets in subjects with postoperative dental pain.

Eligible subjects will complete all screening procedures within 28 days before the surgery and randomisation.

At Screening, subjects will provide written informed consent to participate in the study before any protocol specified procedures or assessments are completed. On Day 1, subjects who continue to be eligible for study participation after completing screening procedures and assessments will undergo extraction of 2 or more third molars. At least 1 of the third molars must be a fully or partially bone impacted mandibular molar. If only 2 molars are removed, then they must be ipsilateral.

All subjects will receive local anaesthesia (2% lidocaine with 1:100,000 epinephrine). Nitrous oxide will be allowed at the discretion of the investigator. Subjects who experience moderate to severe pain intensity (a score of ≥5 on a numeric rating scale \[NRS\] from 0-10 where 0 = no pain, 10 = worst pain ever) within 6 hours after surgery and who continue to meet all study entry criteria will be randomised in a 3:3:1 ratio to receive 2 × 300 mg ibuprofen PR tablets every 12 hours (Q12h), 2 × 200 mg ibuprofen immediate release (IR) tablets every 8 hours (Q8h), or placebo. The randomisation will be stratified by baseline pain category (moderate or severe) using a categorical scale that includes the categories of none (0), mild (1-4), moderate (5-7), and severe (8-10).

Subjects will re-assess their baseline pain intensity using the NRS immediately before receiving study drug (pre-dose, Time 0) and their pain intensity (NRS) and pain relief (5-point categorical scale) at the following time points (pre-dose, if at one of the dosing time points of 0, 8, 12 and/or 16 hours): 15, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, and 24 hours after Time 0; and immediately before each dose of rescue medication, if any. For assessments less than 1 hour apart a window of +/-2 min is allowable whilst for assessments at least 1 hour apart a +/-5 min window is allowable.

The double stopwatch method will be used to record the time to perceptible pain relief and time to meaningful pain relief during the 8 hours following the first dose or until subject takes rescue medication. Subjects will complete a global evaluation of study drug 24 hours (+/- 5 minutes) after Time 0 or immediately before the first dose of rescue medication (whichever occurs first). Vital signs will be recorded after the subject has been in a sitting position for 3 minutes at the following times: before surgery, within 30 minutes before Time 0, 12 and 24 hours after Time 0, and/or immediately before the first dose of rescue medication. Adverse events (AEs) will be monitored and recorded from the time of signing of the informed consent form (ICF) until the Follow-up Visit (or Early Termination Visit). During the 24 hours following Time 0, subjects will complete efficacy and safety assessments. Subjects will remain at the study site overnight and will be discharged on Day 2.

Paracetamol / acetaminophen (1000 mg) will be permitted as the initial rescue medication. Subjects will be encouraged to wait at least 60 minutes after receiving study drug before taking rescue medication. If acetaminophen rescue medication is not effective in relieving the subject's pain, 5 mg oxycodone rescue medication may be administered at the discretion of the investigator.

Subjects are not permitted to take any concomitant medications that might confound assessments of pain relief, such as psychotropic drugs, antidepressants, sedative-hypnotics (other than those permitted for conscious sedation), or other analgesics taken within five times of their elimination half-lives (other than those used at the surgery). Selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) are permitted if the subject has been on a stable dose for at least four weeks prior to Visit 1 (screening).

Other restrictions include the following: alcohol use is prohibited from 24 hours before surgery until discharge on Day 2; nothing by mouth from midnight before surgery until 1 hour after surgery; clear liquids only are allowed starting 1 hour after surgery until 1 hour after dosing; 1 hour after dosing, the subject's diet may be advanced according to standard practice.

Upon discharge from the study site, subjects may be prescribed pain medication for use at home according to the standard practice of the study site. On Day 8 (± 2 days), subjects will return to the study site for an abbreviated confirmatory physical assessment and AE assessments.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Pain

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

The dental pain model used in this study is a robust and well established postsurgical pain model that produces pain that is predictable in its character, duration, and intensity. The model is widely accepted and has a proven record of assay sensitivity (i.e., separating active drugs from each other, as well as from placebo). The model is frequently used to evaluate NSAID type analgesics. Results from dental pain studies are accepted by the US Food and Drug Administration (FDA) and European authorities and have been widely extrapolated to other general pain conditions.

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

This is a double-blind, double dummy-study. There will be two placebo tablets designed to be comparable to each of the active products (PR and Immediate Release \[IR\]) in both shape, size, colour and weight. All subject packs have been designed and labelled to ensure blinding is maintained. Subjects, investigators and site staff will all be blind to the treatments.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Prolonged Release Group

2 × 300 mg ibuprofen PR tablets at Hours 0 and 12

2 × placebo of PR tablets at Hours 8 and 16

2 × placebo of IR tablets at Hours 0, 8, 12, and 16

Group Type EXPERIMENTAL

Ibuprofen 300 mg Oral Tablet

Intervention Type DRUG

2 × 300 mg tablets at Hours 0 and 12

Placebo of PR tablet

Intervention Type DRUG

2 tablets up to four times in 24 hours

Placebo of IR tablet

Intervention Type DRUG

2 tablets up to four times in 24 hours

Immediate Release Group

2 × 200 mg ibuprofen IR tablets at Hours 0, 8, and 16

2 × placebo of IR tablets at Hour 12

2 × placebo of PR tablets at Hours 0, 8, 12, and 16

Group Type ACTIVE_COMPARATOR

Ibuprofen 200 mg Oral Tablet

Intervention Type DRUG

2 × 200 mg tablets at Hours 0, 8, and 16

Placebo of PR tablet

Intervention Type DRUG

2 tablets up to four times in 24 hours

Placebo of IR tablet

Intervention Type DRUG

2 tablets up to four times in 24 hours

Placebo Group

2 × placebo of PR tablets at Hours 0, 8, 12, and 16

2 × placebo of IR tablets at Hours 0, 8, 12, and 16

Group Type PLACEBO_COMPARATOR

Placebo of PR tablet

Intervention Type DRUG

2 tablets up to four times in 24 hours

Placebo of IR tablet

Intervention Type DRUG

2 tablets up to four times in 24 hours

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Ibuprofen 300 mg Oral Tablet

2 × 300 mg tablets at Hours 0 and 12

Intervention Type DRUG

Ibuprofen 200 mg Oral Tablet

2 × 200 mg tablets at Hours 0, 8, and 16

Intervention Type DRUG

Placebo of PR tablet

2 tablets up to four times in 24 hours

Intervention Type DRUG

Placebo of IR tablet

2 tablets up to four times in 24 hours

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Prolonged Release Tablet Nurofen, Immediate Release Tablet

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Is male or female ≥ 18 and ≤ 50 years of age.
* Requires extraction of 2 or more third molars. At least 1 of the third molars must be a fully or partially bone impacted mandibular molar. If only 2 molars are removed, then they must be ipsilateral.
* Experiences moderate to severe pain intensity within 6 hours after surgery, as measured by a numeric rating scale (NRS) score of ≥ 5 on a 0-10 scale.
* Has a body weight ≥ 45 kg and a body mass index (BMI) ≤ 35 kg/m².
* Female subjects of child-bearing potential must have been using an acceptable method of contraception for at least 30 days prior to randomisation and be willing to continue use until at least 48 hours post discharge from the clinic.

To be considered not of child-bearing potential, females must be surgically sterile (defined as bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) or post-menopausal (defined as no menses for 12 months without an alternative medical cause).

* Free of clinically significant abnormal findings as determined by medical history, physical examination, vital signs, laboratory tests and ECG.
* Is able to provide written informed consent.
* Is willing and able to comply with study requirements (including diet and smoking restrictions), complete the pain evaluations, remain at the study site overnight, and return for follow up 7 (± 2) days after surgery (Day 8 ± 2 days).

Exclusion Criteria

* Known hypersensitivity reactions or allergy (e.g., asthma, rhinitis, angioedema or urticaria) in response to nonsteroidal anti-inflammatory drugs (NSAIDs; including ibuprofen), acetylsalicylic acid (aspirin), ingredients of the study drug, or any other drugs used in the study, including anaesthetics and antibiotics that may be required on the day of surgery.
* A history of active or previous peptic ulceration/ haemorrhage, gastrointestinal bleeding or perforation, heart failure, renal or hepatic failure, uncontrolled hypertension, asthma, nasal polyps, or chronic rhinitis.
* Has complications from the tooth extraction or any other clinically significant medical history that, in the opinion of the investigator, would affect the subject's ability to comply or otherwise contraindicate study participation, including but not limited to the following: cardiac, respiratory, gastroenterological, neurological, psychological, immunological, haematological, oncological, or renal disease.
* Has undergone another dental surgery within 60 days prior to the day of surgery.
* A positive urine drugs of abuse screen or alcohol breathalyser test at screening and during the study (with the exception of a positive drugs of abuse screen that is a consequence of permitted prescription medicines).
* If female, has a positive pregnancy test at screening (serum) or on the day of surgery prior to surgery (urine), or is lactating.
* Has known or suspected (in the opinion of the investigator), history of alcoholism or drug abuse within 2 years of screening or evidence of tolerance or physical dependence before dosing with study drug.
* Taking any concomitant medications that might confound assessments of pain relief, such as psychotropic drugs, antidepressants, sedative-hypnotics (other than those permitted for conscious sedation), or other analgesics taken within five times of their elimination half-lives. Selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) are permitted if the subject has been on a stable dose for at least four weeks prior to Visit 1 (screening).
* Is considered by the investigator, for any reason (including, but not limited to the risks described as precautions, warnings and contraindications in the current version of the investigator's brochure (IB) for 300 mg ibuprofen PR tablets), to be an unsuitable candidate to receive the study drug.
* Has a history of chronic use (defined as daily use for \> 2 weeks) of NSAIDs, opiates, or glucocorticoids (except inhaled nasal steroids and topical corticosteroids), for any condition within 6 months before dosing with study drug.
* Has significant difficulties swallowing capsules or tablets or is unable to tolerate oral medication.
* Subject has received an investigational product or participated in another trial involving a marketed or investigational drug in the 30 days (or for investigational agents with a long half-life, a washout of 5 half-lives) prior to first drug administration (washout period between studies is defined as the period of time elapsed between the last dose of the previous study and first dose for this study), or if the investigator believes that any previous participation in an investigational study would be to the detriment of the safety of the participant or the conduct of the study.
* Enrolment of the Investigator, his / her family members, employees, and other dependent persons.
* Failure to satisfy the investigator of fitness to participate for any other reason.

Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No