Neuroderm BouNDless

Editor’s Note

To those fresh to the challenges of Parkinson’s, look away now, this study is unlikely to be for you.

Many of us who have spent some years on Planet Parkinson’s will be keenly aware of the persistent creeping reduction of on-time. Previously levodopa-responsive without side effects, you may now have met the fellow travellers of bradykinesia, dyskinesia and unpredictable dose response.  You are running out of road with oral medication tweaks. Quality of life is taking a big hit.

Levodopa is a prodrug, so-called because they are inactive until converted in the body into an active ingredient, in this case dopamine. Let’s step away from the complexities of biology and biochemistry for a moment. Treat the situation as a product delivery for which you are responsible, getting levodopa up to the blood-brain barrier. Trouble is, at least 80% of your product is vanishing in transit despite your efforts to protect the shipments with carbidopa (e.g. Sinemet) or benzerazide (e.g. Madopar).

To add to the challenge your customer is now demanding more frequent and precise deliveries as the brain warehouse can no longer manage a stock of the product.

You investigate the losses in transit and find that the gut wall and the liver are together eating or skimming more than half of the product. As the saying goes, “What would you do”?

The majority of levodopa transfer across the gut wall happens in the small intestine, not the stomach. The Duodopa intestinal gel pump (Duopa in the US) is derived from this clinical observation, although the science of the transfer is not so clear. It is a proven method, safe and well tolerated but invasive and can only mitigate the main problem. Cue the next generation of levodopa delivery techniques, subcutaneous infusion, thus almost direct into the bloodstream.

The science of subcutaneous infusion transfer to the bloodstream is relatively straightforward, and the technology is proven in many different circumstances, notably for diabetes and palliative care. These applications together have created a competitive market for infusion pumps and associated consumables, which Parkinson’s treatment is now in a position to take advantage of.

The BouNDless Study is the second subcutaneous levodopa infusion method to come to Phase 3 trial in the UK, AbbVie being the first (ABBV-951). BouNDless employs a different approach to the delivery of the medication, although both studies share the common characteristics of a long study period, a complicated trial protocol, a double-blind double-dummy investigation phase, the obligatory involvement of a partner, considerable amounts of data collection and post-trial open label supply of the product.

The Study material provided to the Site Investigation Team (locally, the Lind Centre at Derriford Hospital) is of a high standard, as is the material and face-to-face support provided to the participants to train them for the daily infusion process.

For the whole story go to the Participant Information Sheet. This is a heavyweight 28 pages that is not a bed-time read. (By the way, 10/10 for “Participant”)

The Partner Information Sheet makes it clear that this trial is a joint enterprise.

An option for Genetic Testing consolidates the impression of  a serious attempt to identify relationships between response to the medication and different strands of the Parkinson’s syndrome.

The ultimate sponsor of BouNDless (ND0612) is Mitsubishi Tanabe, a Japanese Pharma company, but this not apparent in the BouNDless material and the Study is not being conducted in Japan. For practical purposes the sponsor is Neuroderm, the  Israeli Pharma company that the Japanese conglomerate  purchased in 2017.  The UK Contract Testing Organisation is Syneos, who  the infusion support programme is the responsibility of IQVIA.