Safety, Tolerance, Pharmacokinetics and Activity of HE3286 in Patients With Rheumatoid Arthritis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00712114
Recruitment Status : Completed
First Posted : July 9, 2008
Last Update Posted : June 14, 2011
Information provided by:
Harbor Therapeutics

Brief Summary:
The purpose of this pilot, exploratory study is to evaluate the safety, tolerance, pharmacokinetics and potential anti-inflammatory activity of an investigational agent, HE3286, when administered orally for 29 days to patients with rheumatoid arthritis that are taking a stable dose of methotrexate.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: HE3286 Phase 1 Phase 2

Detailed Description:
This is a Phase I/II, open label, dose ranging study of the safety, tolerance, and anti-inflammatory activity of HE3286 in patients with rheumatoid arthritis. Patients will receive study treatment (one of three open label doses) in addition to their current stable dose of methotrexate. Safety (via monitoring of vital signs, physical examination changes, ECG results, laboratory results, and adverse events), pharmacokinetics profiles (of HE3286 and methotrexate) and anti-inflammatory activity will be assessed over a treatment period of 29 days.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II, Open Label, Dose Ranging Study of the Safety, Tolerance, Pharmacokinetics and Potential Anti-Inflammatory Activity of HE3286 When Administered Orally for 29 Days to Patients With Rheumatoid Arthritis on a Stable Dose of Methotrexate
Study Start Date : July 2008
Actual Primary Completion Date : July 2009
Actual Study Completion Date : July 2009

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Cohort 1
10 mg HE3286 (1 x 5 mg HE3286, BID)
Drug: HE3286
HE3286 will be administered orally. Dosing will be 10 mg per day for 29 days.
Other Name: Triolex

Experimental: Cohort 2
20 mg HE3286 (2 x 5 mg HE3286 BID)
Drug: HE3286
HE3286 will be administered orally. Dosing will be 20 mg per day for 29 days
Other Name: Triolex

Experimental: Cohort 3
40 mg HE3286 (4 x 5 mg HE3286 BID)
Drug: HE3286
HE3286 will be administered orally. Dosing will be 40 mg per day for 29 days
Other Name: Triolex

Primary Outcome Measures :
  1. Safety and pharmacokinetics [ Time Frame: Duration of the study ]

Secondary Outcome Measures :
  1. To assess the potential activity of HE3286 to decrease inflammation via evaluation of inflammatory cytokine activity. [ Time Frame: Duration of study ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Main Inclusion Criteria:

  • Male or female patient 18-75 years of age
  • Patient with stable or active disease on a stable dose of methotrexate for at least 30 days prior to Day 1
  • Patient has normal thyroid stimulating hormone (TSH) levels with or without thyroid replacement therapy
  • Patient is willing to abstain from consuming grapefruit containing products from 24 hours prior to dosing until the end of the study as it may affect the pharmacokinetic measurements
  • Patient has not experienced renal or liver disease by history and/or based on laboratory results
  • Patient has not experienced acute cardiac disease within 6 months prior to Screening
  • Patient must provide voluntary, written, informed consent prior to screening evaluations and be able to follow verbal and written instructions.

Main Exclusion Criteria:

  • Functional status class IV according to The American College of Rheumatology (ACR) criteria
  • Patient who has a history of clinically significant cardiovascular disease (including coronary artery disease), clinically significant hepatic, respiratory or renal abnormalities, or clinically significant endocrine disorders (including diabetes)
  • Patient with active Tuberculosis (TB) or evidence of latent TB without previous adequate therapy
  • Systemic autoimmune disorder (including, but not limited to, systemic lupus erythematosus, inflammatory bowel disease, scleroderma, inflammatory myopathy, mixed connective tissue disease or any overlap syndrome)
  • Inflammatory joint disease other than RA
  • Patient who has received any of the following immunosuppressive drugs:

    • Etanercept within 1 month of Day 1;
    • Abatacept, adalimumab, infliximab, leflunomide, imuran, cyclosporin, anakinra, sulfasalazine, bextra, celebrex or gold within 2 months of Day 1 or for biological agents 6 half lives, whichever is greater;
    • Rituximab within 1 year of Day 1
  • Patient that is bed or wheelchair bound
  • Patients taking prednisone within 2 weeks prior to Screening
  • Patient requiring or receiving any of the following within thirty (30) days prior to the screening visit: interleukins, steroids (i.e., anabolic steroids, glucocorticoids), hormone replacement therapy (except stable low-dose HRT for at least 6-months prior to screening), birth control pills, anti-cancer chemotherapeutic agents (except methotrexate), metabolic inhibitors (except methotrexate), concomitant medications that prolong the QT/QTc interval
  • Patient who has any clinically significant abnormalities in laboratory results at Screening

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00712114

United States, California
Beverly Hills, California, United States, 90211
Sponsors and Collaborators
Harbor Therapeutics
Study Director: Dwight Stickney, MD Hollis-Eden

Responsible Party: Nanette Onizuka-Handa/Sr. Vice President, Regulatory Affairs and Quality, Hollis-Eden Pharmaceuticals Identifier: NCT00712114     History of Changes
Other Study ID Numbers: HE3286-0201
First Posted: July 9, 2008    Key Record Dates
Last Update Posted: June 14, 2011
Last Verified: June 2011

Keywords provided by Harbor Therapeutics:
phase I
rheumatoid arthritis

Additional relevant MeSH terms:
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Anti-Inflammatory Agents
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Adjuvants, Immunologic