Colitis, Ulcerative
Conditions
Keywords
ulcerative colitis, Budesonide
Brief summary
Open-label, 8 week study, to assess the efficacy and safety of oral Budesonide-MMX 9 mg Extended-release Tablets in patients with mild to moderate, active ulcerative colitis who are not in remission based on the Ulcerative Colitis Disease Activity Index in study CB-01-02/01 (parent study \[NCT00679432\]).
Detailed description
Patients who complete the parent study and who do not achieve clinical remission will be eligible to receive 8 weeks of open-label treatment with Budesonide-MMX 9mg if they satisfy the entry criteria for this study.
Interventions
DRUGBudesonide
One Budesonide-MMX 9 mg tablet will be taken in the morning after breakfast for 8 weeks.
Sponsors
Cosmo Technologies Ltd
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 75 Years
Healthy volunteers
No
Inclusion criteria
* Male and female patients 18 to 74 years of age, who are able to understand and voluntarily provide written informed consent * Completed all Final Visit assessments for study CB-01-02/01 (NCT00679432) and are not in clinical remission * Diagnosis of ulcerative colitis of mild to moderate severity with an Ulcerative Colitis Disease Activity Index (UCDAI) \<or= 10 according to Sutherland * Females of child-bearing potential must have had a serum pregnancy test performed at the Final Visit of the parent study, and must use an acceptable contraceptive method throughout the treatment period. Female subjects must also not be actively breast-feeding through the entire study period. * Ability to comprehend the full nature and purpose of the study, including possible risks and side effects * Ability to co-operate with the investigator and to comply with the requirements of the entire study
Exclusion criteria
* Did not complete study CB-01-02/01 * Achieved clinical remission in study CB-01-02/01 * Patients with severe ulcerative colitis (UCDAI \>10) * Patients with infectious colitis * Evidence or history of toxic megacolon * Severe anemia, leucopenia, or granulocytopenia * Use of immunosuppressive agents in the last 8 weeks before the study * use of anti-tumor necrosis factor alpha agents in the last three months * Concomitant use of any rectal preparation for the treatment of ulcerative colitis * Concomitant use of antibiotics * Concurrent use of cytochrome P-450 3A4 (CYP3A4) inducers and CYP3A4 inhibitors. * Patients with verified, presumed of expected pregnancy or ongoing lactation * Patients with liver cirrhosis, or evident hepatic or renal disease or insufficiency and/or severe impairment of the bio-humoral parameters (i.e., 2x upper limit of normal for alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, or creatinine) * Patients with severe disease(s) in other organs of systems * Patients with local of systemic complications of other pathological states requiring a therapy with corticosteroids and/or immunosuppressive agents * Patients diagnosed with Type 1 diabetes * Patients diagnosed with or with a family history of glaucoma * Patients with known hepatitis B, hepatitis C, or with human immunodeficiency virus (HIV), according to the local privacy policy * Any other medical condition that in the principal investigator's opinion would make the administration of the study drug or study procedures hazardous to the subject or obscure the interpretation of adverse events
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Patients Achieving Clinical Remission | At the end of the 8 week treatment period | The primary efficacy endpoint is clinical remission at 8 weeks, defined as a Ulcerative Colitis Disease Activity Index score of \< or = 1 with a score of 0 for both rectal bleeding and stool frequency, and \> or = 1 point reduction from baseline in endoscopy score, without any sign of mucosal friability (a score of 0 for mucosal appearance). The UCDAI has 4 components. Each component is scored on scale of 0 to 3 (total maximum \[worst\] score = 12). Definitions of component scores are as follows: stool frequency: 0 = normal frequency, 1 = 1 - 2 stools per day greater than normal frequency, 2 = 3 - 4 stools per day greater than normal frequency, and 3 = \> 4 stools per day greater than normal frequency; rectal bleeding: 0 = none, 1 = streaks of blood, 2 = obvious blood, 3 = mostly blood; physician's rating of disease activity: 0 = normal, 1 = mild, 2 = moderate, 3 = severe; mucosal appearance: 0 = normal, 1 = mild friability, 2 = moderate friability, 3 = exudation, spontaneous bleeding. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Secondary Efficacy Endpoint is Clinical Improvement | After 8 weeks treatment period | The secondary efficacy endpoint is clinical improvement, defined as a drop in the Ulcerative Colitis Disease Activity Index score of \> or = 3 points from baseline. |
| Safety Evaluations: the Numbers of Patients Who Experience Serious Adverse Events (SAEs) or Other Nonserious Adverse Events (AEs) During the Course of the Study. | Throughout the 8 week treatment period | Safety will be assessed by evaluating SAEs and AEs. The outcome measure data are the numbers of patients who experienced SAEs or other nonserious AEs. |
| Endoscopic Improvement | 8 weeks | Greater or equal to a 1 point improvement in the mucosal appearance subscore of the ulcerative colitis disease activity index (UCDAI), from baseline to week 8. The UCDAI mucosal appearance subscore is graded as follows: 0 = normal, 1 = mild friability, 2 = moderate friability, 3 = exudation, spontaneous bleeding. |
Countries
India
Participant flow
Recruitment details
Recruited from February 2010 to July 2010
Pre-assignment details
Patient had to have failed to achieve clinical remission in parent study CB-01-02/01. One of the 61 enrolled patients did not receive study drug. Therefore, 60 patients were evaluable for safety and efficacy analyses.
Participants by arm
| Arm | Count |
|---|---|
| Budesonide Budesonide-MMX 9 mg tablet
Budesonide : One Budesonide-MMX 9 mg tablet will be taken in the morning after breakfast for 8 weeks. | 60 |
| Total | 60 |
Baseline characteristics
| Characteristic | Budesonide |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 60 Participants |
| Age, Continuous | 40.3 years STANDARD_DEVIATION 11.41 |
| Region of Enrollment India | 60 participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 29 / 60 |
| serious Total, serious adverse events | 2 / 60 |
Outcome results
Primary
The Percentage of Patients Achieving Clinical Remission
The primary efficacy endpoint is clinical remission at 8 weeks, defined as a Ulcerative Colitis Disease Activity Index score of \< or = 1 with a score of 0 for both rectal bleeding and stool frequency, and \> or = 1 point reduction from baseline in endoscopy score, without any sign of mucosal friability (a score of 0 for mucosal appearance). The UCDAI has 4 components. Each component is scored on scale of 0 to 3 (total maximum \[worst\] score = 12). Definitions of component scores are as follows: stool frequency: 0 = normal frequency, 1 = 1 - 2 stools per day greater than normal frequency, 2 = 3 - 4 stools per day greater than normal frequency, and 3 = \> 4 stools per day greater than normal frequency; rectal bleeding: 0 = none, 1 = streaks of blood, 2 = obvious blood, 3 = mostly blood; physician's rating of disease activity: 0 = normal, 1 = mild, 2 = moderate, 3 = severe; mucosal appearance: 0 = normal, 1 = mild friability, 2 = moderate friability, 3 = exudation, spontaneous bleeding.
Time frame: At the end of the 8 week treatment period
Population: All patients who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Budesonide | The Percentage of Patients Achieving Clinical Remission | 25 percentage of patients |
Secondary
Endoscopic Improvement
Greater or equal to a 1 point improvement in the mucosal appearance subscore of the ulcerative colitis disease activity index (UCDAI), from baseline to week 8. The UCDAI mucosal appearance subscore is graded as follows: 0 = normal, 1 = mild friability, 2 = moderate friability, 3 = exudation, spontaneous bleeding.
Time frame: 8 weeks
Population: All patients who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Budesonide | Endoscopic Improvement | 40 percentage of patients |
Secondary
Safety Evaluations: the Numbers of Patients Who Experience Serious Adverse Events (SAEs) or Other Nonserious Adverse Events (AEs) During the Course of the Study.
Safety will be assessed by evaluating SAEs and AEs. The outcome measure data are the numbers of patients who experienced SAEs or other nonserious AEs.
Time frame: Throughout the 8 week treatment period
Population: All patients who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Budesonide | Safety Evaluations: the Numbers of Patients Who Experience Serious Adverse Events (SAEs) or Other Nonserious Adverse Events (AEs) During the Course of the Study. | Serious Adverse Events | 2 participants |
| Budesonide | Safety Evaluations: the Numbers of Patients Who Experience Serious Adverse Events (SAEs) or Other Nonserious Adverse Events (AEs) During the Course of the Study. | Other non-serious adverse events | 29 participants |
Secondary
The Secondary Efficacy Endpoint is Clinical Improvement
The secondary efficacy endpoint is clinical improvement, defined as a drop in the Ulcerative Colitis Disease Activity Index score of \> or = 3 points from baseline.
Time frame: After 8 weeks treatment period
Population: All patients who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Budesonide | The Secondary Efficacy Endpoint is Clinical Improvement | 26.7 percentage of patients |