Multicentre, Double-blind, Placebo-controlled, Randomized, Parallel Group Comparison of the Analgesic Effects of Different Maxigesic Doses Versus Acetaminophen, Ibuprofen and Placebo for the Teeth Extraction Pain
Trial Snapshot
- Phase
- Phase 2
- Status
- Withdrawn
- Sponsor
- Locations
- 1
- Primary Endpoint
- the time-adjusted SPIDs of the VAS pain intensity scores
Study Overview
Brief Summary
The aim of the study is to examine the dose response relationship in the treatment of dental pain (teeth extraction) for the different potential doses of the investigational drug, i.e. 2 tablets, 1 tablet or ½ a tablet given 4 times a day.
Detailed Description
The combination of 500 mg acetaminophen and 150 mg ibuprofen has been shown to improve analgesia compared with the individual components, when given as 2 tablets (i.e., total of 1,000/300 mg) 4 times a day for dental pain.
The analgesic relief from 2 tablets of the combination was around 6 hours, and so consistent with 4 times a day dosing.
The combination tablets are scored to allow for lower doses and can be given as 2 tablets (total of 1,000/300 mg), 1 tablet (500/150 mg) or ½ tablet (250/75 mg) in multiple doses.
However different dose response combinations need to be investigated to confirm the dose response curve of the combination and to compare the relative efficacy with acetaminophen and different doses of ibuprofen (lower and higher dose).
The study hypothesis is the analgesic response to three different combination doses, the three single component doses 500mg acetaminophen and 150mg and 300mg ibuprofen, and placebo administered four times daily over 24 hours for post-operative dental pain will form a representative dose response curve.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 16 Years to 40 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Provide written informed consent before initiation of any study-related procedures.
- •Males and females aged at least 16 years and not more than 40 years old on the day of consent.
- •Undergoing oral surgery for the extraction of 2 impacted 3rd molar teeth, one of which must be mandibular and require bone removal.
- •Experiencing moderate to severe post-operative pain, as defined by a 4 point categorical pain intensity rating scale with 0 = no pain; 1 = mild pain; 2 = moderate pain and 3 = severe pain(at rest) within 6 hours after completion of surgery.
- •Baseline VAS pain intensity score of > 50mm on a 100mm VAS scale with 0 = no pain and 100 = worst pain imaginable.
Exclusion Criteria
- •Study contra-indications:
- •Has taken any NSAID or acetaminophen within 12 hours prior to the start of surgery other than aspirin ≤ 150mg/day.
- •Subjects who have received any anesthetics from midnight the night prior to surgery, except for lidocaine with epinephrine, nitrous oxide, diazepam (Valium®), methohexital (Brevital®).
- •Known to be pregnant or possibly pregnant.
- •Women of childbearing potential who are unwilling to take adequate contraceptive precautions, i.e., a hormonal contraceptive, an intrauterine device, double-barrier method, or abstinence (should the subject become sexually active, she must agree to use a double-barrier method of contraception). A woman of childbearing potential is defined as any female who is less than 2 years post-menopausal or has not undergone a partial or total hysterectomy or surgical sterilization, e.g., bilateral tubal ligation, bilateral oophorectomy.
- •Suffering from a neurological disorder relating to pain perception or any acute or chronic condition that, in the opinion of the investigator, makes the subject unsuitable from an efficacy or safety perspective.
- •In the opinion of the investigator, unable to understand the visual analogue pain score or comply with the protocol requirements.
- •Currently or in last 30 days, has been in a clinical trial involving another study drug.
- •Currently treated with an ACE inhibitor, warfarin, steroid (other than nasal steroids or topical steroids with the approval of the investigator), cyclosporin, tacrolimus or methotrexate, or any other medication felt by the investigator to interfere with safety or efficacy evaluations.
- •Participant weight < 50kg.Suffering from any other diseases or condition which, in the opinion of the investigator, means that it would not be in the participant's best interests to participate in this study.
- •NSAID and/or acetaminophen contra-indications:
- •Hypersensitivity to aspirin or other NSAID.
- •Hypersensitivity to acetaminophen.
- •Severe known hemopoietic, renal or hepatic disease, or immunosuppressed.
- •History of gastric ulceration or other GI disorders that, in the opinion of the investigator make the subject unsuitable (e.g., frequent treatment of GERD, inflammatory bowel disease, etc.).
- •History of severe asthma defined as asthma requiring frequent or ongoing treatment to control symptoms. Exercise-induced asthma or mild asthma not requiring ongoing treatment may not be exclusionary at the discretion of the investigator.
Arms & Interventions
Half dose strength
Investigational drug half dose strength (acetaminophen 250mg + ibuprofen 75mg), i.e 2 tablets equating to ½ the dose in the standard investigational drug
Intervention: Half dose strength (Drug)
Quarter dose strength
Investigational drug quarter dose strength (acetaminophen125mg + Ibuprofen 37.5mg) i.e. 2 tablets equating to ¼ the dose in the standard investigational drug.
Intervention: Quarter dose strength (Drug)
Acetaminophen standard dose
Acetaminophen standard dose 500mg i.e. 2 tablets equating to the same acetaminophen dose as in the standard investigational drug
Intervention: Acetaminophen standard dose (Drug)
ibuprofen low dose
Ibuprofen low dose 150mg tablet i.e. 2 tablets equating to the same ibuprofen dose as in the standard investigational product
Intervention: Ibuprofen low dose (Drug)
Ibuprofen high dose
Ibuprofen High dose 300mg i.e. 2 tablets equating to twice the ibuprofen dose as in the standard investigational drug
Intervention: Ibuprofen high dose (Drug)
placebo
2 Placebo tablets
Intervention: Placebo (Drug)
Full Dose Strength
Investigational drug full dose strength (acetaminophen 500mg + ibuprofen 150mg) i.e. 2 tablets
Intervention: Full Dose Strength (Drug)
Outcomes
Primary Outcomes
the time-adjusted SPIDs of the VAS pain intensity scores
Time Frame: 24 hours after the first dose
The primary efficacy objective is to compare the time-adjusted SPIDs of the VAS pain intensity scores up to 24 hours after the first dose of study medication among the 7 treatment groups to determine the form of the dose-response relationship.
Secondary Outcomes
- the maximum VAS pain score(24 hours after the first dose)
- The Response Rate(24 hours after the first dose)
- The time to peak reduction in VAS pain intensity scores(24 hours after the first dose)
- The time to perceptible and meaningful pain relief(24 hours after the first dose)
- The time to requirement for rescue medication(24 hours after the first dose)
- The amount of rescue medication used(24 hours after the first dose)
- The percentage of participants requiring rescue medication(24 hours after the first dose)
- The categorical global pain rating(24 hours after the first dose)
- The incidence of adverse events(up to 30 days after the last dose)