Clinical trial NCT01044498: A Study of Tocilizumab in Combination With an Oral Contraceptive in Patients With Rheumatoid Arthritis
Official title: An Open-label, Multi-center, One Sequence Cross-over Drug Interaction Study to Investigate the Effect of Tocilizumab (TCZ, RO4877533) on the Pharmacokinetics and Pharmacodynamics of an Oral Contraceptive (OC) in Female Patients With Active Rheumatoid Arthritis (RA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2010-01-08
Enrollment: 46
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 44
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This open-label, randomized, cross-over study evaluated the effect of tocilizumab (TCZ) on the pharmacokinetics and pharmacodynamics of a common oral contraceptive (OC) in female patients with active rheumatoid arthritis (RA) and in healthy female volunteers of child bearing age. The RA patients received OC in combination with TCZ, whereas the healthy volunteers received OC only. The RA patients received OC in 3 cycles of 21 days each; TCZ 8 mg/kg was administered once as an intravenous infusion on the first day of Cycle 2. The healthy volunteers received OC for only one 21-day cycle.


Eligibility criteria: Inclusion Criteria:

* Adult patients with child bearing potential, 18-44 years of age.
* Rheumatoid arthritis (RA) for over 6 months duration.
* On oral contraceptive without interruption for at least 3 months with normal cycle control.
* Treatment with disease-modifying anth-rheumatic drugs (DMARD) for at least 12 weeks prior to study start.
* Body weight \< 150 kg.

Exclusion Criteria:

* Functional class IV rheumatoid arthritis (American College of Rheumatology \[ACR\] classification).
* History of amenorrhea (unrelated to pregnancy).
* History or current inflammatory joint disease other than RA.
* Rheumatic autoimmune disease other than RA.

Primary outcomes:
measure: Serum Progesterone Level
timeFrame: Day 21 of Cycles 1-3 for Group 1 and Day 21 of Cycle 1 for Group 2
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Ethinyl Estradiol and Norethindrone
timeFrame: Day 7 of Cycles 1-3 for Group 1 and Day 7 of Cycle 1 for Group 2
measure: Time to Reach the Maximum Plasma Concentration (Tmax) of Ethinyl Estradiol and Norethindrone
timeFrame: Day 7 of Cycles 1-3 for Group 1 and Day 7 of Cycle 1 for Group 2
measure: Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC0-24) of Ethinyl Estradiol and Norethindrone
timeFrame: Day 7 of Cycles 1-3 for Group 1 and Day 7 of Cycle 1 for Group 2
measure: Terminal Half-life (t½) of Ethinyl Estradiol and Norethindrone
timeFrame: Day 7 of Cycles 1-3 for Group 1 and Day 7 of Cycle 1 for Group 2
measure: Apparent Oral Clearance (CL/F) of Ethinyl Estradiol and Norethindrone
timeFrame: Day 7 of Cycles 1-3 for Group 1 and Day 7 of Cycle 1 for Group 2
measure: Maximum Observed Serum Concentration (Cmax) of Tocilizumab
timeFrame: From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1
measure: Time to Reach Maximum Serum Concentration (Tmax) of Tocilizumab
timeFrame: From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1
measure: Area Under the Serum Concentration-time Curve From 0 to Infinity (AUCinf) of Tocilizumab
timeFrame: From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1
measure: Terminal Half-life (t½) of Tocilizumab
timeFrame: From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1
measure: Clearance (CL) of Tocilizumab
timeFrame: From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1
measure: Apparent Volume of Distribution (Vz) of Tocilizumab
timeFrame: From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1
measure: Serum Soluble Interleukin-6 Receptor (sIL-6R) Level
timeFrame: From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1
measure: Serum C-reactive Protein (CRP) Level
timeFrame: From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1
Other outcomes:
Locations:
city: Little Rock
country: United States
state: Arkansas
city: Beverly Hills
country: United States
state: California
city: Ormond Beach
country: United States
state: Florida
city: Port Orange
country: United States
state: Florida
city: Duncansville
country: United States
state: Pennsylvania
city: San Antonio
country: United States
state: Texas
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Zhang X, Rowell L, Fettner S, Lau C, Teuber D. Assessment of disease-drug-drug interaction between single-dose tocilizumab and oral contraceptives in women with active rheumatoid arthritis. Int J Clin Pharmacol Ther. 2014 Jan;52(1):27-38. doi: 10.5414/CP201951.