A Study of Tocilizumab in Combination With an Oral Contraceptive in Patients With Rheumatoid Arthritis

NCT01044498 | Completed Phase 3 Results

• 1 other identifier: NP22775
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 6

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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Serum Progesterone Level

  Blood samples were collected prior to the administration of Ortho-Novum® 1/35 on Day 21 of each cycle. Serum levels of progesterone were quantitatively determined using the ADVIA Centaur and ADVIA Centaur XP systems (Siemens Healthcare Diagnostics Inc., Tarrytown, NY, USA). The assay was a competitive immunoassay using direct chemiluminescent technology.

  Day 21 of Cycles 1-3 for Group 1 and Day 21 of Cycle 1 for Group 2

Secondary Outcomes (13)

• Maximum Observed Plasma Concentration (Cmax) of Ethinyl Estradiol and Norethindrone

  Day 7 of Cycles 1-3 for Group 1 and Day 7 of Cycle 1 for Group 2

• Time to Reach the Maximum Plasma Concentration (Tmax) of Ethinyl Estradiol and Norethindrone

  Day 7 of Cycles 1-3 for Group 1 and Day 7 of Cycle 1 for Group 2

• Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC0-24) of Ethinyl Estradiol and Norethindrone

  Day 7 of Cycles 1-3 for Group 1 and Day 7 of Cycle 1 for Group 2

• Terminal Half-life (t½) of Ethinyl Estradiol and Norethindrone

  Day 7 of Cycles 1-3 for Group 1 and Day 7 of Cycle 1 for Group 2

• Apparent Oral Clearance (CL/F) of Ethinyl Estradiol and Norethindrone

  Day 7 of Cycles 1-3 for Group 1 and Day 7 of Cycle 1 for Group 2

Study Arms (2)

Tocilizumab 8 mg/kg + Ortho-Novum® 1/35 (Group 1)

EXPERIMENTAL

Patients with rheumatoid arthritis received Ortho-Novum® 1/35 daily on Days 1-21 of 3 consecutive 28-day cycles. On the first day of Cycle 2, patients received tocilizumab 8 mg/kg administered intravenously.

Drug: Tocilizumab; Drug: Ortho-Novum® 1/35

Ortho-Novum® 1/35 (Group 2)

OTHER

Healthy volunteers received Ortho-Novum® 1/35 tablets daily on Days 1-21 of one 28-day cycle.

Drug: Ortho-Novum® 1/35

Interventions

Tocilizumab DRUG

Tocilizumab 8 mg/kg was administered in a single 1-hour infusion on Day 1 of Cycle 2.

Also known as: RoActemra, Actemra

Tocilizumab 8 mg/kg + Ortho-Novum® 1/35 (Group 1)

Ortho-Novum® 1/35 DRUG

Each Ortho-Novum® 1/35 tablet contained 1 mg of norethindrone and 0.035 mg of ethinyl estradiol.

Ortho-Novum® 1/35 (Group 2); Tocilizumab 8 mg/kg + Ortho-Novum® 1/35 (Group 1)

Eligibility Criteria

• Age: 18 Years - 44 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (6)

Unknown Facility

Little Rock, Arkansas, 72212, United States

Location

Unknown Facility

Beverly Hills, California, 90211, United States

Location

Unknown Facility

Ormond Beach, Florida, 32174, United States

Location

Unknown Facility

Port Orange, Florida, 32127, United States

Location

Unknown Facility

Duncansville, Pennsylvania, 16635, United States

Location

Unknown Facility

San Antonio, Texas, 78222, United States

Location

Related Publications (1)

• 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.

  PMID: 24161161 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2010
• First Posted: January 8, 2010
• Study Start: December 1, 2009
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: April 1, 2013
• Results First Posted: March 12, 2013

Record last verified: 2013-03

Locations

US (6)