Trial Outcomes & Findings for Safety and Efficacy of Milnacipran in Pediatric Patients With Primary Fibromyalgia (NCT NCT01328002)
NCT ID: NCT01328002
Last Updated: 2019-05-14
Results Overview
During the open-label period, 20 patients out of 116 enrolled had a reduction from baseline (Visit 2) of at least 50% in their pain, were classified as responders and were randomized (Visit 7). A Loss of Therapeutic Response was said to occur if, during the double-blind treatment period, any of the following occurred: • A worsening of fibromyalgia requiring an alternate treatment OR • An increase in 1-week mean of daily pain ratings (11-point numeric rating scale) to greater than 70% of Baseline (Visit 2) OR • Withdrawal from the study for any reason except withdrawals due to extenuating circumstances
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
116 participants
Primary outcome timeframe
Change from Visit 7 (Week 8) to Visit 10 (Week 16)
Results posted on
2019-05-14
Participant Flow
Participants were recruited over a 12 month period from April of 2011 to April of 2012 at 47 study sites in the United States.
116 patients took at least 1 dose of open-label investigational product; 20 patients were randomized to receive double-blind treatment.
Participant milestones
| Measure |
Milnacipran
Maximum tolerated dose (50, 75, or 100 mg/day tablets) was determined during the open-label phase of the study. Oral administration, twice daily dosing
|
Placebo
|
|---|---|---|
|
Open-Label Period
STARTED
|
116
|
0
|
|
Open-Label Period
COMPLETED
|
20
|
0
|
|
Open-Label Period
NOT COMPLETED
|
96
|
0
|
|
Double-Blind Period
STARTED
|
14
|
6
|
|
Double-Blind Period
COMPLETED
|
12
|
6
|
|
Double-Blind Period
NOT COMPLETED
|
2
|
0
|
Reasons for withdrawal
| Measure |
Milnacipran
Maximum tolerated dose (50, 75, or 100 mg/day tablets) was determined during the open-label phase of the study. Oral administration, twice daily dosing
|
Placebo
|
|---|---|---|
|
Open-Label Period
Inclusion/exclusion criteria not met
|
66
|
0
|
|
Open-Label Period
Adverse Event
|
8
|
0
|
|
Open-Label Period
Lack of Efficacy
|
3
|
0
|
|
Open-Label Period
Protocol Violation
|
2
|
0
|
|
Open-Label Period
Withdrawal by Subject
|
9
|
0
|
|
Open-Label Period
Lost to Follow-up
|
6
|
0
|
|
Open-Label Period
Other Reason
|
2
|
0
|
|
Double-Blind Period
Adverse Event
|
1
|
0
|
|
Double-Blind Period
Lack of Efficacy
|
1
|
0
|
Baseline Characteristics
Safety and Efficacy of Milnacipran in Pediatric Patients With Primary Fibromyalgia
Baseline characteristics by cohort
| Measure |
Open-Label Milnacipran
n=116 Participants
Maximum tolerated dose (50, 75, or 100 mg/day tablets) determined during the open label treatment phase. Oral administration, twice daily dosing
|
|---|---|
|
Age, Continuous
|
15.6 years
STANDARD_DEVIATION 1.4 • n=5 Participants
|
|
Age, Customized
13 years old
|
10 Participants
n=5 Participants
|
|
Age, Customized
14 years old
|
21 Participants
n=5 Participants
|
|
Age, Customized
15 years old
|
21 Participants
n=5 Participants
|
|
Age, Customized
16 years old
|
23 Participants
n=5 Participants
|
|
Age, Customized
17 years old
|
41 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
98 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
116 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Change from Visit 7 (Week 8) to Visit 10 (Week 16)Population: The Open-Label Safety Population consists of 116 patients who took at least 1 dose of open-label milnacipran. 20 patients who were randomized to a treatment group (Randomized Population) took at least 1 dose of double-blind treatment (Double-blind Safety Population) and were analyzed as randomized (Double-blind Intent-to-Treat \[ITT\] Population).
During the open-label period, 20 patients out of 116 enrolled had a reduction from baseline (Visit 2) of at least 50% in their pain, were classified as responders and were randomized (Visit 7). A Loss of Therapeutic Response was said to occur if, during the double-blind treatment period, any of the following occurred: • A worsening of fibromyalgia requiring an alternate treatment OR • An increase in 1-week mean of daily pain ratings (11-point numeric rating scale) to greater than 70% of Baseline (Visit 2) OR • Withdrawal from the study for any reason except withdrawals due to extenuating circumstances
Outcome measures
| Measure |
Placebo
n=6 Participants
Dose matched placebo, oral administration, twice daily dosing
|
Milnacipran
n=14 Participants
Maximum tolerated dose (50, 75, or 100 mg/day tablets) was determined during the open-label phase of the study. Oral administration, twice daily dosing
|
|---|---|---|
|
Time to First Loss of Therapeutic Response (LTR) Following Randomization to Milnacipran or Placebo.
|
NA Days
Standard Deviation NA
No patients in the placebo arm experienced a loss of therapeutic effect during the double-blind study period.
|
7.0 Days
Standard Deviation 1.4
|
SECONDARY outcome
Timeframe: Change from Visit 7 (Week 8) to Visit 10 (Week 16)Population: The Open-Label Safety Population consists of 116 patients who took at least 1 dose of open-label milnacipran. 20 patients were randomized to a treatment group (Randomized Population) took at least 1 dose of double-blind treatment (Double-blind Safety Population) and were analyzed as randomized (Double-blind Intent-to-Treat \[ITT\] Population).
The wording of the PGIS assessment was as follows: "Considering all aspects of your illness, how do you evaluate the severity of your fibromyalgia?" The possible responses to this question were 1. Normal, not at all ill 2. Borderline ill 3. Mildly ill 4. Moderately ill 5. Severely ill 6. Extremely ill
Outcome measures
| Measure |
Placebo
n=6 Participants
Dose matched placebo, oral administration, twice daily dosing
|
Milnacipran
n=14 Participants
Maximum tolerated dose (50, 75, or 100 mg/day tablets) was determined during the open-label phase of the study. Oral administration, twice daily dosing
|
|---|---|---|
|
Patient Global Impression of Severity (PGIS)
|
0.5 units on a scale
Standard Deviation 0.8
|
0.4 units on a scale
Standard Deviation 0.9
|
Adverse Events
Milnacipran - Open-Label Treatment Period
Serious events: 0 serious events
Other events: 62 other events
Deaths: 0 deaths
Placebo - Double Blind-Treatment
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Milnacipran - Double-Blind Treatment Period
Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Milnacipran - Open-Label Treatment Period
n=116 participants at risk
Maximum tolerated dose (50, 75, or 100 mg/day tablets) was determined during a four-week dose escalation period, and then continued at the maximum tolerated dose for an additional four weeks. Oral administration, twice daily dosing
|
Placebo - Double Blind-Treatment
n=6 participants at risk
Dose matched placebo, oral administration, twice daily dosing
|
Milnacipran - Double-Blind Treatment Period
n=14 participants at risk
Maximum tolerated dose (50, 75, or 100 mg/day tablets) was determined during the open-label phase of the study. Oral administration, twice daily dosing
|
|---|---|---|---|
|
Psychiatric disorders
Suicidal Ideation
|
0.00%
0/116 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
0.00%
0/6 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
7.1%
1/14 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
Other adverse events
| Measure |
Milnacipran - Open-Label Treatment Period
n=116 participants at risk
Maximum tolerated dose (50, 75, or 100 mg/day tablets) was determined during a four-week dose escalation period, and then continued at the maximum tolerated dose for an additional four weeks. Oral administration, twice daily dosing
|
Placebo - Double Blind-Treatment
n=6 participants at risk
Dose matched placebo, oral administration, twice daily dosing
|
Milnacipran - Double-Blind Treatment Period
n=14 participants at risk
Maximum tolerated dose (50, 75, or 100 mg/day tablets) was determined during the open-label phase of the study. Oral administration, twice daily dosing
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.86%
1/116 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
16.7%
1/6 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
0.00%
0/14 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
|
Cardiac disorders
Tachycardia
|
6.0%
7/116 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
0.00%
0/6 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
7.1%
1/14 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
|
Eye disorders
Blepharospasm
|
0.00%
0/116 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
16.7%
1/6 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
0.00%
0/14 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.86%
1/116 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
16.7%
1/6 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
0.00%
0/14 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
|
Gastrointestinal disorders
Abdominal discomfort
|
1.7%
2/116 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
0.00%
0/6 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
7.1%
1/14 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
|
General disorders
Pyrexia
|
0.00%
0/116 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
16.7%
1/6 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
0.00%
0/14 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
|
General disorders
Noncardiac chest pain
|
0.86%
1/116 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
0.00%
0/6 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
7.1%
1/14 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
|
Infections and infestations
Anorectal infection
|
0.00%
0/116 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
0.00%
0/6 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
7.1%
1/14 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
|
Infections and infestations
Bronchitis
|
0.86%
1/116 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
16.7%
1/6 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
0.00%
0/14 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
|
Infections and infestations
Upper respiratory tract infection
|
4.3%
5/116 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
0.00%
0/6 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
7.1%
1/14 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
|
Investigations
Blood pressure diastolic increased
|
0.00%
0/116 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
0.00%
0/6 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
7.1%
1/14 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
|
Investigations
Liver function test abnormal
|
0.00%
0/116 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
16.7%
1/6 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
0.00%
0/14 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
|
Investigations
Weight increased
|
0.00%
0/116 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
16.7%
1/6 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
0.00%
0/14 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
|
Metabolism and nutrition disorders
Decreased appetite
|
4.3%
5/116 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
0.00%
0/6 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
14.3%
2/14 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
|
Nervous system disorders
Headache
|
10.3%
12/116 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
16.7%
1/6 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
0.00%
0/14 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/116 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
0.00%
0/6 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
7.1%
1/14 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/116 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
0.00%
0/6 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
7.1%
1/14 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
|
Gastrointestinal disorders
Nausea
|
32.8%
38/116 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
0.00%
0/6 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
0.00%
0/14 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
|
Gastrointestinal disorders
Vomiting
|
13.8%
16/116 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
0.00%
0/6 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
0.00%
0/14 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
|
Nervous system disorders
Dizziness
|
8.6%
10/116 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
0.00%
0/6 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
0.00%
0/14 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
|
General disorders
Fatigue
|
6.0%
7/116 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
0.00%
0/6 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
0.00%
0/14 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
|
Vascular disorders
Hot flush
|
6.0%
7/116 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
0.00%
0/6 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
0.00%
0/14 • Adverse Event data was collected over a 17-month period from April, 2011 to September, 2012
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee All data generated in this study will be the property of Forest Research Institute, Inc. An integrated clinical and statistical report will be 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