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

Phase 3
Completed
Conditions
Vasomotor Symptoms
Interventions
Registration Number
NCT00401245
Lead Sponsor
Pfizer
Brief 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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
500
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.
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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.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Adesvenlafaxine succinate sustained release-
Bdesvenlafaxine succinate sustained release-
Cdesvenlafaxine succinate sustained release-
Ddesvenlafaxine succinate sustained release-
EPlacebo-
Fdesvenlafaxine succinate sustained release-
Gdesvenlafaxine succinate sustained release-
Hdesvenlafaxine succinate sustained release-
Primary Outcome Measures
NameTimeMethod
Number of Participants With Nausea During the First 2 Weeks of TreatmentBaseline up to Week 2

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.

Discontinuation Emergent Signs and Symptoms (DESS) Total Score at the End of First Week of TaperingWeek 17

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.

DESS Total Score at End of Second Week of TaperingWeek 18

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.

DESS Total Score at 1 Week After the End of TaperingWeek 19

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.

Secondary Outcome Measures
NameTimeMethod
Number of Participants With Other Spontaneously Reported Adverse Events (AEs) in First 2 Weeks of TreatmentBaseline up to Week 2

Any untoward medical occurrence in a participant who received study drug was considered an AE, without regard to possibility of causal relationship.

Percentage of Participants Discontinuing Treatment Due to AEs in First 2 Weeks of TreatmentBaseline up to Week 2

Any untoward medical occurrence in a participant who received study drug was considered an AE, without regard to possibility of causal relationship.

Number of Participants With Each DESS at the End of First Week of TaperingWeek 17

DESS: a clinician-administered 43-item assessment that evaluates discontinuation-emergent symptoms resulting from the withdrawal from test article.

Number of Participants With Each DESS at the End of Second Week of TaperingWeek 18

DESS: a clinician-administered 43-item assessment that evaluates discontinuation-emergent symptoms resulting from the withdrawal from test article.

Number of Participants With Each DESS One Week After End of TaperingWeek 19

DESS: a clinician-administered 43-item assessment that evaluates discontinuation-emergent symptoms resulting from the withdrawal from test article.

Number of Participants Showing Satisfaction With Tolerability During the First Two Weeks of TreatmentWeek 1 and Week 2

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.

Number of Participants Showing Satisfaction With Tolerability at the End of TaperingWeek 19

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.

Menopause Symptoms-treatment Satisfaction Questionnaire (MS-TSQ) ScoreWeek 16

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).

Change From Baseline in Menopause-specific Quality of Life Questionnaire (MenQOL) Score at Week 4, Week 8, Week 12 and Week 16Baseline, 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.

Trial Locations

Locations (1)

Pfizer Investigational Site

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