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A Phase 3b Multicenter Study of Pregabalin in Fibromyalgia Subjects Who Have Comorbid Depression

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01432236
First received: September 8, 2011
Last updated: October 21, 2014
Last verified: October 2014
  Purpose

The intent of this study is to identify and treat fibromyalgia subjects with comorbid depression who are receiving an SSRI (selective serotonin reuptake inhibitor) or SNRI (selective norepinephrine reuptake inhibitor) primarily for their depression and to determine whether pregabalin demonstrates improvement relative to placebo in improving pain associated with fibromyalgia.


Condition Intervention Phase
Fibromyalgia
Drug: Pregabalin
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3b Multicenter, Double-blind, Randomized, Placebo-controlled, 2-way Crossover Study Of Pregabalin In The Treatment Of Fibromyalgia With Concurrent Antidepressant Therapy For Comorbid Depression (Protocol A0081275)

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Mean NRS Pain Score at End of Period. [ Time Frame: End of each period, at Weeks 6 and 14 ] [ Designated as safety issue: No ]
    The daily pain diary consists of an 11-point numeric scale (NRS) ranging from 0 ("no pain") to 10 ("worst possible pain"). Participants describe their pain during the past 24 hours by choosing the appropriate number between 0 and 10. The endpoint mean pain scores for Period 1 and Period 2 are defined as the mean of the last 7 non-missing daily diary pain ratings while taking study medication in the double-blind phase during Period 1 and Period 2, respectively.


Secondary Outcome Measures:
  • Fibromyalgia Impact Questionnaire (FIQ) Score at Baseline. [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    This was a 20-item participant reported outcome instrument. It contained 10 subscales, which were combined to yield a total score. The first 11 questions were related specifically to physical functioning subscale, ranging from 0 to 10. The remaining 9 questions assessed pain, fatigue, stiffness, difficulty working, and symptoms of anxiety and depression ranging from 0 to 10. The higher values indicated greater impairment. All 20 were combined to form a total score ranging from 0 to 100, provides an estimation of fibromyalgia impact with higher scores indicating more impairment. The severity categorizations for the FIQ are: less than 40 (mild), 40-60 (moderate), and above 60 (severe).

  • FIQ Score at End of Period. [ Time Frame: End of each period, at Weeks 6 and 14 ] [ Designated as safety issue: No ]
    This was a 20-item participant reported outcome instrument. It contained 10 subscales, which were combined to yield a total score. The first 11 questions were related specifically to physical functioning subscale, ranging from 0 to 10. The remaining 9 questions assessed pain, fatigue, stiffness, difficulty working, and symptoms of anxiety and depression ranging from 0 to 10. The higher values indicated greater impairment. All 20 were combined to form a total score ranging from 0 to 100, provides an estimation of fibromyalgia impact with higher scores indicating more impairment. The severity categorizations for the FIQ are: less than 40 (mild), 40-60 (moderate), and above 60 (severe).

  • Patient Global Impression of Change (PGIC) at the End of Period 1. [ Time Frame: End of Period 1 at Week 6 ] [ Designated as safety issue: No ]
    PGIC: participant rated instrument to measure participant's change in overall status on a 7-point scale; range from 1 (very much improved) to 7 (very much worse).

  • Percentage of Participants With >=30% and >=50% Pain Reduction Based on Daily Pain Diary. [ Time Frame: Visits 2, 6, and 12 ] [ Designated as safety issue: No ]
    Participant with at least a 30% reduction in mean pain score from baseline (at randomization) to the endpoint at the end of each period (Visits 6 and 12) is considered a 30% responder, for the respective period. Similarly, a subject with at least a 50% reduction in mean pain score from baseline (at randomization) to the endpoint at the end of each period (Visits 6 and 12) is considered a 50% responder, for the respective period.

  • Subjective Sleep Questionnaire - Mean Sleep Quality at End of Period. [ Time Frame: End of each period, at Weeks 6 and 14 ] [ Designated as safety issue: No ]
    Subjective Sleep Questionnaire included 5 items: participants report latency (how long it took them to fall asleep), how many hours they slept, the number of times they woke up, the total wake time after sleep onset, and then rate the quality of their sleep (NRS) for the previous night. Subjective rating of quality of sleep during the past night was done by selecting a number between 0 (very poor) and 10 (excellent). Mean sleep quality was calculated as the mean of the last seven days, the potential range of responses was therefore 0-10.

  • Subjective Sleep Questionnaire - Mean Subjective Wake After Sleep Onset at End of Period. [ Time Frame: End of each period, at Weeks 6 and 14 ] [ Designated as safety issue: No ]
    Subjective Sleep Questionnaire included, participants report latency (how long it took them to fall asleep), how many hours they slept, the number of times they woke up, the total wake time after sleep onset, and then rate the quality of their sleep (numeric rating scale) for the previous night. Subjective wake after sleep onset was the subjective estimate of the total amount of time the participant was awake after initial sleep onset until final awakening.

  • Subjective Sleep Questionnaire - Mean Latency to Sleep Onset at End of Period. [ Time Frame: End of each period, at Weeks 6 and 14 ] [ Designated as safety issue: No ]
    Subjective Sleep Questionnaire included, participants report latency (how long it took them to fall asleep), how many hours they slept, the number of times they woke up, the total wake time after sleep onset, and then rate the quality of their sleep (numeric rating scale) for the previous night. Subjective latency to sleep onset was the subjective estimate of the amount of time to fall asleep after lights out.

  • Subjective Sleep Questionnaire - Mean Subjective Total Sleep Time at End of Period. [ Time Frame: End of each period, at Weeks 6 and 14 ] [ Designated as safety issue: No ]
    Subjective Sleep Questionnaire included, participants report latency (how long it took them to fall asleep), how many hours they slept, the number of times they woke up, the total wake time after sleep onset, and then rate the quality of their sleep (numeric rating scale) for the previous night. Subjective total sleep time was the subjective estimate of the total amount of time the participant was asleep after lights out until final awakening.

  • Subjective Sleep Questionnaire - Parameter Estimates for Subjective Number of Awakenings Per Night After Sleep Onset at End of Period. [ Time Frame: End of each period, at Weeks 6 and 14 ] [ Designated as safety issue: No ]
    Subjective Sleep Questionnaire included, participants report latency (how long it took them to fall asleep), how many hours they slept, the number of times they woke up, the total wake time after sleep onset, and then rate the quality of their sleep (numeric rating scale) for the previous night. Subjective number of awakenings after sleep onset was the subjective estimate of the total number of times the participant awakened during the night until final awakening.

  • Hospital Anxiety and Depression Scale (HADS) at Baseline. [ Time Frame: Baseline ] [ Designated as safety issue: Yes ]
    HADS: participant rated questionnaire with 2 subscales. HADS-A (anxiety) assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D (depression) assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms.

  • HADS at End of Period. [ Time Frame: End of each period, at Weeks 6 and 14 ] [ Designated as safety issue: Yes ]
    HADS: participant rated questionnaire with 2 subscales. HADS-A (anxiety) assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D (depression) assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms.

  • Mean EuroQoL 5-Dimensions (EQ-5D) Score at Baseline. [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    EQ-5D is a standardized, participant-administered measure of health outcome. It provides a descriptive profile for 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), using 3 levels (no, moderate, or extreme problems) and a single index value characterizing current health status using a 100-point visual analog scale (0=worst, 100=best). EQ-5D summary index is obtained with a formula that weights each level of the dimensions. The index-based score is interpreted along a continuum of 0 (death) to 1 (perfect health).

  • EQ-5D Score at End of Period. [ Time Frame: End of each period, at Weeks 6 and 14 ] [ Designated as safety issue: No ]
    EQ-5D is a standardized, participant-administered measure of health outcome. It provides a descriptive profile for 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), using 3 levels (no, moderate, or extreme problems) and a single index value characterizing current health status using a 100-point visual analog scale (0=worst, 100=best). EQ-5D summary index is obtained with a formula that weights each level of the dimensions. The index-based score is interpreted along a continuum of 0 (death) to 1 (perfect health).


Other Outcome Measures:
  • PGIC at the End of Period 2. [ Time Frame: End of Period 2 at Week 14 ] [ Designated as safety issue: No ]
    PGIC: participant rated instrument to measure participant's change in overall status on a 7-point scale; range from 1 (very much improved) to 7 (very much worse). Because of the crossover design and PGIC recall period (since starting study medication), the Period 1 PGIC data were felt to provide the clearest comparison across treatments, whereas Period 2 PGIC data were felt to have a more complex interpretation. Thus PGIC at End of Period 2 was separately analyzed from PGIC at End of Period 1.

  • Mean Patient Static Global Assessment (PSGA) Score at Baseline. [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    PSGA was a single-item self-rated instrument that measured the participant's overall status on an 11-point NRS ranging from 0 (very poor) to 10 (very good).

  • Mean PSGA Score at End of Period. [ Time Frame: End of each period, at Weeks 6 and 14 ] [ Designated as safety issue: No ]
    PSGA was a single-item self-rated instrument that measured the participant's overall status on an 11-point numeric rating scale (NRS) ranging from 0 (very poor) to 10 (very good).

  • Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) at Baseline. [ Time Frame: Baseline ] [ Designated as safety issue: Yes ]
    C-SSRS assessed whether participant experienced following: completed suicide (1), suicide attempt (2) (response of "Yes" on "actual attempt"), preparatory acts toward imminent suicidal behavior (3) ("Yes" on "preparatory acts or behavior"), suicidal ideation (4) ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent), any suicidal behavior or ideation, self-injurious behavior (7) ("Yes" on "Has participant engaged in non-suicidal self-injurious behavior").

  • Number of Participants With Categorical Scores on the C-SSRS at Post-Baseline. [ Time Frame: From Visit 3 to Visit 14 ] [ Designated as safety issue: Yes ]
    C-SSRS assessed whether participant experienced following:completed suicide (1), suicide attempt (2) (response of Yes on "actual attempt"), preparatory acts toward imminent suicidal behavior (3) (Yes on "preparatory acts or behavior"), suicidal ideation (4) (Yes on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent), any suicidal behavior or ideation, self-injurious behavior (7) (Yes on "Has subject engaged in non-suicidal self-injurious behavior"). Below table indicated one participant (10141023) treated with Pregabalin reported preparatory act. However upon study unblinding it was clarified that preparatory act occurred while the participant was taking placebo. Since preparatory act was reported at first visit of Period 2, by convention statistical summaries classified this under Pregabalin treatment.

  • Work Productivity and Activity Index-Specific Health Problem (WPAI-SHP) Questionnaire at Baseline. [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    WPAI-SHP assessed work productivity and impairment. It was a participant-rated, six-item questionnaire regarding current employment, hours missed and actually worked, and degree to which a specified health problem affected work productivity and regular activities over the past 7 days. Subscale scores included percent work time missed due to the health problem; percent impairment while working due to problem; percent overall work impairment due to problem; and percent activity impairment due to problem. Each subscale score was expressed as an impairment percentage (0-100) where higher numbers indicated greater impairment and less productivity.

  • Health Utilization Assessment (Total Office Visits, Number of Hospitalizations and Number of Emergency Room Visits) at Baseline. [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    The healthcare utilization assessment was used to capture healthcare utilization data at Baseline. This assessment contained 10 questions related to aspects of healthcare services.

  • Health Utilization Assessment (Time for Help no Payment) at Baseline. [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    The healthcare utilization assessment was used to capture healthcare utilization data at Baseline. This assessment contained 10 questions related to aspects of healthcare services. 'Time for help no payment' refers to time other people spent without receiving payment to help with activities the patient cannot perform due to fibromyalgia.


Enrollment: 197
Study Start Date: October 2011
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pregabalin
Group 1 as Pregabalin vs. Placebo (cross over study in which period one has this group)
Drug: Pregabalin
Pregabalin 300 or 450 mg/day dosed BID ( twice a day) for 14 weeks; 150 mg/day starting dose
Placebo Comparator: Placebo
Group 2 as placebo vs. pregabalin (cross over study in which period two will have this group)
Drug: placebo
placebo capsules twice a day for 14 weeks

  Eligibility

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

Inclusion Criteria:

  • Men or women of any race or ethnicity who are at least 18 years of age.
  • Adult women and men with a diagnosis of fibromyalgia and stable depression (major depressive disorder, depression not otherwise specified (NOS), or dysthymia) who have been taking an antidepressant (SSRI or SNRI) primarily for their depression for at least 3 months.

Exclusion Criteria:

  • Have failed pregabalin treatment due to lack of improvement of symptoms at doses of greater than or equal to 300 mg daily, cannot tolerate pregabalin or any pregabalin ingredient, or participated in a pregabalin clinical trial. If the subject has taken pregabalin and discontinued for reason other than lack of improvement or intolerance, then they will be eligible. Pregabalin use within the last 30 days (prior to V1) is not permitted.
  • Patients with severe or unstable depression are not eligible.
  • Patients with other types of pain or conditions that may make it difficult to evaluate fibromyalgia symptoms are not eligible
  • Any subject considered at risk of suicide or self harm based on investigator judgment and/or the details of a risk assessment
  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: NCT01432236

  Show 37 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: NCT01432236     History of Changes
Other Study ID Numbers: A0081275, 2011-002480-19
Study First Received: September 8, 2011
Results First Received: May 12, 2014
Last Updated: October 21, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Pregabalin
Lyrica
depression

Additional relevant MeSH terms:
Depression
Depressive Disorder
Fibromyalgia
Myofascial Pain Syndromes
Behavioral Symptoms
Mental Disorders
Mood Disorders
Muscular Diseases
Musculoskeletal Diseases
Nervous System Diseases
Neuromuscular Diseases
Rheumatic Diseases
Gamma-Aminobutyric Acid
Pregabalin
Analgesics
Anticonvulsants
Calcium Channel Blockers
Cardiovascular Agents
Central Nervous System Agents
GABA Agents
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 19, 2014