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

Ulcerative Colitis Clinical Trial

Official title:

A Study to Evaluate the Pharmacokinetics of Adalimumab in Combination With Methotrexate for the Treatment of Patients With Ulcerative Colitis

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01716039
• Other study ID #: RP1204
• Status: Terminated
• Phase: Phase 2
• Start date: June 2013
• Est. completion date: July 18, 2016

Study information

• Verified date: June 2021
• Source: Alimentiv Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Assess the body's reaction to dose-response relationship for the adalimumab/Methotrexate interaction in subjects with moderately to severely active ulcerative colitis.

Description:

Assess the Pharmacokinetic dose-response relationship for the adalimumab/Methotrexate interaction in subjects with moderately to severely active UC.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 22
• Est. completion date: July 18, 2016
• Est. primary completion date: July 18, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Male or non-pregnant, non-lactating females. Females of child bearing potential must have a negative serum pregnancy test prior to randomization, and must use a hormonal (oral, implantable or injectable) or barrier method of birth control throughout the study. Females unable to bear children must have documentation of such in the source records (i.e., tubal ligation, hysterectomy, or post-menopausal [defined as a minimum of one year since the last menstrual period]).

• Diagnosis of UC confirmed by established criteria, regardless of disease duration.

• Moderate to severely active UC, defined by a modified Mayo Score =6, with confirmed endoscopic activity by central reader (Mayo endoscopic subscore =2).

• Require initiation with adalimumab for induction of remission.

• Ability of subject to swallow study drug capsules.

• Ability of subject to participate fully in all aspects of this clinical trial.

• Written informed consent must be obtained and documented.

Exclusion Criteria:

• Prior treatment with a TNF antagonist or biological therapy.

• Prior treatment with MTX.

• Disease limited to the rectum (proctitis).

• Documented presence of antibodies against adalimumab.

• Contraindication for anti-TNF or MTX therapy.

• Contraindication for endoscopy.

• Ostomy.

• Planned surgery.

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• MTX 12.5
once weekly oral dosing with MTX 12.5 mg (n=40) two weeks prior to the initiation of adalimumab. Randomization will be stratified by disease activity (modified Mayo Score =9 or >9). Subjects will receive 18 weekly doses of MTX in addition to doses of adalimumab
• MTX 25
once weekly oral dosing with MTX 25 mg (n=40) two weeks prior to the initiation of adalimumab. Randomization will be stratified by disease activity (modified Mayo Score =9 or >9). Subjects will receive 18 weekly doses of MTX in addition to doses of adalimumab
• Adalimumab
Subjects will receive 18 weekly doses of adalimumab

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Alimentiv Inc.	Abbott

References & Publications (4)

Baert F, Noman M, Vermeire S, Van Assche G, D' Haens G, Carbonez A, Rutgeerts P. Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease. N Engl J Med. 2003 Feb 13;348(7):601-8. — View Citation

Reinisch W, Sandborn WJ, Hommes DW, D'Haens G, Hanauer S, Schreiber S, Panaccione R, Fedorak RN, Tighe MB, Huang B, Kampman W, Lazar A, Thakkar R. Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial. Gut. 2011 Jun;60(6):780-7. doi: 10.1136/gut.2010.221127. Epub 2011 Jan 5. — View Citation

Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005 Dec 8;353(23):2462-76. Erratum in: N Engl J Med. 2006 May 18;354(20):2200. — View Citation

Rutgeerts P, Van Assche G, Sandborn WJ, Wolf DC, Geboes K, Colombel JF, Reinisch W; EXTEND Investigators, Kumar A, Lazar A, Camez A, Lomax KG, Pollack PF, D'Haens G. Adalimumab induces and maintains mucosal healing in patients with Crohn's disease: data from the EXTEND trial. Gastroenterology. 2012 May;142(5):1102-1111.e2. doi: 10.1053/j.gastro.2012.01.035. Epub 2012 Feb 8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in the Modified Baron Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups	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	Baseline up to Week 18
Secondary	Change in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups.	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	Baseline up to Week 18