Trial Outcomes & Findings for Pharmacokinetics of Adalimumab With Methotrexate for Treatment of Patients With Ulcerative Colitis (UC) (NCT NCT01716039)

Last Updated: 2021-06-23

Results Overview

The modified Baron score is scored on a 0-4 scale that evaluates friability, vascular pattern, bleeding and ulceration on a 5-point grading scale with a higher score indicating more severe disease activity. The mean change and 95% CI are based on least square means from the analysis of covariance

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

22 participants

Primary outcome timeframe

Baseline up to Week 18

Results posted on

2021-06-23

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Participants randomized to receive placebo at Week 0 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks Adalimumab: 18 weekly doses of adalimumab	MTX 12.5 mg Participants randomized to receive Methotrexate 12.5 mg at Week 0 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks Adalimumab: 18 weekly doses of adalimumab	MTX 25 mg Participants randomized to receive Methotrexate 25.0 mg at Week 0 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks Adalimumab: 18 weekly doses of adalimumab
Overall Study STARTED	4	8	10
Overall Study COMPLETED	3	6	8
Overall Study NOT COMPLETED	1	2	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacokinetics of Adalimumab With Methotrexate for Treatment of Patients With Ulcerative Colitis (UC)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=4 Participants Participants randomized to receive placebo at Week 0 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks Adalimumab: 18 weekly doses of adalimumab	MTX 12.5 mg n=8 Participants Participants randomized to receive Methotrexate 12.5 mg at Week 0 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks Adalimumab:18 weekly doses of adalimumab	MTX 25 mg n=10 Participants Participants randomized to receive Methotrexate 25.0 mg at Week 00 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks Adalimumab: 18 weekly doses of adalimumab	Total n=22 Participants Total of all reporting groups
Age, Continuous	41.9 years STANDARD_DEVIATION 14.6 • n=5 Participants	46.2 years STANDARD_DEVIATION 13.7 • n=7 Participants	48.5 years STANDARD_DEVIATION 13.5 • n=5 Participants	46.5 years STANDARD_DEVIATION 13.3 • n=4 Participants
Sex/Gender, Customized Male	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants	14 Participants n=4 Participants
Sex/Gender, Customized Female	0 Participants n=5 Participants	5 Participants n=7 Participants	3 Participants n=5 Participants	8 Participants n=4 Participants
Disease Duration (Years)	10.8 years STANDARD_DEVIATION 8.0 • n=5 Participants	5.1 years STANDARD_DEVIATION 3.7 • n=7 Participants	7.0 years STANDARD_DEVIATION 9.3 • n=5 Participants	7.0 years STANDARD_DEVIATION 7.4 • n=4 Participants
Weight	75.0 kg STANDARD_DEVIATION 15.3 • n=5 Participants	75.5 kg STANDARD_DEVIATION 15.2 • n=7 Participants	89.6 kg STANDARD_DEVIATION 20.5 • n=5 Participants	81.8 kg STANDARD_DEVIATION 18.5 • n=4 Participants
C-Reactive protein (CRP)	6.6 mg/L STANDARD_DEVIATION 3.9 • n=5 Participants	5.2 mg/L STANDARD_DEVIATION 2.7 • n=7 Participants	15.1 mg/L STANDARD_DEVIATION 16.1 • n=5 Participants	9.9 mg/L STANDARD_DEVIATION 11.8 • n=4 Participants
Fecal Calprotectin	606.7 ug/g STANDARD_DEVIATION 566.6 • n=5 Participants	675.8 ug/g STANDARD_DEVIATION 431.6 • n=7 Participants	545.2 ug/g STANDARD_DEVIATION 362.0 • n=5 Participants	603.7 ug/g STANDARD_DEVIATION 400.1 • n=4 Participants
Mayo Clinic Score	9.0 units on a scale STANDARD_DEVIATION 1.2 • n=5 Participants	8.6 units on a scale STANDARD_DEVIATION 2.1 • n=7 Participants	8.7 units on a scale STANDARD_DEVIATION 2.1 • n=5 Participants	8.7 units on a scale STANDARD_DEVIATION 1.9 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline up to Week 18

Outcome measures

Outcome measures
Measure	Placebo n=4 Participants Participants randomized to receive placebo at Week 0 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks. Adalimumab: 18 weekly doses of adalimumab	MTX 12.5mg n=8 Participants Participants randomized to receive Methotrexate 12.5 mg at Week 0 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks. Adalimumab: 18 weekly doses of adalimumab	MTX 25 mg n=10 Participants Participants randomized to receive Methotrexate 25.0 mg at Week 0 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks Adalimumab: 18 weekly doses of adalimumab
Change in the Modified Baron Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups	0.7 score on a scale Standard Deviation 1.2	1.1 score on a scale Standard Deviation 1.6	0.9 score on a scale Standard Deviation 1.8

SECONDARY outcome

Timeframe: Baseline up to Week 18

UCEIS is a simple scoring tool that contains3 items (vascular pattern, bleeding, and ulceration). The UCEIS scores 3 endoscopic items: vascular pattern (ranges 0-2 points), bleeding (ranges 0-3 points), and the presence of ulcers and erosions (ranges 0-3 points).The total UCEIS is calculated by adding up the 3 item scores(range,0-8points), with higher scores representing more severe disease activity. The mean change and 95% CI are based on least square means from the analysis of covariance

Outcome measures

Outcome measures
Measure	Placebo n=4 Participants Participants randomized to receive placebo at Week 0 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks. Adalimumab: 18 weekly doses of adalimumab	MTX 12.5mg n=8 Participants Participants randomized to receive Methotrexate 12.5 mg at Week 0 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks. Adalimumab: 18 weekly doses of adalimumab	MTX 25 mg n=10 Participants Participants randomized to receive Methotrexate 25.0 mg at Week 0 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks Adalimumab: 18 weekly doses of adalimumab
Change in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups.	0.5 score on a scale Interval -2.3 to 3.4	0.7 score on a scale Interval -1.0 to 2.4	1.1 score on a scale Interval -0.6 to 2.7

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

MTX 12.5 mg

Serious events: 2 serious events

Other events: 8 other events

Deaths: 0 deaths

MTX 25 mg

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=4 participants at risk Participants randomized to receive placebo at Week 0 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks Adalimumab: 18 weekly doses of adalimumab	MTX 12.5 mg n=8 participants at risk Participants randomized to receive Methotrexate 12.5 mg at Week 0 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks Adalimumab: 18 weekly doses of adalimumab	MTX 25 mg n=10 participants at risk Participants randomized to receive Methotrexate 25.0 mg at Week 00 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks Adalimumab:18 weekly doses of adalimumab
Gastrointestinal disorders Colitis ulcerative	0.00% 0/4 • Through study completion, an average of 18 weeks	12.5% 1/8 • Through study completion, an average of 18 weeks	10.0% 1/10 • Through study completion, an average of 18 weeks
Infections and infestations Urosepsis	0.00% 0/4 • Through study completion, an average of 18 weeks	12.5% 1/8 • Through study completion, an average of 18 weeks	0.00% 0/10 • Through study completion, an average of 18 weeks

Other adverse events

Additional Information

Dr.Jenny Jeyarajah (Sr. Biostatistician)

Alimentiv (Formerly Robarts Clinical Trails)

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The PI of this Investigator-Initiated study had right to prior publication. If PI did not commence publication within 12months after the close of trial at all sites or after PI's manuscript was accepted for publication, whichever occurs first, the Sub-I and Sub-Institution were free to publish or present, provided that the Sub-I provided to the PI any doc. to be submitted for publication at least 30days prior to the planned date of submission for publication to permit a review of the Manuscript.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=4 participants at risk Participants randomized to receive placebo at Week 0 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks Adalimumab: 18 weekly doses of adalimumab	MTX 12.5 mg n=8 participants at risk Participants randomized to receive Methotrexate 12.5 mg at Week 0 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks Adalimumab: 18 weekly doses of adalimumab	MTX 25 mg n=10 participants at risk Participants randomized to receive Methotrexate 25.0 mg at Week 00 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks Adalimumab:18 weekly doses of adalimumab
Gastrointestinal disorders Abdominal pain	0.00% 0/4 • Through study completion, an average of 18 weeks	12.5% 1/8 • Through study completion, an average of 18 weeks	10.0% 1/10 • Through study completion, an average of 18 weeks
Gastrointestinal disorders Colitis ulcerative	25.0% 1/4 • Through study completion, an average of 18 weeks	12.5% 1/8 • Through study completion, an average of 18 weeks	0.00% 0/10 • Through study completion, an average of 18 weeks
Gastrointestinal disorders Dysgeusia	0.00% 0/4 • Through study completion, an average of 18 weeks	12.5% 1/8 • Through study completion, an average of 18 weeks	0.00% 0/10 • Through study completion, an average of 18 weeks
Gastrointestinal disorders Nausea	0.00% 0/4 • Through study completion, an average of 18 weeks	12.5% 1/8 • Through study completion, an average of 18 weeks	0.00% 0/10 • Through study completion, an average of 18 weeks
Infections and infestations Viral upper respiratory tract infection	0.00% 0/4 • Through study completion, an average of 18 weeks	12.5% 1/8 • Through study completion, an average of 18 weeks	10.0% 1/10 • Through study completion, an average of 18 weeks
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/4 • Through study completion, an average of 18 weeks	12.5% 1/8 • Through study completion, an average of 18 weeks	0.00% 0/10 • Through study completion, an average of 18 weeks
Nervous system disorders Headache	25.0% 1/4 • Through study completion, an average of 18 weeks	0.00% 0/8 • Through study completion, an average of 18 weeks	10.0% 1/10 • Through study completion, an average of 18 weeks
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/4 • Through study completion, an average of 18 weeks	0.00% 0/8 • Through study completion, an average of 18 weeks	10.0% 1/10 • Through study completion, an average of 18 weeks
Skin and subcutaneous tissue disorders Contusion	25.0% 1/4 • Through study completion, an average of 18 weeks	0.00% 0/8 • Through study completion, an average of 18 weeks	0.00% 0/10 • Through study completion, an average of 18 weeks
Skin and subcutaneous tissue disorders Rash	25.0% 1/4 • Through study completion, an average of 18 weeks	0.00% 0/8 • Through study completion, an average of 18 weeks	10.0% 1/10 • Through study completion, an average of 18 weeks
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/4 • Through study completion, an average of 18 weeks	12.5% 1/8 • Through study completion, an average of 18 weeks	0.00% 0/10 • Through study completion, an average of 18 weeks
Vascular disorders Pallor	0.00% 0/4 • Through study completion, an average of 18 weeks	0.00% 0/8 • Through study completion, an average of 18 weeks	10.0% 1/10 • Through study completion, an average of 18 weeks
Gastrointestinal disorders Diarrhoea	0.00% 0/4 • Through study completion, an average of 18 weeks	12.5% 1/8 • Through study completion, an average of 18 weeks	0.00% 0/10 • Through study completion, an average of 18 weeks
Gastrointestinal disorders Epigastric discomfort	0.00% 0/4 • Through study completion, an average of 18 weeks	12.5% 1/8 • Through study completion, an average of 18 weeks	0.00% 0/10 • Through study completion, an average of 18 weeks
Gastrointestinal disorders Haematochezia	0.00% 0/4 • Through study completion, an average of 18 weeks	12.5% 1/8 • Through study completion, an average of 18 weeks	0.00% 0/10 • Through study completion, an average of 18 weeks
Gastrointestinal disorders Constipation	0.00% 0/4 • Through study completion, an average of 18 weeks	0.00% 0/8 • Through study completion, an average of 18 weeks	10.0% 1/10 • Through study completion, an average of 18 weeks
Gastrointestinal disorders Vomiting	0.00% 0/4 • Through study completion, an average of 18 weeks	0.00% 0/8 • Through study completion, an average of 18 weeks	10.0% 1/10 • Through study completion, an average of 18 weeks
Gastrointestinal disorders Throat irritation	0.00% 0/4 • Through study completion, an average of 18 weeks	12.5% 1/8 • Through study completion, an average of 18 weeks	0.00% 0/10 • Through study completion, an average of 18 weeks
Infections and infestations Urinary tract infection	0.00% 0/4 • Through study completion, an average of 18 weeks	12.5% 1/8 • Through study completion, an average of 18 weeks	0.00% 0/10 • Through study completion, an average of 18 weeks
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/4 • Through study completion, an average of 18 weeks	0.00% 0/8 • Through study completion, an average of 18 weeks	10.0% 1/10 • Through study completion, an average of 18 weeks
Skin and subcutaneous tissue disorders Erythema nodosum	0.00% 0/4 • Through study completion, an average of 18 weeks	12.5% 1/8 • Through study completion, an average of 18 weeks	0.00% 0/10 • Through study completion, an average of 18 weeks
Eye disorders Eye pain	0.00% 0/4 • Through study completion, an average of 18 weeks	12.5% 1/8 • Through study completion, an average of 18 weeks	0.00% 0/10 • Through study completion, an average of 18 weeks
Eye disorders Ocular hyperaemia	0.00% 0/4 • Through study completion, an average of 18 weeks	12.5% 1/8 • Through study completion, an average of 18 weeks	0.00% 0/10 • Through study completion, an average of 18 weeks
General disorders Asthenia	0.00% 0/4 • Through study completion, an average of 18 weeks	0.00% 0/8 • Through study completion, an average of 18 weeks	10.0% 1/10 • Through study completion, an average of 18 weeks
General disorders Injection site erythema	0.00% 0/4 • Through study completion, an average of 18 weeks	0.00% 0/8 • Through study completion, an average of 18 weeks	10.0% 1/10 • Through study completion, an average of 18 weeks
Metabolism and nutrition disorders Dehydration	0.00% 0/4 • Through study completion, an average of 18 weeks	0.00% 0/8 • Through study completion, an average of 18 weeks	10.0% 1/10 • Through study completion, an average of 18 weeks