Trial Outcomes & Findings for Discontinuation Study of the Durability of Effect of Milnacipran for the Treatment of Fibromyalgia (NCT NCT01014585)
NCT ID: NCT01014585
Last Updated: 2011-09-07
Results Overview
Time to loss of therapeutic response is defined as the time from the first dose of double-blind investigational product to the first visit when a patient has a \< 30% reduction in Visual Analog Scale (VAS) pain score from pre-milnacipran exposure OR a worsening of fibromyalgia requiring, in the judgment of the investigator, an alternative treatment
COMPLETED
PHASE4
340 participants
From baseline Visit 3 (week 5) to Visit 7 (week 17)
2011-09-07
Participant Flow
Recruitment period was from November 2009 through February 2010 at 58 centers in the United States with the last patient visit occurring on June 7, 2010.
Upon completion of a long term milnacipran open label study MLN-MD-06, patients were enrolled in the current study MLN-MD-27 (NCT01014585), and received open label treatment with milnacipran for four weeks prior to randomization.
Participant milestones
| Measure |
Responders: Placebo (Milnacipran Withdrawn)
The Randomized Population for Responders
|
Responders: Milnacipran (Milnacipran Continued)
The Randomized Population for Responders
|
Non-Responders: Placebo (Milnacipran Withdrawn)
The Randomized Population for Non-Responders
|
Non-Responders: Milnacipran (Milnacipran Continued)
The Randomized Population for Non-Responders
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
51
|
100
|
60
|
129
|
|
Overall Study
COMPLETED
|
31
|
75
|
37
|
99
|
|
Overall Study
NOT COMPLETED
|
20
|
25
|
23
|
30
|
Reasons for withdrawal
| Measure |
Responders: Placebo (Milnacipran Withdrawn)
The Randomized Population for Responders
|
Responders: Milnacipran (Milnacipran Continued)
The Randomized Population for Responders
|
Non-Responders: Placebo (Milnacipran Withdrawn)
The Randomized Population for Non-Responders
|
Non-Responders: Milnacipran (Milnacipran Continued)
The Randomized Population for Non-Responders
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
2
|
0
|
3
|
|
Overall Study
Withdrawal by Subject
|
2
|
0
|
1
|
3
|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
0
|
2
|
|
Overall Study
Withdrawn Due to Worsening Fibromyalgia
|
18
|
23
|
22
|
22
|
Baseline Characteristics
Discontinuation Study of the Durability of Effect of Milnacipran for the Treatment of Fibromyalgia
Baseline characteristics by cohort
| Measure |
Responders: Placebo (Milnacipran Withdrawn)
n=50 Participants
Safety Population for Responders: placebo treatment assignment
One patient in the randomized population for responders assigned to placebo did not take at least one dose of double blind investigational product and therefore was not included in the Safety Population.
|
Responders: Milnacipran (Milnacipran Continued)
n=100 Participants
Safety Population for Responders: milnacipran treatment assignment
|
Non-Responders: Placebo (Milnacipran Withdrawn)
n=60 Participants
Safety Population for Non-Responders: placebo treatment assignment
|
Non-Responders: Milnacipran (Milnacipran Continued)
n=128 Participants
Safety Population for Non-Responders: milnacipran treatment assignment
One patient in the randomized population for non-responders assigned to milnacipran did not take at least one dose of double-blind investigational product and therefore was not included in the Safety population.
|
Total
n=338 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age Continuous
|
54.0 years
STANDARD_DEVIATION 8.3 • n=93 Participants
|
54.5 years
STANDARD_DEVIATION 9.3 • n=4 Participants
|
54.7 years
STANDARD_DEVIATION 9.6 • n=27 Participants
|
54.8 years
STANDARD_DEVIATION 9.4 • n=483 Participants
|
54.6 years
STANDARD_DEVIATION 9.2 • n=36 Participants
|
|
Age, Customized
Between 20 and 60 years
|
39 Years
n=93 Participants
|
73 Years
n=4 Participants
|
38 Years
n=27 Participants
|
86 Years
n=483 Participants
|
236 Years
n=36 Participants
|
|
Age, Customized
>=60 years
|
11 Years
n=93 Participants
|
27 Years
n=4 Participants
|
22 Years
n=27 Participants
|
42 Years
n=483 Participants
|
102 Years
n=36 Participants
|
|
Sex: Female, Male
Female
|
48 Participants
n=93 Participants
|
96 Participants
n=4 Participants
|
59 Participants
n=27 Participants
|
122 Participants
n=483 Participants
|
325 Participants
n=36 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
6 Participants
n=483 Participants
|
13 Participants
n=36 Participants
|
|
Region of Enrollment
United States
|
50 participants
n=93 Participants
|
100 participants
n=4 Participants
|
60 participants
n=27 Participants
|
128 participants
n=483 Participants
|
338 participants
n=36 Participants
|
PRIMARY outcome
Timeframe: From baseline Visit 3 (week 5) to Visit 7 (week 17)Population: The Intent to Treat (ITT) Population for Responders is defined as all patients in the Safety Population for Responders with at least 1 post-baseline assessment of primary efficacy parameter. All patients in the Safety Population were included in the ITT population. No efficacy statistical analyses were performed for the Non-Responder population.
Time to loss of therapeutic response is defined as the time from the first dose of double-blind investigational product to the first visit when a patient has a \< 30% reduction in Visual Analog Scale (VAS) pain score from pre-milnacipran exposure OR a worsening of fibromyalgia requiring, in the judgment of the investigator, an alternative treatment
Outcome measures
| Measure |
Responders: Placebo (Milnacipran Withdrawn)
n=50 Participants
Intent to Treat (ITT) Population for Responders: placebo treatment assignment, matching placebo administered orally twice per day.
|
Responders: Milnacipran (Milnacipran Continued)
n=100 Participants
Intent to Treat (ITT) Population for Responders: milnacipran treatment assignment, milnacipran 50-200 mg per day, administered orally twice per day.
|
Non-Responders: Placebo (Milnacipran Withdrawn)
Intent to Treat (ITT) Population for Non-Responders: placebo treatment assignment, matching placebo, administered orally twice per day.
|
Non-Responders: Milnacipran (Milnacipran Continued)
Intent to Treat (ITT) Population for Non-Responders: milnacipran treatment assignment, 50-200 mg per day, administered orally twice per day.
|
|---|---|---|---|---|
|
Time to Loss of Therapeutic Response (LTR)
|
56 Days
Interval 28.0 to 85.0
|
NA Days
NA represents not estimable. Not enough participants experienced a loss of therapeutic response to calculate the median value and 95 percent confidence interval.
|
—
|
—
|
SECONDARY outcome
Timeframe: From baseline Visit 3 (week 5) to Visit 7 (week 17)Population: The Intent to Treat (ITT) Population for Responders is defined as all patients in the Safety Population for Responders with at least 1 post-baseline assessment of primary efficacy parameter. All patients in the Safety Population were included in the ITT population. No efficacy statistical analyses were performed for the Non-Responder population.
Time to worsening in Patient Global Impression of Change is defined as the time from the first dose of double-blind investigational product to the first visit when a patient has a PGIC score of 6 or 7. The PGIC is an efficacy assessment on a scale of 1-7 taken at visits 4, 5, 6 and 7. 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 |
Responders: Placebo (Milnacipran Withdrawn)
n=50 Participants
Intent to Treat (ITT) Population for Responders: placebo treatment assignment, matching placebo administered orally twice per day.
|
Responders: Milnacipran (Milnacipran Continued)
n=100 Participants
Intent to Treat (ITT) Population for Responders: milnacipran treatment assignment, milnacipran 50-200 mg per day, administered orally twice per day.
|
Non-Responders: Placebo (Milnacipran Withdrawn)
Intent to Treat (ITT) Population for Non-Responders: placebo treatment assignment, matching placebo, administered orally twice per day.
|
Non-Responders: Milnacipran (Milnacipran Continued)
Intent to Treat (ITT) Population for Non-Responders: milnacipran treatment assignment, 50-200 mg per day, administered orally twice per day.
|
|---|---|---|---|---|
|
Time to Worsening in Patient Global Impression of Change (PGIC)
|
86 Days
Interval 30.0 to
NA represents not estimable. Not enough participants experienced a worsening in PGIC to calculate the upper bound of 95 percent confidence interval.
|
NA Days
NA represents not estimable. Not enough participants experienced a worsening in PGIC to calculate the median value and the 95 percent confidence interval.
|
—
|
—
|
SECONDARY outcome
Timeframe: From baseline Visit 3 (week 5) to Visit 7 (week 17)Population: The Intent to Treat (ITT) Population for Responders is defined as all patients in the Safety Population for Responders with at least 1 post-baseline assessment of primary efficacy parameter. All patients in the Safety Population were included in the ITT population. No efficacy statistical analyses were performed for the Non-Responder population.
Time to worsening in MAF is defined as the time from the first dose of double-blind investigational product to the first visit when a patient has a 10-point increase from baseline in the global index of fatigue in MAF. Scores range from 1 (no fatigue) to 50 (severe fatigue). The MAF contains 16 items measuring 4 dimensions of fatigue: severity, distress, degree of interference in activities of daily living, and timing. Fourteen of the items contain numerical rating scales (increasing in severity); the remaining 2 items have multiple-choice responses (decreasing in severity).
Outcome measures
| Measure |
Responders: Placebo (Milnacipran Withdrawn)
n=50 Participants
Intent to Treat (ITT) Population for Responders: placebo treatment assignment, matching placebo administered orally twice per day.
|
Responders: Milnacipran (Milnacipran Continued)
n=100 Participants
Intent to Treat (ITT) Population for Responders: milnacipran treatment assignment, milnacipran 50-200 mg per day, administered orally twice per day.
|
Non-Responders: Placebo (Milnacipran Withdrawn)
Intent to Treat (ITT) Population for Non-Responders: placebo treatment assignment, matching placebo, administered orally twice per day.
|
Non-Responders: Milnacipran (Milnacipran Continued)
Intent to Treat (ITT) Population for Non-Responders: milnacipran treatment assignment, 50-200 mg per day, administered orally twice per day.
|
|---|---|---|---|---|
|
Time to Worsening in Multidimensional Assessment of Fatigue (MAF)
|
NA Days
NA represents not estimable. Not enough participants experienced a worsening in the MAF to calculate the median value and the 95 percent confidence interval.
|
NA Days
NA represents not estimable. Not enough participants experienced a worsening in the MAF to calculate the median value and the 95 percent confidence interval.
|
—
|
—
|
Adverse Events
Responders: Placebo (Milnacipran Withdrawn)
Responders: Milnacipran (Milnacipran Continued)
Non-Responders: Placebo (Milnacipran Withdrawn)
Non-Responders: Milnacipran (Milnacipran Continued)
Serious adverse events
| Measure |
Responders: Placebo (Milnacipran Withdrawn)
n=50 participants at risk
Safety Population for Responders: placebo treatment assignment
One patient in the randomized population for responders assigned to placebo did not take at least one dose of double blind investigational product and therefore was not included in the Safety Population.
|
Responders: Milnacipran (Milnacipran Continued)
n=100 participants at risk
Safety Population for Responders: milnacipran treatment assignment
|
Non-Responders: Placebo (Milnacipran Withdrawn)
n=60 participants at risk
Safety Population for Non-Responders: placebo treatment assignment
|
Non-Responders: Milnacipran (Milnacipran Continued)
n=128 participants at risk
Safety Population for Non-Responders: milnacipran treatment assignment
One patient in the randomized population for non-responders assigned to milnacipran did not take at least one dose of double blind investigational product and therefore was not included in the Safety population.
|
|---|---|---|---|---|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/50
|
1.0%
1/100
|
0.00%
0/60
|
0.00%
0/128
|
|
Cardiac disorders
Bradycardia
|
0.00%
0/50
|
0.00%
0/100
|
0.00%
0/60
|
0.78%
1/128
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/50
|
0.00%
0/100
|
0.00%
0/60
|
0.78%
1/128
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/50
|
0.00%
0/100
|
0.00%
0/60
|
0.78%
1/128
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/50
|
0.00%
0/100
|
0.00%
0/60
|
0.78%
1/128
|
|
Skin and subcutaneous tissue disorders
Hidradenitis
|
0.00%
0/50
|
0.00%
0/100
|
0.00%
0/60
|
0.78%
1/128
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/50
|
0.00%
0/100
|
1.7%
1/60
|
0.00%
0/128
|
Other adverse events
| Measure |
Responders: Placebo (Milnacipran Withdrawn)
n=50 participants at risk
Safety Population for Responders: placebo treatment assignment
One patient in the randomized population for responders assigned to placebo did not take at least one dose of double blind investigational product and therefore was not included in the Safety Population.
|
Responders: Milnacipran (Milnacipran Continued)
n=100 participants at risk
Safety Population for Responders: milnacipran treatment assignment
|
Non-Responders: Placebo (Milnacipran Withdrawn)
n=60 participants at risk
Safety Population for Non-Responders: placebo treatment assignment
|
Non-Responders: Milnacipran (Milnacipran Continued)
n=128 participants at risk
Safety Population for Non-Responders: milnacipran treatment assignment
One patient in the randomized population for non-responders assigned to milnacipran did not take at least one dose of double blind investigational product and therefore was not included in the Safety population.
|
|---|---|---|---|---|
|
Infections and infestations
Sinusitis
|
6.0%
3/50
|
4.0%
4/100
|
1.7%
1/60
|
8.6%
11/128
|
|
General disorders
Oedema peripheral
|
6.0%
3/50
|
2.0%
2/100
|
1.7%
1/60
|
0.00%
0/128
|
|
General disorders
Irritability
|
6.0%
3/50
|
0.00%
0/100
|
0.00%
0/60
|
0.00%
0/128
|
|
Nervous system disorders
Headache
|
0.00%
0/50
|
4.0%
4/100
|
1.7%
1/60
|
7.0%
9/128
|
|
Infections and infestations
Upper respiratory tract infection
|
4.0%
2/50
|
4.0%
4/100
|
1.7%
1/60
|
5.5%
7/128
|
|
Gastrointestinal disorders
Nausea
|
2.0%
1/50
|
4.0%
4/100
|
5.0%
3/60
|
3.1%
4/128
|
|
Musculoskeletal and connective tissue disorders
Fibromyalgia
|
2.0%
1/50
|
3.0%
3/100
|
5.0%
3/60
|
2.3%
3/128
|
|
Infections and infestations
Bronchitis
|
2.0%
1/50
|
2.0%
2/100
|
5.0%
3/60
|
1.6%
2/128
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/50
|
2.0%
2/100
|
5.0%
3/60
|
1.6%
2/128
|
Additional Information
Joel Trugman, MD
Forest Research Institute, Inc., a subsidiary of Forest Laboratories, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee All data generated in this study is the property of Forest Research Institute, Inc. An integrated clinical and statistical report was prepared at the completion of the study. Publication of the results by the Investigator will be subject to mutual agreement between the Investigator and Forest Research Institute, Inc.
- Publication restrictions are in place
Restriction type: OTHER