OsteoarthritisPhase 4NCT01329406
Study to Evaluate the Efficacy of Milnacipran in the Treatment of Pain Due to Osteoarthritis
A Phase 4 study testing Milnacipran in people with Osteoarthritis, run by Analgesic Solutions at 1 site in United States.
Trial summary
The present study will aim to evaluate the efficacy of milnacipran in the treatment of pain due to osteoarthritis (OA), that is, to determine whether milnacipran provides superior efficacy to placebo in patients with OA. Read more about this study
- Who is it for?
- Ages 21 to 75 years
- Conditions the study is for
- Osteoarthritis
- What is being tested?
- Milnacipran
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2011to Sep 2012
- Phase
- Phase 4
- 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 21 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Be 21-75 years of age and in good general medical and psychological health
- Be able to speak, read, write, and understand English, understand the consent form, complete study related procedures, and communicate with the study staff
- Have a negative urine pregnancy test at screening, and use appropriate birth control
- Have documented painful Osteoarthritis (OA) of at least one knee for at least 6 months; OA should be of Class I-III and meet the American College of Rheumatology (ACR) clinical classification criteria, defined as:
- Knee pain and at least 3 of the following 6:
- Age > 50
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- Morning stiffness < 30 minutes
- Crepitus on active motion
- Bony tenderness
- Bony enlargement
- No palpable warmth of synovium
- The target joint must not contain any type of orthopedic and/or prosthetic device
- Have a target joint pain average of 5 days per week and have an average pain intensity of at least 4/10 on the 0-10 NRS over the last 24 hours prior to screening
- Have stable treatment modalities, e.g. acupuncture, physical therapy
- Be willing to stop taking Non-steroidal Anti-inflammatory drugs (NSAIDs) and opioids for the duration of the study
Who cannot join
- Are allergic or intolerant to SNRI; have a previous poor response to a SNRI for OA pain; are currently taking an SNRI or tricyclic antidepressant
- Have a body mass index (BMI) >40 kg/m2
- Have an Hospital Anxiety and Depression Scale (HADS) score >12 on either subscale or has an established history of major depressive disorder not controlled with medication
- Have significant pain outside the target knee, including significant hip or back pain. (Bilateral knee OA allowed.)
- Have pain affecting the target knee that is due to any other etiology than OA
- Have documented history of inflammatory arthritis including rheumatoid arthritis
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- Have had local injections in target joint within the past 3 months prior to screening
- Have had oral or intramuscular corticosteroids within the past 30 days
- Have had worker's compensation claim, disability, or litigation
- Have a known history of uncontrolled narrow-angle glaucoma
- Have a known history of suicidal ideation
- Use monoamine oxidase inhibitors (MAOI) concomitantly
- Are allergic or intolerant to acetaminophen
- Using opioids 4 or more days per week during the month preceding the screening visit
- Have significant history or renal impairment/failure.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Analgesic Solutions
Natick, Massachusetts, 01760
Karen Cowles, RN, MPH, 781-444-9605 ext. 121, kcowles@analgesicsolutions.com
Courtney Lincoln, 781-444-9605 ext. 119, clincoln@analgesicsolutions.com
About this study
Official title: A Double-Blind, Placebo-Controlled, Enriched Enrollment Randomized Withdrawal Study to Evaluate the Efficacy of Milnacipran in the Treatment of Pain Due to Osteoarthritis
The present study will aim to evaluate the efficacy of milnacipran in the treatment of pain due to osteoarthritis (OA), that is, to determine whether milnacipran provides superior efficacy to placebo in patients with OA. Milnacipran is a serotonin-norepinephrine reuptake inhibitor (SNRI) that is currently approved in the United States in the treatment of major depressive disorder and fibromyalgia. There is increased evidence to suggest that SNRIs may be effective in the treatment of chronic pain conditions, such as OA.
The hypothesis in this study is that the survival time (time from randomization to loss of efficacy) of milnacipran group is superior to that of placebo group.
Read the detailed description
The study design is a Double-Blind, Placebo-Controlled, Enriched Enrollment Randomized Withdrawal Study. This means that, upon entry into the study, all subjects will enter an open-label period during which they will take milnacipran for 4 weeks. Subjects will taper their dose up to one 100mg tablet twice daily for a total of 200mg per day. After 4 weeks, the subject will return to the clinic and be re-evaluated.
Only subjects who meet certain criteria are then randomized to continue in the double-blind period of the study. Once a subject is randomized, he or she will take either milnacipran or placebo for another 4 weeks. Following the double-blind period, subjects will be tapered off the study medication and will receive a phone call once each week for 2 weeks for follow-up assessments.
Throughout the study, subjects will complete various questionnaires and other test procedures aimed at sub-typing subjects based on pain mechanisms.
- Conditions
- Osteoarthritis
- Being tested
- Milnacipran, Placebo
- Keywords
- Osteoarthritis (OA), Milnacipran, Serotonin-norepinephrine reuptake inhibitor (SNRI), Knee pain
- Medical subject headings
- Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MilnacipranDrug
1 tablet (100mg) by mouth twice daily for 28 days
PlaceboDrug
1 tablet by mouth twice daily for 28 days
| Study group | Role | What they receive |
|---|---|---|
| Milnacipran | Experimental | If subjects meet the criteria to enter the Double-Blind Period, they will be randomized at a 1:1 ratio to take either milnacipran or placebo for 4 weeks. The milnacipran arm will take milnacipran at 200mg/day (100mg twice daily). Receives: Drug: Milnacipran |
| Placebo | Placebo comparator | If subjects meet the criteria to enter the Double-Blind Period, they will be randomized at a 1:1 ratio to take either milnacipran or placebo for 4 weeks. The placebo group will take 1 tablet twice daily. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to loss of efficacy in the Double-Blind Period
The time to pain worsening by 30% compared to the value at baseline and a pain score of at least 4 on the 0-10 numerical rating scale on weekly pain assessment. Subjects who drop out due to "lack of efficacy" will be counted as efficacy failures regardless of their pain scores.
Measured: 28 days
Secondary outcomes (7)
Mean change in pain intensity
Mean change in pain intensity on the 0-10 numerical rating scale from baseline in the Double-Blind Period.
Measured: 28 days
Mean change in Western Ontario and McMaster Osteoarthritis Index (WOMAC) scores
Mean change in Western Ontario and McMaster Osteoarthritis Index (WOMAC) scores from Baseline in the Open-Label Period and Double-Blind Period.
Measured: 28 days
The efficacy of milnacipran vs. placebo by time to dropout for all causes
Measured: 70 days
The efficacy of milnacipran in the Open-Label Period
The efficacy of milnacipran in the Open-Label Period defined by the change in pain intensity from Baseline to the end of the period and responder proportion.
Measured: 28 days
The difference between milnacipran and placebo in responder proportion in the Double-Blind Period
Measured: 28 days
The predictive value of "OA sensory sub-type" for predicting the response to milnacipran vs. placebo
Measured: 70 days
Safety and tolerability by monitoring adverse events
Measured: 70 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2011 (estimated)
- Study startJul 2011
- Primary completionFeb 2012 (estimated)
- Study completionSep 2012 (estimated)
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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Analgesic Solutions
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Forest Laboratories
- Investigators
- Stephen L. Wright, M.D., Principal investigator, Analgesic Solutions
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01329406
- Sponsor's protocol ID
- FRX001-2010
- Status last verified
- Aug 2011
- First submitted
- 4 Apr 2011
- Last updated
- 17 Aug 2011
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind, Placebo-Controlled, Enriched Enrollment Randomized Withdrawal Study to Evaluate the Efficacy of Milnacipran in the Treatment of Pain Due to Osteoarthritis
- ClinicalTrials.gov ID
- NCT01329406
- Acronym / sponsor ID
- FRX001-2010
- Conditions
- Osteoarthritis
- Keywords
- Osteoarthritis (OA), Milnacipran, Serotonin-norepinephrine reuptake inhibitor (SNRI), Knee pain
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Analgesic SolutionsIndustry (pharma, biotech, devices)
- Collaborators
- Forest Laboratories
- Study start
- Jul 2011
- Primary completion
- Feb 2012 (estimated)
- Study completion
- Sep 2012 (estimated)
- First posted
- 5 Apr 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 present study will aim to evaluate the efficacy of milnacipran in the treatment of pain due to osteoarthritis (OA), that is, to determine whether milnacipran provides superior efficacy to placebo in patients with OA. Milnacipran is a serotonin-norepinephrine reuptake inhibitor (SNRI) that is currently approved in the United States in the treatment of major depressive disorder and fibromyalgia. There is increased evidence to suggest that SNRIs may be effective in the treatment of chronic pain conditions, such as OA.
The hypothesis in this study is that the survival time (time from randomization to loss of efficacy) of milnacipran group is superior to that of placebo group.
Detailed description
The study design is a Double-Blind, Placebo-Controlled, Enriched Enrollment Randomized Withdrawal Study. This means that, upon entry into the study, all subjects will enter an open-label period during which they will take milnacipran for 4 weeks. Subjects will taper their dose up to one 100mg tablet twice daily for a total of 200mg per day. After 4 weeks, the subject will return to the clinic and be re-evaluated.
Only subjects who meet certain criteria are then randomized to continue in the double-blind period of the study. Once a subject is randomized, he or she will take either milnacipran or placebo for another 4 weeks. Following the double-blind period, subjects will be tapered off the study medication and will receive a phone call once each week for 2 weeks for follow-up assessments.
Throughout the study, subjects will complete various questionnaires and other test procedures aimed at sub-typing subjects based on pain mechanisms.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Milnacipran | Experimental | Drug: MilnacipranIf subjects meet the criteria to enter the Double-Blind Period, they will be randomized at a 1:1 ratio to take either milnacipran or placebo for 4 weeks. The milnacipran arm will take milnacipran at 200mg/day (100mg twice daily). |
| Placebo | Placebo comparator | Drug: PlaceboIf subjects meet the criteria to enter the Double-Blind Period, they will be randomized at a 1:1 ratio to take either milnacipran or placebo for 4 weeks. The placebo group will take 1 tablet twice daily. |
Who may qualify
- Ages
- 21 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Be 21-75 years of age and in good general medical and psychological health
- Be able to speak, read, write, and understand English, understand the consent form, complete study related procedures, and communicate with the study staff
- Have a negative urine pregnancy test at screening, and use appropriate birth control
- Have documented painful Osteoarthritis (OA) of at least one knee for at least 6 months; OA should be of Class I-III and meet the American College of Rheumatology (ACR) clinical classification criteria, defined as:
- Have a target joint pain average of 5 days per week and have an average pain intensity of at least 4/10 on the 0-10 NRS over the last 24 hours prior to screening
Key exclusion criteria (15 listed)
- Are allergic or intolerant to SNRI; have a previous poor response to a SNRI for OA pain; are currently taking an SNRI or tricyclic antidepressant
- Have a body mass index (BMI) >40 kg/m2
- Have an Hospital Anxiety and Depression Scale (HADS) score >12 on either subscale or has an established history of major depressive disorder not controlled with medication
- Have significant pain outside the target knee, including significant hip or back pain. (Bilateral knee OA allowed.)
- Have pain affecting the target knee that is due to any other etiology than OA
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 |
|---|---|---|
| Milnacipran1 tablet (100mg) by mouth twice daily for 28 days | Drug | Milnacipran |
| Placebo1 tablet by mouth twice daily for 28 days | Drug | Placebo |
Primary outcome
Time to loss of efficacy in the Double-Blind Period
Time frame: 28 days
The time to pain worsening by 30% compared to the value at baseline and a pain score of at least 4 on the 0-10 numerical rating scale on weekly pain assessment. Subjects who drop out due to "lack of efficacy" will be counted as efficacy failures regardless of their pain scores.
7 secondary outcomes
Mean change in pain intensity
Time frame: 28 days
Mean change in Western Ontario and McMaster Osteoarthritis Index (WOMAC) scores
Time frame: 28 days
The efficacy of milnacipran vs. placebo by time to dropout for all causes
Time frame: 70 days
The efficacy of milnacipran in the Open-Label Period
Time frame: 28 days
The difference between milnacipran and placebo in responder proportion in the Double-Blind Period
Time frame: 28 days
The predictive value of "OA sensory sub-type" for predicting the response to milnacipran vs. placebo
Time frame: 70 days
Safety and tolerability by monitoring adverse events
Time frame: 70 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2011.
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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.
Stephen L. Wright, M.D. principal investigator
Analgesic Solutions
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Milnacipran in people with Osteoarthritis, run by Analgesic Solutions at 1 site in United States.
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 15 inclusion and 15 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: status not confirmed, as of the sponsor's last update on 17 Aug 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to loss of efficacy in the Double-Blind Period (time frame: 28 days). 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 17 Aug 2011.