Methods and compositions for reducing symptoms of Parkinson's disease
Inventors
Adar, Liat • Lopes, Nelson Felix • Salin, Laurence • Yardeni, Tamar • Sasson, Nissim • Oren, Sheila • Yarita, Hikari • Himizu, Mikio • Vostokova, Natalia
Assignees
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Publication Number
US-12161612-B2
Publication Date
2024-12-10
Expiration Date
Abstract
Disclosed is a method for the treatment of a neurological or movement disorder, e.g., Parkinson's disease, in a patient in need thereof, by parenteral administration of levodopa and a dopa decarboxylase inhibitor (DDCI), such as carbidopa, benserazide or any combination thereof.
Core Innovation
The disclosed invention provides a method of treating a patient with Parkinson’s disease by subcutaneously administering, substantially continuously for about 24 hours/day and for about 2 to 3 consecutive days, a pharmaceutically acceptable liquid composition. The liquid composition comprises levodopa and carbidopa in a ratio of about 8:1 w/w and further comprises arginine. By the third consecutive day, the administration results in specified changes from baseline in daily Good ON-time and related ON/OFF and dyskinesia outcomes.
At least one of the following occurs by the third consecutive day: an increase from baseline in daily Good ON-time; a reduction from baseline in daily ON-time with moderate-severe dyskinesia; a reduction from baseline in daily OFF-time; an increase from baseline in daily ON-time without dyskinesia; and a reduction from baseline in total daily troublesome dyskinesia. The disclosed method also includes improvement from baseline in motor experiences of daily living as assessed by the Movement Disorder Society-Sponsored revision of Unified Parkinson’s Disease Rating Scale Part III (UPDRS Part III) score.
The document further describes embodiments in which the subcutaneous administration is carried out with time-varying activity across waking or high-activity hours versus low-activity or night hours, with a higher activity during day hours and a lower activity during night hours. The document also describes concomitant administration of an oral levodopa/carbidopa-DDCI composition together with a subcutaneous levodopa/carbidopa-DDCI regimen, and converting patients from a prior levodopa formulation regimen to oral immediate-release levodopa/carbidopa while initiating subcutaneous infusion.
Claims Coverage
The partial document includes three independent claims directed to substantially continuous subcutaneous administration for about 24 hours/day over about 2 to 3 consecutive days with levodopa and carbidopa at about 8:1 w/w and added arginine, producing at least one predefined improvement by the third consecutive day.
Substantially continuous subcutaneous 24 hours/day for 2 to 3 consecutive days
Subcutaneously administering, substantially continuously for about 24 hours/day and for about 2 to 3 consecutive days, a pharmaceutically acceptable liquid composition to a patient with Parkinson’s disease.
Levodopa and carbidopa at about 8:1 w/w with arginine
Using a pharmaceutically acceptable liquid composition comprising levodopa and carbidopa in a ratio of about 8:1 w/w and further comprising arginine.
At least one predefined on/off, dyskinesia, or motor outcome by the third day
Wherein by the third consecutive day the administration results in at least one of an increase from baseline in daily Good ON-time, a reduction from baseline in daily ON-time with moderate-severe dyskinesia, a reduction from baseline in daily OFF-time, an increase from baseline in daily ON-time without dyskinesia, a reduction from baseline in total daily troublesome dyskinesia, or an improvement in UPDRS Part III score.
Specified levodopa and carbidopa concentrations with delivered amounts over 24 hours
Administering a pharmaceutically acceptable liquid composition comprising about 60 mg/ml levodopa and 7.5 mg/mL carbidopa, and administering the composition to deliver about 720 mg of levodopa and about 90 mg of carbidopa over about 24 hours.
Increasing good on-time by the third day
A method of increasing Good ON-time in a patient with Parkinson’s disease, wherein by the third consecutive day the administration results in an increase from baseline of at least about 0.3 to 3.5 hours in daily Good ON-time.
The independent-claim coverage is directed to substantially continuous subcutaneous administration for about 24 hours/day over about 2 to 3 consecutive days of a liquid levodopa/carbidopa composition at about an 8:1 w/w ratio with arginine, where by the third consecutive day the patient achieves at least one predefined improvement in Good ON-time and/or related ON/OFF, dyskinesia, or UPDRS Part III outcomes. One independent claim additionally specifies the liquid’s levodopa and carbidopa concentrations and the delivered total amounts over about 24 hours, and another independent claim specifically requires an increase in daily Good ON-time by the third day.
Stated Advantages
Increased daily Good ON-time.
Reduced daily ON-time with moderate-severe dyskinesia.
Reduced daily OFF-time.
Increased daily ON-time without dyskinesia.
Reduced total daily troublesome dyskinesia.
Improved motor experiences of daily living as assessed by a reduction from baseline in UPDRS Part III score.
Documented Applications
Treating Parkinson’s disease in a patient using substantially continuous subcutaneous administration of a liquid levodopa/carbidopa composition with arginine, with outcome changes measured by daily Good ON-time, daily ON-time with and without dyskinesia, daily OFF-time, total daily troublesome dyskinesia, and UPDRS Part III score.
Increasing Good ON-time in a patient with Parkinson’s disease by substantially continuous subcutaneous administration for about 24 hours/day over about 2 to 3 consecutive days.
Concomitant administration of an oral levodopa/carbidopa-DDCI composition together with a subcutaneous levodopa/carbidopa-DDCI regimen.
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