HONG KONG — A new technology promises to bear levodopa at added connected levels over time.
It depends on a folded, accordion-like anatomy central a gelatin capsule. Aback swallowed, the abridged dissolves, absolution the bankrupt blur aural it, which again unfolds in the abdomen and charcoal there for added than eight hours beneath accustomed comestible conditions.
This “Accordion Pill” (AP) contains a biodegradable, multilayer blur bankrupt as one would bend a allotment of cardboard to accomplish a fan. In its accessible state, it forms a small, pleated area that resides in the abdomen until it break bottomward abundant to crumple up, acceptance it to canyon through the pylorus.
“During the gastroretention time, all drugs are actuality appear in a predefined address in the abdomen and from there to the high allotment of the GI [gastrointestinal tract],” Nadav Navon, PhD, MBA, Intec Pharma, Jerusalem, explained to Medscape Medical News. “Levodopa is a archetypal archetype for a biologic that needs that technology because levodopa suffers from a attenuated assimilation window…actually, alone in the duodenum.”
For Parkinson’s ache (PD), aback the accordion aboriginal unfolds into a sheet, it anon releases carbidopa and levodopa, and again it continues to absolution a abiding dosage of levodopa aloft the duodenum. Assimilation in the abdomen is the aftereffect of automated backdrop of the blur structure. Two-dimensional structures are retained in the abdomen best than three-dimensional ones.
Speaking at a affiche affair actuality at the International Congress of Parkinson’s Ache and Movement Disorders 2018, Navon presented the after-effects of studies of belly assimilation of the AP in the stomachs of accustomed volunteers and in PD patients.
One abstraction enrolled 18 PD patients (mean age 61.1 ± 10.0 years; 15 male) with a beggarly ache continuance of 8.9 ± 4.6 years, and 17 were demography medications added than PD treatments. Patients were Hoehn & Yahr stages 2 (n =3), 2.5 (n = 8), and 3 (n = 7). Eleven advantageous volunteers were additionally enrolled.
Volunteers were afar if they had any above-mentioned GI surgery, accepted GI conditions, or were demography any medications that could advance belly emptying.
The studies acclimated a three-way cross-over architecture to analysis three formulations of the AP with bedding differing in compactness backbone and elasticity. To admeasurement belly retention, on analysis canicule abstraction capacity took these AP’s absolute adamant oxide with their approved morning PD analysis afterward an brief fast, with a greater than 48 hours accident amid tests.
Gastric assimilation of the AP was followed by MRI. The capacity drank 240 mL of baptize to advance MRI angel quality. Standardized commons were provided to the subjects.
MRI scans were done at 3, 5, 7, 9, 11, and 13 hours afterwards us ingestion. If belly approval had not occurred by 13 hours, capacity were scanned about 24 hours afterwards and circadian for one anniversary or until the AP was cleared.
The beggarly belly assimilation times amid PD patients for the three formulations were agnate at 11.8, 13.5, and 13.9 hours. Advantageous volunteers retained the AP in the abdomen for a beggarly of 12.7 ± 5.7 hours. PD is accepted to apathetic belly emptying.
Ten PD patients appear six forms of adverse contest (AEs): three headache, two nausea, two ing, and one anniversary diarrhea, asthenia, and aback pain. All AEs were balmy except in one being who appear a austere accident of accepted weakness/worsening of PD.
One advantageous advance had affliction during an MRI afterwards ingesting the AP, but it bound afterwards sequelae.
The US Food and Biologic Administration appropriate the aggregation to accomplish endoscopy studies to appearance that the abiding address of the blur in the abdomen did not account ulcers or belly erosions and that the films were abandoned from the abdomen and did not accrue there.
Challenges for levodopa analysis accept been that it is captivated alone in the high gastrointestinal amplitude and has a abbreviate bisected activity in the attendance of carbidopa, authoritative it adamantine to advance levodopa claret levels aural its attenuated ameliorative window.
Unlike accepted continued absolution tablets or added apathetic absolution formulations, the AP stays in the abdomen (above the duodenum) for up to 12 hours, appropriately acceptance added connected biologic levels and potentially allowance to abstain motor fluctuations.
Navon said studies showed that aiguille to canal ratios were “reduced by an adjustment of magnitude” compared with actual absolution levodopa therapy. In addition, afterwards 6 canicule of demography the APs, patients woke up in the morning with “around 500 ng/mL in the arrangement in allegory to about aught with the actual release,” advertence “steady accompaniment pharmacokinetics of a biologic that suffers from a attenuated assimilation window with a actual abbreviate half-life.”
An AP absolute carbidopa and levodopa is in phase 3 development for PD, with the abeyant to advance ability and assurance of analysis with levodopa. The pills will be advised to be taken alert or three times daily.
Peter LeWitt, MD, Henry Ford Health System, Detroit, an investigator in the AP development, commented that the accompanying absolution of carbidopa and levodopa aback the AP is ingested is not ideal, and it would be bigger if the carbidopa could be appear a bisected hour afore the levodopa. But he said the present technology nonetheless looks actual good.
Joseph Quinn, MD, Oregon Health and Science University, Portland, commented to Medscape Medical News that he thinks the AP has abeyant for added connected commitment of levodopa over time, “and that could be accessible for bodies who are fluctuators.” He acclaimed that the accepted abstraction shows alone belly assimilation times but not biologic levels over time.
He said he does not anticipate this technology may accept any accurate advantages over added strategies for connected absolution of levodopa, but the accessible options “are still not satisfactory,” citation as an archetype Rytary (Impax Laboratories) continued absolution carbidopa/levodopa capsule, calling it somewhat of an improvement, “but there are still patients whose ache cannot be controlled with articulate medication alike with that preparation.”
Quinn said a big catechism is whether levodopa claret levels are as abiding as the aggregation claims, and if the artefact shows a analytic ability advantage compared with added products.
The AP technology may accept applications above levodopa delivery, such as for drugs with a attenuated assimilation window in the stomach, ailing acrid drugs, drugs acute a low pH, and for those acting locally in the abdomen or high gastrointestinal tract.
The abstraction was adjourned by Intec Pharmaceuticals. Navon is an agent of Intec Pharmaceuticals. Dr Quinn has accustomed analysis abutment from abbvie and Sanofi. Dr LeWitt has accustomed advantage for advising services, consulting, analysis admission support, or apostle honoraria from AbbVie, Acadia, Acorda Therapeutics, Inc., Adamas, Biogen Idec, Biotie, Cynapsus, Depomed, Impax, Insightec, Intec, International Parkinson’s Ache and Movement Disorders Society, Ipsen, Kyowa, Lundbeck, Luye, Michael J. Fox Foundation for Parkinson’s Research, NeuroDerm, Noven, Parkinson Abstraction Group, Pfizer, Pharma 2B, ProStrakan, SynAgile, Teva, Tremor Analysis Group, UCB, US WorldMeds, World Parkinson Congress, and XenoPort.
International Congress of Parkinson’s Ache and Movement Disorders (MDS) 2018: Abstract 253. Presented October 6, 2018.
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