Ulcerative Colitis
Conditions
Keywords
UC, Ulcerative colitis, Inflammatory bowel disease, IBD
Brief summary
To evaluate the long-term safety and tolerability of encapsulated mesalamine Granules (eMG) (formerly referred to as Mesalamine Pellets \[MP\]) in participants with ulcerative colitis currently in remission.
Detailed description
This is a Phase 3, multicenter, open-label, treatment extension study evaluating the long-term safety and tolerability of eMG given once daily (QD) in participants who successfully participated in a double-blind lead-in study (MPUC3003 \[NCT00744016 \] or MPUC3004 \[NCT00767728 \]) or new participants who are currently in remission from symptoms of ulcerative colitis.
Interventions
DRUGEncapsulated Mesalamine Granules (eMG)
eMG capsules will be administered per dose and schedule specified in the arm.
Sponsors
Bausch Health Americas, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. An Institutional Review Board (IRB)/Ethics Committee (EC) approved informed consent is signed and dated prior to any study-related activities. 2. Participant has successfully participated in a previous MP clinical study per investigator's discretion with successful participation minimally defined as compliant with study-related procedures and study drug dosing schedule in the previous study and did not discontinue from the previous study due to study drug-related AE(s) or if new participants: a. Participant is a male or, If the participant is female, she is eligible to enter if she is of: Non-childbearing potential (that is; physiologically incapable of becoming pregnant, including any female who has undergone sterilization \[hysterectomy or bilateral tubal ligation\] or is post-menopausal. For purposes of this study, postmenopausal is defined as 1 year without menses); or childbearing potential, has a negative serum pregnancy test at screen and, if heterosexually active, agrees to one of the following: i) Double barrier method of contraception, specifically, use of a condom and spermicide, for 1 week prior to study drug administration, throughout the 6-month Treatment Phase, and the 2-week follow-up phase. ii) Oral contraceptives administered for at least 2 monthly cycles prior to study drug administration during all 6 months of study drug administration and administered for 1 monthly cycle following completion of the study. iii) An intrauterine device (IUD), inserted by a qualified clinician, with published data showing that the lowest expected failure rate is less than (\<)1% per year (not all IUDs meet this criterion). iv) Medroxyprogesterone acetate (DEPO-PROVERA) administered for a minimum of 1 monthly cycle prior to the study drug administration, during all 6 months of study drug administration, and administered for 1 monthly cycle following study completion. Norelgestromin/ ethinyl estradiol transdermal system (Ortho Evra patch) administered for at least 2 monthly cycles prior to study drug administration and administered for 2 monthly cycles following study completion. v) Partner has undergone vasectomy and participant is in a monogamous relationship. The investigator is responsible for determining whether the participant has adequate birth control for study participation. b. Participant is greater than or equal to (≥) 18 years of age. c. Participant has historically confirmed diagnosis (physician letter for newly/recently diagnosed and by medical records for previously diagnosed participants) of mild to moderate UC in remission for greater than (\>) 1 month and \<12 months. d. Confirmed current remission defined as both: A screening rectal bleeding score of 0 as described in the Disease Activity Index (DAI) (Sutherland Index) where 0 = None A screening sigmoidoscopy score of 0 to 1 for mucosal appearance as described in the (Sutherland Index where 0 = intact mucosa with preserved or distorted vessels and 1 = Erythema, decreased vascular pattern, granularity, no mucosal hemorrhage. 3. Participant and investigator consider there is the potential for benefit to the participant with MP treatment. 4. Participant is capable and willing to comply with all study procedures.
Exclusion criteria
1. Participant has any condition or circumstance that would, in the opinion of the investigator, prevent completion of the study or interfere with analysis of study results, including history of noncompliance with treatments or visits. If a new participant, the following additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Baseline (Day 1) up to follow-up (24.5 months) | 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. |
| Number of Participants Who Prematurely Discontinued Treatment | Baseline up to Month 24 | Number of participants who prematurely discontinued treatment due to any reason were reported. |
| Number of Participants With Potentially Clinically Significant (PCS) Hematology and Blood Chemistry Abnormalities | Baseline up to follow-up (24.5 months) | 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. |
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Baseline, up to follow-up visit (Month 24.5) | Vital signs included systolic and diastolic blood pressure, pulse rate, body temperature, or body weight. |
Countries
United States
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Encapsulated Mesalamine Granules (eMG) Participants received eMG 1.5 grams (4 capsules of eMG 0.375 grams each) QD orally in the morning for up to 24 months. | 388 |
| Total | 388 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 28 |
| Overall Study | Lack of Efficacy | 31 |
| Overall Study | Lost to Follow-up | 18 |
| Overall Study | Participant non-compliant | 6 |
| Overall Study | Pregnancy | 1 |
| Overall Study | Prohibited medication use | 1 |
| Overall Study | Sponsor closed study | 173 |
| Overall Study | Violation of entry criteria | 1 |
| Overall Study | Withdrawal by Subject | 22 |
| Overall Study | Withdrawn in error | 1 |
Baseline characteristics
| Characteristic | Encapsulated Mesalamine Granules (eMG) |
|---|---|
| Age, Continuous | 47.1 years STANDARD_DEVIATION 13.6 |
| Age, Customized <65 years | 342 Participants |
| Age, Customized ≥65 years | 46 Participants |
| Region of Enrollment Russia | 162 Participants |
| Region of Enrollment United States | 226 Participants |
| Sex: Female, Male Female | 203 Participants |
| Sex: Female, Male Male | 185 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 280 / 388 |
| serious Total, serious adverse events | 28 / 388 |
Outcome results
Primary
Number of Participants Who Prematurely Discontinued Treatment
Number of participants who prematurely discontinued treatment due to any reason were reported.
Time frame: Baseline up to Month 24
Population: Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Encapsulated Mesalamine Granules (eMG) | Number of Participants Who Prematurely Discontinued Treatment | 282 Participants |
Primary
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Vital signs included systolic and diastolic blood pressure, pulse rate, body temperature, or body weight.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Encapsulated Mesalamine Granules (eMG) | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
Primary
Number of Participants With Potentially Clinically Significant (PCS) Hematology and Blood Chemistry Abnormalities
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Encapsulated Mesalamine Granules (eMG) | Number of Participants With Potentially Clinically Significant (PCS) Hematology and Blood Chemistry Abnormalities | Hemoglobin (g/dL) | 8 Participants |
| Encapsulated Mesalamine Granules (eMG) | Number of Participants With Potentially Clinically Significant (PCS) Hematology and Blood Chemistry Abnormalities | Hematocrit (%) | 7 Participants |
| Encapsulated Mesalamine Granules (eMG) | Number of Participants With Potentially Clinically Significant (PCS) Hematology and Blood Chemistry Abnormalities | Platelets (*10^9 cells/L) | 5 Participants |
| Encapsulated Mesalamine Granules (eMG) | Number of Participants With Potentially Clinically Significant (PCS) Hematology and Blood Chemistry Abnormalities | White blood cells (*10^9 cells/L) | 13 Participants |
| Encapsulated Mesalamine Granules (eMG) | Number of Participants With Potentially Clinically Significant (PCS) Hematology and Blood Chemistry Abnormalities | Alanine aminotransferase (U/L) | 3 Participants |
| Encapsulated Mesalamine Granules (eMG) | Number of Participants With Potentially Clinically Significant (PCS) Hematology and Blood Chemistry Abnormalities | Aspartate aminotransferase (U/L) | 3 Participants |
| Encapsulated Mesalamine Granules (eMG) | Number of Participants With Potentially Clinically Significant (PCS) Hematology and Blood Chemistry Abnormalities | Total bilirubin (µmol/L) | 6 Participants |
| Encapsulated Mesalamine Granules (eMG) | Number of Participants With Potentially Clinically Significant (PCS) Hematology and Blood Chemistry Abnormalities | Calcium creatinine clearance (mL/min) | 2 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Encapsulated Mesalamine Granules (eMG) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 280 Participants |