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

Primary Purpose

Osteoarthritis

Status

Unknown status

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Milnacipran

Placebo

About this trial

This is an interventional treatment trial for Osteoarthritis focused on measuring Osteoarthritis (OA), Milnacipran, Serotonin-norepinephrine reuptake inhibitor (SNRI), Knee pain

Eligibility Criteria

21 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Analgesic SolutionsRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Milnacipran

Placebo

Arm Description

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).

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Mean change in pain intensity

Mean change in pain intensity on the 0-10 numerical rating scale from baseline in the Double-Blind Period.

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.

The efficacy of milnacipran vs. placebo by time to dropout for all causes

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.

The difference between milnacipran and placebo in responder proportion in the Double-Blind Period

The predictive value of "OA sensory sub-type" for predicting the response to milnacipran vs. placebo

Safety and tolerability by monitoring adverse events

Full Information

NCT ID

NCT01329406

First Posted

April 4, 2011

Last Updated

August 16, 2011

Sponsor

Analgesic Solutions

Collaborators

Forest Laboratories

1. Study Identification

Unique Protocol Identification Number

NCT01329406

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2011

Overall Recruitment Status

Unknown status

Study Start Date

July 2011 (undefined)

Primary Completion Date

February 2012 (Anticipated)

Study Completion Date

September 2012 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor

Analgesic Solutions

Collaborators

Forest Laboratories

4. Oversight

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Osteoarthritis

Keywords

Osteoarthritis (OA), Milnacipran, Serotonin-norepinephrine reuptake inhibitor (SNRI), Knee pain

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Milnacipran

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Milnacipran

Intervention Description

1 tablet (100mg) by mouth twice daily for 28 days

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

1 tablet by mouth twice daily for 28 days

Primary Outcome Measure Information:

Title

Time to loss of efficacy in the Double-Blind Period

Description

Time Frame

28 days

Secondary Outcome Measure Information:

Title

Mean change in pain intensity

Description

Mean change in pain intensity on the 0-10 numerical rating scale from baseline in the Double-Blind Period.

Time Frame

28 days

Title

Mean change in Western Ontario and McMaster Osteoarthritis Index (WOMAC) scores

Description

Mean change in Western Ontario and McMaster Osteoarthritis Index (WOMAC) scores from Baseline in the Open-Label Period and Double-Blind Period.

Time Frame

28 days

Title

The efficacy of milnacipran vs. placebo by time to dropout for all causes

Time Frame

70 days

Title

The efficacy of milnacipran in the Open-Label Period

Description

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.

Time Frame

28 days

Title

The difference between milnacipran and placebo in responder proportion in the Double-Blind Period

Time Frame

28 days

Title

The predictive value of "OA sensory sub-type" for predicting the response to milnacipran vs. placebo

Time Frame

70 days

Title

Safety and tolerability by monitoring adverse events

Time Frame

70 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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: 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 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Stephen L. Wright, M.D.

Organizational Affiliation

Analgesic Solutions

Official's Role

Principal Investigator

Facility Information:

Facility Name

Analgesic Solutions

City

Natick

State/Province

Massachusetts

ZIP/Postal Code

01760

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Karen Cowles, RN, MPH

Phone

781-444-9605

Ext

121

kcowles@analgesicsolutions.com

First Name & Middle Initial & Last Name & Degree

Courtney Lincoln

Phone

781-444-9605

Ext

119

clincoln@analgesicsolutions.com

First Name & Middle Initial & Last Name & Degree

Stephen L. Wright, M.D.

First Name & Middle Initial & Last Name & Degree

Nathaniel P. Katz, M.D., M.S.

First Name & Middle Initial & Last Name & Degree

Eric Osgood, M.D.

12. IPD Sharing Statement

Learn more about this trial

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

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