Trial Outcomes & Findings for Long-Term Safety and Tolerability of Mesalamine Pellets in Participants With Ulcerative Colitis in Remission (NCT NCT00326209)
NCT ID: NCT00326209
Last Updated: 2019-11-01
Results Overview
An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A TEAE was defined as any event with a start date occurring on or after treatment Day 1 or, if pre-existing, worsening after treatment Day 1. Serious AEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
393 participants
Primary outcome timeframe
Baseline (Day 1) up to follow-up (24.5 months)
Results posted on
2019-11-01
Participant Flow
Enrolled participants were rolled over from a double-blind lead-in study (MPUC3003 \[NCT00744016 \] or MPUC3004 \[NCT00767728 \]), or were new participants with demonstrated remission of ulcerative colitis (UC) were enrolled in this study.
A total of 393 participants were enrolled into the study. Of the participants included in the study, 280 participants were rolled over from a lead-in study (MPUC3003 or MPUC3004) and 113 were new participants.
Participant milestones
| Measure |
Encapsulated Mesalamine Granules (eMG)
Participants received eMG 1.5 grams (4 capsules of eMG 0.375 grams each) once daily (QD) orally in the morning for up to 24 months.
|
|---|---|
|
Overall Study
STARTED
|
393
|
|
Overall Study
Safety Population
|
388
|
|
Overall Study
COMPLETED
|
111
|
|
Overall Study
NOT COMPLETED
|
282
|
Reasons for withdrawal
| Measure |
Encapsulated Mesalamine Granules (eMG)
Participants received eMG 1.5 grams (4 capsules of eMG 0.375 grams each) once daily (QD) orally in the morning for up to 24 months.
|
|---|---|
|
Overall Study
Adverse Event
|
28
|
|
Overall Study
Withdrawal by Subject
|
22
|
|
Overall Study
Lack of Efficacy
|
31
|
|
Overall Study
Lost to Follow-up
|
18
|
|
Overall Study
Participant non-compliant
|
6
|
|
Overall Study
Sponsor closed study
|
173
|
|
Overall Study
Prohibited medication use
|
1
|
|
Overall Study
Violation of entry criteria
|
1
|
|
Overall Study
Withdrawn in error
|
1
|
|
Overall Study
Pregnancy
|
1
|
Baseline Characteristics
Long-Term Safety and Tolerability of Mesalamine Pellets in Participants With Ulcerative Colitis in Remission
Baseline characteristics by cohort
| Measure |
Encapsulated Mesalamine Granules (eMG)
n=388 Participants
Participants received eMG 1.5 grams (4 capsules of eMG 0.375 grams each) QD orally in the morning for up to 24 months.
|
|---|---|
|
Age, Continuous
|
47.1 years
STANDARD_DEVIATION 13.6 • n=99 Participants
|
|
Age, Customized
<65 years
|
342 Participants
n=99 Participants
|
|
Age, Customized
≥65 years
|
46 Participants
n=99 Participants
|
|
Sex: Female, Male
Female
|
203 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
185 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
226 Participants
n=99 Participants
|
|
Region of Enrollment
Russia
|
162 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Baseline (Day 1) up to follow-up (24.5 months)Population: Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A TEAE was defined as any event with a start date occurring on or after treatment Day 1 or, if pre-existing, worsening after treatment Day 1. Serious AEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Outcome measures
| Measure |
Encapsulated Mesalamine Granules (eMG)
n=388 Participants
Participants received eMG 1.5 grams (4 capsules of eMG 0.375 grams each) QD orally in the morning for up to 24 months.
|
|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
|
280 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Month 24Population: Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
Number of participants who prematurely discontinued treatment due to any reason were reported.
Outcome measures
| Measure |
Encapsulated Mesalamine Granules (eMG)
n=388 Participants
Participants received eMG 1.5 grams (4 capsules of eMG 0.375 grams each) QD orally in the morning for up to 24 months.
|
|---|---|
|
Number of Participants Who Prematurely Discontinued Treatment
|
282 Participants
|
PRIMARY outcome
Timeframe: Baseline up to follow-up (24.5 months)Population: Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
Criteria for potentially clinically significant abnormal hematology and blood chemistry values included: hemoglobin (grams/deciliter \[g/dL\]): \<10 and ≥3 decrease, or \>20; hematocrit (%): \<30 and ≥10 decrease, or \>60; platelets (\*10\^9 cells/liter): \<100 or \>700 (normal: 150-400); white blood cells (\*10\^9 cells/liter): \<2.3 or \>16.2 (normal: 3.5-11.1); alanine aminotransferase (units/liter \[U/L\]): ≥3 \* upper limit of normal (ULN) (normal range 0-47 U/L); aspartate aminotransferase (U/L): ≥3 \* ULN (normal range 0-37 U/L); total bilirubin (micromoles/liter \[µmol/L\]): \>2 times; and calcium creatinine clearance (milliliters/minute \[mL/min\]): ≤50.
Outcome measures
| Measure |
Encapsulated Mesalamine Granules (eMG)
n=388 Participants
Participants received eMG 1.5 grams (4 capsules of eMG 0.375 grams each) QD orally in the morning for up to 24 months.
|
|---|---|
|
Number of Participants With Potentially Clinically Significant (PCS) Hematology and Blood Chemistry Abnormalities
Alanine aminotransferase (U/L)
|
3 Participants
|
|
Number of Participants With Potentially Clinically Significant (PCS) Hematology and Blood Chemistry Abnormalities
Aspartate aminotransferase (U/L)
|
3 Participants
|
|
Number of Participants With Potentially Clinically Significant (PCS) Hematology and Blood Chemistry Abnormalities
Total bilirubin (µmol/L)
|
6 Participants
|
|
Number of Participants With Potentially Clinically Significant (PCS) Hematology and Blood Chemistry Abnormalities
Calcium creatinine clearance (mL/min)
|
2 Participants
|
|
Number of Participants With Potentially Clinically Significant (PCS) Hematology and Blood Chemistry Abnormalities
Hemoglobin (g/dL)
|
8 Participants
|
|
Number of Participants With Potentially Clinically Significant (PCS) Hematology and Blood Chemistry Abnormalities
Hematocrit (%)
|
7 Participants
|
|
Number of Participants With Potentially Clinically Significant (PCS) Hematology and Blood Chemistry Abnormalities
Platelets (*10^9 cells/L)
|
5 Participants
|
|
Number of Participants With Potentially Clinically Significant (PCS) Hematology and Blood Chemistry Abnormalities
White blood cells (*10^9 cells/L)
|
13 Participants
|
PRIMARY outcome
Timeframe: Baseline, up to follow-up visit (Month 24.5)Population: Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
Vital signs included systolic and diastolic blood pressure, pulse rate, body temperature, or body weight.
Outcome measures
| Measure |
Encapsulated Mesalamine Granules (eMG)
n=388 Participants
Participants received eMG 1.5 grams (4 capsules of eMG 0.375 grams each) QD orally in the morning for up to 24 months.
|
|---|---|
|
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
|
0 Participants
|
Adverse Events
Encapsulated Mesalamine Granules (eMG)
Serious events: 28 serious events
Other events: 280 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Encapsulated Mesalamine Granules (eMG)
n=388 participants at risk
Participants received eMG 1.5 grams (4 capsules of eMG 0.375 grams each) QD orally in the morning for up to 24 months.
|
|---|---|
|
Gastrointestinal disorders
Periproctitis
|
0.26%
1/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Cardiac disorders
Atrial fibrillation
|
0.52%
2/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Gastrointestinal disorders
Colitis ulcerative
|
1.5%
6/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Gastrointestinal disorders
Diverticular perforation
|
0.26%
1/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Gastrointestinal disorders
Ileus
|
0.26%
1/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Gastrointestinal disorders
Proctitis
|
0.26%
1/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
General disorders
Chest pain
|
0.26%
1/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
General disorders
Non-cardiac chest pain
|
0.26%
1/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Infections and infestations
Abscess limb
|
0.26%
1/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Infections and infestations
Cellulitis
|
0.77%
3/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Infections and infestations
Diverticulitis
|
0.26%
1/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Infections and infestations
Localised infection
|
0.26%
1/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Infections and infestations
Lower respiratory tract infection
|
0.26%
1/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Infections and infestations
Tooth abscess
|
0.26%
1/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Injury, poisoning and procedural complications
Upper limb fracture
|
0.52%
2/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer
|
0.26%
1/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon Cancer
|
0.26%
1/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung Neoplasm Malignant
|
0.26%
1/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Nervous system disorders
Convulsion
|
0.26%
1/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
|
0.49%
1/203 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Pregnancy, puerperium and perinatal conditions
Ectopic pregnancy
|
0.49%
1/203 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Pregnancy, puerperium and perinatal conditions
Hyperemesis gravidarum
|
0.49%
1/203 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Reproductive system and breast disorders
Uterine perforation
|
0.49%
1/203 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Vascular disorders
Deep vein thrombosis
|
0.26%
1/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
Other adverse events
| Measure |
Encapsulated Mesalamine Granules (eMG)
n=388 participants at risk
Participants received eMG 1.5 grams (4 capsules of eMG 0.375 grams each) QD orally in the morning for up to 24 months.
|
|---|---|
|
Gastrointestinal disorders
Diarrhea
|
10.8%
42/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Gastrointestinal disorders
Abdominal Pain
|
8.0%
31/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Gastrointestinal disorders
Colitis ulcerative
|
6.2%
24/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Gastrointestinal disorders
Nausea
|
5.7%
22/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Gastrointestinal disorders
Constipation
|
4.4%
17/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Gastrointestinal disorders
Dyspepsia
|
4.1%
16/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
General disorders
Haemorrhoids
|
4.1%
16/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Gastrointestinal disorders
Vomiting
|
4.1%
16/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
3.6%
14/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Gastrointestinal disorders
Abdominal distension
|
3.4%
13/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Gastrointestinal disorders
Haematochezia
|
3.4%
13/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
3.1%
12/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Infections and infestations
Nasopharyngitis
|
13.9%
54/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Infections and infestations
Sinusitis
|
7.2%
28/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Infections and infestations
Upper respiratory tract infection
|
6.7%
26/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Infections and infestations
Gastroenteritis viral
|
4.9%
19/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Infections and infestations
Influenza
|
4.9%
19/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Infections and infestations
Respiratory tract infection viral
|
4.6%
18/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Infections and infestations
Urinary tract infection
|
4.4%
17/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Infections and infestations
Bronchitis
|
3.9%
15/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.0%
27/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.7%
26/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Nervous system disorders
Headache
|
11.6%
45/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Psychiatric disorders
Insomnia
|
3.1%
12/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
|
Skin and subcutaneous tissue disorders
Rash
|
3.6%
14/388 • Baseline up to follow-up (24.5 months)
Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Please contact Sponsor directly for additional information.
- Publication restrictions are in place
Restriction type: OTHER