Napp Pharmaceuticals Limited has announced that Targinact, a fixed combination of prolonged-release oxycodone/naloxone, has received approval for use in the UK.
This follows the European Commission’s positive decision in January 2015 to recommend Targinact as a second line symptomatic treatment for patients with severe to very severe idiopathic restless legs syndrome (RLS), after failure of dopaminergic therapy. (1,2)
Oxycodone/naloxone is the first opioid that has been granted a licence in the UK for the treatment of RLS. (1) This new licence indication provides a viable treatment option for patients who cannot tolerate the existing available treatments or who are not able to gain the level of symptom relief required. (2)
Up until now, symptomatic treatment of idiopathic RLS included mainly dopamine agonists or dopaminergic substances such as L-dopa, however long-term use can lead to worsening of the symptoms in many individuals. (3)
Data published in the December 2013 issue of The Lancet Neurology supports the basis of this new indication approval. Findings from the 12 week double-blind, randomised placebo-controlled trial with a 40 week open-label extension, showed (4):
- A significant improvement in the Mean International RLS Study Group rating scale (IRLS) in the prolonged release oxycodone/naloxone group versus placebo (-16.5 versus -9.4; p<0.0001) at 12 weeks. (4) This translates into a significant clinical improvement from “very severe” at start of treatment to on average “mild” or “moderate” at the end of the double-blind phase.
- A beneficial effect of treatment with prolonged release oxycodone/naloxone at the end of the 40-week open-label extension phase (mean sum score of 9.7 at week 40 compared to a starting score of 15.4), providing evidence of longer term efficacy for prolonged release oxycodone/naloxone.
- Improvements in the quality and quantity of sleep for patients in the oxycodone/naloxone group versus placebo, with fewer RLS symptoms when going to sleep and during the night versus placebo.
- That 42% of patients in the oxycodone/naloxone group were considered IRLS remitters at 12 weeks, versus 19% in the placebo group. Furthermore, at the end of the 40 week extension, 43% of patients were considered remitters, and 22% of remitters (by International RLS Study Group severity rating scale) were asymptomatic.
- No augmentation seen over the entire 52 week study period.
- An adverse event profile for oxycodone/naloxone over the entire study period that was consistent with the safety profile of opioids, with “very common side effects” (those occurring in ≥1/10 patients) including gastrointestinal disorders, headache, somnolence, fatigue, pruritus and hyperhidrosis.
“Restless leg syndrome (RLS) can have a devastating impact on a patient’s life. With symptoms mostly occurring at night when patients are trying to sleep, this often leads to sleeplessness and acute distress, which can in turn cause a major upheaval in the personal and working lives of those it effects. To-date there has only been one approach to treatment, however the new indication for Targinact provides clinicians with an alternative to traditional approaches, and will enable us to offer new hope to many of our patients living with this disease in the UK.” said Professor Ray Chaudhuri, Professor of Movement Disorders, King’s College London.
- European Commission. List of referrals for human medicinal products. Available at: http://ec.europa.eu/health/documents/community-register/html/ho25423.htm [Accessed April 2015].
- European Medicines Agency – Committee for Medicinal Products for Human Use (CHMP). Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/referrals/Oxynal-Targin_and_associated_names/human_referral_000384.jsp&mid=WC0b01ac05805c516f [Accessed April 2015].
- National Heart Lung and Blood Institute. Restless Legs Syndrome: Detection and Management in Primary Care. Am Fam Physician. 2000;62(1):108–14.
- Trenkwalder C et al. Prolonged release oxycodone–naloxone for treatment of severe restless legs syndrome after failure of previous treatment: a double-blind, randomised, placebo-controlled trial with an open-label extension. The Lancet Neurology 2013;12(12):1141–50. Available at: http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(13)70239-4/fulltext [Accessed April 2015].