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

NCT05484401 | Completed Phase 3 FDA Drug

• 1 other identifier: 5016401
• Study Type: interventional
• Target: 294
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single centre, three-arm randomised, double-blind, double-dummy, parallel group, single-dose, active and placebo-controlled efficacy and pharmacokinetics/ pharmacodynamics study to evaluate the efficacy and safety of 2 x 200 mg Ibuprofen Liquid Capsules in subjects with post-operative dental pain.

Conditions

Tooth, Impacted; Tooth Diseases; Stomatognathic Diseases

Keywords

Ibuprofen; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non Narcotic; Analgesics

Outcome Measures

Primary Outcomes (2)

• Summed Pain Intensity Difference 0-8 hours (SPID0-8) vs placebo using the Numeric Rating Scale (NRS) for pain

  SPID0-8 will be used to compare the test product against the placebo product. Pain Intensity Difference (Difference in NRS for baseline and each timepoint) will be plotted against timepoint up to the 8 hour timepoint, the SPID0-8 will be take as the area under the curve. The NRS will be used to assess the Pain Intensity, the NRS for pain is an 11-point scale (0-10) where a higher score indicates a greater amount of pain.

  0-8 hours

• Time to Meaningful pain relief vs active comparator using double stopwatch method

  Time to onset of meaningful pain relief (measured as time to meaningful pain relief) using double stopwatch will be used to compare the test product with the active comparator. Two stopwatches will be started immediately after the subject has swallowed the study drug with 8 ounces of water. Each subject will be instructed, "Stop the first stopwatch when you first feel any pain relief whatsoever. This does not mean you feel completely better, although you might, but when you first feel any relief in the pain you have now" (perceptible pain relief). The subject will also be instructed, "Stop the second stopwatch when you feel the pain relief is meaningful to you" (meaningful pain relief). If the subject does not press the stopwatches within 8 hours after Time 0 the subject will discontinue use of the stopwatches.

  0-8 hours

Secondary Outcomes (43)

• Time to onset of pain relief using double stopwatch method vs Placebo

  0-8 hours

• Total Pain Relief 0-6 hours (TOTPAR6) for Test Product vs Active Comparator After Time 0

  0-6 hours

• Proportion of subjects using rescue medication vs Active Comparator

  0- 6 hours

• Time to first use of rescue medication vs Active Comparator

  0-12 hours

• Time to onset of pain relief using double stopwatch method vs Active Comparator

  0-8 hours

Other Outcomes (5)

• 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)

Test Product

EXPERIMENTAL

Ibuprofen 200mg Oral Liquid Capsule, Placebo of Ibuprofen 200mg Oral Tablet

Drug: Ibuprofen 200Mg Oral Cap; Other: Placebo Tablets

Reference Product

ACTIVE COMPARATOR

Ibuprofen 200mg Oral Tablet, Placebo of Ibuprofen 200mg Oral Liquid Capsule

Drug: Ibuprofen 200Mg Oral Tablet; Other: Placebo Liquid Capsule

Placebo

PLACEBO COMPARATOR

Placebo of Ibuprofen 200mg Oral Liquid Capsule, Placebo of Ibuprofen 200mg Oral Tablet

Other: Placebo Liquid Capsule; Other: Placebo Tablets

Interventions

Ibuprofen 200Mg Oral Cap DRUG

2 x 200mg Liquid Capsules once in 12 hours

Also known as: Test Product, 200mg Ibuprofen Liquid Capsule, Nurofen 200mg Ibuprofen Liquid Capsule

Test Product

Ibuprofen 200Mg Oral Tablet DRUG

2 x 200mg Tablets once in 12 hours

Also known as: Reference Product, 200mg Ibuprofen Tablet, Nurofen 200mg Ibuprofen Tablet

Reference Product

Placebo Liquid Capsule OTHER

2 x Liquid Capsules once in 12 hours

Placebo; Reference Product

Placebo Tablets OTHER

2 x Tablets once in 12 hours

Placebo; Test Product

Eligibility Criteria

• Age: 16 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Subject has provided written informed consent (for subjects who are below the age of legal consent, parent(s) or legally authorized representative(s) provides written informed consent and the subject provides written assent).
• Subject is male or female and aged ≥16 and ≤55 years of age at screening.
• 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.
• Experiences moderate to severe pain intensity within 6 hours after surgery, as measured by a NRS score of ≥ 5 on a 0-10 scale.
• Has a body weight ≥ 45 kg and a BMI ≥17 kg/m2 and ≤ 30 kg/m2.
• Female subjects or the female partners of male subjects of childbearing potential must be using a highly effective method of contraception for at least one month prior to screening, throughout the study and for one menstrual cycle after last drug administration. \[A highly effective method of contraception is defined as a method that can achieve a low failure rate of less than 1% per year when used consistently and correctly. Such methods include combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, injectable \& implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), vasectomised partner (who has received medical assessment of the surgical success), or sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments and must be the preferred and usual lifestyle of the subject)\].
• Free of clinically significant abnormal findings as determined by medical history, physical examination, vital signs, laboratory tests and ECG.
• Is willing and able to comply with study requirements (including diet and smoking restrictions), complete the pain evaluations, remain at the study site overnight (if necessary) 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.
• In the opinion of the investigator, any subject with a clinically relevant history of peptic ulceration, gastrointestinal bleeding or perforation, heart failure, renal or hepatic failure, uncontrolled hypertension, nasal polyps, or chronic rhinitis.
• In the opinion of the investigator, the participant has a clinically significant history of asthma or a documented intolerance to NSAIDs resulting in exacerbation of symptoms.
• 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 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) or positive alcohol breathalyser test during the study.
• 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.
• Is a current smoker (including any nicotine products e.g., e-cigarettes or chewing tobacco) or ex-smoker who has smoked or used nicotine replacement products within 1 year of screening
• 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.
• Those taking medicinal products prone to drug-drug interactions described in the investigator's brochure \[IB\]. These include Acetyl Salicylic Acid, other NSAIDs including cyclo-oxygenase-2 selective inhibitors, anticoagulants, antihypertensives (ACE inhibitors and Angiotensin II receptor antagonists) and diuretics, corticosteroids, anti-platelet agents and Selective Serotonin Re-uptake Inhibitors (SSRIs), cardiac glycosides, lithium, methotrexate, ciclosporin, mifepristone, tacrolimus, zidovudine and quinolone antibiotics.
• 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 200 mg ibuprofen liquid capsules), to be an unsuitable candidate to receive the study drug.
• Has a history of chronic use (defined as daily use for \> 2 weeks) of nonsteroidal anti-inflammatory (NSAIDs, including topical), opiates, or corticosteroids (except inhaled nasal steroids), for any condition within 3 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 90 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.

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 (4)

• 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

• 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

• Mehlisch DR, Sykes J. Ibuprofen blood plasma levels and onset of analgesia. Int J Clin Pract Suppl. 2013 Jan;(178):3-8. doi: 10.1111/ijcp.12053.

  PMID: 23163542 BACKGROUND

Related Links

• Guidance for Industry Food-Effect Bioavailability and Fed Bioequivalence Studies
• Guideline on the clinical development of medicinal products intended for the treatment of pain

MeSH Terms

Conditions

Tooth, Impacted; Tooth Diseases; Stomatognathic Diseases

Interventions

Ibuprofen; Capsules; Tablets

Intervention Hierarchy (Ancestors)

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

Study Officials

• Todd Bertoch, MD

  JBR Clinical Research

  PRINCIPAL INVESTIGATOR

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 (200mg Ibuprofen Liquid Capsules and 200mg Ibuprofen Tablets) 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: July 27, 2022
• First Posted: August 2, 2022
• Study Start: August 9, 2022
• Primary Completion: June 15, 2023
• Study Completion: June 15, 2023
• Last Updated: June 22, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)