Trial Outcomes & Findings for Ability to Maintain or Achieve Clinical and Endoscopic Remission With MMX Mesalamine Once Daily in Adults With Ulcerative Colitis (NCT NCT01124149)

NCT ID: NCT01124149

Last Updated: 2021-06-09

Results Overview

Complete remission was defined as a modified Ulcerative Colitis Disease Activity Index (UC-DAI) \<=1 with a score of 0 for rectal bleeding and stool frequency and at least a 1-point reduction in endoscopy score from baseline. The modified UC-DAI score is the sum of the scores of 4 parameters (stool frequency, rectal bleeding, endoscopy score, and physician global assessment), each scoring between 0 and 3, making 12 the worst score. Endoscopy score (mucosal appearance) ranges from 0-3 (0 = normal, 1 = mild , 2 = moderate, 3 = severe). Rectal bleeding is assessed on a scale from 0-3 (0 = no rectal bleeding, 1 = streaks of blood, 2 = obvious blood, 3 = mostly blood). Stool frequency is assessed on a scale of 0-2 (0 = 0-1 more than normal per day, 1 = 2-3 more than normal per day, 2 = 4 or more than normal per day).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

759 participants

Primary outcome timeframe

12 months

Results posted on

2021-06-09

Participant Flow

Although 639 subjects completed the Acute Phase, 167 were not eligible to enter the Maintenance Phase due to lack of efficacy and 2 others withdrew prior to entering the maintenance Phase and 1 was withdrawn per IVRS prior to entering the Mainenance Phase. Therefore, 469 subjects entered the Maintenance Phase.

Participant milestones

Participant milestones
Measure
MMX Mesalamine/ Mesalazine
4.8g/day given QD for 8 weeks in the Acute Phase and 2.4g/day given QD for 12 months in the Maintenance Phase
Acute Phase
STARTED
722
Acute Phase
COMPLETED
639
Acute Phase
NOT COMPLETED
83
Maintenance Phase
STARTED
469
Maintenance Phase
COMPLETED
373
Maintenance Phase
NOT COMPLETED
96

Reasons for withdrawal

Reasons for withdrawal
Measure
MMX Mesalamine/ Mesalazine
4.8g/day given QD for 8 weeks in the Acute Phase and 2.4g/day given QD for 12 months in the Maintenance Phase
Acute Phase
Withdrawal by Subject
22
Acute Phase
Adverse Event
21
Acute Phase
Lack of Efficacy
17
Acute Phase
Protocol Violation
14
Acute Phase
Lost to Follow-up
2
Acute Phase
Prolonged antibiotic therapy
1
Acute Phase
Sponsor request
1
Acute Phase
UC symptoms not ameliorated
1
Acute Phase
Non-compliance
1
Acute Phase
Low hemoglobin
1
Acute Phase
Travelling to another country
1
Acute Phase
Sponsor decision
1
Maintenance Phase
Lack of Efficacy
40
Maintenance Phase
Adverse Event
24
Maintenance Phase
Lost to Follow-up
15
Maintenance Phase
Withdrawal by Subject
10
Maintenance Phase
Protocol Violation
5
Maintenance Phase
Coordinator error
1
Maintenance Phase
Non-compliance
1

Baseline Characteristics

Ability to Maintain or Achieve Clinical and Endoscopic Remission With MMX Mesalamine Once Daily in Adults With Ulcerative Colitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
MMX Mesalamine/ Mesalazine
n=717 Participants
4.8g/day given QD for 8 weeks in the Acute Phase and 2.4g/day given QD for 12 months in the Maintenance Phase
Age, Continuous
42.9 Years
STANDARD_DEVIATION 13.97 • n=99 Participants
Age, Customized
>=65 years
51 Participants
n=99 Participants
Age, Customized
<=18 years
10 Participants
n=99 Participants
Age, Customized
Between 18 and 65 years
656 Participants
n=99 Participants
Sex: Female, Male
Female
308 Participants
n=99 Participants
Sex: Female, Male
Male
409 Participants
n=99 Participants
Region of Enrollment
BELGIUM
22 Participants
n=99 Participants
Region of Enrollment
CANADA
39 Participants
n=99 Participants
Region of Enrollment
COLOMBIA
74 Participants
n=99 Participants
Region of Enrollment
CZECH REPUBLIC
130 Participants
n=99 Participants
Region of Enrollment
FRANCE
2 Participants
n=99 Participants
Region of Enrollment
HUNGARY
30 Participants
n=99 Participants
Region of Enrollment
INDIA
200 Participants
n=99 Participants
Region of Enrollment
IRELAND
9 Participants
n=99 Participants
Region of Enrollment
POLAND
52 Participants
n=99 Participants
Region of Enrollment
ROMANIA
41 Participants
n=99 Participants
Region of Enrollment
SOUTH AFRICA
21 Participants
n=99 Participants
Region of Enrollment
SPAIN
3 Participants
n=99 Participants
Region of Enrollment
UNITED KINGDOM
3 Participants
n=99 Participants
Region of Enrollment
UNITED STATES
96 Participants
n=99 Participants

PRIMARY outcome

Timeframe: 12 months

Population: Maintenance Phase Efficacy Population included all subjects who, during the Maintenance Phase, took at least 1 dose of investigational product and had at least 1 post-dose efficacy assessment.

Complete remission was defined as a modified Ulcerative Colitis Disease Activity Index (UC-DAI) \<=1 with a score of 0 for rectal bleeding and stool frequency and at least a 1-point reduction in endoscopy score from baseline. The modified UC-DAI score is the sum of the scores of 4 parameters (stool frequency, rectal bleeding, endoscopy score, and physician global assessment), each scoring between 0 and 3, making 12 the worst score. Endoscopy score (mucosal appearance) ranges from 0-3 (0 = normal, 1 = mild , 2 = moderate, 3 = severe). Rectal bleeding is assessed on a scale from 0-3 (0 = no rectal bleeding, 1 = streaks of blood, 2 = obvious blood, 3 = mostly blood). Stool frequency is assessed on a scale of 0-2 (0 = 0-1 more than normal per day, 1 = 2-3 more than normal per day, 2 = 4 or more than normal per day).

Outcome measures

Outcome measures
Measure
MMX Mesalamine/ Mesalazine (Complete Remission Acute Phase)
n=182 Participants
Subjects received 4.8g/day given QD for 8 weeks in the Acute Phase and were classified as having complete remission at the end of the Acute Phase. Complete (clinical and endoscopic) remission was defined as a modified UC-DAI \<=1 with a score of 0 for rectal bleeding and stool frequency and at least a 1-point reduction in endoscopy score from baseline. These subjects then received 2.4g/day given QD for 12 months in the Maintenance Phase.
MMX Mesalamine/ Mesalazine (Partial Remission Acute Phase)
n=277 Participants
Subjects received 4.8g/day given QD for 8 weeks in the Acute Phase and were classified as having partial remission at the end of the Acute Phase. Partial remission was defined as a modified UC-DAI \<=3 with a combined stool frequency and rectal bleeding score of \<=1 and not in complete remission. These subjects then received 2.4g/day given QD for 12 months in the Maintenance Phase.
Percentage of Subjects in Complete Remission at Month 12 of Maintenance Phase
47.8 percentage of subjects
26.0 percentage of subjects

SECONDARY outcome

Timeframe: 12 months

Population: Maintenance Phase Efficacy Population included all subjects who, during the Maintenance Phase, took at least 1 dose of investigational product and had at least 1 post-dose efficacy assessment.

Clinical remission was defined as a score of 0 for rectal bleeding and stool frequency. Rectal bleeding is assessed on a scale from 0-3 (0 = no rectal bleeding, 1 = streaks of blood, 2 = obvious blood, 3 = mostly blood). Stool frequency is assessed on a scale of 0-2 (0 = 0-1 more than normal per day, 1 = 2-3 more than normal per day, 2 = 4 or more than normal per day).

Outcome measures

Outcome measures
Measure
MMX Mesalamine/ Mesalazine (Complete Remission Acute Phase)
n=182 Participants
Subjects received 4.8g/day given QD for 8 weeks in the Acute Phase and were classified as having complete remission at the end of the Acute Phase. Complete (clinical and endoscopic) remission was defined as a modified UC-DAI \<=1 with a score of 0 for rectal bleeding and stool frequency and at least a 1-point reduction in endoscopy score from baseline. These subjects then received 2.4g/day given QD for 12 months in the Maintenance Phase.
MMX Mesalamine/ Mesalazine (Partial Remission Acute Phase)
n=277 Participants
Subjects received 4.8g/day given QD for 8 weeks in the Acute Phase and were classified as having partial remission at the end of the Acute Phase. Partial remission was defined as a modified UC-DAI \<=3 with a combined stool frequency and rectal bleeding score of \<=1 and not in complete remission. These subjects then received 2.4g/day given QD for 12 months in the Maintenance Phase.
Percentage of Subjects in Clinical Remission at Month 12 of Maintenance Phase
58.8 percentage of subjects
40.4 percentage of subjects

SECONDARY outcome

Timeframe: 12 months

Population: Maintenance Phase Efficacy Population included all subjects who, during the Maintenance Phase, took at least 1 dose of investigational product and had at least 1 post-dose efficacy assessment.

Relapse was defined in the Maintenance Phase as the need for alternative treatment for UC (including surgery); subjects were classified as having a relapse if they had withdrawn from the study due to a lack of efficacy.

Outcome measures

Outcome measures
Measure
MMX Mesalamine/ Mesalazine (Complete Remission Acute Phase)
n=182 Participants
Subjects received 4.8g/day given QD for 8 weeks in the Acute Phase and were classified as having complete remission at the end of the Acute Phase. Complete (clinical and endoscopic) remission was defined as a modified UC-DAI \<=1 with a score of 0 for rectal bleeding and stool frequency and at least a 1-point reduction in endoscopy score from baseline. These subjects then received 2.4g/day given QD for 12 months in the Maintenance Phase.
MMX Mesalamine/ Mesalazine (Partial Remission Acute Phase)
n=277 Participants
Subjects received 4.8g/day given QD for 8 weeks in the Acute Phase and were classified as having partial remission at the end of the Acute Phase. Partial remission was defined as a modified UC-DAI \<=3 with a combined stool frequency and rectal bleeding score of \<=1 and not in complete remission. These subjects then received 2.4g/day given QD for 12 months in the Maintenance Phase.
Relapse in Ulcerative Colitis at Month 12 of Maintenance Phase
6.0 percentage of subjects
10.5 percentage of subjects

SECONDARY outcome

Timeframe: 12 months

Population: Maintenance Phase Efficacy Population included all subjects who, during the Maintenance Phase, took at least 1 dose of investigational product and had at least 1 post-dose efficacy assessment.

Subjects with mucosal healing were defined as subjects who had an endoscopy score \<=1. Endoscopy score (mucosal appearance) ranges from 0-3 (0 = normal, 1 = mild , 2 = moderate, 3 = severe).

Outcome measures

Outcome measures
Measure
MMX Mesalamine/ Mesalazine (Complete Remission Acute Phase)
n=182 Participants
Subjects received 4.8g/day given QD for 8 weeks in the Acute Phase and were classified as having complete remission at the end of the Acute Phase. Complete (clinical and endoscopic) remission was defined as a modified UC-DAI \<=1 with a score of 0 for rectal bleeding and stool frequency and at least a 1-point reduction in endoscopy score from baseline. These subjects then received 2.4g/day given QD for 12 months in the Maintenance Phase.
MMX Mesalamine/ Mesalazine (Partial Remission Acute Phase)
n=277 Participants
Subjects received 4.8g/day given QD for 8 weeks in the Acute Phase and were classified as having partial remission at the end of the Acute Phase. Partial remission was defined as a modified UC-DAI \<=3 with a combined stool frequency and rectal bleeding score of \<=1 and not in complete remission. These subjects then received 2.4g/day given QD for 12 months in the Maintenance Phase.
Percentage of Subjects With Mucosal Healing at 12 Months of Maintenance Phase
76.4 percentage of subjects
63.5 percentage of subjects

SECONDARY outcome

Timeframe: 3 and 8 weeks

Population: Acute Phase Safety Population included all subjects who, during the Acute Phase, took at least 1 dose of investigational product.

Improvement was defined as at least a 1-point reduction in the rectal bleeding score from baseline at each assessment point. Rectal bleeding is assessed on a scale from 0-3 (0 = no rectal bleeding, 1 = streaks of blood, 2 = obvious blood, 3 = mostly blood).

Outcome measures

Outcome measures
Measure
MMX Mesalamine/ Mesalazine (Complete Remission Acute Phase)
n=717 Participants
Subjects received 4.8g/day given QD for 8 weeks in the Acute Phase and were classified as having complete remission at the end of the Acute Phase. Complete (clinical and endoscopic) remission was defined as a modified UC-DAI \<=1 with a score of 0 for rectal bleeding and stool frequency and at least a 1-point reduction in endoscopy score from baseline. These subjects then received 2.4g/day given QD for 12 months in the Maintenance Phase.
MMX Mesalamine/ Mesalazine (Partial Remission Acute Phase)
Subjects received 4.8g/day given QD for 8 weeks in the Acute Phase and were classified as having partial remission at the end of the Acute Phase. Partial remission was defined as a modified UC-DAI \<=3 with a combined stool frequency and rectal bleeding score of \<=1 and not in complete remission. These subjects then received 2.4g/day given QD for 12 months in the Maintenance Phase.
Improvement in Rectal Bleeding Score During the Acute Phase
Week 3
42.4 percentage of subjects
Improvement in Rectal Bleeding Score During the Acute Phase
Week 8
59.8 percentage of subjects

SECONDARY outcome

Timeframe: 3 and 8 weeks

Population: Acute Phase Safety Population included all subjects who, during the Acute Phase, took at least 1 dose of investigational product.

Improvement was defined as at least a 1-point reduction in the stool frequency score from baseline at each assessment point. Stool frequency is assessed on a scale of 0-2 (0 = 0-1 more than normal per day, 1 = 2-3 more than normal per day, 2 = 4 or more than normal per day).

Outcome measures

Outcome measures
Measure
MMX Mesalamine/ Mesalazine (Complete Remission Acute Phase)
n=717 Participants
Subjects received 4.8g/day given QD for 8 weeks in the Acute Phase and were classified as having complete remission at the end of the Acute Phase. Complete (clinical and endoscopic) remission was defined as a modified UC-DAI \<=1 with a score of 0 for rectal bleeding and stool frequency and at least a 1-point reduction in endoscopy score from baseline. These subjects then received 2.4g/day given QD for 12 months in the Maintenance Phase.
MMX Mesalamine/ Mesalazine (Partial Remission Acute Phase)
Subjects received 4.8g/day given QD for 8 weeks in the Acute Phase and were classified as having partial remission at the end of the Acute Phase. Partial remission was defined as a modified UC-DAI \<=3 with a combined stool frequency and rectal bleeding score of \<=1 and not in complete remission. These subjects then received 2.4g/day given QD for 12 months in the Maintenance Phase.
Improvement in Stool Frequency Symptoms During the Acute Phase
3 Weeks
38.5 percentage of subjects
Improvement in Stool Frequency Symptoms During the Acute Phase
8 Weeks
58.9 percentage of subjects

SECONDARY outcome

Timeframe: 8 Weeks

Population: Acute Phase Safety Population included all subjects who, during the Acute Phase, took at least 1 dose of investigational product.

Complete (clinical and endoscopic) remission was defined as a modified UC-DAI \<=1 with a score of 0 for rectal bleeding and stool frequency and at least a 1-point reduction in endoscopy score from baseline. The modified UC-DAI score is the sum of the scores of 4 parameters (stool frequency, rectal bleeding, endoscopy score, and physician global assessment), each scoring between 0 and 3, making 12 the worst score. Endoscopy score (mucosal appearance) ranges from 0-3 (0 = normal, 1 = mild , 2 = moderate, 3 = severe). Rectal bleeding is assessed on a scale from 0-3 (0 = no rectal bleeding, 1 = streaks of blood, 2 = obvious blood, 3 = mostly blood). Stool frequency is assessed on a scale of 0-2 (0 = 0-1 more than normal per day, 1 = 2-3 more than normal per day, 2 = 4 or more than normal per day).

Outcome measures

Outcome measures
Measure
MMX Mesalamine/ Mesalazine (Complete Remission Acute Phase)
n=717 Participants
Subjects received 4.8g/day given QD for 8 weeks in the Acute Phase and were classified as having complete remission at the end of the Acute Phase. Complete (clinical and endoscopic) remission was defined as a modified UC-DAI \<=1 with a score of 0 for rectal bleeding and stool frequency and at least a 1-point reduction in endoscopy score from baseline. These subjects then received 2.4g/day given QD for 12 months in the Maintenance Phase.
MMX Mesalamine/ Mesalazine (Partial Remission Acute Phase)
Subjects received 4.8g/day given QD for 8 weeks in the Acute Phase and were classified as having partial remission at the end of the Acute Phase. Partial remission was defined as a modified UC-DAI \<=3 with a combined stool frequency and rectal bleeding score of \<=1 and not in complete remission. These subjects then received 2.4g/day given QD for 12 months in the Maintenance Phase.
Percentage of Subjects in Complete Remission at Week 8 of Acute Phase
25.9 percentage of subjects

SECONDARY outcome

Timeframe: 8 weeks

Population: Acute Phase Safety Population included all subjects who, during the Acute Phase, took at least 1 dose of investigational product.

Partial remission was defined as a modified UC-DAI \<=3 with a combined stool frequency and rectal bleeding score of \<=1 and not in complete remission. The modified UC-DAI score is the sum of the scores of 4 parameters (stool frequency, rectal bleeding, endoscopy score, and physician global assessment), each scoring between 0 and 3, making 12 the worst score. Endoscopy score (mucosal appearance) ranges from 0-3 (0 = normal, 1 = mild , 2 = moderate, 3 = severe). Rectal bleeding is assessed on a scale from 0-3 (0 = no rectal bleeding, 1 = streaks of blood, 2 = obvious blood, 3 = mostly blood). Stool frequency is assessed on a scale of 0-2 (0 = 0-1 more than normal per day, 1 = 2-3 more than normal per day, 2 = 4 or more than normal per day).

Outcome measures

Outcome measures
Measure
MMX Mesalamine/ Mesalazine (Complete Remission Acute Phase)
n=717 Participants
Subjects received 4.8g/day given QD for 8 weeks in the Acute Phase and were classified as having complete remission at the end of the Acute Phase. Complete (clinical and endoscopic) remission was defined as a modified UC-DAI \<=1 with a score of 0 for rectal bleeding and stool frequency and at least a 1-point reduction in endoscopy score from baseline. These subjects then received 2.4g/day given QD for 12 months in the Maintenance Phase.
MMX Mesalamine/ Mesalazine (Partial Remission Acute Phase)
Subjects received 4.8g/day given QD for 8 weeks in the Acute Phase and were classified as having partial remission at the end of the Acute Phase. Partial remission was defined as a modified UC-DAI \<=3 with a combined stool frequency and rectal bleeding score of \<=1 and not in complete remission. These subjects then received 2.4g/day given QD for 12 months in the Maintenance Phase.
Percentage of Subjects in Partial Remission at Week 8 of Acute Phase
39.3 percentage of subjects

Adverse Events

MMX Mesalamine/ Mesalazine (Acute Phase)

Serious events: 13 serious events
Other events: 60 other events
Deaths: 0 deaths

MMX Mesalamine/ Mesalazine (Maintenance Phase)

Serious events: 14 serious events
Other events: 65 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
MMX Mesalamine/ Mesalazine (Acute Phase)
n=717 participants at risk
4.8g/day given QD for 8 weeks in the Acute Phase
MMX Mesalamine/ Mesalazine (Maintenance Phase)
n=461 participants at risk
2.4 g/day given QD for 12 months in the Maintenance Phase
Cardiac disorders
Myocardial infarction
0.14%
1/717
0.00%
0/461
Gastrointestinal disorders
Colitis ulcerative
0.28%
2/717
0.22%
1/461
Gastrointestinal disorders
Pancreatitis acute
0.14%
1/717
0.00%
0/461
Infections and infestations
Arthritis bacterial
0.14%
1/717
0.00%
0/461
Infections and infestations
Lung infection
0.14%
1/717
0.00%
0/461
Infections and infestations
Pneumonia staphylococcal
0.14%
1/717
0.00%
0/461
Infections and infestations
Pyelonephritis acute
0.14%
1/717
0.00%
0/461
Injury, poisoning and procedural complications
Femoral neck fracture
0.14%
1/717
0.00%
0/461
Investigations
HIV test positive
0.14%
1/717
0.00%
0/461
Metabolism and nutrition disorders
Dehydration
0.14%
1/717
0.22%
1/461
Musculoskeletal and connective tissue disorders
Arthritis reactive
0.14%
1/717
0.00%
0/461
Pregnancy, puerperium and perinatal conditions
Pregnancy
0.14%
1/717
0.00%
0/461
Renal and urinary disorders
Nephrolithiasis
0.14%
1/717
0.00%
0/461
Blood and lymphatic system disorders
Anemia
0.00%
0/717
0.43%
2/461
Cardiac disorders
Atrial fibrillation
0.00%
0/717
0.22%
1/461
Cardiac disorders
Bundle branch block left
0.00%
0/717
0.22%
1/461
Gastrointestinal disorders
Abdominal pain
0.00%
0/717
0.43%
2/461
Gastrointestinal disorders
Diarrhea
0.00%
0/717
0.65%
3/461
General disorders
Pyrexia
0.00%
0/717
0.22%
1/461
Infections and infestations
Appendicitis
0.00%
0/717
0.22%
1/461
Infections and infestations
Gastroenteritis
0.00%
0/717
0.22%
1/461
Infections and infestations
Hepatitis B
0.00%
0/717
0.22%
1/461
Injury, poisoning and procedural complications
Forearm fracture
0.00%
0/717
0.22%
1/461
Injury, poisoning and procedural complications
Road traffic accident
0.00%
0/717
0.43%
2/461
Investigations
C-reactive protein increased
0.00%
0/717
0.22%
1/461
Musculoskeletal and connective tissue disorders
Back pain
0.00%
0/717
0.22%
1/461
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Brain neoplasm
0.00%
0/717
0.22%
1/461
Nervous system disorders
Cerebrovascular accident
0.00%
0/717
0.22%
1/461
Nervous system disorders
Hemorrhagic stroke
0.00%
0/717
0.22%
1/461
Nervous system disorders
Radiculopathy
0.00%
0/717
0.22%
1/461
Reproductive system and breast disorders
Metrorrhagia
0.00%
0/717
0.22%
1/461
Vascular disorders
Venous thrombosis limb
0.00%
0/717
0.22%
1/461

Other adverse events

Other adverse events
Measure
MMX Mesalamine/ Mesalazine (Acute Phase)
n=717 participants at risk
4.8g/day given QD for 8 weeks in the Acute Phase
MMX Mesalamine/ Mesalazine (Maintenance Phase)
n=461 participants at risk
2.4 g/day given QD for 12 months in the Maintenance Phase
Gastrointestinal disorders
Colitis ulcerative
1.4%
10/717
9.3%
43/461
General disorders
Drug ineffective
7.0%
50/717
4.8%
22/461

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Results disclosure agreements

  • Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
  • Publication restrictions are in place

Restriction type: OTHER