Trial Outcomes & Findings for Study of Milnacipran in Patients With Inadequate Response to Duloxetine for the Treatment of Fibromyalgia (NCT NCT01077375)

Last Updated: 2012-01-26

Results Overview

The PGIC is a patient-reported measure of improvement in pain sensation and quality of life scored on a scale from 1 (very much improved) to 7 (very much worse). To meet the criteria for a responder in this study, patients must report a score of 1 (very much improved) or 2 (much improved) on the PGIC.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

107 participants

Primary outcome timeframe

Assessed at Visit 4 (Week 9) and Visit 5 (Week 13) or early termination. Presented results generated via LOCF approach.

Results posted on

2012-01-26

Participant Flow

Recruitment occurred over an 8 month period from February 2010 to September 2010 at 25 study centers in the United States. Last patient last visit occurred on December 22nd, 2010.

All participants were given an open-label treatment of duloxetine 60 mg once daily for a two week period before randomization. Patients randomized to placebo received 1 week of duloxetine 30 mg to effect a duloxetine down-taper. Patients randomized to milnacipran received 1 week of placebo capsules to maintain the blind.

Participant milestones

Participant milestones
Measure	Placebo Randomized Population: placebo treatment assignment, dose-matched placebo tablets, twice a day, oral administration.	Milnacipran Randomized Population: milnacipran treatment assignment, 100 to 200 mg/day, twice a day in divided doses, oral administration.
Overall Study STARTED	21	86
Overall Study COMPLETED	11	51
Overall Study NOT COMPLETED	10	35

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Randomized Population: placebo treatment assignment, dose-matched placebo tablets, twice a day, oral administration.	Milnacipran Randomized Population: milnacipran treatment assignment, 100 to 200 mg/day, twice a day in divided doses, oral administration.
Overall Study Adverse Event	2	15
Overall Study Lack of Efficacy	6	8
Overall Study Withdrawal by Subject	0	6
Overall Study Lost to Follow-up	2	5
Overall Study Other Reason	0	1

Baseline Characteristics

Study of Milnacipran in Patients With Inadequate Response to Duloxetine for the Treatment of Fibromyalgia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=21 Participants Double-blind Safety Population: Placebo treatment assignment, dose-matched placebo tablets, twice a day, oral administration.	Milnacipran n=85 Participants Double-blind Safety Population: milnacipran treatment assignment, 100 to 200 md/day, twice a day in divided doses, oral administration. One patient randomized to the milnacipran treatment group did not take at least one dose of double-blind study drug and was therefore not included in the Double-blind Safety Population.	Total n=106 Participants Total of all reporting groups
Age Continuous	48.5 years STANDARD_DEVIATION 11.3 • n=5 Participants	48.5 years STANDARD_DEVIATION 10.5 • n=7 Participants	48.5 years STANDARD_DEVIATION 10.6 • n=5 Participants
Age, Customized 18 to 59	17 participants n=5 Participants	77 participants n=7 Participants	94 participants n=5 Participants
Age, Customized 60 to 70	4 participants n=5 Participants	8 participants n=7 Participants	12 participants n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	79 Participants n=7 Participants	98 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants
Region of Enrollment United States	21 participants n=5 Participants	85 participants n=7 Participants	106 participants n=5 Participants

PRIMARY outcome

Timeframe: Assessed at Visit 4 (Week 9) and Visit 5 (Week 13) or early termination. Presented results generated via LOCF approach.

Population: ITT Population: patients in the Double-blind Safety Population with ≥ 1 PGIC post-baseline assessment. Double-blind Safety Population includes 6 patients who were not included in ITT population. Presented results generated via LOCF approach. No statistical comparisons between groups are presented; study was exploratory, not hypothesis-testing.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Intent-to-treat (ITT) Population, placebo treatment assignment, dose-matched placebo tablets, twice a day, oral administration.	Milnacipran n=79 Participants Intent-to-treat Population, milnacipran treatment assignment, 100 to 200 mg/day, twice a day, oral administration. Flexible dosing from 50 mg/day to 200 mg/day was allowed except at a) the initial dosage after randomization had to be 100 mg/day, b) the dose range during week 1 of the randomized double-blind treatment period was 50 to 100 mg/day, and c) patients had to be on at least 100 mg/day at Visit 3 (Week 5).
Responder Status Based on Patient Global Impression of Change (PGIC) Score at Visit 5 (Week 13)	5 participants	26 participants

SECONDARY outcome

Timeframe: Change from Baseline (Week 3) to Visit 5 (Week 13)

The VAS assessment ranges from a scale of 0 (no pain) to 100 (worst possible pain).

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Intent-to-treat (ITT) Population, placebo treatment assignment, dose-matched placebo tablets, twice a day, oral administration.	Milnacipran n=79 Participants Intent-to-treat Population, milnacipran treatment assignment, 100 to 200 mg/day, twice a day, oral administration. Flexible dosing from 50 mg/day to 200 mg/day was allowed except at a) the initial dosage after randomization had to be 100 mg/day, b) the dose range during week 1 of the randomized double-blind treatment period was 50 to 100 mg/day, and c) patients had to be on at least 100 mg/day at Visit 3 (Week 5).
Change From Baseline to Visit 5 (Week 13) in the Visual Analog Scale (VAS) 1-week Pain Recall Score	-1.3 Units on a scale Standard Deviation 22.5	-12.3 Units on a scale Standard Deviation 27.3

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Milnacipran

Serious events: 2 serious events

Other events: 63 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=21 participants at risk Double-blind Safety Population: placebo treatment assignment, dose-matched placebo tablets, twice a day, oral administration.	Milnacipran n=85 participants at risk Double-blind Safety Population: milnacipran treatment assignment, 100 to 200 mg/day, twice a day, oral administration. One patient randomized to the milnacipran treatment group did not take at least one dose of double-blind study drug and was therefore not included in the Double-blind Safety Population. Flexible dosing from 50 mg/day to 200 mg/day was allowed except at a) the initial dosage after randomization had to be 100 mg/day, b) the dose range during week 1 of the randomized double-blind treatment period was 50 to 100 mg/day, and c) patients had to be on at least 100 mg/day at Visit 3 (Week 5).
Immune system disorders Hypersensitivity	0.00% 0/21 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.	1.2% 1/85 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.
Psychiatric disorders Suicidal ideation	0.00% 0/21 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.	1.2% 1/85 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.

Other adverse events

Additional Information

Allan Spera, Director, Clinical Development

Forest Research Institute

Phone: (201) 427-8399

Email: [email protected]

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

Measure	Placebo n=21 participants at risk Double-blind Safety Population: placebo treatment assignment, dose-matched placebo tablets, twice a day, oral administration.	Milnacipran n=85 participants at risk Double-blind Safety Population: milnacipran treatment assignment, 100 to 200 mg/day, twice a day, oral administration. One patient randomized to the milnacipran treatment group did not take at least one dose of double-blind study drug and was therefore not included in the Double-blind Safety Population. Flexible dosing from 50 mg/day to 200 mg/day was allowed except at a) the initial dosage after randomization had to be 100 mg/day, b) the dose range during week 1 of the randomized double-blind treatment period was 50 to 100 mg/day, and c) patients had to be on at least 100 mg/day at Visit 3 (Week 5).
Gastrointestinal disorders Nausea	28.6% 6/21 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.	21.2% 18/85 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.
Nervous system disorders Dizziness	4.8% 1/21 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.	15.3% 13/85 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.
Nervous system disorders Headache	9.5% 2/21 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.	11.8% 10/85 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.
Psychiatric disorders Insomnia	9.5% 2/21 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.	10.6% 9/85 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.
Vascular disorders Hot flush	4.8% 1/21 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.	8.2% 7/85 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.
General disorders Irritability	4.8% 1/21 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.	7.1% 6/85 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.
Infections and infestations Nasopharyngitis	0.00% 0/21 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.	7.1% 6/85 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.
Psychiatric disorders Anxiety	0.00% 0/21 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.	5.9% 5/85 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.
Investigations Blood pressure increased	0.00% 0/21 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.	5.9% 5/85 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/21 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.	5.9% 5/85 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.
Gastrointestinal disorders Diarrhea	14.3% 3/21 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.	4.7% 4/85 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.
General disorders Fatigue	9.5% 2/21 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.	3.5% 3/85 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.
Nervous system disorders Migraine	9.5% 2/21 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.	1.2% 1/85 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.
Nervous system disorders Paresthesia	9.5% 2/21 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.	1.2% 1/85 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.
Musculoskeletal and connective tissue disorders Muscle spasms	9.5% 2/21 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.	0.00% 0/85 • Adverse event data was collected over a nearly 10 month period from March 4th, 2010 through December 22, 2010.