Trial Outcomes & Findings for Study of Milnacipran Added to Pregabalin for Treatment of Fibromyalgia (NCT NCT00797797)

Last Updated: 2011-02-16

Results Overview

The primary efficacy parameter was the PGIC responder rate, defined as the percentage of patients who rated themselves as "very much improved" or "much improved" (ie, having a score of 1 or 2 on the 7-point scale) for the PGIC at end of study (Visit 6 or Early Termination) compared to Visit 1.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

364 participants

Primary outcome timeframe

End of Randomized treatment period (11 weeks)

Results posted on

2011-02-16

Participant Flow

Participants were recruited and enrolled in this study within the US from December 2008 to June 2009.

Participants entered an open label pregabalin period concurrent with prohibited medication washout. Incomplete responders to pregabalin were randomized to receive either milnacipran (100 mg/d) or no added treatment for 11 weeks. All participant continued background stable dose pregabalin (300 or 450 mg/d) throughout the randomized treatment period.

Participant milestones

Participant milestones
Measure	No Treatment Added No treatment added for 11 weeks of randomized treatment period	Milnacipran Added Milnacipran (100 mg/day) added for 11 weeks of randomized treatment period
Overall Study STARTED	178	184
Overall Study COMPLETED	123	141
Overall Study NOT COMPLETED	55	43

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of Milnacipran Added to Pregabalin for Treatment of Fibromyalgia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	No Treatment Added n=178 Participants No treatment added for 11 weeks of randomized treatment period	Milnacipran Added n=184 Participants Milnacipran (100 mg/day) added for 11 weeks of randomized treatment period	Total n=362 Participants Total of all reporting groups
Age Categorical Between 18 and 60 years	151 participants n=39 Participants	146 participants n=41 Participants	297 participants n=35 Participants
Age Categorical >=60 years	27 participants n=39 Participants	38 participants n=41 Participants	65 participants n=35 Participants
Age Continuous	48.8 years STANDARD_DEVIATION 10.4 • n=39 Participants	49.8 years STANDARD_DEVIATION 10.3 • n=41 Participants	49.3 years STANDARD_DEVIATION 10.3 • n=35 Participants
Sex: Female, Male Female	159 Participants n=39 Participants	170 Participants n=41 Participants	329 Participants n=35 Participants
Sex: Female, Male Male	19 Participants n=39 Participants	14 Participants n=41 Participants	33 Participants n=35 Participants
Region of Enrollment United States	178 participants n=39 Participants	184 participants n=41 Participants	362 participants n=35 Participants

PRIMARY outcome

Timeframe: End of Randomized treatment period (11 weeks)

Population: All efficacy analyses are based on the Intent-to-Treat population, defined as all randomized patients who received at least one dose of randomized study drug and had at least one post-baseline PGIC assessment.

Outcome measures

Outcome measures
Measure	No Treatment Added n=173 Participants No treatment added for 11 weeks of randomized treatment period	Milnacipran Added n=179 Participants Milnacipran (100 mg/day) added for 11 weeks of randomized treatment period
Patient Global Impression of Change (PGIC) Responder Rate at End of Study Responder	36 participants	83 participants
Patient Global Impression of Change (PGIC) Responder Rate at End of Study Non-Responder	137 participants	96 participants

SECONDARY outcome

Timeframe: Baseline (0 weeks) and End of Randomized Treatment Period (11 weeks)

The secondary efficacy measure was the change from Visit 2 (Week 0) in the 1-week pain recall at Visit 6 (Week 11) or End of Study, measured using a 100-mm VAS assessment of pain (0 indicating no pain and 100 indicating the worst possible pain).

Outcome measures

Outcome measures
Measure	No Treatment Added n=173 Participants No treatment added for 11 weeks of randomized treatment period	Milnacipran Added n=179 Participants Milnacipran (100 mg/day) added for 11 weeks of randomized treatment period
Change From Baseline in Visual Analog Scale (VAS) 1-week Pain Recall at End of Study	-6.43 mm Standard Error 1.93	-20.77 mm Standard Error 1.92

Adverse Events

No Treatment Added

Serious events: 6 serious events

Other events: 38 other events

Deaths: 0 deaths

Milnacipran Added

Serious events: 5 serious events

Other events: 90 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	No Treatment Added n=178 participants at risk No treatment added for 11 weeks of randomized treatment period	Milnacipran Added n=184 participants at risk Milnacipran (100 mg/day) added for 11 weeks of randomized treatment period
Psychiatric disorders Suicidal ideation	0.56% 1/178 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.	1.1% 2/184 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.
Renal and urinary disorders Calculus ureteric	0.56% 1/178 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.	0.00% 0/184 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.
General disorders Chest discomfort	0.56% 1/178 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.	0.00% 0/184 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.
Injury, poisoning and procedural complications Chest injury	0.56% 1/178 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.	0.00% 0/184 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.
Gastrointestinal disorders Duodenitis	0.56% 1/178 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.	0.00% 0/184 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.
Gastrointestinal disorders Gastric ulcer	0.56% 1/178 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.	0.00% 0/184 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.
Musculoskeletal and connective tissue disorders Inverteral disc disorder	0.56% 1/178 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.	0.00% 0/184 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.
Injury, poisoning and procedural complications Road traffic accident	0.56% 1/178 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.	0.00% 0/184 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.
Vascular disorders Hypertensive crisis	0.00% 0/178 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.	0.54% 1/184 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.
Surgical and medical procedures Hysterectomy	0.00% 0/178 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.	0.54% 1/184 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.
Gastrointestinal disorders Irritable bowel syndrome	0.00% 0/178 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.	0.54% 1/184 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.

Other adverse events

Other adverse events
Measure	No Treatment Added n=178 participants at risk No treatment added for 11 weeks of randomized treatment period	Milnacipran Added n=184 participants at risk Milnacipran (100 mg/day) added for 11 weeks of randomized treatment period
General disorders Oedema peripheral	8.4% 15/178 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.	3.3% 6/184 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.
Investigations Weight Increased	8.4% 15/178 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.	6.5% 12/184 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.
Nervous system disorders Headache	2.2% 4/178 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.	9.2% 17/184 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.
Nervous system disorders Dizziness	0.56% 1/178 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.	7.6% 14/184 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.
Psychiatric disorders Anxiety	1.7% 3/178 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.	6.5% 12/184 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.
Psychiatric disorders Insomnia	1.1% 2/178 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.	5.4% 10/184 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.
Vascular disorders Hot flush	0.00% 0/178 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.	6.0% 11/184 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.
Gastrointestinal disorders Dry Mouth	0.00% 0/178 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.	5.4% 10/184 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.
General disorders Fatigue	2.2% 4/178 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.	10.3% 19/184 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.
Cardiac disorders Palpitations	0.00% 0/178 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.	5.4% 10/184 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.
Gastrointestinal disorders Nausea	2.8% 5/178 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.	12.5% 23/184 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.
Gastrointestinal disorders Constipation	0.56% 1/178 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.	9.8% 18/184 • Treatment emergent adverse events, defined as adverse events which occurred or worsened after starting randomized study drug, were collected from December 2008 to November 2009.

Additional Information

Robert Palmer, MD

Forest Research Institute, a subsidiary of Forest Laboratories, Inc.

Phone: 1-201-427-8218

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER