A Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Study of Milnacipran 100 And 200 MG Daily in Patients With Fibromyalgia: Effects On 24 Hour Ambulatory Blood Pressure
Overview
- Phase
- Phase 3
- Intervention
- Milnacipran hydrochloride
- Conditions
- Fibromyalgia
- Sponsor
- Forest Laboratories
- Enrollment
- 321
- Locations
- 38
- Primary Endpoint
- Change From Baseline in Mean Systolic Blood Pressure Following 12-hour Period Post-AM Dose at Visit 4
- Status
- Completed
- Last Updated
- 16 years ago
Overview
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.
Detailed Description
This study is double blind (neither you nor the physician will know if you are receiving active study drug or placebo, an inactive compound such as a sugar pill) and it is being conducted at various research centers in the United States. If the study staff determines that you are eligible and you decide to participate, there will be approximately 11 study visits in about 3 months. During these visits, you will undergo routine health exams and complete different kinds of questionnaires. This study requires that you wear a blood pressure cuff continuously for 24 hours on three separate occasions. You will also be required to make multiple same-day visits to the study site on three separate occasions for blood draws.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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).
Exclusion Criteria
- •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
Arms & Interventions
1
Intervention: Milnacipran hydrochloride
2
Intervention: Placebo
Outcomes
Primary Outcomes
Change From Baseline in Mean Systolic Blood Pressure Following 12-hour Period Post-AM Dose at Visit 4
Time Frame: 4 weeks (1 week of dose-escalation, 3 weeks of 100 mg/d)
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.
Change From Baseline in Mean Systolic Blood Pressure Following 12-hour Period Post-AM Dose at Visit 6
Time Frame: 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 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.
Secondary Outcomes
- 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))