A study investigating the effect on heart rate and rhythm of ponesimod

• Research type

  Research Study

• Full title

  Single-center, double-blind, placebo-controlled, randomized, two-way cross-over, multiple-dose study to investigate the effects on heart rate and rhythm of two up-titration regimens of ponesimod in healthy male and female subjects

• IRAS ID

  123504

• Contact name

  Jim Bush

• Sponsor organisation

  Actelion Pharmaceuticals Ltd

• Eudract number

  2012-005620-15

• ISRCTN Number

  N/A

• Research summary

  Ponesimod is an investigational drug being developed with the aim of helping people with immune disorders such as psoriasis, multiple sclerosis, rheumatoid arthritis, and Crohn??s disease. In immune disorders like these lymphocytes (a type of white blood cell) are released from the lymphoid tissues (bone marrow, lymph nodes and spleen), where they develop, into the lymphatic circulation and bloodstream. They then travel towards different areas of the body (e.g. skin, brain, joints and gut) where they cause inflammation. This leads to symptoms of the disease. An enzyme called S1P1 is found on the surface of cells within lymphoid tissues and is involved in the release of lymphocytes into the circulation. Ponesimod is an S1P1 receptor modulator; it is hoped that ponesimod will work by blocking the action of the S1P1 enzyme to prevent the release of lymphocytes. One S1P1 Receptor Modulator called fingolimod has been approved for use and is already used to treat patients with severe Multiple Sclerosis. As with fingolimod, ponesimod causes some temporary effects on the heart. The most common of these is a decrease in heart rate. Rarely the decreased heart rate is associated with a delay in the passage of electric impulses through the heart which occasionally causes the heart to miss beats. These delays are predominately seen following the first dose of the drug and at higher dose levels. To reduce the risk of these delays ponesimod is started at a low dose level and increased up to a dose level of 20mg, which is the dose level to be used to treat patients. The purpose of this study is to investigate the effects of two different dose escalation regimens on heart rate and the conduction of electrical impulses through the heart.

• REC name

  North East - York Research Ethics Committee

• REC reference

  13/NE/0037

• Date of REC Opinion

  13 Feb 2013

• REC opinion

  Favourable Opinion