Trial Outcomes & Findings for Study of Milnacipran for the Treatment of Fibromyalgia (NCT NCT00314249)
NCT ID: NCT00314249
Last Updated: 2010-01-20
Results Overview
Composite Syndrome Responder Status is the number of responders based on 3 domains: (1) 30% reduction in pain (as recorded in the Patient Experience Diary \[PED\], electronic diary, during the morning report; 24 hour recall); (2) patient global impression of change (PGIC) score of "very much improved" and "much improved;" and (3) physical function improvement of 6 or more points on Short Form-36 Physical Component Summary (SF-36 PCS)
COMPLETED
PHASE3
1025 participants
At the end of the three-month stable dose treatment phase
2010-01-20
Participant Flow
Recruitment period was from 4/28/06 through 12/27/07 with last patient last visit on 6/30/08 at 65 centers in the US and 3 centers in Canada
Upon completion of the washout period, a two-week baseline period was completed prior to randomization. Patients were then randomized in a 1:1 ratio to either placebo or milnacipran 100 mg/day (50 mg BID \[twice a day\])
Participant milestones
| Measure |
Placebo
Placebo administered orally BID (twice a day) for 12 weeks of stable dose treatment phase
|
Milnacipran
Milnacipran 100 mg per day, administered orally (BID \[twice a day\]) for 12 weeks of stable dose treatment phase
|
|---|---|---|
|
Overall Study
STARTED
|
509
|
516
|
|
Overall Study
COMPLETED
|
357
|
353
|
|
Overall Study
NOT COMPLETED
|
152
|
163
|
Reasons for withdrawal
| Measure |
Placebo
Placebo administered orally BID (twice a day) for 12 weeks of stable dose treatment phase
|
Milnacipran
Milnacipran 100 mg per day, administered orally (BID \[twice a day\]) for 12 weeks of stable dose treatment phase
|
|---|---|---|
|
Overall Study
Adverse Event
|
73
|
94
|
|
Overall Study
Lack of Efficacy
|
33
|
24
|
|
Overall Study
Withdrawal by Subject
|
21
|
28
|
|
Overall Study
Lost to Follow-up
|
15
|
9
|
|
Overall Study
Physician Decision
|
1
|
1
|
|
Overall Study
Withdrawn for other reasons
|
4
|
1
|
|
Overall Study
Non-Compliant
|
5
|
6
|
Baseline Characteristics
Study of Milnacipran for the Treatment of Fibromyalgia
Baseline characteristics by cohort
| Measure |
Placebo
n=509 Participants
Placebo administered orally BID (twice a day) for 12 weeks of stable dose treatment phase
|
Milnacipran
n=516 Participants
Milnacipran 100 mg per day, administered orally (BID \[twice a day\]) for 12 weeks of stable dose treatment phase
|
Total
n=1025 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
48.73 years
STANDARD_DEVIATION 10.56 • n=93 Participants
|
49.07 years
STANDARD_DEVIATION 10.79 • n=4 Participants
|
48.90 years
STANDARD_DEVIATION 10.67 • n=27 Participants
|
|
Age, Customized
<=20 years
|
2 participants
n=93 Participants
|
2 participants
n=4 Participants
|
4 participants
n=27 Participants
|
|
Age, Customized
Between 20 and 60 years
|
437 participants
n=93 Participants
|
429 participants
n=4 Participants
|
866 participants
n=27 Participants
|
|
Age, Customized
>=60 years
|
70 participants
n=93 Participants
|
85 participants
n=4 Participants
|
155 participants
n=27 Participants
|
|
Sex: Female, Male
Female
|
477 Participants
n=93 Participants
|
500 Participants
n=4 Participants
|
977 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
32 Participants
n=93 Participants
|
16 Participants
n=4 Participants
|
48 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
463 participants
n=93 Participants
|
469 participants
n=4 Participants
|
932 participants
n=27 Participants
|
|
Region of Enrollment
Canada
|
46 participants
n=93 Participants
|
47 participants
n=4 Participants
|
93 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: At the end of the three-month stable dose treatment phasePopulation: The primary efficacy analysis was performed based on intent-to-treat population defined as all randomized patients who took at least one dose of double-blind study medication. All subjects with missing assessments at the end of the three-month stable dose treatment phase were considered non-responders (baseline value carried forward (BOCF)).
Composite Syndrome Responder Status is the number of responders based on 3 domains: (1) 30% reduction in pain (as recorded in the Patient Experience Diary \[PED\], electronic diary, during the morning report; 24 hour recall); (2) patient global impression of change (PGIC) score of "very much improved" and "much improved;" and (3) physical function improvement of 6 or more points on Short Form-36 Physical Component Summary (SF-36 PCS)
Outcome measures
| Measure |
Placebo
n=509 Participants
Placebo administered orally BID (twice a day) for 12 weeks of stable dose treatment phase
|
Milnacipran
n=516 Participants
Milnacipran 100 mg per day, administered orally (BID \[twice a day\]) for 12 weeks of stable dose treatment phase
|
|---|---|---|
|
Composite Syndrome Responder Status
|
56 Syndrome Responder Participants
|
103 Syndrome Responder Participants
|
PRIMARY outcome
Timeframe: At the end of three-month stable dose treatment phasePopulation: The primary efficacy analysis was performed based on intent-to-treat population defined as all randomized patients who took at least one dose of double-blind study medication. All subjects with missing assessments at the end of three-month stable dose treatment phase were considered non-responders (baseline value carried forward (BOCF)).
Composite Pain Responder Status is the number of responders based on two domains: (1) 30% reduction in pain (as recorded in the Patient Experience Diary \[PED\], electronic diary, during the morning report; 24 hour recall); and (2) Patient Global Impression of Change (PGIC) score of "very much improved" or "much improved."
Outcome measures
| Measure |
Placebo
n=509 Participants
Placebo administered orally BID (twice a day) for 12 weeks of stable dose treatment phase
|
Milnacipran
n=516 Participants
Milnacipran 100 mg per day, administered orally (BID \[twice a day\]) for 12 weeks of stable dose treatment phase
|
|---|---|---|
|
Composite Pain Responder Status
|
90 Pain Responder Participants
|
147 Pain Responder Participants
|
SECONDARY outcome
Timeframe: Weeks 1 through 12 of the stable dose treatment phase (Visit TX0-TX12)Population: The analysis was performed based on intent-to-treat population defined as all randomized patients who took at least one dose of double-blind study medication. For all subjects with missing assessments for weeks 1-12 of the stable dose treatment phase, values were imputed using last observation carried forward (LOCF).
Time-weighted average (area under the curve \[AUC\]) of the weekly average Patient Experience Diary (PED)-reported morning recall pain scores for weeks 1 through 12 of the stable dose treatment phase is the area under the Patient Experience Diary (PED)-time curve estimated using the trapezoidal method and normalized by time. PED is the Patient Experience Diary, an electronic diary system used for collection of patient self-reported pain data. Outcome measure is assessed using the VAS Pain Intensity Scale from 0-100 millimeters anchored at 0 mm (no pain) to 100 mm (worst possible pain).
Outcome measures
| Measure |
Placebo
n=509 Participants
Placebo administered orally BID (twice a day) for 12 weeks of stable dose treatment phase
|
Milnacipran
n=516 Participants
Milnacipran 100 mg per day, administered orally (BID \[twice a day\]) for 12 weeks of stable dose treatment phase
|
|---|---|---|
|
Time-Weighted Average of Patient Experience Diary (PED) Reported Morning 24-Hour Recall Pain Scores for Weeks 1-12 of the Stable Dose Phase
|
48.0 units on scale
Standard Error 0.83
|
41.2 units on scale
Standard Error 0.87
|
SECONDARY outcome
Timeframe: Weeks 1-12 (Visit TX0-TX12) of the stable dose treatment phasePopulation: The analysis was performed based on intent-to-treat population defined as all randomized patients who took at least one dose of double-blind study medication. For all subjects with missing assessments from weeks 1-12 of the stable dose treatment phase, values were imputed using last observation carried forward (LOCF).
Time-weighted average (area under the curve \[AUC\]) for Patient Global Impression of Change (PGIC) from Visit TX0-TX12 is the area under the PGIC-time curve estimated using the trapezoidal method and normalized by time. PGIC is an efficacy assessment on a scale of 1-7 taken at visits TX0-TX12. The wording of the assessment is as follows: "Since the start of the study, overall my fibromyalgia is:" 1=Very Much Improved, 2=Much Improved, 3=Minimally Improved, 4=No Change, 5=Minimally Worse, 6=Much Worse, and 7-Very Much Worse.
Outcome measures
| Measure |
Placebo
n=486 Participants
Placebo administered orally BID (twice a day) for 12 weeks of stable dose treatment phase
|
Milnacipran
n=495 Participants
Milnacipran 100 mg per day, administered orally (BID \[twice a day\]) for 12 weeks of stable dose treatment phase
|
|---|---|---|
|
Time-Weighted Average of Patient Global Impression of Change (PGIC) From Visit TX0-TX12.
|
3.4 units on scale
Standard Error 0.06
|
2.9 units on scale
Standard Error 0.06
|
SECONDARY outcome
Timeframe: Baseline through end of week 12 (Visit TX12)Population: The analysis was performed based on intent-to-treat population defined as all randomized patients who took at least one dose of double-blind study medication. For all subjects with missing assessments at the end of week 12 (Visit TX12), values were imputed using Last Observation Carried Forward (LOCF).
Change from Baseline in the Multi-Dimensional Fatigue Inventory (MFI) total score at TX12. Negative differences indicate decrease of fatigue. MFI is a subjective report of fatigue symptoms consisting of 20 items that can be scored to produce 5 dimensions: general fatigue, physical fatigue, mental fatigue, reduced motivation, and reduced activity. The MFI is a 1-5 scale with 1="yes, that is true" and 5="no, that is not true."
Outcome measures
| Measure |
Placebo
n=502 Participants
Placebo administered orally BID (twice a day) for 12 weeks of stable dose treatment phase
|
Milnacipran
n=508 Participants
Milnacipran 100 mg per day, administered orally (BID \[twice a day\]) for 12 weeks of stable dose treatment phase
|
|---|---|---|
|
Change From Baseline in the Multi-Dimensional Fatigue Inventory (MFI) Total Score at Visit TX12.
|
-3.96 units on scale
Standard Error 0.549
|
-5.50 units on scale
Standard Error 0.599
|
SECONDARY outcome
Timeframe: Weeks 1-12 (Visit TX0-TX12) of the stable dose treatment phasePopulation: The analysis was performed based on intent-to-treat population defined as all randomized patients who took at least one dose of double-blind study medication. For all subjects with missing assessments from weeks 1-12 (Visit TX0-TX12) of the stable dose treatment phase, values were imputed using the Last Observation Carried Forward (LOCF) approach.
Short Form-36 (SF-36): pt. questionnaire (36 questions) which give rise to 8 domains \& 2 component summaries (mental and physical); assessing quality of life, health \& functional status. SF-36 PCS: weighted summary of physical function using all 8 domains. Scores are standardized so that the range for all domains and component summaries is 0 (worst possible score) to 100 (best possible score). Higher scores indicate better health or functional status. SF-36 PCS AUC (Area under the Curve): estimated using trapezoidal method, normalized by time.
Outcome measures
| Measure |
Placebo
n=509 Participants
Placebo administered orally BID (twice a day) for 12 weeks of stable dose treatment phase
|
Milnacipran
n=516 Participants
Milnacipran 100 mg per day, administered orally (BID \[twice a day\]) for 12 weeks of stable dose treatment phase
|
|---|---|---|
|
Time-Weighted Average of the Short Form-36 Physical Component Summary (SF-36 PCS) Score From Visit TX0-TX12
|
36.4 units on scale
Standard Error 0.37
|
37.9 units on scale
Standard Error 0.37
|
Adverse Events
Placebo
Milnacipran
Serious adverse events
| Measure |
Placebo
n=509 participants at risk
Placebo administered orally BID (twice a day) for 12 weeks of stable dose treatment phase
|
Milnacipran
n=516 participants at risk
Milnacipran 100 mg per day, administered orally (BID \[twice a day\]) for 12 weeks of stable dose treatment phase
|
|---|---|---|
|
Psychiatric disorders
Anxiety
|
0.00%
0/509
|
0.19%
1/516
|
|
Infections and infestations
Apendicitis
|
0.20%
1/509
|
0.00%
0/516
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer
|
0.20%
1/509
|
0.00%
0/516
|
|
General disorders
Chest Pain
|
0.00%
0/509
|
0.39%
2/516
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/509
|
0.19%
1/516
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/509
|
0.19%
1/516
|
|
Psychiatric disorders
Confusional State
|
0.00%
0/509
|
0.19%
1/516
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/509
|
0.19%
1/516
|
|
Nervous system disorders
Embolic Cerebral Infarction
|
0.20%
1/509
|
0.00%
0/516
|
|
Injury, poisoning and procedural complications
Fall
|
0.39%
2/509
|
0.00%
0/516
|
|
Nervous system disorders
Grand Mal Convlusion
|
0.00%
0/509
|
0.19%
1/516
|
|
Blood and lymphatic system disorders
Haemorrhagic Anaemia
|
0.20%
1/509
|
0.00%
0/516
|
|
Injury, poisoning and procedural complications
Humerus Fracture
|
0.20%
1/509
|
0.00%
0/516
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/509
|
0.19%
1/516
|
|
Infections and infestations
Lobar Pneumonia
|
0.00%
0/509
|
0.39%
2/516
|
|
Reproductive system and breast disorders
Menorrhagia
|
0.20%
1/509
|
0.00%
0/516
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Chest Pain
|
0.00%
0/509
|
0.19%
1/516
|
|
General disorders
Non-cardiac Chest Pain
|
0.00%
0/509
|
0.19%
1/516
|
|
Nervous system disorders
Presyncope
|
0.00%
0/509
|
0.19%
1/516
|
|
Injury, poisoning and procedural complications
Radius Fracture
|
0.20%
1/509
|
0.00%
0/516
|
Other adverse events
| Measure |
Placebo
n=509 participants at risk
Placebo administered orally BID (twice a day) for 12 weeks of stable dose treatment phase
|
Milnacipran
n=516 participants at risk
Milnacipran 100 mg per day, administered orally (BID \[twice a day\]) for 12 weeks of stable dose treatment phase
|
|---|---|---|
|
Gastrointestinal disorders
Constipation
|
3.9%
20/509
|
14.7%
76/516
|
|
Gastrointestinal disorders
Diarrhoea
|
5.1%
26/509
|
4.5%
23/516
|
|
Nervous system disorders
Dizziness
|
5.1%
26/509
|
10.5%
54/516
|
|
Gastrointestinal disorders
Dyspepsia
|
6.1%
31/509
|
4.8%
25/516
|
|
General disorders
Fatigue
|
4.3%
22/509
|
6.0%
31/516
|
|
Nervous system disorders
Headache
|
15.7%
80/509
|
17.8%
92/516
|
|
Vascular disorders
Hot Flush
|
3.5%
18/509
|
10.9%
56/516
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
1.4%
7/509
|
7.8%
40/516
|
|
Vascular disorders
Hypertension
|
0.98%
5/509
|
5.2%
27/516
|
|
Psychiatric disorders
Insomnia
|
8.1%
41/509
|
9.9%
51/516
|
|
Gastrointestinal disorders
Nausea
|
20.8%
106/509
|
36.6%
189/516
|
|
Cardiac disorders
Palpitations
|
2.9%
15/509
|
7.4%
38/516
|
|
Cardiac disorders
Tachycardia
|
0.98%
5/509
|
5.4%
28/516
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
5.3%
27/509
|
3.7%
19/516
|
Additional Information
Robert Palmer, MD
Forest Research Institute, a subsidiary of Forest Laboratories, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee Sponsor can review results communications prior to public release \& can embargo communications re: results for 90 days from time submitted to sponsor for review. PI shall not disclose sponsor's confidential info. Upon sponsor's request, PI shall delete any proprietary info \& shall not include raw data in pub. On sponsor's request, PI shall delay submission for any pub while sponsor files patent apps. If trial is multi-center, PI agrees that first publication shall be a multi-center pub.
- Publication restrictions are in place
Restriction type: OTHER