OsteoarthritisPhase 3NCT01420666
Maxi-Analgesic Osteoarthritis (OA) Study
A Phase 3 study testing Acetaminophen, Maxigesic 325 and Ibuprofen in people with Osteoarthritis, run by AFT Pharmaceuticals, Ltd..
Trial summary
The purpose of this study is to determine whether the analgesic effects of Maxigesic USA are greater than acetaminophen, ibuprofen or placebo in patients who have painful osteoarthritis of the hip or knee. Read more about this study
- Who is it for?
- Ages 45 to 80 years
- Conditions the study is for
- Osteoarthritis
- What is being tested?
- Acetaminophen, Maxigesic 325 and Ibuprofen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Start not givento not given
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provides written informed consent before initiation of any study-related procedures.
- Have had symptoms of OA of the knee or hip for at least 6 months that has required analgesic medication.
- Have confirmed radiological evidence of OA.
- Be between 45 - 80 years of age inclusive, on the day of consent.
- In the opinion of a physician, require long term medication for treatment of painful OA.
- Have painful OA of the knee or hip with a pain score of at least 40 mm and no more than 80 mm on the WOMAC VAS pain scale at rest following a 3 - 7 day washout of existing analgesics.
Who cannot join
- Weigh less than 50 kg
- Rheumatoid arthritis or other inflammatory arthritis.
- Gout or recurrent episodes of pseudogout.
- Paget's disease.
- Articular fracture.
- Ochronosis.
Show all 27Show fewer
- Acromegaly.
- Haemochromatosis.
- Wilson's Disease.
- Primary Osteochondromatosis.
- Heritable disorders (e.g. hypermobility).
- Have received or taken oral or parenteral corticosteroids within 2 months or intra-articular hyaluronic acid within 9 months.
- Has taken any single dose of an NSAID or acetaminophen within 12 hours prior to first dose of study drug
- Known to be pregnant or possibly pregnant
- Women of childbearing potential who, in the opinion of the investigator, are not using reliable contraception.
- Alcohol intake in excess of 14 units per week for females and 21 units per week for males.
- Have a history of drug abuse.
- Suffering from a neurological disorder relating to pain perception.
- In the opinion of the investigator, unable to understand the visual analogue pain score.
- Currently, or in the last 30 days, participating in a clinical trial involving another study drug.
- Suffering from any other diseases or conditions which, in the opinion of the investigator, means that it would not be in the patients best interests to participant in this study.
- Hypersensitivity to aspirin or other NSAID
- Hypersensitivity to acetaminophen
- Severe known haemopoietic, renal or hepatic disease, immunosuppression
- History of gastric ulceration, indigestion, stomach pain or GI bleeding or bleeding disorders
- Currently suffering from dehydration through diarrhoea and/or vomiting
- History of severe asthma defined as previous steroid treatment or hospital admission within the last 5 years.
About this study
Official title: Maxi-Analgesic OA Study: Multicentre, Double-blind, Placebo-controlled, Randomized, Parallel Group Comparison of the Effects of Maxigesic 325 With Acetaminophen or Ibuprofen on Patients With Pain From Osteoarthritis
The purpose of this study is to determine whether the analgesic effects of Maxigesic USA are greater than acetaminophen, ibuprofen or placebo in patients who have painful osteoarthritis of the hip or knee.
Read the detailed description
Osteoarthritis is a significant and disabling disease in the developed world.
Published guidelines for medical management of osteoarthritis from expert groups, in general advocate acetaminophen as first line treatment. The European League Against Rheumatism (EULAR) guidelines (1)recommend acetaminophen should be first choice therapy in OA, and that NSAIDs should be reserved for those patients unresponsive to acetaminophen. The American College of Rheumatology Guidelines (2) recommend acetaminophen be considered as reasonable initial therapy in patients with mild to moderate OA pain and that NSAIDs be considered as an initial alternative in moderate to severe OA pain. The Canadian guidelines recommend acetaminophen for mild OA pain and NSAIDs for moderate to severe OA (3).
A Cochrane Review of acetaminophen in osteoarthritis concluded that NSAIDs were superior to acetaminophen for improving knee and hip pain in people with OA. However, it was noted that the size of the treatment effect was modest with NSAIDs appearing to be more effective in OA subjects with moderate-to-severe pain (4).
There are many situations in clinical practice where either acetaminophen alone or low dose ibuprofen is not sufficiently effective. In these cases the dose of acetaminophen cannot be increased to more than 4000mg/day due to toxicity concerns. In the case of ibuprofen the dose can be increased from 1200mg/day to 2400mg/day. However comparison of low dose ibuprofen with high dose showed gastrointestinal (GI) toxicity increased: the relative risk (RR) of GI complications increased from 1.6 (95% CI 0.8, 3.2) with low dose ibuprofen to 4.2 (95% CI 1.8, 9.8) with high dose ibuprofen (5). Ibuprofen is associated with a low risk of serious gastrointestinal complications, but this advantage is probably lost at doses above 1800 mg/day (6).
A simple combination treatment whereby both acetaminophen and ibuprofen can be taken together as one single tablet and at the same time each day would, if effective, have the advantage of increasing analgesia without having to raise the ibuprofen dose above 1200mg/day (1170mg if administered every 6 hours) and lose the improved safety profile associated with a lower dose of ibuprofen.
- Pendleton A, Arden N, Dougados M, Doherty M, Bannwarth B, Bijlsma JW, et al. EULAR recommendations for the management of knee osteoarthritis: report of a task force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Ann Rheum Dis. 2000;59(12):936-44.
- Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arthritis Rheum. 2000;43(9):1905-15.
- Tannenbaum H, Peloso PM, Russell AS, Marlow B. An evidence-based approach to prescribing NSAIDs in the treatment of osteoarthritis and rheumatoid arthritis: The Second Canadian Consensus Conference. Can J Clin Pharmacol. 2000;7 Suppl A:4A-16A.
- Towheed TE, Maxwell L, Judd MG, Catton M, Hochberg MC, Wells G. Acetaminophen for osteoarthritis. Cochrane Database Syst Rev. 2006(1):CD004257.
- Henry D, Lim LLY, Garcia Rodriguez LA, Perez Gutthann S, Carson JL, Griffin M, et al. Variability in risk of gastrointestinal complications with individual non-steroidal anti-inflammatory drugs: Results of a collaborative meta-analysis. British Medical Journal. 1996;312 (7046):1563-6.
- Henry D, McGettigan P. Epidemiology overview of gastrointestinal and renal toxicity of NSAIDs. Int J Clin Pract Suppl. 2003;Supplement.(135):43-9.
- Conditions
- Osteoarthritis
- Being tested
- Acetaminophen, Maxigesic 325, Ibuprofen, Placebo
- Medical subject headings
- Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcetaminophenDrug
Also called Paracetamol
Acetaminophen 325 mg, three tablets four times a day, orally, with food
Maxigesic 325Drug
Also called Actaminophen/paracetamol + ibuprofen
Maxigesic 325 (Acetaminophen 325 mg+ ibuprofen 97.5mg), three tablets four times a day, orally, with food
IbuprofenDrug
Ibuprofen 97.5mg, three tablets four times a day, orally, with food
PlaceboDrug
placebo, three tablets four times a day, orally, with food
| Study group | Role | What they receive |
|---|---|---|
| Maxigesic 325 | Active comparator | Maxigesic 325 (acetaminophen 325 mg + ibuprofen 97.5mg), three tablets four times a day, orally, with food Receives: Drug: Maxigesic 325 |
| Acetaminophen | Active comparator | Acetaminophen 325 mg, three tablets four times a day, orally, with food Receives: Drug: Acetaminophen |
| Ibuprofen | Active comparator | ibuprofen 97.5mg, three tablets four times a day, orally, with food Receives: Drug: Ibuprofen |
| Placebo | Placebo comparator | Placebo tablets Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
WOMAC pain intensity VAS
The difference between the week 13 average WOMAC pain intensity VAS and the baseline WOMAC VAS
Measured: 13 weeks
Secondary outcomes (9)
Time to peak analgesic effect
Time to peak analgesic effect using the WOMAC VAS pain intensity score (the average pain intensity score of that week).
Measured: 13 weeks
Time-adjusted SPID
Time adjusted SPID obtained from the mean weekly WOMAC VAS pain intensity assessments over 13 weeks
Measured: 13 weeks
Difference of WOMAC stiffness score
Difference between the week 13 WOMAC stiffness score and the baseline WOMAC stiffness score
Measured: 13 weeks
Difference of WOMAC function score
Difference between the week 13 WOMAC function score and the baseline WOMAC function score
Measured: 13 weeks
Time to rescue medication
Tie to rescue medication (oxycodone)
Measured: 13 weeks
Safety
Adverse events (serious and non-serious) will be assessed during the blinded study period and up to 30 days after the last dose of study medication. Known NSAID adverse effects (i.e. GI ulceration, indigestion/stomach pain, bleeding, bronchospasm, water retention, renal failure, skin reactions and thromboembolic events) and known acetaminophen adverse effects (i.e. clinical evidence of hepatitis) will be compared between groups.
Measured: 13 weeks
Time-adjusted WOMAC stiffness score
Time-adjusted WOMAC stiffness score over 13 weeks
Measured: Over 13 weeks
Time-adjusted WOMAC function score
Time-adjusted WOMAC function score over 13 weeks
Measured: over 13 weeks
Patient global assessment
A categorical global pain rating will be obtained weekly during the double blind treatment period.
Measured: 13 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2011 (estimated)
Why it stopped: The study was withdrawn for administrative reason
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for OsteoarthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- AFT Pharmaceuticals, Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- John Moodie, Doctor, Principal investigator, Clinical Trial New Zealand Ltd, 32 Kahikatea Drive, Hamilton, New Zealand
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01420666
- Sponsor's protocol ID
- AFT-MX-7
- Status last verified
- Jan 2016
- First submitted
- 16 Aug 2011
- Last updated
- 6 Jan 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Maxi-Analgesic OA Study: Multicentre, Double-blind, Placebo-controlled, Randomized, Parallel Group Comparison of the Effects of Maxigesic 325 With Acetaminophen or Ibuprofen on Patients With Pain From Osteoarthritis
- ClinicalTrials.gov ID
- NCT01420666
- Acronym / sponsor ID
- AFT-MX-7
- Conditions
- Osteoarthritis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The study was withdrawn for administrative reason
- Enrolment
- 0 participants (actual)
- Lead sponsor
- AFT Pharmaceuticals, Ltd.Industry (pharma, biotech, devices)
- First posted
- 22 Aug 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether the analgesic effects of Maxigesic USA are greater than acetaminophen, ibuprofen or placebo in patients who have painful osteoarthritis of the hip or knee.
Detailed description
Osteoarthritis is a significant and disabling disease in the developed world.
Published guidelines for medical management of osteoarthritis from expert groups, in general advocate acetaminophen as first line treatment. The European League Against Rheumatism (EULAR) guidelines (1)recommend acetaminophen should be first choice therapy in OA, and that NSAIDs should be reserved for those patients unresponsive to acetaminophen. The American College of Rheumatology Guidelines (2) recommend acetaminophen be considered as reasonable initial therapy in patients with mild to moderate OA pain and that NSAIDs be considered as an initial alternative in moderate to severe OA pain. The Canadian guidelines recommend acetaminophen for mild OA pain and NSAIDs for moderate to severe OA (3).
A Cochrane Review of acetaminophen in osteoarthritis concluded that NSAIDs were superior to acetaminophen for improving knee and hip pain in people with OA. However, it was noted that the size of the treatment effect was modest with NSAIDs appearing to be more effective in OA subjects with moderate-to-severe pain (4).
There are many situations in clinical practice where either acetaminophen alone or low dose ibuprofen is not sufficiently effective. In these cases the dose of acetaminophen cannot be increased to more than 4000mg/day due to toxicity concerns. In the case of ibuprofen the dose can be increased from 1200mg/day to 2400mg/day. However comparison of low dose ibuprofen with high dose showed gastrointestinal (GI) toxicity increased: the relative risk (RR) of GI complications increased from 1.6 (95% CI 0.8, 3.2) with low dose ibuprofen to 4.2 (95% CI 1.8, 9.8) with high dose ibuprofen (5). Ibuprofen is associated with a low risk of serious gastrointestinal complications, but this advantage is probably lost at doses above 1800 mg/day (6).
A simple combination treatment whereby both acetaminophen and ibuprofen can be taken together as one single tablet and at the same time each day would, if effective, have the advantage of increasing analgesia without having to raise the ibuprofen dose above 1200mg/day (1170mg if administered every 6 hours) and lose the improved safety profile associated with a lower dose of ibuprofen.
- Pendleton A, Arden N, Dougados M, Doherty M, Bannwarth B, Bijlsma JW, et al. EULAR recommendations for the management of knee osteoarthritis: report of a task force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Ann Rheum Dis. 2000;59(12):936-44.
- Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arthritis Rheum. 2000;43(9):1905-15.
- Tannenbaum H, Peloso PM, Russell AS, Marlow B. An evidence-based approach to prescribing NSAIDs in the treatment of osteoarthritis and rheumatoid arthritis: The Second Canadian Consensus Conference. Can J Clin Pharmacol. 2000;7 Suppl A:4A-16A.
- Towheed TE, Maxwell L, Judd MG, Catton M, Hochberg MC, Wells G. Acetaminophen for osteoarthritis. Cochrane Database Syst Rev. 2006(1):CD004257.
- Henry D, Lim LLY, Garcia Rodriguez LA, Perez Gutthann S, Carson JL, Griffin M, et al. Variability in risk of gastrointestinal complications with individual non-steroidal anti-inflammatory drugs: Results of a collaborative meta-analysis. British Medical Journal. 1996;312 (7046):1563-6.
- Henry D, McGettigan P. Epidemiology overview of gastrointestinal and renal toxicity of NSAIDs. Int J Clin Pract Suppl. 2003;Supplement.(135):43-9.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Maxigesic 325 | Active comparator | Drug: Maxigesic 325Maxigesic 325 (acetaminophen 325 mg + ibuprofen 97.5mg), three tablets four times a day, orally, with food |
| Acetaminophen | Active comparator | Drug: AcetaminophenAcetaminophen 325 mg, three tablets four times a day, orally, with food |
| Ibuprofen | Active comparator | Drug: Ibuprofenibuprofen 97.5mg, three tablets four times a day, orally, with food |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo tablets |
Who may qualify
- Ages
- 45 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Provides written informed consent before initiation of any study-related procedures.
- Have had symptoms of OA of the knee or hip for at least 6 months that has required analgesic medication.
- Have confirmed radiological evidence of OA.
- Be between 45 - 80 years of age inclusive, on the day of consent.
- In the opinion of a physician, require long term medication for treatment of painful OA.
Key exclusion criteria (27 listed)
- Weigh less than 50 kg
- Rheumatoid arthritis or other inflammatory arthritis.
- Gout or recurrent episodes of pseudogout.
- Paget's disease.
- Articular fracture.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AcetaminophenAlso: ParacetamolAcetaminophen 325 mg, three tablets four times a day, orally, with food | Drug | Acetaminophen |
| Maxigesic 325Also: Actaminophen/paracetamol + ibuprofenMaxigesic 325 (Acetaminophen 325 mg+ ibuprofen 97.5mg), three tablets four times a day, orally, with food | Drug | Maxigesic 325 |
| IbuprofenIbuprofen 97.5mg, three tablets four times a day, orally, with food | Drug | Ibuprofen |
| Placeboplacebo, three tablets four times a day, orally, with food | Drug | Placebo |
Primary outcome
WOMAC pain intensity VAS
Time frame: 13 weeks
The difference between the week 13 average WOMAC pain intensity VAS and the baseline WOMAC VAS
9 secondary outcomes
Time to peak analgesic effect
Time frame: 13 weeks
Time-adjusted SPID
Time frame: 13 weeks
Difference of WOMAC stiffness score
Time frame: 13 weeks
Difference of WOMAC function score
Time frame: 13 weeks
Time to rescue medication
Time frame: 13 weeks
Safety
Time frame: 13 weeks
Time-adjusted WOMAC stiffness score
Time frame: Over 13 weeks
Time-adjusted WOMAC function score
Time frame: over 13 weeks
Patient global assessment
Time frame: 13 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Moodie, Doctor principal investigator
Clinical Trial New Zealand Ltd, 32 Kahikatea Drive, Hamilton, New Zealand
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Acetaminophen, Maxigesic 325 and Ibuprofen in people with Osteoarthritis, run by AFT Pharmaceuticals, Ltd..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 6 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
WOMAC pain intensity VAS (time frame: 13 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2016.