Published: Oct 8, 2015 7:23 a.m.
ET
SynAgile Corporation
- Continuous intraoral
administration of levodopa-carbidopa reduced variability in plasma levodopa
concentrations and reduced OFF time associated with Parkinson's disease- Met
primary endpoint with statistically significant reduction in levodopa plasma
variability versus standard intermittent oral tablet therapy- Met secondary
endpoints with statistically significant reduction in OFF time and with
improvement in UPDRS III motor score versus standard intermittent oral tablet
therapy- No clinically significant adverse events- No observed delivery-site
reactions
WILSON, Wyo., Oct. 8, 2015
/PRNewswire/ -- SynAgile Corporation (www.SynAgile.com), a privately held
pharmaceutical company that develops and commercializes drug delivery systems
using its proprietary OraFuse™ intraoral technology platform, today announced
positive results from a proof-of-concept, Phase 2a, open-label clinical trial
of continuous intraoral administration of levodopa-carbidopa (LD/CD).
"We are extremely pleased
that the primary and secondary endpoints in our Phase 2a trial were met,
demonstrating that continuous intraoral delivery of LD/CD provides reduced
variability in plasma levodopa concentrations and a significant reduction in
motor complications. OFF time was reduced by 43% compared to standard oral
LD/CD tablet therapy," said Ephraim Heller, CEO of SynAgile.
"SynAgile is developing its DopaFuse™ product as a continuous, noninvasive
LD/CD therapy to address the problem of levodopa-induced motor complications, a
large, unmet need facing Parkinson's patients today. These results were
achieved with a noninvasive therapy that requires no surgery, bulky pumps, or
needles. Continuous intraoral LD/CD therapy will appeal to many patients whose
motor complications are not adequately controlled with standard oral
medications. Furthermore, DopaFuse™ will potentially avoid the side effects and
human factor problems associated with deep brain stimulation and Duodopa™
therapy."
Motor complications include OFF
time and dyskinesia associated with chronic levodopa treatment. Motor
complications affect most patients with advanced Parkinson's disease and are
considered to be one of the most important issues facing Parkinson's disease
patients today.
"Motor complications, and
specifically OFF time, can have a profoundly negative impact on the lives of
Parkinson's disease patients. A safe, convenient, noninvasive, nonsurgical, oral
levodopa therapy would be a major advance in treatment," said Prof. Warren
Olanow, co-Principal Investigator of the study, Chairman Emeritus, Department
of Neurology, Mount Sinai School of Medicine, CEO of Clintrex LLC,
and a member of the SynAgile Scientific Advisory Board. "The reduction in
OFF time was clinically significant, and there were no treatment-related
adverse events. The results suggest that continuous intraoral LD/CD
administration may provide a safe, noninvasive approach for controlling OFF
time," said Prof. Olanow.
The study compared continuous
intraoral administration of LD/CD versus standard intermittent LD/CD tablets
taken 4–8 times daily in patients with advanced Parkinson's disease. Continuous
administration was defined as administration of a dose of LD/CD suspension
every 5–10 minutes. Each patient served as his/her own control (described
below). For the primary endpoint, statistically significant improvements were
observed for variability in plasma levodopa concentration (as determined by
linearity) and for reduction in 1-hour and 2-hour fluctuation indexes (p
< 0.001 for each). OFF time was reduced by 43% (p < 0.001), and
the UPDRS Part III motor score improved (p = 0.010).
Trial Design
The Phase 2a trial was an
open-label, single-center study of 18 Parkinson's disease patients who
experienced ≥2 hours of OFF time per day. Profs. Warren Olanow and Fabrizzio
Stocchi served as Co-Principal Investigators. Standard intermittent oral LC/CD
tablets were compared with the same total doses of LD/CD suspension delivered
into the mouth every 5–10 minutes. The study was conducted at Hospital San
Raffaele in Rome, Italy. Patients were admitted to the clinic on Day 1 for
baseline evaluations. On Day 2 (the "Control Day"), LD/CD was administered
as commercially available LD/CD tablets at each patient's pre-baseline dosing
regimen. Plasma levels of levodopa as well as ON and OFF time were measured
repeatedly over the course of 8 hours. On Day 3 (the "PK Day"), a
suspension of LD/CD was administered intraorally every 5–10 minutes over a
period of 8 hours at a dose equal to the total dose of standard oral LD/CD that
the patient consumed over the same 8-hour period on the Control Day, and plasma
levels of levodopa were obtained. On Day 4 (the "Efficacy Day"), each
patient received his or her first LD/CD morning dose as an oral tablet at the
same dosage as the first morning dose on the Control Day. They then received
the balance of the total 8-hour dose that they took on the Control Day by way
of intraoral administration of a suspension of LD/CD every 5–10 minutes over a
period of 8 hours. ON and OFF time were assessed as on Day 2. Patients were
then discharged from the clinic on their standard medication and returned on
Day 18 for a safety evaluation.
The primary endpoint was defined
as the variability of the levodopa concentrations; we compared standard
intermittent oral and continuous intraoral administration. Pharmacokinetic
endpoints included deviation from linearity and the mean levodopa fluctuation
index (Cmax^’Cmin)/Caverage). Efficacy was measured by neurologist-based
assessment of motor state and dyskinesia at 30-minute intervals over the 8
hours and by UPDRS Part III, assessed at 0, 2, 4, and 8 hours on the Control
Day (Day 2) and the Efficacy Day (Day 4).
Safety parameters measured
included physical examinations, neurological examinations, ECGs, vital signs,
blood and urine laboratory assessments, and oral site assessments by both the
neurologist and the patient.
Full results of the study will be
presented at an upcoming scientific meeting.
About OraFuse™ and DopaFuse™
SynAgile is developing the
OraFuse™ drug delivery platform for the continuous oral delivery of drugs with
poor pharmacokinetics. OraFuse™ consists of a miniature, disposable,
drug-delivery device carried on a small, tooth-attached retainer that
continuously infuses medication into the mouth. SynAgile's first product is
DopaFuse™, which uses the OraFuse™ device to infuse a proprietary formulation
of LD/CD into the mouth for the treatment of Parkinson's disease. DopaFuse™ is
being developed for daily use by Parkinson's disease patients. The LD/CD is
swallowed with the patient's saliva and absorbed via the conventional
gastrointestinal route. The DopaFuse™ drug formulation has no taste, and the
infusion is imperceptible to the patient. The DopaFuse™ system is not visible
to others, is comfortable to wear, and does not interfere with speech,
swallowing, or drinking. DopaFuse™ is intended to enable patients with
Parkinson's disease to achieve more-constant plasma levodopa levels and
reduce their motor complications. DopaFuse™ will provide patients with a safe,
convenient, noninvasive therapy to reduce motor complications. In contrast to
other continuous levodopa delivery systems, DopaFuse™ requires no surgical
procedures or needles.
Levodopa is widely recognized as
the most efficacious treatment for Parkinson's disease symptoms. However,
levodopa is quickly broken down in the body and its absorption is unpredictable.
Even when taken 4–8 times per day, standard oral levodopa tablets often produce
widely varying plasma levodopa concentrations over the course of the day. Low
plasma levodopa concentrations typically result in OFF time, characterized by
tremor, rigidity, slowness of movement, and postural instability. High plasma
levodopa concentrations often result in dyskinesia, characterized by
involuntary muscle movements. Patients with advanced Parkinson's disease can
spend many hours each day in the OFF state or with dyskinesia.
About Parkinson's Disease
Over one million people in the US
and over seven million people worldwide suffer from Parkinson's disease, a
neurodegenerative disorder caused by the diminished production of dopamine,
which results in progressive impairment of motor function, including tremors at
rest, rigidity, and impaired movement. Even when treated with the current
standard of care, the majority of patients with advanced Parkinson's disease
continue to experience motor complications (OFF periods and dyskinesia). These
motor complications reduce patients' ability to lead productive, independent
lives and are recognized by patients, caregivers, and healthcare professionals
as one of the most troubling and debilitating issues associated with the
disease.
About SynAgile
SynAgile is a biopharmaceutical
company focused on developing and commercializing transformative therapeutics
using its proprietary OraFuse™ intraoral continuous dosing technology, with an
initial focus on treating debilitating motor complications in patients with
Parkinson's disease using its DopaFuse™ levodopa-carbidopa therapy.
OraFuse and DopaFuse are
trademarks of SynAgile Corporation. Duodopa is a trademark of AbbVie Inc.
Contact
SynAgile Corporation
Ephraim Heller, CEO
(510) 788-4435
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PR Newswire, visit:http://www.prnewswire.com/news-releases/synagile-corporation-announces-positive-phase-2a-results-for-continuous-noninvasive-intraoral-levodopa-carbidopa-administration-to-treat-parkinsons-disease-300156341.html
http://health.einnews.com/article/290510978/FGCvnzxbrordt8Z-
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