Premenstrual dysphoric disorder (PMDD) affects 3% to 5% of menstruating women. PMDD is defined by markedly depressed mood, anxiety, and/or affective lability during the last week of the late luteal phase with absence of these symptoms in the postmenses week. These symptoms markedly interfere with work or school or with usual social activities and relationships with others. Suppression of ovarian cyclicity is known to alleviate symptoms of PMDD.
Conditions
Interventions
Product Name: Levonorgestrel 90µg/Ethinyl Estradiol 20µg (LNG/EE)
Pharmaceutical Form: Tablet
INN or Proposed INN: Levonorgestrel
CAS Number: 797-63-7
Sponsors
Wyeth Research Division of Wyeth Pharmaceuticals Inc., Clinical Research and Development
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Generally healthy women aged 18 to 49 years who meet Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), criteria for PMDD and who are willing to take a combination OC. 2.Subjects must have symptoms consistent with PMDD by history over the past year. 3.Subjects must prospectively meet the following criteria using the DRSP instrument and worksheet : a. Subjects must have an average (across 5 days) daily follicular phase (days 8 to 12 after the first day of menses) score or = 4) for at least 2 days - At least mild (> or = 3) for at least 2 of the remaining days on 5 or more of the 11 PMDD symptoms during both the pretreatment screening cycle 2 and placebo run-in cycle 3, with at least 1 of the symptoms being either items 1 (a, b or c), (2), 3 (a or b), or 4 (a or b). c.Subjects must have an average daily efficacy period (the 6 days before menses through day 1 of menses [7 days total]) score > or = 50 with a > or = 50% increase from the previous average daily total follicular phase score to the efficacy period score during both the pretreatment screening cycle 2 and placebo run-in cycle 3.d.Subjects must have an efficacy period (the 6 days before menses through day 1 of menses [7 days total]) score of at least moderate (> or = 4) for at least 2 days on any of the 3 functional impairment items during both the pretreatment screening cycle 2 and placebo run-in cycle 3. 4.Subjects must not be at risk for pregnancy during the study, or they must be using an effective, nonhormonal method of birth control (eg, diaphragm, condom with spermicide, sterilization, or nonhormonal intrauterine device [IUD]) or must be practicing complete abstinence. 5. Subjects must have had regular (21- to 35-day) menstrual cycles by history for the 2-month period preceding the pretreatment screening cycle 1 (visit 1). 6. Subjects must have a cervical cytological smear report of negative for intraepithelial lesion or malignancy. If atypical squamous cells of undeterminedsignificance (ASCUS) is reported, the subject must have a negative test for humanpapilloma virus (HPV). The cervical cytological smear must be performed atpretreatment screening cycle 1 (visit 1) or within 6 months of pretreatmentscreening cycle 1 (visit 1) provided that a copy of the report is available. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. The presence or history of the following will prevent enrollment: Thrombophlebitis, thrombosis, thromboembolic disorders, deep vein thrombosis, pulmonary embolism, or known coagulopathy. Ischemic heart disease or myocardial infarction. Cerebrovascular disease, cardiovascular disease, or thrombogenic valvular heart disease. Headaches with focal neurological symptoms in the 90 days before visit 1.Known or suspected estrogen-dependent neoplasia, known or suspected carcinoma of the breast, or ovarian carcinoma.Undiagnosed abnormal genital bleeding within the past 180 days of pretreatment screening cycle 1 (visit 1).Major depressive disorder requiring antidepressant treatment or hospitalization, or associated with suicide attempt or risk for suicide within the last 3 years before pretreatment screening cycle 1 (visit 1). Known hypersensitivity to estrogens, progestins, or any components of the study medication.Use of depot medroxyprogesterone acetate (ie, Depo-Provera) within 6 months of pretreatment screening cycle 1 (visit 1) and for the duration of the study.Use of monthly hormonal contraceptive injections, a hormonal IUD, implantable contraceptive hormones, oral contraceptives, estrogens, progestins, androgens, or gonadotropin-releasing hormone (GnRH) analogs within 60 days of pretreatment screening cycle 1 (visit 1) and for the duration of the study.Use of any experimental drug or device or participation in another research study within 10 days of pretreatment screening cycle 1 (visit 1) and for the duration of the study. Use of antidepressants/anxiolytics including but not limited to, tricyclic antidepressants, selective serotonin reuptake inhibitors (excluding fluoxetine), selective serotonin and norepinephrine reuptake inhibitors (eg, venlafaxine), serotonin agonists, monoamine oxidase inhibitors, benzodiazepines, bupropion, nefazadone, mirtazipine, and herbal preparations (eg, St. John’s wort, kava) within 10 days of pretreatment screening cycle 1 (visit 1) and for the duration of the study.Use of fluoxetine within the 30 days of pretreatment screening cycle 1 (visit 1) and for the duration of the study. 2. The presence of any of the following will prevent enrollment:Hamilton Depression Rating Scale (HAM-D17) score >11 administered during pretreatment screening cycle 2, days 8 to 12 (visit 2).Diagnosis of a current Axis I psychiatric disorder, based on the Mini International Neuropsychiatric regarding major depressive episode criteria administered during pretreatment screening cycle 2, days 8 to 12 (visit 2).Seasonal affective disorder, bipolar depression, psychotic disorder, somatoform disorder, dysthymic disorder, schizophrenia, obsessive-compulsive disorder, or antisocial/borderline/schizotypal personality disorder.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of treatment with LNG/EE administered in a continuous daily regimen versus placebo on the mean change in average Daily Record of Severity of Problems (DRSP) 21-item total daily score from baseline to the cycle 1 efficacy period and from baseline to the last on-therapy efficacy period.; Secondary Objective: To evaluate the effect of treatment with LNG/EE administered in a continuous daily regimen versus placebo on the following: - Change from baseline in the DRSP 21-item total daily score based on the 5 days with the highest DRSP scores in each “estimated” treatment cycle. - Mean change from baseline in Clinical Global Impression-Severity (CGI S) scores. - Responder analyses based on CGI-S scores, percentage improvements in DRSP scores and PMDD criteria. - Change from baseline in mean clinically defined DRSP cluster (symptom subgroup) scores. - Change from baseline in Work Limitations Questionnaire (WLQ). - Area under the curve (AUC) analysis of DRSP scores for the entire 112-day period. - Subject global evaluation mean scores. - Change in weight. ;Primary end point(s): Comparison of the active treatment and placebo groups on mean change in the DRSP score from the baseline efficacy period to the cycle 1 efficacy period and from the baseline efficacy period to the last on-therapy efficacy period. Each subject will be asked to complete the DRSP questionnaire during pretreatment screening cycle 2, during placebo run-in cycle 3, and during each of the four 28-day pill packs of double-blind treatment. For each subject, the baseline DRSP 21-item score will be the mean of the scores determined during the pretreatment screening cycle 2 and placebo run-in cycle 3, using data from the average of the 5 most symptomatic days (highest daily 21-item scores) of the efficacy period of thos | — |
Countries
Denmark, Finland, Germany, Sweden, United Kingdom
Outcome results
None listed