Trial Outcomes & Findings for The Safety and Tolerability of Budesonide Foam in Participants With Active Ulcerative Proctitis or Proctosigmoiditis (NCT NCT01349673)

NCT ID: NCT01349673

Last Updated: 2019-08-14

Results Overview

A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 114 participants
• Primary outcome timeframe: Baseline through up to Cycle 8 (Cycle=6 weeks)
• Results posted on: 2019-08-14

Participant Flow

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.

Participant milestones

Measure	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.
Overall Study STARTED	114
Overall Study Participants Entered Cycle 1	114
Overall Study Participants Entered Cycle 2	65
Overall Study Participants Entered Cycle 3	41
Overall Study Participants Entered Cycle 4	22
Overall Study Participants Entered Cycle 5	12
Overall Study Participants Entered Cycle 6	5
Overall Study Participants Entered Cycle 7	3
Overall Study Participants Entered Cycle 8	1
Overall Study Received At Least 1 Dose Of Study Drug	114
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	114

Reasons for withdrawal

Measure	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.
Overall Study Progression Of Disease Past 40 cm	1
Overall Study No Longer Qualified For Study	1
Overall Study Site Closure	10
Overall Study Withdrawal by Subject	21
Overall Study Lost to Follow-up	6
Overall Study Adverse Event	17
Overall Study Study Terminated By Sponsor	50
Overall Study Lack of Efficacy	8

Baseline Characteristics

The Safety and Tolerability of Budesonide Foam in Participants With Active Ulcerative Proctitis or Proctosigmoiditis

Baseline characteristics by cohort

Measure	Budesonide Foam n=114 Participants 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.
Age, Continuous	44.2 years STANDARD_DEVIATION 12.78 • n=5 Participants
Sex: Female, Male Female	64 Participants n=5 Participants
Sex: Female, Male Male	50 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline through up to Cycle 8 (Cycle=6 weeks)

Population: All participants who received at least 1 dose of study drug.

A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.

Outcome measures

Measure	Budesonide Foam n=114 Participants 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.
Number Of Participants Reporting A Non-serious Adverse Event And A Serious Adverse Event Non-serious Adverse Event	66 Participants
Number Of Participants Reporting A Non-serious Adverse Event And A Serious Adverse Event Serious Adverse Event	0 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Budesonide Foam n=114 Participants 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.
Clinically Notable Laboratory Parameters Aspartate Aminotransferase, Baseline	21.7 U/L Interval 12.0 to 37.0
Clinically Notable Laboratory Parameters Aspartate Aminotransferase, Cycle 4	92.3 U/L Interval 21.0 to 440.0
Clinically Notable Laboratory Parameters Alanine Aminotransferase, Baseline	23.0 U/L Interval 7.0 to 58.0
Clinically Notable Laboratory Parameters Alanine Aminotransferase, Cycle 4	119.3 U/L Interval 13.0 to 596.0
Clinically Notable Laboratory Parameters Lactate Dehydrogenase, Baseline	154.1 U/L Interval 82.0 to 223.0
Clinically Notable Laboratory Parameters Lactate Dehydrogenase, Cycle 4	228.5 U/L Interval 143.0 to 506.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Budesonide Foam n=114 Participants 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.
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
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
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
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
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
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
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
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 outcome

Timeframe: Baseline through up to Cycle 8 (Cycle=6 weeks)

Population: All participants who received at least 1 dose of study drug.

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.

Outcome measures

Measure	Budesonide Foam n=114 Participants 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.
Number of Participants With A Clinically Notable Physical Examination Finding Since Baseline	17 Participants

Adverse Events

Budesonide Foam

Serious events: 0 serious events

Other events: 66 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Budesonide Foam n=114 participants at risk 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.
Endocrine disorders Adrenal insufficiency	2.6% 3/114 • Baseline through up to Cycle 8 (Cycle=6 weeks)
Gastrointestinal disorders Abdominal pain	7.9% 9/114 • Baseline through up to Cycle 8 (Cycle=6 weeks)
Gastrointestinal disorders Anorectal discomfort	2.6% 3/114 • Baseline through up to Cycle 8 (Cycle=6 weeks)
Gastrointestinal disorders Abdominal pain upper	2.6% 3/114 • Baseline through up to Cycle 8 (Cycle=6 weeks)
Gastrointestinal disorders Colitis ulcerative	2.6% 3/114 • Baseline through up to Cycle 8 (Cycle=6 weeks)
Gastrointestinal disorders Diarrhoea	2.6% 3/114 • Baseline through up to Cycle 8 (Cycle=6 weeks)
Gastrointestinal disorders Haemorrhoids	3.5% 4/114 • Baseline through up to Cycle 8 (Cycle=6 weeks)
Gastrointestinal disorders Nausea	3.5% 4/114 • Baseline through up to Cycle 8 (Cycle=6 weeks)
Gastrointestinal disorders Vomiting	3.5% 4/114 • Baseline through up to Cycle 8 (Cycle=6 weeks)
Infections and infestations Nasopharyngitis	3.5% 4/114 • Baseline through up to Cycle 8 (Cycle=6 weeks)
Investigations Blood cortisol decreased	17.5% 20/114 • Baseline through up to Cycle 8 (Cycle=6 weeks)
Nervous system disorders Headache	7.0% 8/114 • Baseline through up to Cycle 8 (Cycle=6 weeks)
Psychiatric disorders Depression	2.6% 3/114 • Baseline through up to Cycle 8 (Cycle=6 weeks)
Skin and subcutaneous tissue disorders Rash	2.6% 3/114 • Baseline through up to Cycle 8 (Cycle=6 weeks)

Additional Information

Director of Clinical Operations

Bausch Health Companies

Email: Lindsey.Mathew@bauschhealth.com

Results disclosure agreements

• Principal investigator is a sponsor employee Please contact Sponsor directly for additional information.
• Publication restrictions are in place

Restriction type: OTHER