Sarilumab Effect on the Pharmacokinetics of Simvastatin

NCT02017639 | Completed Phase 1 DMC

• 2 other identifiers: INT12684U1111-1140-5082
• Study Type: interventional
• Target: 19
• Locations: 3 countries
• Sites: 5

Brief Summary

Primary Objective: To evaluate the effect of a single 200 mg subcutaneous injection of sarilumab on the pharmacokinetics of simvastatin in patients with rheumatoid arthritis Secondary Objective: To describe the safety and efficacy (exploratory) of sarilumab

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Assessment of PK parameters - area under curve from zero time until the last measurable concentration (AUClast) and AUC for simvastatin

  Day 1 of Period 1 and Day 8 of Period 2

Secondary Outcomes (3)

• Assessment of additional PK parameters for simvastatin

  Day 1 of Period 1 and Day 8 of Period 2

• Assessment of additional PK parameters for simvastatin acid

  Day 1 of Period 1 and Day 8 of Period 2

• Safety assessment of sarilumab up to 1 year )

  From Day 1 of Period 1 up to a maximum of 1 year (week 58)

Study Arms (1)

Sarilumab SAR153191 (REGN88)

EXPERIMENTAL

Single dose of simvastatin before and after sarilumab administration

Drug: sarilumab SAR153191 (REGN88); Drug: simvastatin

Interventions

sarilumab SAR153191 (REGN88) DRUG

Pharmaceutical form:Prefilled syringe of sarilumab solution Route of administration: Subcutaneous injection

Sarilumab SAR153191 (REGN88)

simvastatin DRUG

Pharmaceutical form:Film-coated 20 mg Tablet Route of administration: oral

Sarilumab SAR153191 (REGN88)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, between 18 and 75 years of age, inclusive. Body weight between 50.0 and 120.0 kg, inclusive, if male, and between 40.0 and 110.0 kg, inclusive, if female.
• Diagnosis of RA, according to the ACR/European League against Rheumatism (EULAR) 2010 Rheumatoid Arthritis Classification Criteria with ≥ 3 months disease duration, ACR Class I-III functional status, based on 1991 revised criteria (Appendix B, 5). Moderate-to-severely active RA, defined as:
• o high sensitivity C-reactive protein (hs-CRP) ≥ 6 mg/L
• Laboratory parameters within the normal range (or defined screening threshold for the Investigator site), unless the Investigator considers an abnormality to be clinically irrelevant for RA patients; however following lab values must be met:
• Hemoglobin \>8.5 g/dL
• White blood cells \>3000/mm3
• Neutrophils \>2000/mm3
• Platelet count \>150 000 cells/mm3

You may not qualify if:

• Prior or current significant concomitant illness(es) that, according to Investigator's judgment, would adversely affect the patient's participation in the study.
• Women of childbearing potential not protected by highly-effective contraceptive method(s) of birth control (as defined in the informed consent form), and/or who are unwilling or unable to be tested for pregnancy.
• Participation in any clinical research study that evaluated an investigational drug or therapy within 5 half-lives or 60 days of the Screening, whichever is longer.
• Patients with active TB or a history of incompletely treated TB. History of chronic infection or active infection. History of, or current, autoimmune or inflammatory systemic or localized joint disease(s) other than RA.
• A systemic hypersensitivity reaction, other than localized injection site reaction, to any biologic drug.
• History or presence of drug or alcohol abuse. Prior or current interstitial lung disease diagnosed by high resolution computed tomography and/or lung biopsy with consistent findings on pulmonary function tests and corroborating clinical findings.
• Prior or current history of malignancy, including lymphoproliferative diseases, other than adequately-treated carcinoma in-situ of the cervix, nonmetastatic squamous cell or basal cell carcinoma of the skin, within 5 years prior to the screening visit.
• Uncontrolled diabetes mellitus, defined as glycosylated hemoglobin (HbA1c) ≥9% at the screening visit.
• The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (5)

Investigational Site Number 840002

Duncansville, Pennsylvania, 16635, United States

Location

Investigational Site Number 840003

Jackson, Tennessee, 38305, United States

Location

Investigational Site Number 840001

Dallas, Texas, 75235, United States

Location

Investigational Site Number 498001

Chisinau, 2025, Moldova

Location

Investigational Site Number 410002

Seoul, 110-744, South Korea

Location

Related Publications (1)

• Lee EB, Daskalakis N, Xu C, Paccaly A, Miller B, Fleischmann R, Bodrug I, Kivitz A. Disease-Drug Interaction of Sarilumab and Simvastatin in Patients with Rheumatoid Arthritis. Clin Pharmacokinet. 2017 Jun;56(6):607-615. doi: 10.1007/s40262-016-0462-8.

  PMID: 27722854 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

sarilumab; Simvastatin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2013
• First Posted: December 23, 2013
• Study Start: January 1, 2014
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: April 7, 2016

Record last verified: 2016-04

Locations

MO (1); KR (1); US (3)