Study to Evaluate the Efficacy of Milnacipran in the Treatment of Pain Due to Osteoarthritis

Osteoarthritis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01329406
• Other study ID #: FRX001-2010
• Status: Recruiting
• Phase: Phase 4
• First received: April 4, 2011
• Last updated: August 16, 2011
• Start date: July 2011
• Est. completion date: September 2012

Study information

• Verified date: August 2011
• Source: Analgesic Solutions
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: September 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years to 75 Years

Eligibility

Inclusion Criteria:

• 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:

1. Knee pain and at least 3 of the following 6:

• Age > 50

• Morning stiffness < 30 minutes

• Crepitus on active motion

• Bony tenderness

• Bony enlargement

• No palpable warmth of synovium

2. 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

Exclusion Criteria:

• 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

• 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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Osteoarthritis

Intervention

Drug:
• Milnacipran
1 tablet (100mg) by mouth twice daily for 28 days
• Placebo
1 tablet by mouth twice daily for 28 days

Locations

Country	Name	City	State
United States	Analgesic Solutions	Natick	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Analgesic Solutions	Forest Laboratories

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	28 days	No
Secondary	Mean change in pain intensity	Mean change in pain intensity on the 0-10 numerical rating scale from baseline in the Double-Blind Period.	28 days	No
Secondary	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.	28 days	No
Secondary	The efficacy of milnacipran vs. placebo by time to dropout for all causes		70 days	No
Secondary	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.	28 days	No
Secondary	The difference between milnacipran and placebo in responder proportion in the Double-Blind Period		28 days	No
Secondary	The predictive value of "OA sensory sub-type" for predicting the response to milnacipran vs. placebo		70 days	No
Secondary	Safety and tolerability by monitoring adverse events		70 days	Yes