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

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
Abbott
Information provided by (Responsible Party):
University of Western Ontario, Canada
ClinicalTrials.gov Identifier:
NCT01716039
First received: October 15, 2012
Last updated: March 19, 2014
Last verified: March 2014

October 15, 2012
March 19, 2014
June 2013
November 2015   (final data collection date for primary outcome measure)
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)
Same as current
Complete list of historical versions of study NCT01716039 on ClinicalTrials.gov Archive Site
  • 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)
Same as current
Not Provided
Not Provided
 
Pharmacokinetics of Adalimumab With Methotrexate for Treatment of Patients With Ulcerative Colitis (UC)
A Study to Evaluate the Pharmacokinetics of Adalimumab in Combination With Methotrexate for the Treatment of Patients With Ulcerative Colitis

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

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

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Ulcerative Colitis
  • 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: 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
  • 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
    Interventions:
    • Drug: MTX 12.5
    • Drug: Adalimumab
  • 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
    Interventions:
    • Drug: MTX 25
    • Drug: Adalimumab
  • 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
    Intervention: Drug: Adalimumab

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Enrolling by invitation
100
May 2016
November 2015   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT01716039
RP1204
No
University of Western Ontario, Canada
University of Western Ontario, Canada
Abbott
Principal Investigator: Brian Feagan, MD Robarts Research Institute - Western University
University of Western Ontario, Canada
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP