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| ID | Type | Description | Link |
|---|---|---|---|
| R01MH072955 | U.S. NIH Grant/Contract | View source | |
| DSIR 83-ATSO | Other Grant/Funding Number | National Institute of Mental Health |
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| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
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This study will evaluate the effectiveness of sertraline in reducing symptoms in women diagnosed with premenstrual dysphoric disorder.
Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome (PMS). PMDD affects nearly 5 percent of menstruating women in the United States. This disorder is very disruptive and can affect a woman's performance at work and her relationships with friends and family. Symptoms typically occur 10 to 14 days before the start of a woman's period and dissipate soon after. Sadness, rapid changes in mood, anxiety, and irritability are common symptoms associated with PMDD. Sertraline is a selective serotonin reuptake inhibitor (SSRI) that has been approved by the U.S. Food and Drug Administration (FDA) to treat PMDD. This study will evaluate the effectiveness of sertraline in reducing symptoms in women diagnosed with PMDD.
All participants will begin this study by recording their symptoms for two complete menstrual cycles. At a baseline study visit, participants will then be randomly assigned to receive either sertraline or placebo for six menstrual cycles. At the onset of PMDD symptoms, participants will take two pills of their assigned treatment daily. Once symptoms have dissipated, usually around the first or second day of the menstrual cycle, participants will stop taking their assigned treatment for that cycle. For the next 4 months, participants will attend study visits on the fifth day of each monthly menstrual cycle. For the following 2 months, participants will be contacted by telephone. Participants will be asked to rate their mood and symptoms at each contact. A final study visit will be scheduled on the first day of the seventh menstrual cycle. At this point, all participants will be offered sertraline for an additional three menstrual cycles, dosed on a daily basis. Two study visits will be scheduled over the course of the three cycles to evaluate the effectiveness of sertraline when dosed continuously. Urine collection and pregnancy tests may occur at selected times during the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sertraline | Experimental | Participants will take sertraline that is dosed between 50 and 100 mgs during the symptomatic period. Women who report moderate to severe side effects will be allowed to reduce their dose to 25 mg of sertraline and to increase the dose at the next cycle unless rate-limiting side effects continue. |
|
| Placebo | Placebo Comparator | Participants will take similar looking placebo during the symptomatic period. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sertraline | Drug | 50 mg of sertraline will be taken at the onset of premenstrual symptoms through the first few days of menses. If a participant shows an insufficient response to this dose, the dose may be increased to 100 mg. Women who report moderate to severe side effects will be allowed to reduce their dose to 25 mg of sertraline and to increase the dose at the next cycle unless rate-limiting side effects continue. |
| Measure | Description | Time Frame |
|---|---|---|
| Premenstrual Tension Scale (PMTS) | The PMTS is a 10-item scale constructed to study premenstrual syndromes. It is sensitive to change with treatment. It includes items of irritability-hostility, tension, efficiency, dysphoria, motor coordination, mental-cognitive functioning, eating habits, social impairment, sex drive, and physical symptoms. PMTS-O or PMTS-SR? Min=0 (asymptomatic), Max=40 (Highly symptomatic), higher scores indicate most severe problems | Measured from baseline to Cycle 6 |
| Inventory of Depression Symptoms (IDS-C) | Inventory of Depressive Symptomatology-Clinician version (IDS-C) - a depression measure that has 28 items and detects appropriate variations between follicular and luteal phases in subjects with PMDD. Min score is 0, max is 84.Lower score is less symptomatic. | Measured from baseline to Cycle 6 |
| Michelson SSRI Withdrawal Checklist | Michelson SSRI Withdrawal Checklist - 16-item (not exactly 17-item, mood swings and crying were in DRSP) including dizziness, nausea, unusual dreams, chills, increased sweating, loose stools, agitation, ringing or noises in the ears. Items were summed for 3 days after pill-taking ended for each menstrual cycle.Scale is 0-80 for total range of the scale with lower less severe. There are no units | Measured from Cycle 1 to Cycle 6 |
| Number of Days Pills Were Taken | The number of days that pills were taken on. | Measured from Cycle 1 to Cycle 6 |
| Number of Symptomatic Days Before Pills Were Taken | Symptomatic days were those that participant experienced at least 3 symptoms at a severity of at least "3", which is a mean of at least mild. | Cycle 1 to Cycle 6 |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical Global Severity (CGI-S) | Clinical Global Impressions-Severity is measured on a scale of 1-7, with 7 as most severe. | Baseline through Cycle 6 |
| DRSP Depression Subscale | Depressive symptoms included: felt depressed, felt hopeless, felt worthless or guilt, slept more, trouble sleeping, felt overwhelmed. Symptoms were scored on a scale of 1-6 The score range is 0-36 with higher indicating greater severity. |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse Events | A measurement of frequency of adverse events by random assignment | Baseline through Cycle 6 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kimberly A. Yonkers, MD | Yale University | Principal Investigator |
| Margaret Altemus, MD | Weill Medical College of Cornell University | Principal Investigator |
| Susan Kornstein, MD | Virginia Commonwealth University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yale University School of Medicine | New Haven | Connecticut | 06510 | United States | ||
| Cornell University, Weill Medical College |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18395582 | Background | Yonkers KA, O'Brien PM, Eriksson E. Premenstrual syndrome. Lancet. 2008 Apr 5;371(9619):1200-10. doi: 10.1016/S0140-6736(08)60527-9. | |
| 18328013 | Background | Wallenstein GV, Blaisdell-Gross B, Gajria K, Guo A, Hagan M, Kornstein SG, Yonkers KA. Development and validation of the Premenstrual Symptoms Impact Survey (PMSIS): a disease-specific quality of life assessment tool. J Womens Health (Larchmt). 2008 Apr;17(3):439-50. doi: 10.1089/jwh.2007.0377. |
| Label | URL |
|---|---|
| Click here for the PMS, Perinatal, and Postpartum Research Program's Web site | View source |
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we will share data with a data request that is reviewed by investigators
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Three-center study; New Haven, CT; New York City, NY; Richmond, VA. Participants recruited via direct mail and advertisements. Assessed initially over phone, then face-to-face screening office visit. Screening took place between September 2007 and February 2012.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sertraline | Participants will take sertraline that is dosed between 50 and 100 mgs during the symptomatic period Sertraline: 50 mg of sertraline will be taken at the onset of premenstrual symptoms through the first few days of menses. If a participant shows an insufficient response to this dose, the dose may be increased to 100 mg. Women who report moderate to severe side effects will be allowed to reduce their dose to 25 mg of sertraline and to increase the dose at the next cycle unless rate-limiting side effects continue. |
| FG001 | Placebo | Participants will take similarly looking placebo during the symptomatic period Placebo: 50 mg of placebo will be taken at the onset of premenstrual symptoms through the first few days of menses. If a participant shows an insufficient response to this dose, the dose may be increased to 100 mg. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Analysis included all women enrolled.
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| ID | Title | Description |
|---|---|---|
| BG000 | Sertraline | Participants will take sertraline that is dosed between 50 and 100 mgs during the symptomatic period Sertraline: 50 mg of sertraline will be taken at the onset of premenstrual symptoms through the first few days of menses. If a participant shows an insufficient response to this dose, the dose may be increased to 100 mg. Women who report moderate to severe side effects will be allowed to reduce their dose to 25 mg of sertraline and to increase the dose at the next cycle unless rate-limiting side effects continue. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | mean age in years |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Premenstrual Tension Scale (PMTS) | The PMTS is a 10-item scale constructed to study premenstrual syndromes. It is sensitive to change with treatment. It includes items of irritability-hostility, tension, efficiency, dysphoria, motor coordination, mental-cognitive functioning, eating habits, social impairment, sex drive, and physical symptoms. PMTS-O or PMTS-SR? Min=0 (asymptomatic), Max=40 (Highly symptomatic), higher scores indicate most severe problems | all randomized participants | Posted | Mean | Standard Deviation | units on a scale | Measured from baseline to Cycle 6 |
|
The adverse event data was collected for all participants at each visit. The first visits were in November of 2007 and the trial ended in July of 2012. Adverse event data spanned that 4 and a half year time frame.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Sertraline | Participants will take sertraline that is dosed between 50 and 100 mgs during the symptomatic period Sertraline: 50 mg of sertraline will be taken at the onset of premenstrual symptoms through the first few days of menses. If a participant shows an insufficient response to this dose, the dose may be increased to 100 mg. Women who report moderate to severe side effects will be allowed to reduce their dose to 25 mg of sertraline and to increase the dose at the next cycle unless rate-limiting side effects continue. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | snomed | Non-systematic Assessment |
Limitations of this study include attrition over time and the restricted dose range of 25-100mg sertraline.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kimberly A. Yonkers, M.D. | Yale University School of Medicine | 203-764-5914 | Kimberly.Yonkers@yale.edu |
Not provided
| ID | Term |
|---|---|
| D065446 | Premenstrual Dysphoric Disorder |
| D011293 | Premenstrual Syndrome |
| ID | Term |
|---|---|
| D008599 | Menstruation Disturbances |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D003866 | Depressive Disorder |
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| ID | Term |
|---|---|
| D020280 | Sertraline |
| D000073893 | Sugars |
| ID | Term |
|---|---|
| D015057 | 1-Naphthylamine |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D009281 | Naphthalenes |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| Placebo | Drug | 50 mg of placebo will be taken at the onset of premenstrual symptoms through the first few days of menses. If a participant shows an insufficient response to this dose, the dose may be increased to 100 mg. |
|
|
| DRSP | DRSP (Daily Rating of Severity Problems) is composed of 21 items reflecting the 11 candidate symptoms for PMDD according to DSM IV and DSM V. Each symptom is scored 1-6. A diagnosis of PMDD requires a minimum average luteal phase score of greater than or equal to 3 (mild) for at least 5 PMDD symptoms during the five most symptomatic of the final seven luteal phase days and the first two days of menses onset, and we require that the average follicular phase score not be >2 on these same items. The minimum score is 0 and maximum is 126 for the total score. A higher score indicates greater severity of symptoms. | Baseline to Cycle 6 |
| Baseline to Cycle 6 |
| DRSP Physical Subscale | Physical symptoms included breast tenderness, bloating, headache, joint or muscle pain. Symptoms were scored on a scale of 1-6. The severity range is 0-24 with 24 being more symptomatic. | Baseline to Cycle 6 |
| DRSP Anger/Irritability Subscale | Anger/irritability included anger/irritability and conflicts with people. Symptoms were scored on a scale 1-6. The range is 0 to 12 with a higher score indicating greater symptom severity. | Baseline to Cycle 6 |
| Clinical Global Impressions-Improvement (CGI-I) | The Clinical Global Impressions-Improvement (CGI-I) scale is a 7-point scale with 7 being the least improvement. | Cycle 1 to Cycle 6 |
| New York |
| New York |
| 10021 |
| United States |
| Virginia Commonwealth University | Richmond | Virginia | 23230 | United States |
| 17937566 | Background | Borenstein JE, Dean BB, Leifke E, Korner P, Yonkers KA. Differences in symptom scores and health outcomes in premenstrual syndrome. J Womens Health (Larchmt). 2007 Oct;16(8):1139-44. doi: 10.1089/jwh.2006.0230. |
| 17470584 | Background | Borenstein JE, Dean BB, Yonkers KA, Endicott J. Using the daily record of severity of problems as a screening instrument for premenstrual syndrome. Obstet Gynecol. 2007 May;109(5):1068-75. doi: 10.1097/01.AOG.0000259920.73000.3b. |
| 17454164 | Background | Halbreich U, Backstrom T, Eriksson E, O'brien S, Calil H, Ceskova E, Dennerstein L, Douki S, Freeman E, Genazzani A, Heuser I, Kadri N, Rapkin A, Steiner M, Wittchen HU, Yonkers K. Clinical diagnostic criteria for premenstrual syndrome and guidelines for their quantification for research studies. Gynecol Endocrinol. 2007 Mar;23(3):123-30. doi: 10.1080/09513590601167969. |
| 22393222 | Result | Hartlage SA, Freels S, Gotman N, Yonkers K. Criteria for premenstrual dysphoric disorder: secondary analyses of relevant data sets. Arch Gen Psychiatry. 2012 Mar;69(3):300-5. doi: 10.1001/archgenpsychiatry.2011.1368. |
| 37212651 | Derived | Yonkers KA, Altemus M, Gilstad-Hayden K, Kornstein SG, Gueorguieva R. Does Symptom-Onset Treatment With Sertraline Improve Functional Impairment for Individuals With Premenstrual Dysphoric Disorder?: A Randomized Controlled Trial. J Clin Psychopharmacol. 2023 Jul-Aug 01;43(4):320-325. doi: 10.1097/JCP.0000000000001700. Epub 2023 May 22. |
| 26351969 | Derived | Yonkers KA, Kornstein SG, Gueorguieva R, Merry B, Van Steenburgh K, Altemus M. Symptom-Onset Dosing of Sertraline for the Treatment of Premenstrual Dysphoric Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2015 Oct;72(10):1037-44. doi: 10.1001/jamapsychiatry.2015.1472. |
| Adverse Event |
|
| Rescue |
|
| Pregnancy |
|
| Protocol Violation |
|
| BG001 | Placebo | Participants will take similarly looking placebo during the symptomatic period Placebo: 50 mg of placebo will be taken at the onset of premenstrual symptoms through the first few days of menses. If a participant shows an insufficient response to this dose, the dose may be increased to 100 mg. |
| BG002 | Total | Total of all reporting groups |
| Standard Deviation |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Region of Enrollment | Number | participants |
|
| Education | Number | participants |
|
| Marital status | Number | participants |
|
| Past Psychiatric Conditions: Major Depressive Disorder | Number | participants |
|
| Baseline Length of Menstrual Cycle | Mean | Standard Deviation | days |
|
| Baseline Luteal Phase Daily Rating of Severity of Problems Score | Daily Rating of Severity of Problems (DRSP), composed of 21 items reflecting 11 candidate symptoms for PMDD each scored 1-6. Min=11 (asymptomatic), Max=66 (Highly symptomatic), higher scores indicate most severe problems | Mean | Standard Deviation | units on a scale |
|
| OG001 | Placebo | Participants will take similarly looking placebo during the symptomatic period Placebo: 50 mg of placebo will be taken at the onset of premenstrual symptoms through the first few days of menses. If a participant shows an insufficient response to this dose, the dose may be increased to 100 mg. |
|
|
|
| Primary | Inventory of Depression Symptoms (IDS-C) | Inventory of Depressive Symptomatology-Clinician version (IDS-C) - a depression measure that has 28 items and detects appropriate variations between follicular and luteal phases in subjects with PMDD. Min score is 0, max is 84.Lower score is less symptomatic. | all participants enrolled were analyzed | Posted | Mean | Standard Deviation | units on a scale | Measured from baseline to Cycle 6 |
|
|
|
|
| Primary | Michelson SSRI Withdrawal Checklist | Michelson SSRI Withdrawal Checklist - 16-item (not exactly 17-item, mood swings and crying were in DRSP) including dizziness, nausea, unusual dreams, chills, increased sweating, loose stools, agitation, ringing or noises in the ears. Items were summed for 3 days after pill-taking ended for each menstrual cycle.Scale is 0-80 for total range of the scale with lower less severe. There are no units | all participants enrolled were analyzed | Posted | Mean | Standard Deviation | units on a scale | Measured from Cycle 1 to Cycle 6 |
|
|
|
|
| Secondary | Clinical Global Severity (CGI-S) | Clinical Global Impressions-Severity is measured on a scale of 1-7, with 7 as most severe. | all participants enrolled analyzed | Posted | Mean | Standard Deviation | units on a scale | Baseline through Cycle 6 |
|
|
|
|
| Other Pre-specified | Adverse Events | A measurement of frequency of adverse events by random assignment | all enrolled participants were analyzed | Posted | Number | participants | Baseline through Cycle 6 |
|
|
|
| Primary | Number of Days Pills Were Taken | The number of days that pills were taken on. | all participants enrolled were analyzed | Posted | Mean | Standard Deviation | number of days | Measured from Cycle 1 to Cycle 6 |
|
|
|
|
| Primary | Number of Symptomatic Days Before Pills Were Taken | Symptomatic days were those that participant experienced at least 3 symptoms at a severity of at least "3", which is a mean of at least mild. | all enrolled participants were analyzed | Posted | Mean | Standard Deviation | days | Cycle 1 to Cycle 6 |
|
|
|
|
| Primary | DRSP | DRSP (Daily Rating of Severity Problems) is composed of 21 items reflecting the 11 candidate symptoms for PMDD according to DSM IV and DSM V. Each symptom is scored 1-6. A diagnosis of PMDD requires a minimum average luteal phase score of greater than or equal to 3 (mild) for at least 5 PMDD symptoms during the five most symptomatic of the final seven luteal phase days and the first two days of menses onset, and we require that the average follicular phase score not be >2 on these same items. The minimum score is 0 and maximum is 126 for the total score. A higher score indicates greater severity of symptoms. | Posted | Mean | Standard Deviation | units on a scale | Baseline to Cycle 6 |
|
|
|
|
| Secondary | DRSP Depression Subscale | Depressive symptoms included: felt depressed, felt hopeless, felt worthless or guilt, slept more, trouble sleeping, felt overwhelmed. Symptoms were scored on a scale of 1-6 The score range is 0-36 with higher indicating greater severity. | Posted | Mean | Standard Deviation | units on a scale | Baseline to Cycle 6 |
|
|
|
|
| Secondary | DRSP Physical Subscale | Physical symptoms included breast tenderness, bloating, headache, joint or muscle pain. Symptoms were scored on a scale of 1-6. The severity range is 0-24 with 24 being more symptomatic. | Posted | Mean | Standard Deviation | units on a scale | Baseline to Cycle 6 |
|
|
|
|
| Secondary | DRSP Anger/Irritability Subscale | Anger/irritability included anger/irritability and conflicts with people. Symptoms were scored on a scale 1-6. The range is 0 to 12 with a higher score indicating greater symptom severity. | Posted | Mean | Standard Deviation | units on a scale | Baseline to Cycle 6 |
|
|
|
|
| Secondary | Clinical Global Impressions-Improvement (CGI-I) | The Clinical Global Impressions-Improvement (CGI-I) scale is a 7-point scale with 7 being the least improvement. | all participants who were measured at a visit past baseline were analyzed | Posted | Mean | Standard Deviation | units on a scale | Cycle 1 to Cycle 6 |
|
|
|
|
| 0 |
| 125 |
| 48 |
| 125 |
| EG001 | Placebo | Participants will take similarly looking placebo during the symptomatic period Placebo: 50 mg of placebo will be taken at the onset of premenstrual symptoms through the first few days of menses. If a participant shows an insufficient response to this dose, the dose may be increased to 100 mg. | 0 | 127 | 40 | 127 |
| Diarrhea | Gastrointestinal disorders | snomed | Non-systematic Assessment |
|
| Headache | General disorders | snomed | Non-systematic Assessment |
|
| Insomnia | General disorders | snomed | Non-systematic Assessment |
|
| Fatigue | General disorders | snomed | Non-systematic Assessment |
|
| Mouth Dryness | General disorders | snomed | Non-systematic Assessment |
|
| Difficulty Concentrating | General disorders | snomed | Non-systematic Assessment |
|
| Anxiety, Agitation | Psychiatric disorders | snomed | Non-systematic Assessment |
|
| Diaphoresis | General disorders | snomed | Non-systematic Assessment |
|
| Dizziness/lightheadedness | General disorders | snomed | Non-systematic Assessment |
|
Not provided
Not provided
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
| D011084 |
| Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D002241 | Carbohydrates |
| Cycle 2 |
|
| Cycle 3 |
|
| Cycle 4 |
|
| Cycle 5 |
|
| Cycle 6 |
|
| Average change from baseline |
|
| <0.001 |
| 2-Sided |
| Superiority or Other |
| Group by time: comparison of rates of change | ANOVA | 0.02 | 2-Sided | Superiority or Other |
| Estimated mean difference from baseline to end point between active vs. placebo | Mixed Models Analysis | 0.0015 | Mean Difference (Net) | 5.14 | Standard Error of the Mean | 1.62 | 2-Sided | 95 | 1.97 | 8.31 | Superiority or Other |
| Cycle 3 |
|
| Cycle 4 |
|
| Cycle 5 |
|
| Cycle 6 |
|
| <0.0001 |
| 2-Sided |
| Superiority or Other |
| Group by time: comparison rates of change | ANOVA | 0.69 | 2-Sided | Superiority or Other |
| Estimated mean difference from Cycle 1 to end point between active vs. placebo | Mixed Models Analysis | 0.84 | Mean Difference (Net) | 1.02 | 2-Sided | 95 | 0.83 | 1.26 | Superiority or Other |
| Cycle 2 |
|
| Cycle 3 |
|
| Cycle 4 |
|
| Cycle 5 |
|
| Cycle 6 |
|
| Average change from baseline |
|
| <0.001 |
| 2-Sided |
| Superiority or Other |
| Group by time: comparison rates of change | Chi-squared | 0.28 | 2-Sided | Superiority or Other |
| Estimated mean difference from baseline to end point between active vs. placebo | Mixed Models Analysis | 0.056 | Mean Difference (Net) | 0.59 | 2-Sided | 95 | 0.30 | 1.19 | Superiority or Other |
| Headache |
|
| Insomnia |
|
| Fatigue |
|
| Mouth dryness |
|
| Difficulty concentrating |
|
| Anxiety, agitation |
|
| Diaphoresis |
|
| Dizziness/lightheadedness |
|
| Cycle 3 |
|
| Cycle 4 |
|
| Cycle 5 |
|
| Cycle 6 |
|
| Average Change from Cycle 1 |
|
| <0.01 |
| 2-Sided |
| Superiority or Other |
| Group by time: comparison rates of change | ANOVA | 0.73 | 2-Sided | Superiority or Other |
| Estimated mean difference from baseline to end point between active vs. placebo | Mixed Models Analysis | 0.06 | Mean Difference (Net) | 1.12 | 2-Sided | 95 | 0.92 | 1.35 | Superiority or Other |
| Cycle 3 |
|
| Cycle 4 |
|
| Cycle 5 |
|
| Cycle 6 |
|
| Average Change from Cycle 1 |
|
| <0.001 |
| 2-Sided |
| Superiority or Other |
| Group by time: comparison rates of change | ANOVA | 0.43 | 2-Sided | Superiority or Other |
| Estimated mean difference from baseline to endpoint between active vs. placebo | Mixed Models Analysis | 0.61 | Mean Difference (Net) | 1.11 | 2-Sided | 95 | 0.85 | 1.45 | Superiority or Other |
| Cycle 2 |
|
| Cycle 3 |
|
| Cycle 4 |
|
| Cycle 5 |
|
| Cycle 6 |
|
| Average change from baseline |
|
| <0.001 |
| 2-Sided |
| Superiority or Other |
| Group by time: comparison rates of change | ANOVA | 0.02 | 2-Sided | Superiority or Other |
| Estimated mean difference from baseline to end point between active vs. placebo | Mixed Models Analysis | 0.169 | Mean Difference (Net) | 1.09 | 2-Sided | 95 | 0.96 | 1.25 | Superiority or Other |
| Cycle 2 |
|
| Cycle 3 |
|
| Cycle 4 |
|
| Cycle 5 |
|
| Cycle 6 |
|
| Average change from baseline |
|
| <0.001 |
| 2-Sided |
| Superiority or Other |
| Group by time: comparison rates of change | ANOVA | 0.73 | 2-Sided | Superiority or Other |
| Estimated mean difference from baseline to end point between active vs. placebo | Mixed Models Analysis | 0.13 | Mean Difference (Net) | 1.08 | 2-Sided | 95 | 0.91 | 1.28 | Superiority or Other |
| Cycle 2 |
|
| Cycle 3 |
|
| Cycle 4 |
|
| Cycle 5 |
|
| Cycle 6 |
|
| Average change from baseline |
|
| <0.001 |
| 2-Sided |
| Superiority or Other |
| Group by time: comparison rates of change | ANOVA | 0.46 | 2-Sided | Superiority or Other |
| Estimated mean difference from baseline to end point between active vs. placebo | Mixed Models Analysis | 0.94 | Mean Difference (Net) | 1.09 | 2-Sided | 95 | 0.96 | 1.23 | Superiority or Other |
| Cycle 2 |
|
| Cycle 3 |
|
| Cycle 4 |
|
| Cycle 5 |
|
| Cycle 6 |
|
| Average change from baseline |
|
| <0.001 |
| 2-Sided |
| Superiority or Other |
| Group by time: comparison rates of change | ANOVA | <0.01 | 2-Sided | Superiority or Other |
| Estimated mean difference from baseline to end point between active vs. placebo | Mixed Models Analysis | 0.027 | Median Difference (Net) | 1.22 | 2-Sided | 95 | 1.05 | 1.41 | Superiority or Other |
| Cycle 3 |
|
| Cycle 4 |
|
| Cycle 5 |
|
| Cycle 6 |
|
| Average change from Cycle 1 |
|
| <0.001 |
| 2-Sided |
| Superiority or Other |
| Estimated mean difference between active and placebo groups at end-point only | Mixed Models Analysis | 0.056 | Mean Difference (Final Values) | 0.55 | 2-Sided | 95 | 0.30 | 1.02 | Superiority or Other |