Trial Outcomes & Findings for Dose Escalation and Remission (DEAR) (NCT NCT00652145)

NCT ID: NCT00652145

Last Updated: 2015-05-05

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 119 participants
• Primary outcome timeframe: 6 weeks after randomization
• Results posted on: 2015-05-05

Participant Flow

We screened 150 patients and enrolled 119 patients with UC in remission on the basis of SCCAI score. 58 patients had baseline fecal calprotectin(FC) <50 µg/g. These patients were followed in an observational arm. 61 had FC >= 50 µg/g,whose current mesalamine dose <3g/day. See preassignment details.

Among 61 pts with FC >=50 µg/g at week 0, 26 were taking non-MMX mesalamine at baseline and switched to MMX mesalamine 2.4g/day. Of these, by week 6, 2 had a repeat FC <50 µg/g, 3 had a flare of UC and 4 were noncompliant with study protocol or no longer interested in participating. The remaining 52 patients were included in the randomized trial.

Participant milestones

Measure	Increase Dose of Mesalamine Increase dose of mesalamine by 2.4gm per day over baseline dose for six weeks	Maintain Baseline Mesalamine Dose Maintain baseline mesalamine dose for six weeks
Overall Study STARTED	26	26
Overall Study COMPLETED	26	26
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Dose Escalation and Remission (DEAR)

Baseline characteristics by cohort

Measure	Increase Mesalamine Dose n=26 Participants Participants were randomized to increase dose of mesalamine by 2.4 gm per day over their baseline dose	Maintain Mesalamine Dose n=26 Participants Participants were randomized to maintain their baseline mesalamine dose	Total n=52 Participants Total of all reporting groups
Age, Continuous	43.8 years n=5 Participants	48.8 years n=7 Participants	46.5 years n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	13 Participants n=7 Participants	24 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	13 Participants n=7 Participants	28 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) White	22 Participants n=5 Participants	21 Participants n=7 Participants	43 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	26 participants n=5 Participants	26 participants n=7 Participants	52 participants n=5 Participants
Tobacco use Current	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants
Tobacco use Prior	6 participants n=5 Participants	8 participants n=7 Participants	14 participants n=5 Participants
Tobacco use Never	20 participants n=5 Participants	16 participants n=7 Participants	36 participants n=5 Participants
Extent of disease Proctitis	8 participants n=5 Participants	2 participants n=7 Participants	10 participants n=5 Participants
Extent of disease Left-sided	9 participants n=5 Participants	12 participants n=7 Participants	21 participants n=5 Participants
Extent of disease Extensive	9 participants n=5 Participants	11 participants n=7 Participants	20 participants n=5 Participants
Extent of disease Other	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Median duration of UC	11.9 years n=5 Participants	6.5 years n=7 Participants	8.9 years n=5 Participants
Median of duration of remission at baseline	0.3 years n=5 Participants	0.5 years n=7 Participants	0.4 years n=5 Participants
Median fecal calprotectin immediately before randomization	174 µg/g n=5 Participants	214 µg/g n=7 Participants	195 µg/g n=5 Participants
Currrent oral mesalamine Non-MMX formulation	8 participants n=5 Participants	9 participants n=7 Participants	17 participants n=5 Participants
Currrent oral mesalamine MMX formulation	14 participants n=5 Participants	12 participants n=7 Participants	26 participants n=5 Participants
Currrent oral mesalamine None	4 participants n=5 Participants	5 participants n=7 Participants	9 participants n=5 Participants
Current rectal mesalamine Yes	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Current rectal mesalamine No	24 participants n=5 Participants	24 participants n=7 Participants	48 participants n=5 Participants
Current thiopurine Yes	6 participants n=5 Participants	4 participants n=7 Participants	10 participants n=5 Participants
Current thiopurine No	20 participants n=5 Participants	22 participants n=7 Participants	42 participants n=5 Participants
Prior corticosteroids Yes	11 participants n=5 Participants	17 participants n=7 Participants	28 participants n=5 Participants
Prior corticosteroids No	15 participants n=5 Participants	9 participants n=7 Participants	24 participants n=5 Participants
Prior rectal corticosteroids Yes	6 participants n=5 Participants	7 participants n=7 Participants	13 participants n=5 Participants
Prior rectal corticosteroids No	20 participants n=5 Participants	19 participants n=7 Participants	39 participants n=5 Participants
Prior cyclosporine Yes	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Prior cyclosporine No	26 participants n=5 Participants	25 participants n=7 Participants	51 participants n=5 Participants
Prior anti-tumor necrosis factor agent Yes	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Prior anti-tumor necrosis factor agent No	24 participants n=5 Participants	26 participants n=7 Participants	50 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 weeks after randomization

Outcome measures

Measure	Increase Mesalamine Dose by 2.4g/Day n=26 Participants Increase dose of mesalamine by 2.4 gm per day mesalamine: Increase dose by 2.4gm per day over baseline dose	Maintain Mesalmine Dose n=26 Participants Maintain current mesalamine dose at 2.4 g/day
Fecal Calprotectin Level <50µg/g	7 participants	1 participants

SECONDARY outcome

Timeframe: at 6 weeks after randomization

Population: 38 participants with baseline FC\>=100ug/g

Outcome measures

Measure	Increase Mesalamine Dose by 2.4g/Day n=19 Participants Increase dose of mesalamine by 2.4 gm per day mesalamine: Increase dose by 2.4gm per day over baseline dose	Maintain Mesalmine Dose n=19 Participants Maintain current mesalamine dose at 2.4 g/day
Fecal Calprotectin Level <100 µg/g	10 participants	3 participants

SECONDARY outcome

Timeframe: at 6 weeks after randomization

Population: 25 participants with baseline FC\>=200ug/g

Outcome measures

Measure	Increase Mesalamine Dose by 2.4g/Day n=13 Participants Increase dose of mesalamine by 2.4 gm per day mesalamine: Increase dose by 2.4gm per day over baseline dose	Maintain Mesalmine Dose n=12 Participants Maintain current mesalamine dose at 2.4 g/day
Fecal Calprotectin <200 µg/g	10 participants	2 participants

Adverse Events

Increase Dose of Mesalamine

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Maintain Baseline Mesalamine Dose

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Increase Dose of Mesalamine n=26 participants at risk Increase dose of mesalamine by 2.4gm per day over baseline dose for six weeks	Maintain Baseline Mesalamine Dose n=26 participants at risk Maintain baseline mesalamine dose for six weeks
Gastrointestinal disorders Abdominal pain	0.00% 0/26 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis	3.8% 1/26 • Number of events 1 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis
Skin and subcutaneous tissue disorders acne	0.00% 0/26 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis	3.8% 1/26 • Number of events 1 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis
Gastrointestinal disorders blood in stool	3.8% 1/26 • Number of events 1 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis	7.7% 2/26 • Number of events 2 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis
Gastrointestinal disorders Constipation	0.00% 0/26 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis	3.8% 1/26 • Number of events 1 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis
Gastrointestinal disorders diarrhea	11.5% 3/26 • Number of events 3 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis	3.8% 1/26 • Number of events 1 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis
Gastrointestinal disorders Bloating	7.7% 2/26 • Number of events 2 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis	0.00% 0/26 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis
General disorders dizziness	3.8% 1/26 • Number of events 1 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis	0.00% 0/26 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis
General disorders Fatigue	3.8% 1/26 • Number of events 1 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis	0.00% 0/26 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis
Infections and infestations Fever	3.8% 1/26 • Number of events 1 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis	0.00% 0/26 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis
Gastrointestinal disorders Flatulence	3.8% 1/26 • Number of events 1 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis	3.8% 1/26 • Number of events 1 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis
Infections and infestations Fungal infection	3.8% 1/26 • Number of events 1 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis	0.00% 0/26 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis
General disorders headache	3.8% 1/26 • Number of events 1 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis	0.00% 0/26 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis
Blood and lymphatic system disorders iron deficiency anemia	3.8% 1/26 • Number of events 1 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis	0.00% 0/26 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis
Eye disorders itchy eyes	3.8% 1/26 • Number of events 1 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis	0.00% 0/26 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis
Cardiac disorders Palpitations	3.8% 1/26 • Number of events 1 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis	0.00% 0/26 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis
Infections and infestations Upper respiratory infection	3.8% 1/26 • Number of events 1 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis	3.8% 1/26 • Number of events 1 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis
Infections and infestations Urinary tract infection	3.8% 1/26 • Number of events 1 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis	0.00% 0/26 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis
General disorders Vitamin B12 deficiency	3.8% 1/26 • Number of events 1 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis	0.00% 0/26 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis
Gastrointestinal disorders Worsening Colitis	3.8% 1/26 • Number of events 1 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis	0.00% 0/26 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis
General disorders Lower back pain	0.00% 0/26 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis	3.8% 1/26 • Number of events 1 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis
Gastrointestinal disorders increase mucous	0.00% 0/26 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis	3.8% 1/26 • Number of events 1 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis
Eye disorders Dry eyes	0.00% 0/26 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis	3.8% 1/26 • Number of events 1 Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis

Additional Information

James D. Lewis, MD, MSCE

University of Pennsylvania

Phone: 215-573-5137

Email: lewisjd@mail.med.upenn.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place