Dosing of healthy volunteers has been completed in a Phase 1 clinical trial evaluating Neos Therapeutics‘ experimental therapy NT0502 for chronic sialorrhea (excessive drooling), a common problem in people with amyotrophic lateral sclerosis (ALS).
The open-label study includes 30 healthy adults who were assigned randomly to take one of four oral-disintegrating tablet formulations of NT0502 and its precursor molecule oxybutynin, an approved treatment for overactive bladder.
The trial is testing the safety and tolerability of these formulations, as well as their behavior inside the body in respect to absorption, distribution, metabolism, and excretion.
Data from the trial – expected to become available within the first quarter of 2020 – will provide guidance for the selection of a final formulation and dosing for future clinical trials.
Chronic sialorrhea is defined as an excess spillage of saliva out of the mouth, and normally arises from a patient’s inability to control or swallow oral secretions. This is a common symptom among patients with neurological disorders, such as ALS, Parkinson’s disease, cerebral palsy, and stroke.
Chronic drooling is often problematic, as it may result in additional physiological complications, including chapped lips, dehydration, aspiration, and infection, as well as an overall stigmatization of the patient.
Current medical treatments on the market use the botulinum toxin type A (commonly known as botox) or anticholinergic agents that essentially block the action of the neurotransmitter acetylcholine — important for involuntary movement — in the salivary glands.
However, these are generally ineffective, as they have complicated dosage schedules and many patients are either intolerant or experience side effects that cause them to discontinue treatment.
NT0502 is intended to be a once- or twice-daily medication, which is a much more reasonable treatment schedule than those currently on the market. It also is an anticholinergic agent, but works in a more selective manner, targeting preferentially muscarinic receptors in the salivary glands. These receptors regulate many fundamental functions in the body, one of them being fluid secretion by salivary cells.
By being more selective, NT0502 is expected to induce fewer side effects, being a better option for people with chronic drooling.
Preclinical tests indicate that NT0502 is highly effective in specifically blocking the salivary glands, making it an ideal treatment against chronic drooling in patients who have neurological disorders.
“There is significant market need for new treatments for chronic sialorrhea that can improve the quality of life for the millions of patients with neurological conditions, such as Parkinson’s disease, cerebral palsy and amyotrophic lateral sclerosis (ALS), who also must live with the associated burden of excessive drooling,” Jerry McLaughlin, president and CEO of Neos Therapeutics, said in a press release.
“NT0502 has a novel mechanism that offers the promise of an effective treatment with an improved tolerability profile for patients relative to existing pharmacologic options for chronic sialorrhea,” McLaughlin said. “We are looking forward to the results of this pilot pharmacokinetic study and the continued progress of NT0502 through the clinic.”