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

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)

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.

Study Overview

• Status: Completed
• Conditions: Fibromyalgia
• Intervention / Treatment: Drug: Pregabalin; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 197
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Penticton, British Columbia, Canada, V2A 4M4
      • Dr. Alexander McIntyre Inc.
  • Ontario
    • Thornhill, Ontario, Canada, L4J 1W3
      • Canadian Centre for Clinical Trials
  • Quebec
    • Sherbrooke, Quebec, Canada, J1H 1Z1
      • Diex Research Sherbrooke Inc.
• Italy
  • Milano, Italy, 20157
    • Azienda Ospedaliera Luigi Sacco - Polo Universitario
  • Roma, Italy, 00161
    • Università degli studi di Roma "La Sapienza"
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 08034
    • Servicio de Reumatologia,Institut Ferran de Reumatologia-Clinica CIMA
  • Barcelona, Spain, 08024
    • Hospital de lˊEsperança
  • Barcelona, Spain, 08028
    • Instituto Universitario USP Dexeus
  • Guadalajara, Spain, 19002
    • Hospital General Universitario de Guadalajara
  • Madrid, Spain, 28028
    • Hospital General Universitario Gregorio Maranon
• United States
  • Arizona
    • Tucson, Arizona, United States, 85704
      • Genova Clinical Research
  • California
    • Orange, California, United States, 92868
      • SDS Clinical Trials
    • Santa Ana, California, United States, 92705
      • Research Across America
  • Florida
    • Clearwater, Florida, United States, 33756
      • Innovative Research of West Florida, Inc.
    • Coral Gables, Florida, United States, 33134
      • Florida Medical Center & Research, Inc.
    • Tampa, Florida, United States, 33606
      • Meridien Research
  • Georgia
    • Columbus, Georgia, United States, 31909
      • Medical Research and Health Education Foundation, Inc.
  • Kansas
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates, LLC
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Central Kentucky Research Associates, Inc.
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Boston Clinical Trials
  • Michigan
    • Ann Arbor, Michigan, United States, 48104
      • Michigan Head Pain and Neurological Institute
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Quality Clinical Research, Inc.
  • New York
    • Brooklyn, New York, United States, 11235
      • Social Psychiatry Research Institute
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati
    • Columbus, Ohio, United States, 43212
      • Radiant Research, Inc.
    • Dayton, Ohio, United States, 45417
      • Midwest Clinical Research Center
  • Oregon
    • Medford, Oregon, United States, 97504
      • Sunstone Medical Research, LLC
  • Pennsylvania
    • Wyomissing, Pennsylvania, United States, 19610
      • Clinical Research Center of Reading, LLP
    • Wyomissing, Pennsylvania, United States, 19610
      • Behavioral Medicine Center
  • Rhode Island
    • East Greenwich, Rhode Island, United States, 02818
      • Coastal Medical
    • Warwick, Rhode Island, United States, 02886
      • Omega Medical Research
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Coastal Carolina Research Center
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Trials of Neurology
  • Utah
    • Salt Lake City, Utah, United States, 84102
      • Fatigue Consultation Clinic
    • Salt Lake City, Utah, United States, 84106
      • Lifetree Clinical Research, LC
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Charlottesville Medical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean NRS Pain Score at End of Period.	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.	End of each period, at Weeks 6 and 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fibromyalgia Impact Questionnaire (FIQ) Score at Baseline.	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).	Baseline
FIQ Score at End of Period.	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).	End of each period, at Weeks 6 and 14
Patient Global Impression of Change (PGIC) at the End of Period 1.	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).	End of Period 1 at Week 6
Percentage of Participants With >=30% and >=50% Pain Reduction Based on Daily Pain Diary.	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.	Visits 2, 6, and 12
Subjective Sleep Questionnaire - Mean Sleep Quality at End of Period.	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.	End of each period, at Weeks 6 and 14
Subjective Sleep Questionnaire - Mean Subjective Wake After Sleep Onset at End of Period.	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.	End of each period, at Weeks 6 and 14
Subjective Sleep Questionnaire - Mean Latency to Sleep Onset at End of Period.	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.	End of each period, at Weeks 6 and 14
Subjective Sleep Questionnaire - Mean Subjective Total Sleep Time at End of Period.	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.	End of each period, at Weeks 6 and 14
Subjective Sleep Questionnaire - Parameter Estimates for Subjective Number of Awakenings Per Night After Sleep Onset at End of Period.	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.	End of each period, at Weeks 6 and 14
Hospital Anxiety and Depression Scale (HADS) at Baseline.	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.	Baseline
HADS at End of Period.	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.	End of each period, at Weeks 6 and 14
Mean EuroQoL 5-Dimensions (EQ-5D) Score at Baseline.	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).	Baseline
EQ-5D Score at End of Period.	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).	End of each period, at Weeks 6 and 14

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
PGIC at the End of Period 2.	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.	End of Period 2 at Week 14
Mean Patient Static Global Assessment (PSGA) Score at Baseline.	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).	Baseline
Mean PSGA Score at End of Period.	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).	End of each period, at Weeks 6 and 14
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) at Baseline.	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").	Baseline
Number of Participants With Categorical Scores on the C-SSRS at Post-Baseline.	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.	From Visit 3 to Visit 14
Work Productivity and Activity Index-Specific Health Problem (WPAI-SHP) Questionnaire at Baseline.	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.	Baseline
Health Utilization Assessment (Total Office Visits, Number of Hospitalizations and Number of Emergency Room Visits) at Baseline.	The healthcare utilization assessment was used to capture healthcare utilization data at Baseline. This assessment contained 10 questions related to aspects of healthcare services.	Baseline
Health Utilization Assessment (Time for Help no Payment) at Baseline.	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.	Baseline

Collaborators and Investigators

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Publications and helpful links

General Publications

• Bateman L, Sarzi-Puttini P, Burbridge CL, Landen JW, Masters ET, Bhadra Brown P, Scavone JM, Emir B, Vissing RS, Clair AG, Pauer LR. Burden of illness in fibromyalgia patients with comorbid depression. Clin Exp Rheumatol. 2016 Mar-Apr;34(2 Suppl 96):S106-13. Epub 2016 Mar 10.
• Arnold LM, Sarzi-Puttini P, Arsenault P, Khan T, Bhadra Brown P, Clair A, Scavone JM, Driscoll J, Landen J, Pauer L. Efficacy and Safety of Pregabalin in Patients with Fibromyalgia and Comorbid Depression Taking Concurrent Antidepressant Medication: A Randomized, Placebo-controlled Study. J Rheumatol. 2015 Jul;42(7):1237-44. doi: 10.3899/jrheum.141196. Epub 2015 Jun 1.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (ACTUAL): July 1, 2013
• Study Completion (ACTUAL): July 1, 2013

Study Registration Dates

• First Submitted: September 8, 2011
• First Submitted That Met QC Criteria: September 8, 2011
• First Posted (ESTIMATE): September 12, 2011

Study Record Updates

• Last Update Posted (ACTUAL): January 22, 2021
• Last Update Submitted That Met QC Criteria: January 20, 2021
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: depression; Pregabalin; Lyrica
• Additional Relevant MeSH Terms: Behavioral Symptoms; Nervous System Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Muscular Diseases; Neuromuscular Diseases; Depression; Fibromyalgia; Myofascial Pain Syndromes; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Pregabalin
• Other Study ID Numbers: A0081275; 2011-002480-19 (EUDRACT_NUMBER)