A Study Of Milnacipran In Patients With Fibromyalgia: Effects On 24 Hour Ambulatory Blood Pressure Monitoring

NCT00618956 | Completed Phase 3 Results

• 1 other identifier: MLN-MD-12
• Study Type: interventional
• Target: 321
• Locations: 1 country
• Sites: 38

Brief Summary

The study is designed to accurately assess any changes in blood pressure and pulse at 100 and 200 mg daily dose of milnacipran in patients with fibromyalgia syndrome.

Conditions

Fibromyalgia

Keywords

NSRI; milnacipran; fibromyalgia; blood pressure; hypertension

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Mean Systolic Blood Pressure Following 12-hour Period Post-AM Dose at Visit 4

  Change from baseline to Visit 4 in mean systolic blood pressure (SBP) based on ambulatory blood pressure monitor (ABPM) is defined as the mean SBP value at Visit 4 minus the corresponding mean SBP value at baseline in the same 12-hour period post-AM dose.

  4 weeks (1 week of dose-escalation, 3 weeks of 100 mg/d)

• Change From Baseline in Mean Systolic Blood Pressure Following 12-hour Period Post-AM Dose at Visit 6

  Change from baseline to Visit 6 in mean systolic blood pressure based on ABPM is defined as the mean SBP value at Visit 6 minus the corresponding mean SBP value at baseline in the same 12-hour period post-AM dose.

  7 weeks (1 week of dose-escalation, 3 weeks of 100 mg/d, followed by 1 week at 150 mg/d and 2 weeks of 200 mg/d)

Secondary Outcomes (4)

• Change From Baseline in Mean Systolic Blood Pressure /Diastolic Blood Pressure for 12-hour Period Post-AM Dose at Visit 4

  4 weeks (1 week of dose-escalation, 3 weeks of 100 mg/d)

• Change From Baseline in Mean SBP/DBP Following 12-hour Period Post-AM Dose at Visit 6

  7 weeks (1 week of dose-escalation, 3 weeks of 100 mg/d, followed by 1 week at 150 mg/d and 2 weeks of 200 mg/d)

• Change From Baseline in Mean Heart Rate (HR) Following 24-hour Treatment at Visit 4

  4 weeks (1 week of dose-escalation, 3 weeks of 100 mg/d)

• Change From Baseline in Mean HR Following 24-hour Treatment at Visit 6

  7 weeks (1 week of dose-escalation, 3 weeks of 100 mg/d, followed by 1 week at 150 mg/d and 2 weeks of 200 mg/d)

Study Arms (2)

1

EXPERIMENTAL

Drug: Milnacipran hydrochloride

2

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Milnacipran hydrochloride DRUG

Milnacipran 100 to 200 mg/day tablet (administered in divided doses, twice daily \[BID\]), oral administration.

Also known as: Ixel (outside of United States)

1

Placebo DRUG

Placebo

2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be eligible to participate in the study, patients must meet the following criteria:
• Patients may be male or female between the ages of 18 and 70 years, inclusive
• Patients must have been diagnosed of primary fibromyalgia, as defined by the 1990 ACR Criteria for the Classification of Fibromyalgia
• Females must be either postmenopausal (no menses for at least 1 year), posthysterectomy, postoophorectomy (bilateral), or, if of childbearing potential, must have a negative urine pregnancy test prior to randomization and be using a medically acceptable form of contraception (eg, hormonal birth control, IUD, double-barrier method \[eg, simultaneous use of two of the following: male condom, female condom, diaphragm\], or a barrier method plus a spermicidal agent \[contraceptive foam, jelly, or cream\])
• Patients must have the ability to give written informed consent
• Patients may have hypertension untreated or treated with a maximum of two antihypertensive medications. (Note: medications contributing to a combination product(s) will each be considered as a separate medication.) If untreated, the patient should be stable, with no expectation of initiating treatment during the study. If treated, the patient must have been on stable doses of antihypertensive medications for at least 2 months, with the expectation that dose adjustments will not be necessary for the duration of the study. A patient will be classified as hypertensive if the patient is taking antihypertensive medication, has a SBP equal to or greater than 130 mm Hg, or has a DBP equal to or greater than 85 mm Hg. A patient will be classified as normotensive if he/she is not on antihypertensive medication and has a SBP less than 130 mm Hg and DBP less than 85 mm Hg
• Patients must have a mean of two sitting SBP measurements of less than 160 mm Hg and sitting DBP less than 100 mm Hg at Visit 1 (Screening) and Visit 2 (Baseline/Randomization) using an automatic office blood pressure monitor
• Patients must have normal physical examination findings, clinical laboratory results, and electrocardiogram (ECG) results from Visit 1 (Screening) or abnormal findings judged not clinically significant by the Investigator and documented as such in the eCRF
• Patients must be willing to withdraw from CNS-active therapies marketed as antidepressants, including monoamine oxidase inhibitors, tricyclics, tetracyclics, selective-serotonin reuptake inhibitors (SSRIs), noradrenaline reuptake inhibitors (NARIs), noradrenaline-serotonin reuptake inhibitors (NSRI), serotonin-noradrenaline reuptake inhibitors (SNRIs), and St. John's Wort
• Patients must be willing to withdraw from pregabalin (Lyrica) or gabapentin (Neurontin).
• Patients must be willing to withdraw from stimulant medications such as those used to treat attention deficit disorder/attention deficit hyperactivity disorder (eg, amphetamine/dextroamphetamine \[Adderall\], methylphenidate, dextroamphetamine) or the fatigue associated with sleep apnea or shift work (eg, modafinil)
• Patients must be willing to withdraw from anorectic agents such as diethylpropion , sibutramine (Meridia), and phentermine (Adipex)
• Patients must be willing to withhold certain medications for the 24 hours before, as well as during, any ABPM assessment. These medications include phosphodiesterase type 5 inhibitors (eg, Viagra, Levitra, Cialis, Edex, Muse), decongestants (eg, pseudoephedrine, phenylephrine), and antimigraine therapies (eg, triptans such as Imitrex and Maxalt, ergotamines such as Cafergot and Midrin). If, for any reason, the patient takes any of these medications, the ABPM visit should be rescheduled so that at least 24 hours have transpired since the patient's last use

You may not qualify if:

• Patients who meet any of the following criteria will not be eligible to participate in the study:
• Psychological/Psychiatric Criteria
• Patients with a significant risk of suicide, according to the Investigator's judgment or based on an answer of 2 or 3 for question 9 of the Beck Depression Inventory (BDI) (regarding suicidal ideation) performed at Visit 1 (Screening) or Visit 2 (Baseline/Randomization)
• Patients with a total BDI score greater than 25 at Visit 1 (Screening) or Visit 2 (Baseline/Randomization)
• Patients testing positive for illegal substances prior to Visit 2 (Baseline/Randomization) as demonstrated by positive drug screening or based on the Investigator's judgment
• Patients with any history or behavior that would, in the Investigator's judgment, prohibit compliance for the duration of the study
• Somatic Criteria
• Patients with myocardial infarction and/or stroke within the past 12 months; active cardiac disease (American Heart Association Functional Class 2, 3, or 4); congestive heart failure; hemodynamically significant valvular heart disease (including patients with a prosthetic heart valve); hypertensive cardiovascular disease changes (heart, eyes or kidneys) that in the Investigator's judgment, would preclude patient participation; ischemic changes; and/or clinically significant cardiac rhythm or conduction abnormalities (including atrial fibrillation, left bundle branch block, second- or third-degree heart block)
• Patients with a mean of two sitting systolic blood pressure (SBP) readings equal to or greater than 160 mm Hg or sitting diastolic blood pressure (DBP) equal to or greater than 100 mm Hg at Visits 1 (Screening) and 2 (Baseline/Randomization) using an automatic office blood pressure monitor
• Patients with pacemakers
• Patients with an upper arm circumference less than 24 cm or greater than 42 cm in their nondominant arm
• Patients with evidence of active liver disease (levels of aspartate aminotransferase, alanine aminotransferase, and/or alkaline phosphatase \> 1.5× the upper limit of the normal range for the clinical laboratory performing the test)
• Patients with renal impairment (estimated creatinine clearance \< 50 mL/min)
• Patients with documented autoimmune disease. Patients diagnosed with Hashimoto or Grave disease that has been stable for 3 months prior to Visit 1 (Screening) will be allowed to enroll
• Patients with current systemic infection (eg, human immunodeficiency virus, hepatitis)

Sponsors & Collaborators

• Forest Laboratories: lead
• Cypress Bioscience, Inc.: collaborator

Study Sites (38)

Site #032

Birmingham, Alabama, 35205, United States

Location

Site #035

Birmingham, Alabama, 35209, United States

Location

Site #038

Phoenix, Arizona, 85004, United States

Location

Site #019

Pismo Beach, California, 93449, United States

Location

Site #016

San Diego, California, 92117, United States

Location

Site #008

Walnut Creek, California, 94598, United States

Location

Site #037

Delray Beach, Florida, 33484, United States

Location

Site #025

Jacksonville, Florida, 32216, United States

Location

Site #009

Ocala, Florida, 34471, United States

Location

Site #011

Orlando, Florida, 32806, United States

Location

Site #036

Tampa, Florida, 33614, United States

Location

Site #006

Atlanta, Georgia, 30328, United States

Location

Site #030

Libertyville, Illinois, 60048, United States

Location

Site #018

Evansville, Indiana, 47713, United States

Location

Site #034

Indianapolis, Indiana, 46254, United States

Location

Site #004

Worchester, Massachusetts, 01610, United States

Location

Site #013

Springfield, Missouri, 65807, United States

Location

Site #021

Albuquerque, New Mexico, 87108, United States

Location

Site #005

East Syracuse, New York, 13057, United States

Location

Site #010

Rochester, New York, 14618, United States

Location

Site #029

Charlotte, North Carolina, 28209, United States

Location

Site #022

Winston-Salem, North Carolina, 27103, United States

Location

Site #002

Cleveland, Ohio, 44122, United States

Location

Site #017

Toledo, Ohio, 13623, United States

Location

Site #023

Eugene, Oregon, 97401, United States

Location

Site #007

Eugene, Oregon, 97404, United States

Location

Site #001

Medford, Oregon, 97501, United States

Location

Site #026

Mechanicsburg, Pennsylvania, 17055, United States

Location

Site #014

Greer, South Carolina, 29651, United States

Location

Site #027

Bristol, Tennessee, 37620, United States

Location

Site #024

Memphis, Tennessee, 38119, United States

Location

Site #031

Nashville, Tennessee, 37203, United States

Location

Site #028

Sugarland, Texas, 77479, United States

Location

Site #003

Salt Lake City, Utah, 84102, United States

Location

Site #012

Woodstock, Vermont, 05091, United States

Location

Site #020

Richmond, Virginia, 23294, United States

Location

Site #015

Bellingham, Washington, 98226, United States

Location

Site #033

Racine, Wisconsin, 53406, United States

Location

Related Publications (1)

• Trugman JM, Palmer RH, Ma Y. Milnacipran effects on 24-hour ambulatory blood pressure and heart rate in fibromyalgia patients: a randomized, placebo-controlled, dose-escalation study. Curr Med Res Opin. 2014 Apr;30(4):589-97. doi: 10.1185/03007995.2013.861812. Epub 2013 Nov 20.

  PMID: 24188161 DERIVED

MeSH Terms

Conditions

Fibromyalgia; Hypertension

Interventions

Milnacipran

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neuromuscular Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Cyclopropanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Robert Palmer, MD
• Organization: Forest Research Institute, a subsidiary of Forest Laboratories, Inc.

robert.palmer@frx.com

201-427-8218

Study Officials

• Allan Spera

  Forest Laboratories

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: January 31, 2008
• First Posted: February 20, 2008
• Study Start: October 1, 2007
• Primary Completion: July 1, 2008
• Last Updated: November 20, 2009
• Results First Posted: September 3, 2009

Record last verified: 2009-11

Locations

US (38)