Trial Outcomes & Findings for Milnacipran (Savella) in Irritable Bowel Syndrome (IBS) (NCT NCT01471379)

Results Overview

Visual Analog Scale (VAS) scores (range 0-100 mm; 0 = none, 100 = worst pain) were recorded for pain before the beginning of the study, at 6 weeks of treatment and at the end visit i.e. 10 weeks. Ideally, VAS would have been administered at the 12th week; however, subject was terminated at the 10th week visit. A positive pain response (ie pain relief) was defined as \>30% decrease in the VAS score between baseline and the final study visit.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

2 participants

Primary outcome timeframe

Twelve Weeks

Results posted on

2017-04-13

Participant Flow

The subjects were recruited from community using University of North Carolina (UNC) mass email system, newspaper advertisement and UNC gastrointestinal (GI) clinic referral.

Subjects undergo screening labs and questionnaires to make sure subjects are healthy and don't have any underlying conditions. Subjects who had clinically significant labs or Hospital Anxiety and depression scale(HADS)score more than 17 were excluded.

Participant milestones

Participant milestones
Measure	Group A (50mg - 100mg) Group A will begin treatment with Milnacipran 50mg twice a day (BID) (n=20) during Phase I and will be increased to 100mg BID during Phase II Milnacipran : 50mg Milnacipran per orally (PO), BID, for 6 weeks. Milnacipran : Milnacipran, 100mg PO, BID, for six weeks	Group B (50mg x12) Subjects in this arm will be maintained at Milnacipran 50mg BID for the entirety of the 12 weeks of the study. Milnacipran : Milnacipran, 50mg PO BID for 12 weeks
Overall Study STARTED	1	1
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Group A (50mg - 100mg) Group A will begin treatment with Milnacipran 50mg twice a day (BID) (n=20) during Phase I and will be increased to 100mg BID during Phase II Milnacipran : 50mg Milnacipran per orally (PO), BID, for 6 weeks. Milnacipran : Milnacipran, 100mg PO, BID, for six weeks	Group B (50mg x12) Subjects in this arm will be maintained at Milnacipran 50mg BID for the entirety of the 12 weeks of the study. Milnacipran : Milnacipran, 50mg PO BID for 12 weeks	Group C (Placebo - 50mg) Group C will begin treatment with Placebo BID (n=20) during Phase I and will be given 50mg BID during Phase II Milnacipran : 50mg Milnacipran PO, BID, for 6 weeks. Placebo : Inactive pill, identical in shape, size, and appearance to active drug, PO, BID.
Overall Study Adverse Event	1	0	0
Overall Study Study terminated	0	1	0

Baseline Characteristics

Milnacipran (Savella) in Irritable Bowel Syndrome (IBS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group A (50mg - 100mg) n=1 Participants Group A will begin treatment with Milnacipran 50mg BID (n=20) during Phase I and will be increased to 100mg BID during Phase II Milnacipran : 50mg Milnacipran PO, BID, for 6 weeks. Milnacipran : Milnacipran, 100mg PO, BID, for six weeks	Group B (50mg x12) n=1 Participants Subjects in this arm will be maintained at Milnacipran 50mg BID for the entirety of the 12 weeks of the study. Milnacipran : Milnacipran, 50mg PO BID for 12 weeks	Group C (Placebo - 50mg) Group C will begin treatment with Placebo BID (n=20) during Phase I and will be given 50mg BID during Phase II Milnacipran : 50mg Milnacipran PO, BID, for 6 weeks. Placebo : Inactive pill, identical in shape, size, and appearance to active drug, PO, BID.	Total n=2 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	1 Participants n=7 Participants	—	2 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Age, Continuous	47 years STANDARD_DEVIATION 0 • n=5 Participants	66 years STANDARD_DEVIATION 0 • n=7 Participants	—	56.5 years STANDARD_DEVIATION 9.5 • n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	—	2 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Region of Enrollment United States	1 participants n=5 Participants	1 participants n=7 Participants	—	2 participants n=4 Participants

PRIMARY outcome

Timeframe: Twelve Weeks

Visual Analog Scale (VAS) scores (range 0-100 mm; 0 = none, 100 = worst pain) were recorded for pain before the beginning of the study, at 6 weeks of treatment and at the end visit i.e. 10 weeks. Ideally, VAS would have been administered at the 12th week; however, subject was terminated at the 10th week visit. A positive pain response (ie pain relief) was defined as \>30% decrease in the VAS score between baseline and the final study visit.

Outcome measures

Outcome measures
Measure	Group A (50mg - 100mg) n=1 Participants Group A begins treatment with Milnacipran 50mg BID (n=20) during Phase I and will be increased to 100mg BID during Phase II Milnacipran : 50mg Milnacipran PO, BID, for 6 weeks. Milnacipran : Milnacipran, 100mg PO, BID, for six weeks	Group B (50mg x12) Subjects in this arm will be maintained at Milnacipran 50mg BID for the entirety of the 12 weeks of the study. Milnacipran : Milnacipran, 50mg PO BID for 12 weeks	Group C (Placebo - 50mg) Group C will begin treatment with Placebo BID (n=20) during Phase I and will be given 50mg BID during Phase II Milnacipran : 50mg Milnacipran PO, BID, for 6 weeks. Placebo : Inactive pill, identical in shape, size, and appearance to active drug, PO, BID.
Number of Participants With Pain Response	0 participants	—	—

SECONDARY outcome

Timeframe: Six Weeks

After six weeks of treatment with Milnacipran, treatment groups were compared with placebo for clinically significant improvement in IBS-QOL. 11 point reduction in IBS-QOL compared to baseline was considered as clinically significant improvement.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Twelve Weeks

The study sought to determine if the Milnacipran arms had a greater proportion of adequate relief over the placebo group. Subjects were asked to answer 'yes' or 'no' as to whether or not they had adequate relief of pain due to irritable bowel syndrome.

Outcome measures

Outcome measures
Measure	Group A (50mg - 100mg) n=1 Participants Group A begins treatment with Milnacipran 50mg BID (n=20) during Phase I and will be increased to 100mg BID during Phase II Milnacipran : 50mg Milnacipran PO, BID, for 6 weeks. Milnacipran : Milnacipran, 100mg PO, BID, for six weeks	Group B (50mg x12) Subjects in this arm will be maintained at Milnacipran 50mg BID for the entirety of the 12 weeks of the study. Milnacipran : Milnacipran, 50mg PO BID for 12 weeks	Group C (Placebo - 50mg) Group C will begin treatment with Placebo BID (n=20) during Phase I and will be given 50mg BID during Phase II Milnacipran : 50mg Milnacipran PO, BID, for 6 weeks. Placebo : Inactive pill, identical in shape, size, and appearance to active drug, PO, BID.
Subject Self Reported Adequate Relief of Pain	0 percentage of participants	—	—

SECONDARY outcome

Timeframe: Twelve Weeks

Population: Only one subject was enrolled and was analyzed even though subject did not complete the study.

Treatment Efficacy Questionnaire is a measure of treatment effectiveness. The score ranges from 1 to 48, 1 is minimum score and 48 is the maximum score. The investigators was looking to see if the Milnacipran treatment groups have a higher proportion of subjects with significant improvement in efficacy, judged as a TEQ score of \>28, compared to placebo group.

Outcome measures

Outcome measures
Measure	Group A (50mg - 100mg) n=1 Participants Group A begins treatment with Milnacipran 50mg BID (n=20) during Phase I and will be increased to 100mg BID during Phase II Milnacipran : 50mg Milnacipran PO, BID, for 6 weeks. Milnacipran : Milnacipran, 100mg PO, BID, for six weeks	Group B (50mg x12) Subjects in this arm will be maintained at Milnacipran 50mg BID for the entirety of the 12 weeks of the study. Milnacipran : Milnacipran, 50mg PO BID for 12 weeks	Group C (Placebo - 50mg) Group C will begin treatment with Placebo BID (n=20) during Phase I and will be given 50mg BID during Phase II Milnacipran : 50mg Milnacipran PO, BID, for 6 weeks. Placebo : Inactive pill, identical in shape, size, and appearance to active drug, PO, BID.
Treatment Efficacy Questionnaire (TEQ)	0 percentage of subject with score >28	—	—

SECONDARY outcome

Timeframe: 12 Weeks

The investigator was looking to see if, for group A, when increased from 50 mg BID to 100 mg BID there is significant improvement of pain scores i.e. 30% pain reduction, and for group C, if there was significant improvement of pain scores when switched from placebo to 50 mg BID of Milnacipran

Outcome measures

Outcome measures
Measure	Group A (50mg - 100mg) n=1 Participants Group A begins treatment with Milnacipran 50mg BID (n=20) during Phase I and will be increased to 100mg BID during Phase II Milnacipran : 50mg Milnacipran PO, BID, for 6 weeks. Milnacipran : Milnacipran, 100mg PO, BID, for six weeks	Group B (50mg x12) Subjects in this arm will be maintained at Milnacipran 50mg BID for the entirety of the 12 weeks of the study. Milnacipran : Milnacipran, 50mg PO BID for 12 weeks	Group C (Placebo - 50mg) Group C will begin treatment with Placebo BID (n=20) during Phase I and will be given 50mg BID during Phase II Milnacipran : 50mg Milnacipran PO, BID, for 6 weeks. Placebo : Inactive pill, identical in shape, size, and appearance to active drug, PO, BID.
Dose Related Incremental Benefit in Pain Reduction Based on VAS	0 percentage of participants	—	—

Adverse Events

Group A (50mg - 100mg)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Group B (50mg x12)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Group C (Placebo - 50mg)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Group A (50mg - 100mg) n=1 participants at risk Group A will begin treatment with Milnacipran 50mg BID (n=20) during Phase I and will be increased to 100mg BID during Phase II Milnacipran : 50mg Milnacipran PO, BID, for 6 weeks. Milnacipran : Milnacipran, 100mg PO, BID, for six weeks	Group B (50mg x12) n=1 participants at risk Subjects in this arm will be maintained at Milnacipran 50mg BID for the entirety of the 12 weeks of the study. Milnacipran : Milnacipran, 50mg PO BID for 12 weeks	Group C (Placebo - 50mg) Group C will begin treatment with Placebo BID (n=20) during Phase I and will be given 50mg BID during Phase II Milnacipran : 50mg Milnacipran PO, BID, for 6 weeks. Placebo : Inactive pill, identical in shape, size, and appearance to active drug, PO, BID.
Cardiac disorders hypertension	100.0% 1/1 • Number of events 1 • 3 months	— 0/0 • 3 months	— 0/0 • 3 months

Additional Information

Dr. Spencer Dorn Associate Professor

UNC Chapel Hill

Phone: 919-966-0141

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place