(CB-01-02/06) Oral Budesonide-Multi-Matrix System (MMX) 9mg Extended Release Tablets

• Sponsor: Bausch Health Americas, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01100112
• Collaborator: Cosmo Technologies Ltd (Industry)
• Enrollment: 61
• Locations: 15
• Arm: 1
• Duration (Months): 5.9
• Patients Per Site: 4.1
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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]).

Condition or Disease	Intervention/Treatment	Phase
Colitis, Ulcerative	Drug: Budesonide	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 61 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Multicenter, Open-Label Efficacy and Safety Study of Oral Budesonide-MMX 9mg Extended Release Tablets in Patients With Mild to Moderate, Active Ulcerative Colitis
• Study Start Date: Feb 1, 2010
• Actual Primary Completion Date: Jul 1, 2010
• Actual Study Completion Date: Aug 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Budesonide Budesonide-MMX 9 mg tablet	Drug: Budesonide; One Budesonide-MMX 9 mg tablet will be taken in the morning after breakfast for 8 weeks.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Santarus Clinical Investigational Site 9001	Andhra Pradesh		India
2	Santarus Clinical Investigational Site 9009	Andhra Pradesh		India
3	Santarus Clinical Investigational Site 9012	Andhra Pradesh		India
4	Santarus Clinical Investigational Site 9016	Andhra Pradesh		India
5	Santarus Clinical Investigational Site 9006	Assam		India
6	Santarus Clinical Investigational Site 9007	Gujarat		India
7	Santarus Clinical Investigational Site 9004	Karnataka		India
8	Santarus Clinical Investigational Site 9015	Karnataka		India
9	Santarus Clinical Investigational Site 9003	Kerala		India
10	Santarus Clinical Investigational Site 9002	Maharashtra		India
11	Santarus Clinical Investigational Site 9008	Maharashtra		India
12	Santarus Clinical Investigational Site 9013	Maharashtra		India
13	Santarus Clinical Investigational Site 9018	Rajasthan		India
14	Santarus Clinical Investigational Site 9005	Tamil Nadu		India
15	Santarus Clinical Investigational Site 9014	Uttar Pradesh		India

Sponsors and Collaborators

• Bausch Health Americas, Inc.
• Cosmo Technologies Ltd

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bausch Health Americas, Inc.
• ClinicalTrials.gov Identifier: NCT01100112
• Other Study ID Numbers: CB-01-02/06
• First Posted: Apr 8, 2010
• Last Update Posted: Nov 29, 2019
• Last Verified: Nov 1, 2019

• Keywords provided by Bausch Health Americas, Inc.: ulcerative colitis; Budesonide
• Additional relevant MeSH terms: Colitis; Colitis, Ulcerative; Ulcer; Budesonide

Study Results

Participant Flow

Recruitment Details	Recruited from February 2010 to July 2010
Pre-assignment Detail	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.

Arm/Group Title	Budesonide
Arm/Group Description	Budesonide-multi-matrix system (MMX) 9 mg tablet Budesonide : One Budesonide-MMX 9 mg tablet will be taken in the morning after breakfast for 8 weeks.
Period Title: Overall Study
STARTED	60
COMPLETED	52
NOT COMPLETED	8

Baseline Characteristics

Arm/Group Title	Budesonide
Arm/Group Description	Budesonide-MMX 9 mg tablet Budesonide : One Budesonide-MMX 9 mg tablet will be taken in the morning after breakfast for 8 weeks.
Overall Participants	60
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	60 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.3 (11.41)
Sex: Female, Male (Count of Participants)
Female	19 31.7%
Male	41 68.3%
Region of Enrollment (participants) [Number]
India	60 100%

Outcome Measures

1. Primary Outcome

Title	The Percentage of Patients Achieving Clinical Remission
Description	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

Outcome Measure Data

Analysis Population Description

All patients who received at least 1 dose of study drug.

Arm/Group Title	Budesonide
Arm/Group Description	Budesonide-MMX 9 mg tablet Budesonide : One Budesonide-MMX 9 mg tablet will be taken in the morning after breakfast for 8 weeks.
Measure Participants	60
Number [percentage of patients]	25

2. Secondary Outcome

Title	The Secondary Efficacy Endpoint is Clinical Improvement
Description	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

Outcome Measure Data

Analysis Population Description

All patients who received at least 1 dose of study drug.

Arm/Group Title	Budesonide
Arm/Group Description	Budesonide-MMX 9 mg tablet Budesonide : One Budesonide-MMX 9 mg tablet will be taken in the morning after breakfast for 8 weeks.
Measure Participants	60
Number [percentage of patients]	26.7

3. Secondary Outcome

Title	Safety Evaluations: the Numbers of Patients Who Experience Serious Adverse Events (SAEs) or Other Nonserious Adverse Events (AEs) During the Course of the Study.
Description	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

Outcome Measure Data

Analysis Population Description

All patients who received at least 1 dose of study drug.

Arm/Group Title	Budesonide
Arm/Group Description	Budesonide-MMX 9 mg tablet Budesonide : One Budesonide-MMX 9 mg tablet will be taken in the morning after breakfast for 8 weeks.
Measure Participants	60
Serious Adverse Events	2 3.3%
Other non-serious adverse events	29 48.3%

4. Secondary Outcome

Title	Endoscopic Improvement
Description	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

Outcome Measure Data

Analysis Population Description

All patients who received at least one dose of study drug.

Arm/Group Title	Budesonide
Arm/Group Description	Budesonide-MMX 9 mg tablet Budesonide : One Budesonide-MMX 9 mg tablet will be taken in the morning after breakfast for 8 weeks.
Measure Participants	60
Number [percentage of patients]	40

Adverse Events

Time Frame	56 day ± 2 day (study duration) + 30 day safety followup period.
Arm/Group Title	Budesonide
Arm/Group Description	Budesonide-MMX 9 mg tablet Budesonide : One Budesonide-MMX 9 mg tablet will be taken in the morning after breakfast for 8 weeks.
All Cause Mortality
	Budesonide
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Budesonide
	Affected / at Risk (%)	# Events
Total	2/60 (3.3%)
Gastrointestinal disorders
Colitis ulcerative	1/60 (1.7%)	1
Reproductive system and breast disorders
Endometrial hyperplasia	1/60 (1.7%)	1
Other (Not Including Serious) Adverse Events
	Budesonide
	Affected / at Risk (%)	# Events
Total	29/60 (48.3%)
Endocrine disorders
Cushingoid	3/60 (5%)	3
Gastrointestinal disorders
Diarrhoea	2/60 (3.3%)	2
General disorders
Asthenia	2/60 (3.3%)	2
Pyrexia	2/60 (3.3%)	2
Infections and infestations
Urinary tract infection	7/60 (11.7%)	7
Investigations
Blood cortisol decreased	9/60 (15%)	9
Blood glucose decreased	2/60 (3.3%)	2
Blood potassium increased	2/60 (3.3%)	2

Limitations/Caveats

This was an open label study. There was no reference therapy for statistical analysis.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.