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

NCT03785756 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 5003601
• Study Type: interventional
• Target: 280
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pain

Outcome Measures

Primary Outcomes (1)

• Summed Pain Intensity Difference Over 0 to 12 Hours (SPID12) After Time 0

  SPID12 was used to compare the test product (2 × 300 mg ibuprofen PR tablets) and comparator product (2 × 200 mg ibuprofen IR tablets three times a day \[TID\]) against the placebo product. An 11-point (0-10) numeric rating scale (NRS) for pain was used to assess pain intensity, where a higher score indicates a greater amount of pain. SPID12 was calculated using the summed pain intensity difference (change from Time 0) under the NRS-time curve from 15 minutes through 12 hours calculated using the linear trapezoidal rule and the actual time points, where Time 0 is the time of the first dose of study drug. The minimum value of SPID12 is 0 (no change in pain intensity from Time 0 to 12 hours); the theoretical maximum is 120 (if a patient had a score of 10 \[worst pain intensity\] at baseline, which decreased to 0 \[no pain\] at the next time point and remained at 0 after); a higher SPID12 score indicates a better outcome.

  0-12 hours

Secondary Outcomes (23)

• Summed Pain Intensity Difference Over 0 to 24 Hours (SPID24) After Time 0

  0-24 hours

• Summed Pain Intensity Difference Over 0 to 4 Hours (SPID4) After Time 0

  0-4 hours

• Summed Pain Intensity Difference Over 0 to 8 Hours (SPID8) After Time 0

  0-8 hours

• Sum of Total Pain Relief Over 0 to 4 Hours (TOTPAR4) After Time 0

  0-4 hours

• Sum of Total Pain Relief Over 0 to 8 Hours (TOTPAR8) After Time 0

  0-8 hours

Other Outcomes (6)

• Incidence of Treatment Emergent Adverse Events as Assessed by Patient Response to Questions and Spontaneous Reporting of TEAEs

  0-10 days

• Vital Signs Measurements - Blood Pressure in mm/Hg

  0-10 days

• Vital Signs Measurements - Heart Rate in Beats Per Minute

  0-10 days

Study Arms (3)

Prolonged Release Group

EXPERIMENTAL

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

Drug: Ibuprofen 300 mg Oral Tablet; Drug: Placebo of PR tablet; Drug: Placebo of IR tablet

Immediate Release Group

ACTIVE COMPARATOR

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

Drug: Ibuprofen 200 mg Oral Tablet; Drug: Placebo of PR tablet; Drug: Placebo of IR tablet

Placebo Group

PLACEBO COMPARATOR

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

Drug: Placebo of PR tablet; Drug: Placebo of IR tablet

Interventions

Ibuprofen 300 mg Oral Tablet DRUG

2 × 300 mg tablets at Hours 0 and 12

Also known as: Prolonged Release Tablet

Prolonged Release Group

Ibuprofen 200 mg Oral Tablet DRUG

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

Also known as: Nurofen, Immediate Release Tablet

Immediate Release Group

Placebo of PR tablet DRUG

2 tablets up to four times in 24 hours

Immediate Release Group; Placebo Group; Prolonged Release Group

Placebo of IR tablet DRUG

2 tablets up to four times in 24 hours

Immediate Release Group; Placebo Group; Prolonged Release Group

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Reckitt Benckiser Healthcare (UK) Limited: lead
• Premier Research: collaborator

Study Sites (1)

JBR Clinical Research

Salt Lake City, Utah, 84107, United States

Location

Related Publications (5)

• Farrar JT, Young JP Jr, LaMoreaux L, Werth JL, Poole MR. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 2001 Nov;94(2):149-158. doi: 10.1016/S0304-3959(01)00349-9.

  PMID: 11690728 BACKGROUND

• Davies NM. Clinical pharmacokinetics of ibuprofen. The first 30 years. Clin Pharmacokinet. 1998 Feb;34(2):101-54. doi: 10.2165/00003088-199834020-00002.

  PMID: 9515184 BACKGROUND

• Miles L, Hall J, Jenner B, Addis R, Hutchings S. Predicting rapid analgesic onset of ibuprofen salts compared with ibuprofen acid: Tlag, Tlow, Tmed, and a novel parameter, TCmaxRef. Curr Med Res Opin. 2018 Aug;34(8):1483-1490. doi: 10.1080/03007995.2018.1466697. Epub 2018 Apr 27.

  PMID: 29667449 BACKGROUND

• Cooper SA, Desjardins PJ, Turk DC, Dworkin RH, Katz NP, Kehlet H, Ballantyne JC, Burke LB, Carragee E, Cowan P, Croll S, Dionne RA, Farrar JT, Gilron I, Gordon DB, Iyengar S, Jay GW, Kalso EA, Kerns RD, McDermott MP, Raja SN, Rappaport BA, Rauschkolb C, Royal MA, Segerdahl M, Stauffer JW, Todd KH, Vanhove GF, Wallace MS, West C, White RE, Wu C. Research design considerations for single-dose analgesic clinical trials in acute pain: IMMPACT recommendations. Pain. 2016 Feb;157(2):288-301. doi: 10.1097/j.pain.0000000000000375.

  PMID: 26683233 BACKGROUND

• Singla NK, Desjardins PJ, Chang PD. A comparison of the clinical and experimental characteristics of four acute surgical pain models: dental extraction, bunionectomy, joint replacement, and soft tissue surgery. Pain. 2014 Mar;155(3):441-456. doi: 10.1016/j.pain.2013.09.002. Epub 2013 Sep 6.

  PMID: 24012952 BACKGROUND

Related Links

• Wyeth Consumer Healthcare. (2002). Nonprescription Drug Advisory Committee (NDAC) Meeting on Risks of NSAIDs

MeSH Terms

Conditions

Pain

Interventions

Ibuprofen; Tablets

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Clinical Project Manager
• Organization: Reckitt Benckiser (Health) Limited

clinicaldatacontroller@reckitt.com

+44 1482 326151

Study Officials

• Todd Bertoch, MD

  JBR Clinical Research

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 17, 2018
• First Posted: December 24, 2018
• Study Start: April 29, 2019
• Primary Completion: February 20, 2020
• Study Completion: February 28, 2020
• Last Updated: June 3, 2024
• Results First Posted: June 3, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)