SPD489 Adult Major Depressive Disorder (MDD) Open-label Safety and Tolerability Rollover Extension Study

This study has been terminated.
(SPD489 failed to demonstrate a benefit as adjunctive treatment to antidepressants. Termination was not related to any new safety findings.)
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT01436175
First received: September 15, 2011
Last updated: February 5, 2015
Last verified: March 2014
  Purpose

This study is an optional continuation of previous short-term adult major depressive disorder (MDD) augmentation studies. Patients may only take part in this long-term, open-label research study if they completed a previous double-blind MDD augmentation study using SPD489.


Condition Intervention Phase
Major Depressive Disorder
Drug: SPD489 (Lisdexamfetamine dimesylate) + Antidepressant
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 3, Open-label, Multicenter, 12-month Extension Safety and Tolerability Study of SPD489 in Combination With an Antidepressant in the Treatment of Adults With Major Depressive Disorder With Residual Symptoms or Inadequate Response Following Treatment With an Antidepressant

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Week 5 up to Week 52/Early Termination(ET) ] [ Designated as safety issue: Yes ]
    C-SSRS is a semi-structured interview that captures the occurrence, severity, and frequency of suicide-related thoughts and behaviour during the assessment period. The interview includes definitions and suggested questions to solicit the type of information needed to determine if a suicide-related thought or behaviour occurred. The assessment is done by the nature of the responses, not by a numbered scale.

  • Change From Baseline in Systolic Blood Pressure at Week 52 [ Time Frame: Baseline, Week 52/ET ] [ Designated as safety issue: No ]
    Baseline was defined as the Augmentation Baseline Visit of the antecedent study (SPD489-209 [NCT01435759], SPD489-322 [NCT01436149], and SPD489-323 [NCT01436162]).

  • Change From Baseline in Diastolic Blood Pressure at Week 52 [ Time Frame: Baseline, Week 52/ET ] [ Designated as safety issue: No ]
    Baseline was defined as the Augmentation Baseline Visit of the antecedent study (SPD489-209 [NCT01435759], SPD489-322 [NCT01436149], and SPD489-323 [NCT01436162]).

  • Change From Baseline in Pulse Rate at Week 52 [ Time Frame: Baseline, Week 52/ET ] [ Designated as safety issue: No ]
    Baseline was defined as the Augmentation Baseline Visit of the antecedent study (SPD489-209 [NCT01435759], SPD489-322 [NCT01436149], and SPD489-323 [NCT01436162]).


Secondary Outcome Measures:
  • Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 52/ET [ Time Frame: Baseline, Week 52/ET ] [ Designated as safety issue: No ]

    Designed to evaluate the extent to which illness symptoms impact a participant's life in 3 areas: work, social, and family/home. Each area is scored on a scale from 0 (no impairment) to 10 (highly impaired) with a total score ranging from 0 (unimpaired) to 30 (highly impaired). Lower scores translate into less impairment.

    Baseline was defined as the Augmentation Baseline Visit of the antecedent study (SPD489-209 [NCT01435759], SPD489-322 [NCT01436149], and SPD489-323 [NCT01436162]).


  • Number of Participants With Improvement on Clinical Global Impressions - Global Improvement (CGI-I) [ Time Frame: Week 52/ET ] [ Designated as safety issue: No ]
    Participants who did not have Clinical Global Impressions - Severity of Illness (CGI-S) assessed at Week 8 in the antecedent study should not have had CGI-I assessed in this study and were excluded from the summary of CGI-I. CGI-I consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement includes a score of 1 (very much improved) or 2 (much improved) on the scale.

  • Short Form-12 Health Survey Version 2 (SF-12V2) [ Time Frame: Week 52/ET ] [ Designated as safety issue: No ]
    SF-12V2 is a multi-purpose, 7-item survey that measures 8 domains of health: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. It is expressed by two summary measures (Aggregate Physical and Aggregate Mental) for which values can range from 0 to 100. A higher score is indicative of a better health state.

  • EuroQoL Group 5-Dimension 5-Level Self Report Questionnaire (EQ-5D-5L): Mobility [ Time Frame: Week 52/ET ] [ Designated as safety issue: No ]
    Quality of life was assessed using the EQ-5D-5L, which is one of the most widely used generic index measures of health-related quality of life. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses

  • EuroQoL Group 5-Dimension 5-Level Self Report Questionnaire (EQ-5D-5L): Self-Care [ Time Frame: Week 52/ET ] [ Designated as safety issue: No ]
    Quality of life was assessed using the EQ-5D-5L, which is one of the most widely used generic index measures of health-related quality of life. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses

  • EuroQoL Group 5-Dimension 5-Level Self Report Questionnaire (EQ-5D-5L): Usual Activities [ Time Frame: Week 52/ET ] [ Designated as safety issue: No ]
    Quality of life was assessed using the EQ-5D-5L, which is one of the most widely used generic index measures of health-related quality of life. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses

  • EuroQoL Group 5-Dimension 5-Level Self Report Questionnaire (EQ-5D-5L): Pain/Discomfort [ Time Frame: Week 52/ET ] [ Designated as safety issue: No ]
    Quality of life was assessed using the EQ-5D-5L, which is one of the most widely used generic index measures of health-related quality of life. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses

  • EuroQoL Group 5-Dimension 5-Level Self Report Questionnaire (EQ-5D-5L): Anxiety/Depression [ Time Frame: Week 52/ET ] [ Designated as safety issue: No ]
    Quality of life was assessed using the EQ-5D-5L, which is one of the most widely used generic index measures of health-related quality of life. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses

  • EuroQoL Group 5-Dimension 5-Level Self Report Questionnaire (EQ-5D-5L): Visual Analog Scale [ Time Frame: Week 52/ET ] [ Designated as safety issue: No ]
    EQ-5D-5L is one of the most widely used generic index measures of health-related quality of life. EQ-5D-5L Visual Analog Scale score is numbered from 0 to 100, where a score of 100 is the best health a participant can imagine

  • Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR) [ Time Frame: Week 52/ET ] [ Designated as safety issue: No ]
    QIDS-SR is a validated, self-reported rating scale that contains 16 items scored on a scale from 0-3 with total scores ranging from 0 (no depression) to 27 (very severe depression). Lower scores indicate less depression. The QIDS-SR was only assessed in the SPD489-322 antecedent study. The QIDS-SR total score is calculated as the sum of the highest score on any 1 of Items 1-4, Item 5, the highest score on any 1 of Items 6-9, Items 10-14, the highest score on either Item 15 or 16.

  • Quality of Life Enjoyment Satisfaction Questionnaire Short Form (Q-LES-Q-SF) [ Time Frame: Week 52/ET ] [ Designated as safety issue: No ]
    The Q-LES-Q-SF is a 16-item self-report questionnaire which evaluates general participant satisfaction with health, mood, relationships, functioning in daily life, and their treatment. Each item is rated on a 5-point scale from 1 (very poor) to 5 (very good). The total raw score (summary scale score) was calculated by summing item scores 1 to 14 (total raw score range: 14 to 70). Item 15 (satisfaction with medication, raw score range: 1 to 5) and Item 16 (overall satisfaction and contentment; raw score range: 1 to 5) were stand-alone items. For reporting, summary scale, Item 15 and Item 16 raw scores were transformed into percentage maximum possible score which ranged from 0 to 100, where higher scores are indicative of greater enjoyment or satisfaction.

  • Change From Baseline in Sexual Functioning Questionnaire - 14 Item Scale (CSFQ-14) Total Score at Week 52/ET [ Time Frame: Baseline, Week 52/ET ] [ Designated as safety issue: No ]
    CSFQ-14 is a 14 item self-report tool that evaluates sexual functioning. Each item is scored on a 5-point Likert scale ranging from 1 (never) to 5 (always) with total scores ranging from 14 to 70. Higher scores reflect better sexual functioning. Baseline was defined as the Augmentation Baseline Visit of the antecedent study (SPD489-209 [NCT01435759], SPD489-322 [NCT01436149], and SPD489-323 [NCT01436162]).

  • Amphetamine Cessation Symptom Assessment (ACSA) Total Score [ Time Frame: Week 53 ] [ Designated as safety issue: No ]
    ACSA scale has 16 symptom items rated on a scale from 0 (not at all) to 4 (extremely) with a possible total score range of 0 to 64. Higher scores indicate greater withdrawal symptom severity.

  • Patient Resource Utilization Questionnaire - Major Depressive Disorder (PRUQ-MDD) [ Time Frame: Week 52/ET ] [ Designated as safety issue: No ]

    The PRUQ-MDD assessed the long term economic outcomes. It collects utilization of healthcare resources reported by the study participants. Participants answered the following questions:

    1. Were you hospitalized in the past month, 2. Do you work for pay, 3. If you missed time at work last week, please note all the reasons why, 4. Would you say that the past week was typical, like the rest of the 3 weeks this month, in terms of your working hours, 5. Do you do volunteer work (VW), and 6. If you do not receive money for your work and do not participate in volunteer work, the reason is.

    Number of participants with response is reported.


  • PRUQ-MDD - Number of Days of Resource Utilization [ Time Frame: Week 52/ET ] [ Designated as safety issue: No ]
    The PRUQ-MDD assessed the long term economic outcomes. It collects utilization of healthcare resources reported by the study participants. Number of nights in medical/surgical ward, number of nights in ICU, and number of days a participant received home care in the past month are reported.

  • PRUQ-MDD - Number of Events (Visit to Health Care Provider/Visit to Hospital Facilities/Number of Times a Test Was Performed) [ Time Frame: Week 52/ET ] [ Designated as safety issue: No ]
    The PRUQ-MDD assessed the long term economic outcomes. It collects utilization of healthcare resources reported by the study participants. Participants answered following questions - 1. How many times did you visit the following healthcare providers in the past month: Family doctor/primary care, Non-physician healthcare practitioner (NPHP), Psychiatrist/Psychologist/Counselor (PPC); 2. How many times did you take one of the tests, mentioned below, during the past month: Blood test, CT Scan, X Ray, Renal function, Thyroid function; and 3. How many times did you visit the hospital emergency room (ER), urgent care facility (UCF) or an after-hours clinic (AHC) in the past month. Number of events (visit to health care provider, visit to hospital facilities, and number of times a test was performed) are reported.

  • PRUQ-MDD - Number of Hours [ Time Frame: Week 52/ET ] [ Designated as safety issue: No ]
    The PRUQ-MDD assessed the long term economic outcomes. It collects utilization of healthcare resources reported by the study participants. Participants answered following questions - 1. How many hours do you usually work or would you usually be expected to work (hrs/week); 2. How many hours did you actually work last week; 3. On average, how many hours do you volunteer per week. Number of hours are reported.

  • PRUQ-MDD - Effect of Depressive Symptoms [ Time Frame: Week 52/ET ] [ Designated as safety issue: No ]
    The PRUQ-MDD assessed the long term economic outcomes. It collects utilization of healthcare resources reported by the study participants. Participants answered following questions on a 0 to 10 point scale - 1. During past week, how much did depressive symptoms affect work productivity; 2. During past week, how much did depressive symptoms affect regular non-work daily activities. Higher scores indicates more effect of depressive symptoms on work productivity and non-work daily activities.


Enrollment: 1570
Study Start Date: February 2012
Study Completion Date: February 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SPD489 + Antidepressant Drug: SPD489 (Lisdexamfetamine dimesylate) + Antidepressant
SPD489 20mg, 30mg, 50mg, or 70mg + Antidepressant (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release or duloxetine hydrochloride) oral, once daily for 52 weeks
Other Name: Vyvanse, LDX

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject has completed 1 of the respective short-term antecedent SPD489 MDD studies and did not experience any clinically significant AEs in the antecedent study that would preclude exposure to SPD489.

Exclusion Criteria:

  • Subject has any current co-morbid Axis I or Axis II psychiatric disorder (including a lifetime history of psychosis) which was not present or recognized at entry into the antecedent study or has a concurrent chronic or acute illness or unstable medical condition that may deteriorate that could confound the results of safety assessments, increase risk to the subject or lead to difficulty complying with the protocol
  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: NCT01436175

  Show 212 Study Locations
Sponsors and Collaborators
Shire
Investigators
Principal Investigator: Madhukar H Trivedi, M.D. University of Texas Southwestern Medical School, Dallas, Texas 75235
  More Information

No publications provided

Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01436175     History of Changes
Other Study ID Numbers: SPD489-329, 2011-003019-47
Study First Received: September 15, 2011
Results First Received: February 5, 2015
Last Updated: February 5, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mental Disorders
Mood Disorders
Antidepressive Agents
Dextroamphetamine
Central Nervous System Agents
Central Nervous System Stimulants
Dopamine Agents
Dopamine Uptake Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on July 27, 2015