Ulcerative Colitis
Conditions
Keywords
Ulcerative Colitis
Brief summary
Randomized, double-blind, comparative study versus placebo performed in patients from studies CB-01-02/01 (NCT00679432), CB-01-02/02 (NCT00679380), or CB-01-02/06 (NCT01100112) who achieved ulcerative colitis disease activity index (UCDAI) remission after 8 weeks of treatment. Patients in remission at the End of Study visit will be given the opportunity to enter the 12-month Maintenance Phase study outlined in this protocol (CB-01-02/04). The End of Study visit in studies 01, 02, and 06 will be set as the Visit 1 (Day 0) of this study. There will be no interruption of study treatment between the parent studies and this study. It is planned that approximately 150 patients will be enrolled in the study. Patients will be randomly assigned to two groups to receive either budesonide MMX 6 mg or placebo irrespective of the treatment assigned in studies 01, 02, or 06. Treatments will be administered once a day after breakfast for a maximum of 12 months or up to the occurrence of the first clinical relapse, where clinical relapse is defined as combined recurrence of rectal bleeding and stool frequency ≥ 1-2 stools/day above normal for the patient (score ≥ 1 in both UCDAI items). During the study, patients will be assessed for safety and efficacy at Visit 1 and after 1, 3, 6, 9, and 12 months of treatment. Patients will be contacted by telephone on a monthly basis for safety assessment. In case of occurrence of symptoms suggestive of clinical relapse, patients will attend an unscheduled visit at any time during the study.
Interventions
DRUGBudesonide MMX 6 mg Tablet
Budesonide MMX 6 mg Tablet once daily.
DRUGPlacebo Tablet
Placebo Tablet once daily.
Sponsors
Bausch Health Americas, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients fulfilling the following criteria are eligible for participation in the study: * Male and female patients, 18-75 years old, who are able to understand and voluntarily provide written informed consent. * Patients in UCDAI remission defined as a UCDAI score ≤ 1 point with a score of 0 for rectal bleeding and stool frequency, and a ≥ 1 point reduction from baseline in the endoscopy score without any sign of mucosal friability (score 0 for mucosal appearance). * Patients who have completed all End of Study assessments for the CB-01-02/01, CB-01-02/02 and CB-01-02/06 studies. * Females of child-bearing potential must have had a serum pregnancy test performed at the End of Study visit of the parent studies and must use an acceptable contraceptive method throughout the study treatment period.
Exclusion criteria
* Patients who meet any of the following criteria at screening visit are to be excluded from study participation: * Subjects who have withdrawn from studies CB-01-02/01, CB 01 02/02 or CB-01-02/06. * Subjects who did not achieve induction of remission according to the primary endpoint definition in studies CB-01-02/01, CB 01 02/02 or CB-01-02/06 (i.e. clinical remission defined as a UCDAI score ≤ 1 point with a score of 0 for rectal bleeding and stool frequency, and ≥ 1 point reduction from baseline in the endoscopy score without any sign of mucosal friability \[score 0 for mucosal appearance\]). * Subjects with bone density lower than normal by age and sex (T-score lower than -1) as assessed via dual energy X-ray absorptiometry (DXA) scans.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Clinical Remission | 1, 3, 6, 9, and 12 months | Clinical remission was defined as the combined absence of recurrence of rectal bleeding and absence of increased stool frequency. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Clinical Relapse | 12 months | Clinical relapse was defined as the recurrence of rectal bleeding and/or an abnormal stool frequency \[≥ 1-2 stools/day above normal for the participant. Clinical remission/relapse status was based on participant diary entries prior to each scheduled visit. |
| Percentage of Participants With Endoscopic Relapse | 12 months | Endoscopic relapse was defined as an increase of ≥ 2 points in the Endoscopic Index score from the value calculated at baseline. The score is comprised of four components (granulated scattering reflected light, vascular pattern, vulnerability of mucosa, and mucosal damage). Scores range from 0 to 12, and higher scores indicate more severe (worse) endoscopic findings. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 2: Placebo One placebo tablet self-administered by the patients with a glass of water, in the morning after breakfast.
Placebo Tablet: Placebo Tablet once daily. | 61 |
| 1: Budesonide MMX® 6 mg One Budesonide-MMX® 6 mg tablet self-administered by the patients with a glass of water, in the morning after breakfast.
Budesonide MMX 6 mg Tablet: Budesonide MMX 6 mg Tablet once daily. | 62 |
| Total | 123 |
Baseline characteristics
| Characteristic | 2: Placebo | 1: Budesonide MMX® 6 mg | Total |
|---|---|---|---|
| Age, Continuous | 42.0 years STANDARD_DEVIATION 11.77 | 42.9 years STANDARD_DEVIATION 12.65 | 42.5 years STANDARD_DEVIATION 12.21 |
| Sex: Female, Male Female | 28 Participants | 26 Participants | 54 Participants |
| Sex: Female, Male Male | 33 Participants | 36 Participants | 69 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 30 / 61 | 34 / 62 |
| serious Total, serious adverse events | 1 / 61 | 1 / 62 |
Outcome results
Primary
Percentage of Participants Achieving Clinical Remission
Clinical remission was defined as the combined absence of recurrence of rectal bleeding and absence of increased stool frequency.
Time frame: 1, 3, 6, 9, and 12 months
Population: Number of participants with sufficient diary data to enable determination of clinical remission status at the indicated visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 2: Placebo | Percentage of Participants Achieving Clinical Remission | 3 months | 92.0 percentage of participants |
| 2: Placebo | Percentage of Participants Achieving Clinical Remission | 9 months | 86.7 percentage of participants |
| 2: Placebo | Percentage of Participants Achieving Clinical Remission | 6 months | 76.2 percentage of participants |
| 2: Placebo | Percentage of Participants Achieving Clinical Remission | 12 months | 84.6 percentage of participants |
| 2: Placebo | Percentage of Participants Achieving Clinical Remission | 1 month | 76.7 percentage of participants |
| 1: Budesonide MMX® 6 mg | Percentage of Participants Achieving Clinical Remission | 12 months | 93.3 percentage of participants |
| 1: Budesonide MMX® 6 mg | Percentage of Participants Achieving Clinical Remission | 1 month | 88.2 percentage of participants |
| 1: Budesonide MMX® 6 mg | Percentage of Participants Achieving Clinical Remission | 3 months | 96.8 percentage of participants |
| 1: Budesonide MMX® 6 mg | Percentage of Participants Achieving Clinical Remission | 6 months | 80.0 percentage of participants |
| 1: Budesonide MMX® 6 mg | Percentage of Participants Achieving Clinical Remission | 9 months | 95.0 percentage of participants |
Secondary
Percentage of Participants With Clinical Relapse
Clinical relapse was defined as the recurrence of rectal bleeding and/or an abnormal stool frequency \[≥ 1-2 stools/day above normal for the participant. Clinical remission/relapse status was based on participant diary entries prior to each scheduled visit.
Time frame: 12 months
Population: Participants with sufficient diary data to enable determination of clinical relapse status.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 2: Placebo | Percentage of Participants With Clinical Relapse | 19 Participants |
| 1: Budesonide MMX® 6 mg | Percentage of Participants With Clinical Relapse | 12 Participants |
Secondary
Percentage of Participants With Endoscopic Relapse
Endoscopic relapse was defined as an increase of ≥ 2 points in the Endoscopic Index score from the value calculated at baseline. The score is comprised of four components (granulated scattering reflected light, vascular pattern, vulnerability of mucosa, and mucosal damage). Scores range from 0 to 12, and higher scores indicate more severe (worse) endoscopic findings.
Time frame: 12 months
Population: Participants with sufficient index score data to enable determination of endoscopic relapse status.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 2: Placebo | Percentage of Participants With Endoscopic Relapse | 16 Participants |
| 1: Budesonide MMX® 6 mg | Percentage of Participants With Endoscopic Relapse | 27 Participants |