Pharmacokinetics of Adalimumab With Methotrexate for Treatment of Patients With Ulcerative Colitis (UC) - Full Text View

Purpose

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

Condition	Intervention	Phase
Ulcerative Colitis	Drug: MTX 12.5 Drug: MTX 25 Drug: Adalimumab	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Factorial Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	A Study to Evaluate the Pharmacokinetics of Adalimumab in Combination With Methotrexate for the Treatment of Patients With Ulcerative Colitis

Resource links provided by NLM:

Genetics Home Reference related topics: ulcerative colitis

MedlinePlus related topics: Ulcerative Colitis

Drug Information available for: Methotrexate Methotrexate sodium Adalimumab

U.S. FDA Resources

Further study details as provided by University of Western Ontario, Canada:

Primary Outcome Measures:

Pharmacokinetic Analysis (PK) will measure antidrug antibodies (ADAs)and plasma concentrations of adalimumab and methotrexate. [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
PK parameters will include:
- Maximum plasma concentration (Cmax)
- Time to reach Cmax (Tmax)
- Area under the concentration time curve (AUC)
- Elimination rate constant (k) Elimination half-life (t1/2)

Secondary Outcome Measures:

Clinical and Endoscopic Evaluation of the Efficacy of Combination Therapy [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
The primary efficacy outcome will be assessed by comparing the change in the modified Baron score from baseline to the final visit between the treatment groups
Identify covariates [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
To identify covariates (gender, weight, BMI, albumin, TNF, CRP, disease severity, concomitant medications) that might influence the clearance and or disposition of adalimumab
Relationship between PK and efficacy [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
To evaluate the relationship between PK and efficacy (PD)

Estimated Enrollment:	100
Study Start Date:	December 2012
Estimated Study Completion Date:	December 2013
Estimated Primary Completion Date:	June 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: MTX 12.5 Receive once weekly oral dosing with MTX 12.5 mg (n=40) two weeks prior to the initiation of adalimumab 18 weekly doses of MTX and/or placebo in addition to doses of adalimumab	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 Other Name: MTX Drug: Adalimumab Subjects will receive 18 weekly doses of adalimumab Other Name: Humira
Active Comparator: MTX 25 mg Once weekly oral dosing with MTX 25 mg (n=40) two weeks prior to the initiation of adalimumab 18 weekly doses of MTX in addition to doses of adalimumab	Drug: 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 Other Name: MTX Drug: Adalimumab Subjects will receive 18 weekly doses of adalimumab Other Name: Humira
Placebo Comparator: Placebo Once weekly oral dosing with placebo (n=20) two weeks prior to the initiation of adalimumab. Subjects will receive 18 weekly doses of placebo in addition to doses of adalimumab	Drug: Adalimumab Subjects will receive 18 weekly doses of adalimumab Other Name: Humira

Detailed Description:

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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01716039

Sponsors and Collaborators

University of Western Ontario, Canada

Abbott

Investigators

Principal Investigator:

Brian Feagan, MD

Robarts Research Institute - Western University

More Information

Publications:

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.

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. Epub 2012 Feb 8.

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. Epub 2011 Jan 5.

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.

Responsible Party:	University of Western Ontario, Canada
ClinicalTrials.gov Identifier:	NCT01716039 History of Changes
Other Study ID Numbers:	RP1204
Study First Received:	October 15, 2012
Last Updated:	October 25, 2012
Health Authority:	Canada: Health Canada

Keywords provided by University of Western Ontario, Canada:

Moderately to severely active Ulcerative Colitis

Additional relevant MeSH terms:

Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Inflammatory Bowel Diseases
Pathologic Processes
Methotrexate
Adalimumab
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents

Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on May 19, 2013