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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00401245
First received: November 17, 2006
Last updated: October 24, 2011
Last verified: October 2011
  Purpose

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.


Condition Intervention Phase
Vasomotor Symptoms
Drug: desvenlafaxine succinate sustained release
Drug: Placebo
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Number of Participants With Nausea During the First 2 Weeks of Treatment [ Time Frame: Baseline up to Week 2 ] [ Designated as safety issue: Yes ]
    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 Tapering [ Time Frame: Week 17 ] [ Designated as safety issue: Yes ]
    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 Tapering [ Time Frame: Week 18 ] [ Designated as safety issue: Yes ]
    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 Tapering [ Time Frame: Week 19 ] [ Designated as safety issue: Yes ]
    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:
  • Number of Participants With Other Spontaneously Reported Adverse Events (AEs) in First 2 Weeks of Treatment [ Time Frame: Baseline up to Week 2 ] [ Designated as safety issue: Yes ]
    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 Treatment [ Time Frame: Baseline up to Week 2 ] [ Designated as safety issue: Yes ]
    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 Tapering [ Time Frame: Week 17 ] [ Designated as safety issue: Yes ]
    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 Tapering [ Time Frame: Week 18 ] [ Designated as safety issue: Yes ]
    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 Tapering [ Time Frame: Week 19 ] [ Designated as safety issue: Yes ]
    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 Treatment [ Time Frame: Week 1 and Week 2 ] [ Designated as safety issue: No ]
    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 Tapering [ Time Frame: Week 19 ] [ Designated as safety issue: No ]
    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) Score [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    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 16 [ Time Frame: Baseline, Week 4, Week 8, Week 12 and Week 16 ] [ Designated as safety issue: No ]
    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.


Enrollment: 500
Study Start Date: December 2006
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A Drug: desvenlafaxine succinate sustained release
Titration 100 mg
Active Comparator: B Drug: desvenlafaxine succinate sustained release
Titration 50 mg
Active Comparator: C Drug: desvenlafaxine succinate sustained release
Titration 25 mg, 50mg
Active Comparator: D Drug: desvenlafaxine succinate sustained release
Titration 25 mg
Active Comparator: E Drug: Placebo
Tapering placebo
Active Comparator: F Drug: desvenlafaxine succinate sustained release
Tapering 50 mg, placebo
Active Comparator: G Drug: desvenlafaxine succinate sustained release
Tapering 50 mg, 25 mg
Placebo Comparator: H Drug: desvenlafaxine succinate sustained release
Tapering 50 mg QOD

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00401245

  Show 74 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00401245     History of Changes
Other Study ID Numbers: 3151A2-405
Study First Received: November 17, 2006
Results First Received: September 6, 2011
Last Updated: October 24, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
O-desmethylvenlafaxine
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 30, 2014