A two part study examining the safety and efficacy of fixed-dose combinations of ibuprofen plus acetaminophen for adults with dental pain following molar extraction
| ISRCTN | ISRCTN73768226 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN73768226 |
| Secondary identifying numbers | NL0604 |
- Submission date
- 08/06/2010
- Registration date
- 24/06/2010
- Last edited
- 20/02/2020
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Oral Health
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English Summary
Not provided at time of registration
Contact information
Mr Stephen Daniels
Scientific
Scientific
SCIREX Research Center/ Premier Research Group
3200 Red River
Suite 300
Austin
TX 78705
United States of America
Study information
| Study design | Multicentre double blind randomised placebo controlled parallel group single and multiple dose phase factorial design two-part study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Other |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details below to request a patient information sheet |
| Scientific title | A two part study examining the analgesic efficacy and tolerability of three fixed-dose combinations of ibuprofen plus acetaminophen for adults with dental pain following third molar extraction: A double-blind, parallel-group, placebo-controlled, randomised, repeat dose trial with two-centre factorial design |
| Study hypothesis | This was a two-part study. The objective of Part 1 was to assess the efficacy and tolerability of a fixed-dose combination tablet containing ibuprofen and acetaminophen (paracetamol) (ibuprofen 100mg plus acetaminophen 250 mg, ibuprofen 200 mg plus acetaminophen 500 mg, and ibuprofen 400 mg plus acetaminophen 1000 mg) and compare with placebo, ibuprofen 200 mg, ibuprofen 400 mg, acetaminophen 500 mg, and acetaminophen 1000mg in terms of total analgesic effect, peak analgesic effect onset and duration of action, and the subjects overall assessment of the study medication. The objective of Part 2 was to assess the efficacy and tolerability of a fixed-dose combination tablet containing ibuprofen and acetaminophen (ibuprofen 100 mg plus acetaminophen 250 mg ibuprofen 200 mg plus acetaminophen 500 mg, and ibuprofen 400 mg plus acetaminophen 1000 mg) and compare with each other and placebo in terms of analgesic effect and the subjects overall assessment of the study medication. |
| Ethics approval(s) | Coast Independent Review Board approved on the 5th June 2007 |
| Condition | Dental pain |
| Intervention | This was a two part study, the objective of Part 1 was to assess the efficacy and tolerability of a fixed-dose combination tablet containing ibuprofen and acetaminophen as follow: 1. Ibuprofen 100mg plus acetaminophen 250mg 2. Ibuprofen 200mg plus acetaminophen 500mg 3. Ibuprofen 400mg plus acetaminophen 1000mg and compared with : 1. Placebo 2. Ibuprofen 200mg 3. Ibuprofen 400mg 4. Acetaminophen 500mg and 5. Acetaminophen 1000mg In terms of total analgesic effect, peak analgesic effect, onset and duration of action and the subjects overall assessment od the study medication. The objective of Part 2 was to assess the efficacy and tolerability of a fixed-dose combination tablet containing ibuprofen and acetaminophen as follows: 1. Ibuprofen 100mg plus acetaminophen 250mg 2. Ibuprofen 200mg plus acetaminophen 500mg and 3. Ibuprofen 400mg plus acetaminophen 1000mg and compare with each other and placebo in terms of analgesic effect and the subjects overall assessment of the study medication. Subjects were randomly allocated to one of the eight treatment groups. All subjects remained at the study centre and were monitored for approximately 80 hours after the first dose of study medication (8 hours in Part 1 and 72 hours in Part 2) and returned for a post-operative visit seven to ten days after surgery. Each individual subjects participation in the study could have lasted for up to 43 days. |
| Intervention type | Other |
| Primary outcome measure | The primary endpoint in Part 1 was SPRID0-8h and in Part 2 was the number of complete 24-hours periods (as 0, 1, 2, 3) with no more than one dose of rescue medication and with the subjects overall assessment always rated as at least good (i.e., 3, 4, 5) |
| Secondary outcome measures | 1. The key secondary endpoint for Part 1: 1.2. The first recorded post-baseline assessment of the subjects overall assessment of the study medication as a treatment for pain on a 5-point Overall Assessment Categorical Rating Scale. This variable was assessed at 8 hours or just prior to administration of rescue medication if sooner 1.3. Duration of pain half gone. This was calculated in a analogous was to TOTPAR but using zero (pain not half gone) and one (pain half gone) 1.4. Time to meaningful PAR using the two-stopwatch technique 1.5. Duration of the effect measured as time to first administrate of rescue medication. Rescues medication taken after withdrawal was disregarded for analysis purposes 2. The key secondary endpoint part 2: 2.1. The time of treatment failure was taken as the time of withdrawal or the timing of the inadmissible dose of study/rescue medication, whichever was earlier 2.2. Median score for subjects overall assessment per 24-hours period 2.3. Mean number of dose taken per 24-hours (including rescue) 2.4. Mean duration between doses per 24-hour period and overall (including rescue) 2.5. Peak PAR score per 24-hour period |
| Overall study start date | 16/10/2006 |
| Overall study end date | 10/09/2007 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | A total of 1303 subjects were screened for study enrolment of which 735 were randomised to receive study treatment. |
| Total final enrolment | 735 |
| Participant inclusion criteria | 1. Age: Subjects at least 16 years of age were eligible to participate 2. Sex: Both males and females were eligible for entry 3. Primary Diagnosis: At least three impacted third molars (two of which must have been mandibular impacted molars) indicated for removal. Both mandibular impactions must have required bone removal, and there must have been a total score of 9 or greater on the impaction grading scale for the three or four impacted third molar 4. Baseline pain intensity (PI): Subjects must have been experiencing moderate to severe postoperative pain based on the Pain Intensity Categorical Rating Scale and have a PI Visual Analogue Scale (VAS) score of 50mm or greater on the 100mm within 6 hours of completion of surgery, but more than 3 hours after the last administration of fentanyl 5. Subjects who gave written informed consent. Subjects who were 16 or 17 years of age also required their parents or legal guardian to provide written informed consent in addition to their written assent |
| Participant exclusion criteria | 1. Those who had participated in a clinical trial in the previous 12 weeks. Twelve weeks calculated from the time of last dosing in the prior trial to time of anticipated first dosing in this trial. 2. A current history of significant disease deemed by the Investigator to render the subject unsuitable for inclusion 3. An ongoing painful condition other than that associated with the current third molar surgery 4. Any ongoing condition that may have interfered with the absorption, distribution, metabolism or excretion of the study medication 5. A history of allergy or intolerance (including angioedema, urticaria, bronchospasm and rhinitis) related to the treatment with ibuprofen, acetaminophen, aspirin, other NSAIDs or any other medication used in this study, including anaesthetics and antibiotics that may have been required on the day of the surgery (Day 1) or the formulation constituents of the study medications 6. A history of frequent peptic ulcers, duodenal ulcers or gastrointestinal (GI) bleeding 7. A history of frequent dyspepsia, heartburn or indigestion 8. A history of migraine headaches within the past year 9. A history of psychotic illness, attempted suicide or neurosis 10. Those unable to refrain from smoking during their stay in the research centre 11. A positive history of drug or alcohol abuse within the past six months 12. Those who were taking any concomitant medication that might have confounded assessments of pain relief (PAR), 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 noradrenalin reuptake inhibitors (SNRIs) were permitted if the subject had been on a stable dose for at least four weeks prior to visit 1 (screening). 13. Those previously randomised into this study 14. Subjects who had received ant analgesic, anti-inflammatory drug, sedative-hypnotic, or caffeine containing food or drink from midnight the night prior to surgery and during the entire 80 hours post-dose assessment period, except for the study medication, perioperative sedative, antibiotics or permitted anaesthetics. The following anaesthetics were permitted lidocaine with epinephrine, nitrous oxide, diazepam (Valium), methohexitol (Brevital) and fentanyl. The following antibiotics were permitted: penicillin, macrolide antibiotics, clindamycin and topical tetracycline gelfoam. 15. Those who were unable, in the opinion of the investigator, to comply fully with the study requirements. 16. Those with abnormal liver function tests at screening 17. A history of epileptic seizures |
| Recruitment start date | 16/10/2006 |
| Recruitment end date | 10/09/2007 |
Locations
Countries of recruitment
- United States of America
Study participating centre
SCIREX Research Center/ Premier Research Group
Austin
TX 78705
United States of America
TX 78705
United States of America
Sponsor information
Reckitt Benckiser Healthcare (UK)
Industry
Industry
Dansom Lane
Hull
HU8 7DS
United Kingdom
"ROR" |
https://ror.org/01g87hr29 |
|---|
Funders
Funder type
Industry
Reckitt Benckiser Healthcare (UK)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/06/2010 | 20/02/2020 | Yes | No |
Editorial Notes
20/02/2020: The following changes have been made:
1. Publication reference added.
2. The total final enrolment number has been added from the reference.
