A Study for Adult Patients With Fibromyalgia

A Randomized, Double-Blind Comparison of Duloxetine 30 mg QD and Placebo in Adult Patients With Fibromyalgia

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00965081

Acronym

HMGG

Enrollment

308

Registered

2009-08-25

Start date

2009-09-30

Completion date

2010-11-30

Last updated

2011-11-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Fibromyalgia, Primary, Fibromyalgia, Secondary

Brief summary

The main purpose of this study is to determine if 30 milligrams (mg) of duloxetine is effective in the treatment of fibromyalgia compared to placebo.

Interventions

DRUGDuloxetine

30 milligrams (mg) dose daily (QD) by mouth (po) at the same time each day for 12 weeks

DRUGPlacebo

QD po at the same time each day for 12 weeks

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Meet study criteria for fibromyalgia diagnosis.

Exclusion criteria

* Have previously or are currently taking duloxetine. * Have been diagnosed with certain psychoses, bipolar or schizoaffective disorder * Have pain symptoms that are difficult to differentiate from fibromyalgia. * Have seizure disorder, uncontrolled narrow angle glaucoma, or acute liver injury (such as hepatitis) or severe cirrhosis. * Have had any primary Axis 1 diagnosis other than major depressive disorder or generalized anxiety disorder within the past year. * Are pregnant or breast-feeding * Have a current or previous diagnosis of rheumatoid, infectious or inflammatory arthritis or an autoimmune disease * Have a regional pain syndrome, failed back syndrome or chronic localized pan related to any past surgery * Have a serious unstable medical illness * Have a history of substance abuse or dependence within the past year

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline to 12-Week Endpoint in the Brief Pain Inventory (BPI) 24-Hour Average Pain Item (Question 3) of the BPI-Modified Short Form Score	Baseline, 12 weeks	BPI Average Pain score ranges from 0 (no pain) to 10 (pain as bad as you can imagine). Treatment group difference in Least Squares (LS) Means changes from analysis of covariance (ANCOVA) with terms for treatment group, pooled investigators, baseline. Baseline-observation-carried-forward (BOCF) method used to impute endpoint value for those who discontinued initial double-blind therapy (DBT) due to adverse event (AE); last non-missing observation during initial DBT used to impute missing endpoint for all others. Analyses included all participants having non-missing baseline and endpoint.

Secondary

Measure	Time frame	Description
Patient Global Impression - Improvement (PGI-I) at Endpoint	12 weeks	The PGI-I scale is a patient-rated instrument that measures perceived improvement in symptoms. It is a 7-point scale: score of 1 is very much better, 4 is no change, and 7 is very much worse. Treatment group difference in Least Squares (LS) Means at endpoint is from an analysis of covariance (ANCOVA); model included terms for treatment group, pooled investigators and baseline PGI-Severity (PGI-S).
Clinical Global Impression of Improvement (CGI-I) for Depression at Endpoint	12 weeks	The CGI-I measures clinician's perception of patient improvement at time of assessment compared with start of treatment. Scores range from 1 (very much improved) to 7 (very much worse). The treatment group difference in Least Squares (LS) Means at endpoint is from an analysis of covariance (ANCOVA). The model included terms for treatment group, pooled investigators and baseline CGI-Severity (CGI-S).
Change From Baseline to 12-Week Endpoint Beck Depression Inventory-II (BDI-II)	Baseline, 12 weeks	The BDI-II is a 21-item, patient-completed questionnaire to assess characteristics of depression. Each of the 21 items corresponding to a symptom of depression is summed to give a single score. There is a 4-point scale for each item ranging from 0 to 3 (0 = not present; 3 = present in the extreme). The treatment group difference in the Least Squares (LS) Means change from baseline to endpoint is from an analysis of covariance (ANCOVA). The model included terms for treatment group, pooled investigators and baseline.
Change From Baseline to 12-Week Endpoint in the Brief Pain Inventory (BPI) - Modified Short Form	Baseline, 12 weeks	BPI-Modified Short Form mean interference score ranges from 0 (does not interfere) to 10 (completely interferes) for pain in past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Treatment group difference in the Least Squares (LS) Means changes from baseline to endpoint is from an analysis of covariance (ANCOVA) with terms for treatment group, pooled investigators and baseline. Last-observation-carried forward (LOCF) endpoint defined as last available post-baseline value obtained during initial double-blind therapy.
Change From Baseline to 12-Week Endpoint Beck Anxiety Inventory (BAI)	Baseline, 12 weeks	The BAI is a 21-item patient-completed questionnaire designed to assess the characteristics of anxiety. Each item is rated on a 4-point scale (0=not present; 3=present in the extreme). The total score ranges from 0 to 63; the higher the score, the more severe the anxiety symptoms. The treatment group difference in the Least Squares (LS) Means at endpoint is from an analysis of covariance (ANCOVA). The model included terms for treatment group, pooled investigators and baseline.
Change From Baseline to 12-Week Endpoint 36-Item Short-Form Health Survey (SF-36)	Baseline, 12 weeks	SF-36 has 36 items with 8 domains: physical functioning, social functioning, bodily pain, vitality, mental health, role-physical, role-emotional, general health; each scored on 0 to 100 scale. Higher scores indicate better status. Mental component summary (MCS) and physical component summary (PCS) based on 8 SF-36 domains. Scales scored using norm-based methods; mean is 50 and standard deviation is 10 in U.S. population. Treatment group difference in Least Squares (LS) Means at endpoint from analysis of covariance. Terms for treatment group, pooled investigators, baseline in model.
Number of Participants With Suicidal Behaviors and Ideations Collected by Columbia -Suicide Severity Rating Scale (C-SSRS)	Baseline through 12 weeks	The C-SSRS is a scale capturing occurrence, severity, and frequency of suicide-related thoughts and behaviors. The number of participants with suicidal behaviors and ideations are provided. Suicidal behavior: a yes answer to any of 5 suicidal behavior questions which include: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation: a yes answer to any 1 of 5 suicidal ideation questions which include wish to be dead and 4 different categories of active suicidal ideation.
Change From Baseline to 12-Week Endpoint Fibromyalgia Impact Questionnaire (FIQ)	Baseline, 12 weeks	FIQ is a 20-item self-administered questionnaire that measures fibromyalgia (FM) patient status, progress, and outcomes over the past week. The total score ranges from 0 to 80 with higher scores reflecting a more negative impact of FM. The treatment group difference in the Least Squares (LS) Means change from baseline to endpoint is from an analysis of covariance (ANCOVA). The model included terms for treatment group, pooled investigators and baseline.

Countries

Mexico

Participant flow

Pre-assignment details

Participants who enter the study with a diagnosis of major depressive disorder (MDD) and who also meet the predefined blinded criteria for worsening of depression during the acute therapy phase will be rescued to daily duloxetine 60 mg for the remainder of the acute therapy phase.

Participants by arm

Arm	Count
Duloxetine Duloxetine 30 milligrams (mg) dose daily (QD) by mouth (po) at the same time each day for 12 weeks Participants who enter the study with a diagnosis of major depressive disorder (MDD) will be rescued to duloxetine 60 mg QD if they meet the predefined blinded criteria for worsening of depression.	155
Placebo Placebo (inactive capsules identical in appearance to duloxetine capsules) QD po at the same time each day for 12 weeks Participants who enter the study with a diagnosis of MDD will be rescued to duloxetine 60 mg QD if they meet the predefined blinded criteria for worsening of depression.	153
Total	308

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	14	9
Overall Study	Lack of Efficacy	2	5
Overall Study	Lost to Follow-up	4	5
Overall Study	Physician Decision	2	0
Overall Study	Protocol Violation	2	5
Overall Study	Sponsor Decision	1	0
Overall Study	Switched to Rescue Arm	5	12
Overall Study	Withdrawal by Subject	4	7

Baseline characteristics

Characteristic	Duloxetine	Placebo	Total
Age Continuous	50.89 Years STANDARD_DEVIATION 11.9	50.72 Years STANDARD_DEVIATION 12.45	50.80 Years STANDARD_DEVIATION 12.16
Beck Anxiety Inventory (BAI) Total Score	14.26 Units on a scale STANDARD_DEVIATION 9.35	15.04 Units on a scale STANDARD_DEVIATION 10.69	14.65 Units on a scale STANDARD_DEVIATION 10.04
Beck Depression Inventory (BDI) Total Score	15.00 Units on a scale STANDARD_DEVIATION 9.64	16.84 Units on a scale STANDARD_DEVIATION 11.47	15.92 Units on a scale STANDARD_DEVIATION 10.61
Body Mass Index (BMI)	28.91 kilograms/meters squared (kg/m2) STANDARD_DEVIATION 6	29.49 kilograms/meters squared (kg/m2) STANDARD_DEVIATION 6.9	29.20 kilograms/meters squared (kg/m2) STANDARD_DEVIATION 6.46
Brief Pain Inventory (BPI) Average Pain Score	6.50 Units on a scale STANDARD_DEVIATION 1.47	6.37 Units on a scale STANDARD_DEVIATION 1.67	6.44 Units on a scale STANDARD_DEVIATION 1.57
Brief Pain Inventory (BPI) Mean Interference Score	5.97 Units on a scale STANDARD_DEVIATION 2.17	5.78 Units on a scale STANDARD_DEVIATION 2.28	5.88 Units on a scale STANDARD_DEVIATION 2.23
Clinical Global Impression of Severity (CGI-S) for Depression Score	2.30 Units on a scale STANDARD_DEVIATION 1.38	2.45 Units on a scale STANDARD_DEVIATION 1.45	2.38 Units on a scale STANDARD_DEVIATION 1.42
Diagnosis of Generalized Anxiety Disorder (GAD) Diagnosis of GAD	11 Participants	8 Participants	19 Participants
Diagnosis of Generalized Anxiety Disorder (GAD) No diagnosis of GAD	144 Participants	145 Participants	289 Participants
Diagnosis of Major Depressive Disorder (MDD) Diagnosis of MDD	32 Participants	37 Participants	69 Participants
Diagnosis of Major Depressive Disorder (MDD) No diagnosis of MDD	123 Participants	116 Participants	239 Participants
Fibromyalgia Impact Questionnaire (FIQ) Total Score	51.11 Units on a scale STANDARD_DEVIATION 12.17	50.44 Units on a scale STANDARD_DEVIATION 13.71	50.78 Units on a scale STANDARD_DEVIATION 12.94
Patient's Global Impressions of Severity (PGI-S) Score	3.74 Units on a scale STANDARD_DEVIATION 1.33	3.74 Units on a scale STANDARD_DEVIATION 1.47	3.74 Units on a scale STANDARD_DEVIATION 1.4
Race/Ethnicity, Customized American Indian or Alaska Native	13 Participants	12 Participants	25 Participants
Race/Ethnicity, Customized Asian	3 Participants	0 Participants	3 Participants
Race/Ethnicity, Customized Black or African American	6 Participants	5 Participants	11 Participants
Race/Ethnicity, Customized White	133 Participants	136 Participants	269 Participants
Region of Enrollment Argentina	40 Participants	38 Participants	78 Participants
Region of Enrollment Israel	14 Participants	14 Participants	28 Participants
Region of Enrollment Mexico	42 Participants	42 Participants	84 Participants
Region of Enrollment Puerto Rico	3 Participants	3 Participants	6 Participants
Region of Enrollment United States	56 Participants	56 Participants	112 Participants
Sex: Female, Male Female	146 Participants	147 Participants	293 Participants
Sex: Female, Male Male	9 Participants	6 Participants	15 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	78 / 153	100 / 155	5 / 17
serious Total, serious adverse events	1 / 153	0 / 155	0 / 17

Outcome results

Primary

Change From Baseline to 12-Week Endpoint in the Brief Pain Inventory (BPI) 24-Hour Average Pain Item (Question 3) of the BPI-Modified Short Form Score

BPI Average Pain score ranges from 0 (no pain) to 10 (pain as bad as you can imagine). Treatment group difference in Least Squares (LS) Means changes from analysis of covariance (ANCOVA) with terms for treatment group, pooled investigators, baseline. Baseline-observation-carried-forward (BOCF) method used to impute endpoint value for those who discontinued initial double-blind therapy (DBT) due to adverse event (AE); last non-missing observation during initial DBT used to impute missing endpoint for all others. Analyses included all participants having non-missing baseline and endpoint.