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

Vasomotor Symptoms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00401245
• Other study ID #: 3151A2-405
• Status: Completed
• Phase: Phase 3
• First received: November 17, 2006
• Last updated: October 24, 2011
• Start date: December 2006
• Est. completion date: January 2008

Study information

• Verified date: October 2011
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 500
• Est. completion date: January 2008
• Est. primary completion date: January 2008
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Vasomotor Symptoms

Intervention

Drug:
• desvenlafaxine succinate sustained release
Titration 100 mg
• desvenlafaxine succinate sustained release
Titration 50 mg
• desvenlafaxine succinate sustained release
Titration 25 mg, 50mg
• desvenlafaxine succinate sustained release
Titration 25 mg
• Placebo
Tapering placebo
• desvenlafaxine succinate sustained release
Tapering 50 mg, placebo
• desvenlafaxine succinate sustained release
Tapering 50 mg, 25 mg
• desvenlafaxine succinate sustained release
Tapering 50 mg QOD

Locations

Country	Name	City	State
Canada	Pfizer Investigational Site	Calgary	Alberta
Canada	Pfizer Investigational Site	Coquitlam	British Columbia
Canada	Pfizer Investigational Site	Langley	British Columbia
Canada	Pfizer Investigational Site	Montreal	Quebec
Canada	Pfizer Investigational Site	Newmarket	Ontario
Canada	Pfizer Investigational Site	Pointe Claire	Quebec
Canada	Pfizer Investigational Site	Quebec
Canada	Pfizer Investigational Site	Sarnia	Ontario
Canada	Pfizer Investigational Site	Shawinigan	Quebec
Canada	Pfizer Investigational Site	Sherbrooke	Quebec
Canada	Pfizer Investigational Site	St-Romuald	Quebec
Canada	Pfizer Investigational Site	St. John's	Newfoundland and Labrador
Canada	Pfizer Investigational Site	Surrey	British Columbia
Canada	Pfizer Investigational Site	Toronto	Ontario
Canada	Pfizer Investigational Site	Toronto	Ontario
Canada	Pfizer Investigational Site	Toronto	Ontario
Canada	Pfizer Investigational Site	Unknown	Quebec
Canada	Pfizer Investigational Site	Winnipeg	Manitoba
Canada	Pfizer Investigational Site	Winnipeg	Manitoba
United States	Pfizer Investigational Site	Albuquerque	New Mexico
United States	Pfizer Investigational Site	Albuquerque	New Mexico
United States	Pfizer Investigational Site	Beverly Hills	California
United States	Pfizer Investigational Site	Billings	Montana
United States	Pfizer Investigational Site	Bismarck	North Dakota
United States	Pfizer Investigational Site	Canton	Michigan
United States	Pfizer Investigational Site	Carrollton	Texas
United States	Pfizer Investigational Site	Champaign	Illinois
United States	Pfizer Investigational Site	Chapel Hill	North Carolina
United States	Pfizer Investigational Site	Charlotte	North Carolina
United States	Pfizer Investigational Site	Chicago	Illinois
United States	Pfizer Investigational Site	Clearwater	Florida
United States	Pfizer Investigational Site	Cleveland	Ohio
United States	Pfizer Investigational Site	Crystal River	Florida
United States	Pfizer Investigational Site	Deland	Florida
United States	Pfizer Investigational Site	Denver	Colorado
United States	Pfizer Investigational Site	Encinitas	California
United States	Pfizer Investigational Site	Eugene	Oregon
United States	Pfizer Investigational Site	Fargo	North Dakota
United States	Pfizer Investigational Site	Foothill Ranch	California
United States	Pfizer Investigational Site	Gainesville	Florida
United States	Pfizer Investigational Site	Houston	Texas
United States	Pfizer Investigational Site	Hurst	Texas
United States	Pfizer Investigational Site	Idaho Falls	Idaho
United States	Pfizer Investigational Site	Lake Worth	Florida
United States	Pfizer Investigational Site	Las Vegas	Nevada
United States	Pfizer Investigational Site	Lebanon	New Hampshire
United States	Pfizer Investigational Site	Lexington	Kentucky
United States	Pfizer Investigational Site	Longmont	Colorado
United States	Pfizer Investigational Site	Louisville	Kentucky
United States	Pfizer Investigational Site	Metairie	Louisiana
United States	Pfizer Investigational Site	Metairie	Louisiana
United States	Pfizer Investigational Site	Miami	Florida
United States	Pfizer Investigational Site	Miami	Florida
United States	Pfizer Investigational Site	Miami	Florida
United States	Pfizer Investigational Site	Midland	Texas
United States	Pfizer Investigational Site	New Brunswick	New Jersey
United States	Pfizer Investigational Site	New York	New York
United States	Pfizer Investigational Site	Norfolk	Virginia
United States	Pfizer Investigational Site	Norfolk	Virginia
United States	Pfizer Investigational Site	Omaha	Nebraska
United States	Pfizer Investigational Site	Palm Harbor	Florida
United States	Pfizer Investigational Site	Pittsburgh	Pennsylvania
United States	Pfizer Investigational Site	San Diego	California
United States	Pfizer Investigational Site	San Diego	California
United States	Pfizer Investigational Site	Seattle	Washington
United States	Pfizer Investigational Site	South Bend	Indiana
United States	Pfizer Investigational Site	Tampa	Florida
United States	Pfizer Investigational Site	Tucson	Arizona
United States	Pfizer Investigational Site	Tucson	Arizona
United States	Pfizer Investigational Site	Upland	California
United States	Pfizer Investigational Site	Watertown	South Dakota
United States	Pfizer Investigational Site	Winston-Salem	North Carolina
United States	Pfizer Investigational Site	Winston-Salem	North Carolina
United States	Pfizer Investigational Site	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No

External Links

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