Dental Pain
Conditions
Brief summary
The purpose of this study is to determine whether the analgesic effects of Maxigesic USA are greater than acetaminophen, ibuprofen or placebo.
Detailed description
The combination of 500mg acetaminophen and 150mg 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. Recent concerns over the safety of acetaminophen have led to some regulatory agencies restricting the maximum dose of acetaminophen per tablet to 325 mg, while maintaining the maximum daily dose of 4000mg per day. A dosing regimen of three tablets of Maxigesic 325 four times a day gives a total daily dose of 3900mg acetaminophen and 1170mg ibuprofen. The primary objective of the study is to compare time-adjusted SPID of the VAS pain intensity scores up to 48 hours after the first dose of study medication among the four study groups. Secondary objectives are: To compare the time to onset of pain relief after the first dose of study drug defined as (i) perceptible and (ii) meaningful pain relief among the four study groups using the two stopwatch method. To compare the maximum VAS pain scores up to 48 hours after the first dose of study medication among the four study groups. To compare the response rates (response rate to be defined as the percentage of participants who reduce their pain intensity scores by at least 50% compared with the baseline VAS measure) among the four study groups. To compare the time to peak reduction in VAS pain intensity scores following the first dose of study medication among the four study groups. To compare the time to requirement for rescue medication among the four study groups. To compare the percentage of participants who use rescue medication among the four study groups. To compare the amount of rescue medication used (defined as number of tablets) among the four study groups. To compare the categorical global pain rating among the four study groups. Safety: To compare adverse event rates for the 48-hour study period and up to Day 30 among the four treatment groups. To compare the incidence of known specific NSAID and paracetamol side effects (e.g. GI ulceration or bleeding, indigestion/stomach pain, post-operative bleeding, bronchospasm, skin rashes, water retention, renal failure, thromboembolic events and evidence of clinical hepatitis) during the 48-hour study period and up to Day 30 among the four study groups. Planned hospital admissions and/or surgical operations for an illness or disease which existed before the study drug was given or the participant was randomized in the study will not be considered adverse events.
Interventions
DRUGMaxigesic 325
Maxigesic USA (acetaminophen 325 mg + ibuprofen 97.5mg), three tablets four times a day with food for 48 hours
DRUGAcetaminophen
Acetaminophen 325 mg, 3 tablets four times a day, with food for 48 hours
DRUGIbuprofen
Ibuprofen 97.5mg, three tablets four times a day, with food for 48 hours.
DRUGPlacebo
placebo, three tablets four times a day, with food for 48 hours
Sponsors
AFT Pharmaceuticals, Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Provides written informed consent before initiation of any study-related procedures. * Males and females aged at least 10 years and not more than 60 years old on the day of consent. * Undergoing dental surgery for the extraction of at least 2 impacted third molar teeth. * A resting VAS pain intensity score at baseline (within 6 hours after the completion of surgery) of greater than or equal to 40 mm on a 100 mm VAS scale with 0 = no pain and 100 = worst pain imaginable.
Exclusion criteria
* Has taken any NSAID or acetaminophen within 12 hours prior to the stat of surgery other than asprin less than or equal to 150 mg/day * Subjects who have received any anaesthetics within 24 hours prior to surgery * Hypersensitivity to opioids * Known to be pregnant or possibly pregnant * Women of childbearing potential who are unwilling to take adequate contraceptive precautions, i.e., hormonal contraceptive, an intrauterine device, double-barrier method, or abstinence. A women 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. * Women of childbearing potential who are unwilling to undergo an urine pregnancy test. * 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 the 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 \< 50 kg or \> 120 kg. * Has a history of drug or alcohol abuse. * Suffering from any other disease or condition which, in the opinion of the investigator, means that it would not be in the participants best interests to participant in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SPID (Summed Pain Intensity Differences) | 48 hours afte the first dose | The time-adjusted Summed Pain Intensity Differences (SPIDs) of the VAS pain intensity scores up to 48 hours after the first dose of study medication. This was calculated from the visual analogue scale (VAS) pain intensity scores recorded during the 48 hours double blind treatment period, with the last measure taken just prior to the final dose of blinded study medication. The visual analogue scale is 100mm long with 0= no pain and 100=worst pain imaginable. The Visual Analogue Scale It is expected that treatments which can provide superior analgesic effect will demonstrate a greater Summed Pain Intensity Difference. |
Countries
New Zealand, United States
Participant flow
Recruitment details
455 Subjects have been consented and screened, out of which 47 subjects were screening failures and did not receive the first dose of study medication. Among 408 subjects, 273 subjects enrolled from New Zealand sites and 135 subjects enrolled from USA site from May 2013 to Jan 2015.
Participants by arm
| Arm | Count |
|---|---|
| Maxigesic 325 Acetaminophen 325mg + ibuprofen 97.5mg per tablet, two tablets every 6 hours, orally
Maxigesic 325: Maxigesic USA (acetaminophen 325 mg + ibuprofen 97.5mg), three tablets four times a day with food for 48 hours | 110 |
| Acetaminophen Acetaminophen 325mg per tablet (standard dose acetaminophen), two tablets every 6 hours, orally
Acetaminophen: Acetaminophen 325 mg, 3 tablets four times a day, with food for 48 hours | 111 |
| Ibuprofen Ibuprofen 97.5mg per tablet (i.e. low dose ibuprofen), two tablets every 6 hours, orally
Ibuprofen: Ibuprofen 97.5mg, three tablets four times a day, with food for 48 hours. | 112 |
| Placebo Placebo tablets, every 6 hours, orally
Placebo: placebo, three tablets four times a day, with food for 48 hours | 75 |
| Total | 408 |
Baseline characteristics
| Characteristic | Maxigesic 325 | Acetaminophen | Ibuprofen | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 25.4 years STANDARD_DEVIATION 7 | 25.0 years STANDARD_DEVIATION 6.9 | 24.3 years STANDARD_DEVIATION 5.9 | 24.3 years STANDARD_DEVIATION 6.3 | 24.8 years STANDARD_DEVIATION 6.6 |
| Region of Enrollment New Zealand | 73 participants | 75 participants | 75 participants | 50 participants | 273 participants |
| Region of Enrollment United States | 37 participants | 36 participants | 37 participants | 25 participants | 135 participants |
| Sex: Female, Male Female | 69 Participants | 76 Participants | 82 Participants | 48 Participants | 275 Participants |
| Sex: Female, Male Male | 41 Participants | 35 Participants | 30 Participants | 27 Participants | 133 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 110 | 0 / 111 | 0 / 112 | 0 / 75 |
| other Total, other adverse events | 41 / 110 | 54 / 111 | 40 / 112 | 38 / 75 |
| serious Total, serious adverse events | 1 / 110 | 0 / 111 | 0 / 112 | 0 / 75 |
Outcome results
Primary
SPID (Summed Pain Intensity Differences)
The time-adjusted Summed Pain Intensity Differences (SPIDs) of the VAS pain intensity scores up to 48 hours after the first dose of study medication. This was calculated from the visual analogue scale (VAS) pain intensity scores recorded during the 48 hours double blind treatment period, with the last measure taken just prior to the final dose of blinded study medication. The visual analogue scale is 100mm long with 0= no pain and 100=worst pain imaginable. The Visual Analogue Scale It is expected that treatments which can provide superior analgesic effect will demonstrate a greater Summed Pain Intensity Difference.
Time frame: 48 hours afte the first dose
Population: Primary Efficacy Endpoint was analyzed in ITT population (subjects who have been randomized and received the first dose of study medication)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maxigesic 325 | SPID (Summed Pain Intensity Differences) | 31.56 score on a scale | Standard Error 1.94 |
| Acetaminophen | SPID (Summed Pain Intensity Differences) | 17.71 score on a scale | Standard Error 1.89 |
| Ibuprofen | SPID (Summed Pain Intensity Differences) | 23.18 score on a scale | Standard Error 1.89 |
| Placebo | SPID (Summed Pain Intensity Differences) | 14.86 score on a scale | Standard Error 2.26 |