Proctitis, Proctosigmoiditis
Conditions
Keywords
Open-label, Proctitis, Proctosigmoiditis, Ulcerative, Salix, Budesonide foam, Budesonide, Rectal, Gastrointestinal, Colitis, UC, UP, UPS, Additional relevant MeSH terms:, Proctocolitis, Ulcer, Colitis, Ulcerative, Gastroenteritis, Gastrointestinal Diseases, Digestive System Diseases, Rectal Diseases, Intestinal Diseases, Colonic Diseases, Sigmoid Diseases, Pathologic Processes, Inflammatory Bowel Diseases, Bronchodilator Agents, Autonomic Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Pharmacologic Actions, Anti-Asthmatic Agents, Respiratory System Agents, Therapeutic Uses, Glucocorticoids, Hormones, Hormones, Hormone Substitutes and Hormone Antagonists, Anti-inflammatory Agents
Brief summary
The purpose of this study is to evaluate safety and tolerability of cyclically-dosed rectal budesonide foam in participants with active ulcerative proctitis (UP) or ulcerative proctosigmoiditis (UPS).
Detailed description
This is a Phase 3, multicenter, open-label study in participants who previously participated in a Salix-sponsored budesonide rectal foam study for the treatment of UP or UPS. Approximately 300 participants were to be enrolled into the study and receive budesonide foam cyclically for 6 weeks (twice a day \[BID\] for 2 weeks and once daily \[QD\] for 4 weeks). The study was to continue until regulatory approval of budesonide foam occurred or the sponsor decided to terminate the study.
Interventions
DRUGBudesonide Foam
Topical
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
* Male or non-pregnant, non-breast-feeding females ≥18 years old. * Participant was previously diagnosed with active mild to moderate UP/UPS and was currently experiencing symptoms of active UP/UPS disease after having completed participation in Salix's BUCF3001 (NCT01008410) or BUCF3002 (NCT01008423) study. * Willingness to undergo sigmoidoscopy.
Exclusion criteria
* Active systemic, ocular, or cutaneous infection (for example, parasitic, fungal, amoebic, viral, or bacterial disease). * History of sclerosing cholangitis, cirrhosis, or hepatic impairment, including chronic hepatitis of any etiology. * Participant took systemic, inhaled, oral, topical, or rectal corticosteroids (other than budesonide rectal foam) within 7 days of starting a treatment cycle. * Participant took ketoconazole and other potent CYP3A4 inhibitors within 7 days of starting a treatment cycle. * Participant took diuretics with cardiac glycosides. * Unstable significant cardiovascular, hepatic, renal, endocrine, neurologic, or pulmonary disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number Of Participants Reporting A Non-serious Adverse Event And A Serious Adverse Event | Baseline through up to Cycle 8 (Cycle=6 weeks) | A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinically Notable Laboratory Parameters | Baseline and Cycle 4 (Cycle=6 weeks) | Clinically notable laboratory parameters are defined as clinical laboratory values outside the reference range. Reference ranges for the clinical notable laboratory parameters: Aspartate Aminotransferase - 0-37 microliters (U/L); Alanine Aminotransferase - 0-47 U/L; Lactate Dehydrogenase - 110-250 U/L. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module. |
| Changes In Baseline In Mean Morning (AM) Fasting Serum Cortisol Levels | Baseline of Cycles 1-4, Day 15 and Day 42 of Cycles 1-4 (Cycle=6 weeks) | Fasting cortisol levels were evaluated, and cortisol was taken in the morning (AM cortisol) approximately 2 to 4 hours after waking. Data for cycles with more than 15 participants at the Cycle Baseline is reported. |
| Number of Participants With A Clinically Notable Physical Examination Finding Since Baseline | Baseline through up to Cycle 8 (Cycle=6 weeks) | A full or complete physical examination was performed at the Study Baseline. This physical examination included (but was not limited to): general appearance, head, ear, eyes, nose, throat, respiratory, cardiovascular, gastrointestinal, abdominal, neurological, lymphatic, dermatologic, and musculoskeletal. A symptom-directed physical examination was performed on Visit 2 (Day 1) to Visit 4 (Day 42) per Cycle (at the Investigator's discretion) and as needed for unscheduled clinic visits. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module. |
Countries
United States
Participant flow
Pre-assignment details
Each participant received study drug for 6 weeks per cycle for up to 8 cycles and underwent a 48-hour study drug washout period between each cycle. Study was terminated for non-safety reasons when Sponsor felt sufficient long-term safety data was obtained.
Participants by arm
| Arm | Count |
|---|---|
| Budesonide Foam Participants administered topical rectal budesonide foam at 2 mg/25 mL BID (morning and 12 hours later) for 2 weeks followed by 2 mg/25 mL QD (in the evenings) for 4 weeks for up to 8 cycles. After Cycle 1, participants needed to qualify to be able to participate in subsequent cycles. Participants underwent a 48-hour study drug washout period between each cycle. | 114 |
| Total | 114 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 17 |
| Overall Study | Lack of Efficacy | 8 |
| Overall Study | Lost to Follow-up | 6 |
| Overall Study | No Longer Qualified For Study | 1 |
| Overall Study | Progression Of Disease Past 40 cm | 1 |
| Overall Study | Site Closure | 10 |
| Overall Study | Study Terminated By Sponsor | 50 |
| Overall Study | Withdrawal by Subject | 21 |
Baseline characteristics
| Characteristic | Budesonide Foam |
|---|---|
| Age, Continuous | 44.2 years STANDARD_DEVIATION 12.78 |
| Sex: Female, Male Female | 64 Participants |
| Sex: Female, Male Male | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 66 / 114 |
| serious Total, serious adverse events | 0 / 114 |
Outcome results
Primary
Number Of Participants Reporting A Non-serious Adverse Event And A Serious Adverse Event
A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.
Time frame: Baseline through up to Cycle 8 (Cycle=6 weeks)
Population: All participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Budesonide Foam | Number Of Participants Reporting A Non-serious Adverse Event And A Serious Adverse Event | Non-serious Adverse Event | 66 Participants |
| Budesonide Foam | Number Of Participants Reporting A Non-serious Adverse Event And A Serious Adverse Event | Serious Adverse Event | 0 Participants |
Secondary
Changes In Baseline In Mean Morning (AM) Fasting Serum Cortisol Levels
Fasting cortisol levels were evaluated, and cortisol was taken in the morning (AM cortisol) approximately 2 to 4 hours after waking. Data for cycles with more than 15 participants at the Cycle Baseline is reported.
Time frame: Baseline of Cycles 1-4, Day 15 and Day 42 of Cycles 1-4 (Cycle=6 weeks)
Population: All participants who received at least 1 dose of study drug and with non-missing cortisol value at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Budesonide Foam | Changes In Baseline In Mean Morning (AM) Fasting Serum Cortisol Levels | Cycle 1, Day 15 | -62.7 nanomoles per liter (nmol/L) | Standard Deviation 149.61 |
| Budesonide Foam | Changes In Baseline In Mean Morning (AM) Fasting Serum Cortisol Levels | Cycle 1, Day 42 | 0.9 nanomoles per liter (nmol/L) | Standard Deviation 170.78 |
| Budesonide Foam | Changes In Baseline In Mean Morning (AM) Fasting Serum Cortisol Levels | Cycle 2, Day 15 | -40.1 nanomoles per liter (nmol/L) | Standard Deviation 165.65 |
| Budesonide Foam | Changes In Baseline In Mean Morning (AM) Fasting Serum Cortisol Levels | Cycle 2, Day 42 | -5.8 nanomoles per liter (nmol/L) | Standard Deviation 183.16 |
| Budesonide Foam | Changes In Baseline In Mean Morning (AM) Fasting Serum Cortisol Levels | Cycle 3, Day 15 | -25.5 nanomoles per liter (nmol/L) | Standard Deviation 175.75 |
| Budesonide Foam | Changes In Baseline In Mean Morning (AM) Fasting Serum Cortisol Levels | Cycle 3, Day 42 | -10.4 nanomoles per liter (nmol/L) | Standard Deviation 174.92 |
| Budesonide Foam | Changes In Baseline In Mean Morning (AM) Fasting Serum Cortisol Levels | Cycle 4, Day 15 | -87.8 nanomoles per liter (nmol/L) | Standard Deviation 186.11 |
| Budesonide Foam | Changes In Baseline In Mean Morning (AM) Fasting Serum Cortisol Levels | Cycle 4, Day 42 | -7.1 nanomoles per liter (nmol/L) | Standard Deviation 148.52 |
Secondary
Clinically Notable Laboratory Parameters
Clinically notable laboratory parameters are defined as clinical laboratory values outside the reference range. Reference ranges for the clinical notable laboratory parameters: Aspartate Aminotransferase - 0-37 microliters (U/L); Alanine Aminotransferase - 0-47 U/L; Lactate Dehydrogenase - 110-250 U/L. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.
Time frame: Baseline and Cycle 4 (Cycle=6 weeks)
Population: All participants who received at least 1 dose of study drug and with non-missing clinical laboratory parameter values at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Budesonide Foam | Clinically Notable Laboratory Parameters | Aspartate Aminotransferase, Baseline | 21.7 U/L |
| Budesonide Foam | Clinically Notable Laboratory Parameters | Aspartate Aminotransferase, Cycle 4 | 92.3 U/L |
| Budesonide Foam | Clinically Notable Laboratory Parameters | Alanine Aminotransferase, Baseline | 23.0 U/L |
| Budesonide Foam | Clinically Notable Laboratory Parameters | Alanine Aminotransferase, Cycle 4 | 119.3 U/L |
| Budesonide Foam | Clinically Notable Laboratory Parameters | Lactate Dehydrogenase, Baseline | 154.1 U/L |
| Budesonide Foam | Clinically Notable Laboratory Parameters | Lactate Dehydrogenase, Cycle 4 | 228.5 U/L |
Secondary
Number of Participants With A Clinically Notable Physical Examination Finding Since Baseline
A full or complete physical examination was performed at the Study Baseline. This physical examination included (but was not limited to): general appearance, head, ear, eyes, nose, throat, respiratory, cardiovascular, gastrointestinal, abdominal, neurological, lymphatic, dermatologic, and musculoskeletal. A symptom-directed physical examination was performed on Visit 2 (Day 1) to Visit 4 (Day 42) per Cycle (at the Investigator's discretion) and as needed for unscheduled clinic visits. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.
Time frame: Baseline through up to Cycle 8 (Cycle=6 weeks)
Population: All participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Budesonide Foam | Number of Participants With A Clinically Notable Physical Examination Finding Since Baseline | 17 Participants |