The Effect Of Dose Titration And Dose Tapering On The Tolerability Of DVS SR In Women With Vasomotor Symptoms

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: Vasomotor Symptoms
• 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

Study Locations

• • • Pfizer Investigational Site
• Canada
  • Quebec, Canada, G1V 4X7
    • Pfizer Investigational Site
  • Alberta
    • Calgary, Alberta, Canada, T2N 4L7
      • Pfizer Investigational Site
  • British Columbia
    • Coquitlam, British Columbia, Canada, V3K 3P4
      • Pfizer Investigational Site
    • Langley, British Columbia, Canada, V3A 4H9
      • Pfizer Investigational Site
    • Surrey, British Columbia, Canada, V4A 2H9
      • Pfizer Investigational Site
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1M3
      • Pfizer Investigational Site
    • Winnipeg, Manitoba, Canada, R3T 2E8
      • Pfizer Investigational Site
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1E 2C2
      • Pfizer Investigational Site
  • Ontario
    • Newmarket, Ontario, Canada, L3Y 5G8
      • Pfizer Investigational Site
    • Sarnia, Ontario, Canada, N7T 4X3
      • Pfizer Investigational Site
    • Toronto, Ontario, Canada, M9W 4L6
      • Pfizer Investigational Site
    • Toronto, Ontario, Canada, M4S 1Y2
      • Pfizer Investigational Site
    • Toronto, Ontario, Canada, M5C 1R6
      • Pfizer Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H2X 1N8
      • Pfizer Investigational Site
    • Pointe Claire, Quebec, Canada, H9R 4S3
      • Pfizer Investigational Site
    • Shawinigan, Quebec, Canada, G9N 2H6
      • Pfizer Investigational Site
    • Sherbrooke, Quebec, Canada, J1H 4J6
      • Pfizer Investigational Site
    • St-Romuald, Quebec, Canada, G6W 5M6
      • Pfizer Investigational Site
• United States
  • Arizona
    • Tucson, Arizona, United States, 85715
      • Pfizer Investigational Site
    • Tucson, Arizona, United States, 85710
      • Pfizer Investigational Site
  • California
    • Beverly Hills, California, United States, 90211
      • Pfizer Investigational Site
    • Encinitas, California, United States, 92024
      • Pfizer Investigational Site
    • Foothill Ranch, California, United States, 92610
      • Pfizer Investigational Site
    • San Diego, California, United States, 92108
      • Pfizer Investigational Site
    • San Diego, California, United States, 92123
      • Pfizer Investigational Site
    • Upland, California, United States, 91786
      • Pfizer Investigational Site
  • Colorado
    • Denver, Colorado, United States, 80218
      • Pfizer Investigational Site
    • Longmont, Colorado, United States, 80501
      • Pfizer Investigational Site
  • Florida
    • Clearwater, Florida, United States, 33761
      • Pfizer Investigational Site
    • Crystal River, Florida, United States, 34429
      • Pfizer Investigational Site
    • Deland, Florida, United States, 32720
      • Pfizer Investigational Site
    • Gainesville, Florida, United States, 32606
      • Pfizer Investigational Site
    • Lake Worth, Florida, United States, 33461
      • Pfizer Investigational Site
    • Miami, Florida, United States, 33169
      • Pfizer Investigational Site
    • Miami, Florida, United States, 33136
      • Pfizer Investigational Site
    • Miami, Florida, United States, 33143
      • Pfizer Investigational Site
    • Palm Harbor, Florida, United States, 34684
      • Pfizer Investigational Site
    • Tampa, Florida, United States, 33606
      • Pfizer Investigational Site
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Pfizer Investigational Site
  • Illinois
    • Champaign, Illinois, United States, 61820
      • Pfizer Investigational Site
    • Chicago, Illinois, United States, 60612
      • Pfizer Investigational Site
  • Indiana
    • South Bend, Indiana, United States, 46601
      • Pfizer Investigational Site
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Pfizer Investigational Site
    • Louisville, Kentucky, United States, 40291
      • Pfizer Investigational Site
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Pfizer Investigational Site
    • Metairie, Louisiana, United States, 70002
      • Pfizer Investigational Site
  • Michigan
    • Canton, Michigan, United States, 48187
      • Pfizer Investigational Site
    • Ypsilanti, Michigan, United States, 48197
      • Pfizer Investigational Site
  • Montana
    • Billings, Montana, United States, 59101
      • Pfizer Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States, 68131-2197
      • Pfizer Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Pfizer Investigational Site
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03755
      • Pfizer Investigational Site
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Pfizer Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Pfizer Investigational Site
    • Albuquerque, New Mexico, United States, 87131
      • Pfizer Investigational Site
  • New York
    • New York, New York, United States, 10032
      • Pfizer Investigational Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Pfizer Investigational Site
    • Charlotte, North Carolina, United States, 28209
      • Pfizer Investigational Site
    • Winston-Salem, North Carolina, United States, 27103
      • Pfizer Investigational Site
    • Winston-Salem, North Carolina, United States, 27103-4005
      • Pfizer Investigational Site
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Pfizer Investigational Site
    • Fargo, North Dakota, United States, 58104
      • Pfizer Investigational Site
  • Ohio
    • Cleveland, Ohio, United States, 44122
      • Pfizer Investigational Site
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Pfizer Investigational Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15206
      • Pfizer Investigational Site
  • South Dakota
    • Watertown, South Dakota, United States, 57201
      • Pfizer Investigational Site
  • Texas
    • Carrollton, Texas, United States, 75006
      • Pfizer Investigational Site
    • Houston, Texas, United States, 77030
      • Pfizer Investigational Site
    • Hurst, Texas, United States, 76054
      • Pfizer Investigational Site
    • Midland, Texas, United States, 79705
      • Pfizer Investigational Site
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Pfizer Investigational Site
    • Norfolk, Virginia, United States, 23507
      • Pfizer Investigational Site
  • Washington
    • Seattle, Washington, United States, 98105
      • Pfizer Investigational Site

Participation Criteria

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

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A	Drug: desvenlafaxine succinate sustained release; Titration 100 mg; Drug: desvenlafaxine succinate sustained release; Titration 50 mg; Drug: desvenlafaxine succinate sustained release; Titration 25 mg, 50mg; Drug: desvenlafaxine succinate sustained release; Titration 25 mg; Drug: desvenlafaxine succinate sustained release; Tapering 50 mg, placebo; Drug: desvenlafaxine succinate sustained release; Tapering 50 mg, 25 mg; Drug: desvenlafaxine succinate sustained release; Tapering 50 mg QOD
Active Comparator: B	Drug: desvenlafaxine succinate sustained release; Titration 100 mg; Drug: desvenlafaxine succinate sustained release; Titration 50 mg; Drug: desvenlafaxine succinate sustained release; Titration 25 mg, 50mg; Drug: desvenlafaxine succinate sustained release; Titration 25 mg; Drug: desvenlafaxine succinate sustained release; Tapering 50 mg, placebo; Drug: desvenlafaxine succinate sustained release; Tapering 50 mg, 25 mg; Drug: desvenlafaxine succinate sustained release; Tapering 50 mg QOD
Active Comparator: C	Drug: desvenlafaxine succinate sustained release; Titration 100 mg; Drug: desvenlafaxine succinate sustained release; Titration 50 mg; Drug: desvenlafaxine succinate sustained release; Titration 25 mg, 50mg; Drug: desvenlafaxine succinate sustained release; Titration 25 mg; Drug: desvenlafaxine succinate sustained release; Tapering 50 mg, placebo; Drug: desvenlafaxine succinate sustained release; Tapering 50 mg, 25 mg; Drug: desvenlafaxine succinate sustained release; Tapering 50 mg QOD
Active Comparator: D	Drug: desvenlafaxine succinate sustained release; Titration 100 mg; Drug: desvenlafaxine succinate sustained release; Titration 50 mg; Drug: desvenlafaxine succinate sustained release; Titration 25 mg, 50mg; Drug: desvenlafaxine succinate sustained release; Titration 25 mg; Drug: desvenlafaxine succinate sustained release; Tapering 50 mg, placebo; Drug: desvenlafaxine succinate sustained release; Tapering 50 mg, 25 mg; Drug: desvenlafaxine succinate sustained release; Tapering 50 mg QOD
Active Comparator: E	Drug: Placebo; Tapering placebo
Active Comparator: F	Drug: desvenlafaxine succinate sustained release; Titration 100 mg; Drug: desvenlafaxine succinate sustained release; Titration 50 mg; Drug: desvenlafaxine succinate sustained release; Titration 25 mg, 50mg; Drug: desvenlafaxine succinate sustained release; Titration 25 mg; Drug: desvenlafaxine succinate sustained release; Tapering 50 mg, placebo; Drug: desvenlafaxine succinate sustained release; Tapering 50 mg, 25 mg; Drug: desvenlafaxine succinate sustained release; Tapering 50 mg QOD
Active Comparator: G	Drug: desvenlafaxine succinate sustained release; Titration 100 mg; Drug: desvenlafaxine succinate sustained release; Titration 50 mg; Drug: desvenlafaxine succinate sustained release; Titration 25 mg, 50mg; Drug: desvenlafaxine succinate sustained release; Titration 25 mg; Drug: desvenlafaxine succinate sustained release; Tapering 50 mg, placebo; Drug: desvenlafaxine succinate sustained release; Tapering 50 mg, 25 mg; Drug: desvenlafaxine succinate sustained release; Tapering 50 mg QOD
Placebo Comparator: H	Drug: desvenlafaxine succinate sustained release; Titration 100 mg; Drug: desvenlafaxine succinate sustained release; Titration 50 mg; Drug: desvenlafaxine succinate sustained release; Titration 25 mg, 50mg; Drug: desvenlafaxine succinate sustained release; Titration 25 mg; Drug: desvenlafaxine succinate sustained release; Tapering 50 mg, placebo; Drug: desvenlafaxine succinate sustained release; Tapering 50 mg, 25 mg; Drug: desvenlafaxine succinate sustained release; Tapering 50 mg QOD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Nausea During the First 2 Weeks of Treatment	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.	Baseline up to Week 2
Discontinuation Emergent Signs and Symptoms (DESS) Total Score at the End of First Week of Tapering	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.	Week 17
DESS Total Score at End of Second Week of Tapering	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.	Week 18
DESS Total Score at 1 Week After the End of Tapering	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.	Week 19

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Other Spontaneously Reported Adverse Events (AEs) in First 2 Weeks of Treatment	Any untoward medical occurrence in a participant who received study drug was considered an AE, without regard to possibility of causal relationship.	Baseline up to Week 2
Percentage of Participants Discontinuing Treatment Due to AEs in First 2 Weeks of Treatment	Any untoward medical occurrence in a participant who received study drug was considered an AE, without regard to possibility of causal relationship.	Baseline up to Week 2
Number of Participants With Each DESS at the End of First Week of Tapering	DESS: a clinician-administered 43-item assessment that evaluates discontinuation-emergent symptoms resulting from the withdrawal from test article.	Week 17
Number of Participants With Each DESS at the End of Second Week of Tapering	DESS: a clinician-administered 43-item assessment that evaluates discontinuation-emergent symptoms resulting from the withdrawal from test article.	Week 18
Number of Participants With Each DESS One Week After End of Tapering	DESS: a clinician-administered 43-item assessment that evaluates discontinuation-emergent symptoms resulting from the withdrawal from test article.	Week 19
Number of Participants Showing Satisfaction With Tolerability During the First Two Weeks of Treatment	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.	Week 1 and Week 2
Number of Participants Showing Satisfaction With Tolerability at the End of Tapering	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.	Week 19
Menopause Symptoms-treatment Satisfaction Questionnaire (MS-TSQ) Score	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).	Week 16
Change From Baseline in Menopause-specific Quality of Life Questionnaire (MenQOL) Score at Week 4, Week 8, Week 12 and Week 16	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.	Baseline, Week 4, Week 8, Week 12 and Week 16

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Age of the Participants in Tapering Phase	Participants were re-randomized to tapering phase after OL phase.	Week 17
Gender of the Participants in Tapering Phase	Participants were re-randomized to tapering phase after OL phase.	Week 17

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

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: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Serotonin and Noradrenaline Reuptake Inhibitors; Desvenlafaxine Succinate
• Other Study ID Numbers: 3151A2-405