The Effect Of Dose Titration And Dose Tapering On The Tolerability Of DVS SR In Women With Vasomotor Symptoms
October 24, 2011 updated by: Pfizer
The Effect of Dose Titration and Dose Tapering on the Tolerability of DVS SR in Women With Vasomotor Symptoms Associated With Menopause: The PRIMMUS (PRIstiq for Managing Menopause and Understanding Symptoms) Study
Desvenlafaxine succinate (DVS SR) is a serotonin and norepinephrine reuptake inhibitor (SNRI).
It is a nonhormonal option for the treatment of Vasomotor Symptoms (VMS) associated with menopause.
Nausea is the most common adverse event that is observed in clinical studies and is the main reason for discontinuation during the first week of therapy.
Other adverse events (headache, nausea, and dizziness) associated with DVS SR have been noted to occur when subjects abruptly discontinue the medication.
The purpose of this study is to evaluate several titration and tapering regimens of DVS SR to ensure a better tolerability profile at the start and completion of treatment.
In addition, this study will provide a long posttreatment follow-up to assess any symptoms after treatment is discontinued.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
- Drug: desvenlafaxine succinate sustained release
- Drug: desvenlafaxine succinate sustained release
- Drug: desvenlafaxine succinate sustained release
- Drug: desvenlafaxine succinate sustained release
- Drug: desvenlafaxine succinate sustained release
- Drug: desvenlafaxine succinate sustained release
- Drug: desvenlafaxine succinate sustained release
- Drug: Placebo
Study Type
Interventional
Enrollment (Actual)
500
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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- Pfizer Investigational Site
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Quebec, Canada, G1V 4X7
- Pfizer Investigational Site
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Alberta
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Calgary, Alberta, Canada, T2N 4L7
- Pfizer Investigational Site
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British Columbia
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Coquitlam, British Columbia, Canada, V3K 3P4
- Pfizer Investigational Site
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Langley, British Columbia, Canada, V3A 4H9
- Pfizer Investigational Site
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Surrey, British Columbia, Canada, V4A 2H9
- Pfizer Investigational Site
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Manitoba
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Winnipeg, Manitoba, Canada, R3A 1M3
- Pfizer Investigational Site
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Winnipeg, Manitoba, Canada, R3T 2E8
- Pfizer Investigational Site
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Newfoundland and Labrador
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St. John's, Newfoundland and Labrador, Canada, A1E 2C2
- Pfizer Investigational Site
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Ontario
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Newmarket, Ontario, Canada, L3Y 5G8
- Pfizer Investigational Site
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Sarnia, Ontario, Canada, N7T 4X3
- Pfizer Investigational Site
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Toronto, Ontario, Canada, M9W 4L6
- Pfizer Investigational Site
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Toronto, Ontario, Canada, M4S 1Y2
- Pfizer Investigational Site
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Toronto, Ontario, Canada, M5C 1R6
- Pfizer Investigational Site
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Quebec
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Montreal, Quebec, Canada, H2X 1N8
- Pfizer Investigational Site
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Pointe Claire, Quebec, Canada, H9R 4S3
- Pfizer Investigational Site
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Shawinigan, Quebec, Canada, G9N 2H6
- Pfizer Investigational Site
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Sherbrooke, Quebec, Canada, J1H 4J6
- Pfizer Investigational Site
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St-Romuald, Quebec, Canada, G6W 5M6
- Pfizer Investigational Site
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Arizona
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Tucson, Arizona, United States, 85715
- Pfizer Investigational Site
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Tucson, Arizona, United States, 85710
- Pfizer Investigational Site
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California
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Beverly Hills, California, United States, 90211
- Pfizer Investigational Site
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Encinitas, California, United States, 92024
- Pfizer Investigational Site
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Foothill Ranch, California, United States, 92610
- Pfizer Investigational Site
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San Diego, California, United States, 92108
- Pfizer Investigational Site
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San Diego, California, United States, 92123
- Pfizer Investigational Site
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Upland, California, United States, 91786
- Pfizer Investigational Site
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Colorado
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Denver, Colorado, United States, 80218
- Pfizer Investigational Site
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Longmont, Colorado, United States, 80501
- Pfizer Investigational Site
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Florida
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Clearwater, Florida, United States, 33761
- Pfizer Investigational Site
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Crystal River, Florida, United States, 34429
- Pfizer Investigational Site
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Deland, Florida, United States, 32720
- Pfizer Investigational Site
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Gainesville, Florida, United States, 32606
- Pfizer Investigational Site
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Lake Worth, Florida, United States, 33461
- Pfizer Investigational Site
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Miami, Florida, United States, 33169
- Pfizer Investigational Site
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Miami, Florida, United States, 33136
- Pfizer Investigational Site
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Miami, Florida, United States, 33143
- Pfizer Investigational Site
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Palm Harbor, Florida, United States, 34684
- Pfizer Investigational Site
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Tampa, Florida, United States, 33606
- Pfizer Investigational Site
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Idaho
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Idaho Falls, Idaho, United States, 83404
- Pfizer Investigational Site
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Illinois
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Champaign, Illinois, United States, 61820
- Pfizer Investigational Site
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Chicago, Illinois, United States, 60612
- Pfizer Investigational Site
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Indiana
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South Bend, Indiana, United States, 46601
- Pfizer Investigational Site
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Kentucky
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Lexington, Kentucky, United States, 40536
- Pfizer Investigational Site
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Louisville, Kentucky, United States, 40291
- Pfizer Investigational Site
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Louisiana
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Metairie, Louisiana, United States, 70006
- Pfizer Investigational Site
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Metairie, Louisiana, United States, 70002
- Pfizer Investigational Site
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Michigan
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Canton, Michigan, United States, 48187
- Pfizer Investigational Site
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Ypsilanti, Michigan, United States, 48197
- Pfizer Investigational Site
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Montana
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Billings, Montana, United States, 59101
- Pfizer Investigational Site
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Nebraska
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Omaha, Nebraska, United States, 68131-2197
- Pfizer Investigational Site
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Nevada
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Las Vegas, Nevada, United States, 89128
- Pfizer Investigational Site
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New Hampshire
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Lebanon, New Hampshire, United States, 03755
- Pfizer Investigational Site
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New Jersey
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New Brunswick, New Jersey, United States, 08901
- Pfizer Investigational Site
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New Mexico
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Albuquerque, New Mexico, United States, 87106
- Pfizer Investigational Site
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Albuquerque, New Mexico, United States, 87131
- Pfizer Investigational Site
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New York
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New York, New York, United States, 10032
- Pfizer Investigational Site
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North Carolina
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Chapel Hill, North Carolina, United States, 27514
- Pfizer Investigational Site
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Charlotte, North Carolina, United States, 28209
- Pfizer Investigational Site
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Winston-Salem, North Carolina, United States, 27103
- Pfizer Investigational Site
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Winston-Salem, North Carolina, United States, 27103-4005
- Pfizer Investigational Site
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North Dakota
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Bismarck, North Dakota, United States, 58501
- Pfizer Investigational Site
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Fargo, North Dakota, United States, 58104
- Pfizer Investigational Site
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Ohio
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Cleveland, Ohio, United States, 44122
- Pfizer Investigational Site
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Oregon
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Eugene, Oregon, United States, 97401
- Pfizer Investigational Site
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15206
- Pfizer Investigational Site
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South Dakota
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Watertown, South Dakota, United States, 57201
- Pfizer Investigational Site
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Texas
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Carrollton, Texas, United States, 75006
- Pfizer Investigational Site
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Houston, Texas, United States, 77030
- Pfizer Investigational Site
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Hurst, Texas, United States, 76054
- Pfizer Investigational Site
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Midland, Texas, United States, 79705
- Pfizer Investigational Site
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Virginia
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Norfolk, Virginia, United States, 23502
- Pfizer Investigational Site
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Norfolk, Virginia, United States, 23507
- Pfizer Investigational Site
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Washington
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Seattle, Washington, United States, 98105
- Pfizer Investigational Site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Female
Description
Inclusion Criteria:
- Generally healthy, postmenopausal woman who seeks treatment for hot flushes.
- Meets 1 of the following: At least 12 months of spontaneous amenorrhea; At least 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) levels > 40 mIU/mL; At least 6 weeks postsurgical bilateral oophorectomy (with or without hysterectomy). Hysterectomized without bilateral oophorectomy and with serum FSH levels >40 mIU/mL.
Exclusion Criteria:
- History of a seizure disorder other than a single childhood febrile seizure.
- History or presence of clinically important hepatic or renal disease or other medical disease.
- Presence or recent history of major depressive disorder, bipolar disorder, psychotic disorder, or generalized anxiety disorder requiring therapy.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Active Comparator: A
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Titration 100 mg
Titration 50 mg
Titration 25 mg, 50mg
Titration 25 mg
Tapering 50 mg, placebo
Tapering 50 mg, 25 mg
Tapering 50 mg QOD
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Active Comparator: B
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Titration 100 mg
Titration 50 mg
Titration 25 mg, 50mg
Titration 25 mg
Tapering 50 mg, placebo
Tapering 50 mg, 25 mg
Tapering 50 mg QOD
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Active Comparator: C
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Titration 100 mg
Titration 50 mg
Titration 25 mg, 50mg
Titration 25 mg
Tapering 50 mg, placebo
Tapering 50 mg, 25 mg
Tapering 50 mg QOD
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Active Comparator: D
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Titration 100 mg
Titration 50 mg
Titration 25 mg, 50mg
Titration 25 mg
Tapering 50 mg, placebo
Tapering 50 mg, 25 mg
Tapering 50 mg QOD
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Active Comparator: E
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Tapering placebo
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Active Comparator: F
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Titration 100 mg
Titration 50 mg
Titration 25 mg, 50mg
Titration 25 mg
Tapering 50 mg, placebo
Tapering 50 mg, 25 mg
Tapering 50 mg QOD
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Active Comparator: G
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Titration 100 mg
Titration 50 mg
Titration 25 mg, 50mg
Titration 25 mg
Tapering 50 mg, placebo
Tapering 50 mg, 25 mg
Tapering 50 mg QOD
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Placebo Comparator: H
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Titration 100 mg
Titration 50 mg
Titration 25 mg, 50mg
Titration 25 mg
Tapering 50 mg, placebo
Tapering 50 mg, 25 mg
Tapering 50 mg QOD
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Participants With Nausea During the First 2 Weeks of Treatment
Time Frame: Baseline up to Week 2
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Nausea by spontaneous reports to the investigators was counted if it was reported during first 2 weeks of treatment, and it was not seen before the first dose of treatment, or if it was seen before the first dose and the symptoms got worse.
If multiple incidences occurred on the same participant during the 2 weeks, only 1 incidence was counted.
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Baseline up to Week 2
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Discontinuation Emergent Signs and Symptoms (DESS) Total Score at the End of First Week of Tapering
Time Frame: Week 17
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DESS: a clinician-administered 43-item assessment that evaluates discontinuation-emergent symptoms resulting from the withdrawal from test article.
The DESS total score is the sum of the number of "new symptoms" and "old (but worse) symptoms" (1) and 0 for "old and unchanged symptom", "absent", or "old symptom but improved" for a total possible range of 0 to 43.
A higher score indicates more symptoms.
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Week 17
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DESS Total Score at End of Second Week of Tapering
Time Frame: Week 18
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DESS: a clinician-administered 43-item assessment that evaluates discontinuation-emergent symptoms resulting from the withdrawal from test article.
The DESS total score is the sum of the number of "new symptoms" and "old (but worse) symptoms" (1) and 0 for "old and unchanged symptom", "absent", or "old symptom but improved" for a total possible range of 0 to 43.
A higher score indicates more symptoms.
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Week 18
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DESS Total Score at 1 Week After the End of Tapering
Time Frame: Week 19
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DESS: a clinician-administered 43-item assessment that evaluates discontinuation-emergent symptoms resulting from the withdrawal from test article.
The DESS total score is the sum of the number of "new symptoms" and "old (but worse) symptoms" (1) and 0 for "old and unchanged symptom", "absent", or "old symptom but improved" for a total possible range of 0 to 43.
A higher score indicates more symptoms.
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Week 19
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Participants With Other Spontaneously Reported Adverse Events (AEs) in First 2 Weeks of Treatment
Time Frame: Baseline up to Week 2
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Any untoward medical occurrence in a participant who received study drug was considered an AE, without regard to possibility of causal relationship.
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Baseline up to Week 2
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Percentage of Participants Discontinuing Treatment Due to AEs in First 2 Weeks of Treatment
Time Frame: Baseline up to Week 2
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Any untoward medical occurrence in a participant who received study drug was considered an AE, without regard to possibility of causal relationship.
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Baseline up to Week 2
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Number of Participants With Each DESS at the End of First Week of Tapering
Time Frame: Week 17
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DESS: a clinician-administered 43-item assessment that evaluates discontinuation-emergent symptoms resulting from the withdrawal from test article.
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Week 17
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Number of Participants With Each DESS at the End of Second Week of Tapering
Time Frame: Week 18
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DESS: a clinician-administered 43-item assessment that evaluates discontinuation-emergent symptoms resulting from the withdrawal from test article.
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Week 18
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Number of Participants With Each DESS One Week After End of Tapering
Time Frame: Week 19
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DESS: a clinician-administered 43-item assessment that evaluates discontinuation-emergent symptoms resulting from the withdrawal from test article.
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Week 19
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Number of Participants Showing Satisfaction With Tolerability During the First Two Weeks of Treatment
Time Frame: Week 1 and Week 2
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Satisfaction with tolerability (lack of bothersomeness) was assessed using a questionnaire via an interactive voice response system (IVRS)/interactive web based response system (IWRS), and evaluated based on participants' response of extremely satisfied, satisfied, neutral, dissatisfied or extremely dissatisfied with the study medication.
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Week 1 and Week 2
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Number of Participants Showing Satisfaction With Tolerability at the End of Tapering
Time Frame: Week 19
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Satisfaction with tolerability (lack of bothersomeness) was assessed using a questionnaire via an IVRS/IWRS and evaluated based on participants' response of extremely satisfied, satisfied, neutral, dissatisfied or extremely dissatisfied with the study medication.
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Week 19
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Menopause Symptoms-treatment Satisfaction Questionnaire (MS-TSQ) Score
Time Frame: Week 16
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MS-TSQ is a questionnaire assessing participants' degree of satisfaction with regard to the test article which was administered to the participants via an IVRS/IWRS.
The questionnaire comprised 8 questions and each was rated on a scale from 0 (extremely dissatisfied) to 4 (extremely satisfied).
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Week 16
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Change From Baseline in Menopause-specific Quality of Life Questionnaire (MenQOL) Score at Week 4, Week 8, Week 12 and Week 16
Time Frame: Baseline, Week 4, Week 8, Week 12 and Week 16
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MenQOL questionnaire assessed how bothered participants were with 31 symptoms.
It contains domains: vasomotor (items 1-3); psychosocial (items 4-10); physical (items 11-26); sexual (items 27-29); in addition to nausea and indigestion.
31 individual symptoms are rated on a scale of 0 (not at all bothered) to 6 (extremely bothered).
Total possible score ranged from 0 to 186.
MenQOL summary score was calculated as mean of four domain scores (Physical function, Psychosocial function, Sexual function and Vasomotor function) ranging from 1 to 8, with higher scores indicating worse quality of life.
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Baseline, Week 4, Week 8, Week 12 and Week 16
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Mean Age of the Participants in Tapering Phase
Time Frame: Week 17
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Participants were re-randomized to tapering phase after OL phase.
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Week 17
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Gender of the Participants in Tapering Phase
Time Frame: Week 17
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Participants were re-randomized to tapering phase after OL phase.
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Week 17
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
December 1, 2006
Primary Completion (Actual)
January 1, 2008
Study Completion (Actual)
January 1, 2008
Study Registration Dates
First Submitted
November 17, 2006
First Submitted That Met QC Criteria
November 17, 2006
First Posted (Estimate)
November 20, 2006
Study Record Updates
Last Update Posted (Estimate)
October 26, 2011
Last Update Submitted That Met QC Criteria
October 24, 2011
Last Verified
October 1, 2011
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 3151A2-405
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.