Conversion to IPX066 from standard levodopa formulations in advanced Parkinson's disease: experience in clinical trials

Paul A. Nausieda, Ann Hsu, Lawrence Elmer, Ramon A. Gil, Joerg Spiegel, Carlos Singer, Sarita Khanna, Robert Rubens, Sherron Kell, Nishit B. Modi, Suneel Gupta

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background: Due to the short half-life of levodopa, immediate-release carbidopa-levodopa (IR CD-LD) produces fluctuating LD concentrations, contributing to a risk of eventual motor complications. IPX066 was designed to rapidly attain therapeutic LD concentrations and maintain them to allow a dosing interval of ∼6 hours. Objective: To extensively analyze the dosing data collected in IPX066 studies during open-label conversions from IR CD-LD alone or with entacapone (CLE) and identify patterns relevant for managing conversion in the clinical setting. Methods: Patients had ≥2.5 hours/day of off time despite a stable IR or CLE regimen. Suggested initial dosing conversion tables based on prior LD daily dosage were provided. Results: Of 450 patients previously treated with IR CD-LD and 110 with CLE, 87.3% and 82.7% completed conversion to IPX066, respectively. At the end of conversion, average IPX066 LD daily dosages were higher than pre-conversion dosages, with a mean conversion ratio of 2.1±0.6 for IR CD-LD and 2.8±0.8 for CLE; >90% of patients took IPX066 3 or 4 times/day, compared with a median of 5 times/day at baseline in both studies. After conversion, daily off time significantly decreased, with no significant increase in troublesome dyskinesia. The most common adverse event reported during conversion was nausea, with an incidence of 5.3% for conversion from IR and 7.3% from CLE. Conclusions: Among PD patients with substantial off time, a majority were safely converted to IPX066. The sustained LD profile from the IPX066 formulation allowed an increase in LD dose accompanied by improved motor functions, without increased troublesome dyskinesia.

Original languageEnglish (US)
Pages (from-to)837-845
Number of pages9
JournalJournal of Parkinson's Disease
Volume5
Issue number4
DOIs
StatePublished - Nov 21 2015

Fingerprint

Levodopa
Parkinson Disease
Clinical Trials
Dyskinesias
levodopa drug combination carbidopa
Nausea
Half-Life

Keywords

  • dyskinesia
  • extended-release
  • Levodopa
  • off-time
  • on-time
  • Parkinsons disease

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

Conversion to IPX066 from standard levodopa formulations in advanced Parkinson's disease : experience in clinical trials. / Nausieda, Paul A.; Hsu, Ann; Elmer, Lawrence; Gil, Ramon A.; Spiegel, Joerg; Singer, Carlos; Khanna, Sarita; Rubens, Robert; Kell, Sherron; Modi, Nishit B.; Gupta, Suneel.

In: Journal of Parkinson's Disease, Vol. 5, No. 4, 21.11.2015, p. 837-845.

Research output: Contribution to journalArticle

Nausieda, PA, Hsu, A, Elmer, L, Gil, RA, Spiegel, J, Singer, C, Khanna, S, Rubens, R, Kell, S, Modi, NB & Gupta, S 2015, 'Conversion to IPX066 from standard levodopa formulations in advanced Parkinson's disease: experience in clinical trials', Journal of Parkinson's Disease, vol. 5, no. 4, pp. 837-845. https://doi.org/10.3233/JPD-150622
Nausieda, Paul A. ; Hsu, Ann ; Elmer, Lawrence ; Gil, Ramon A. ; Spiegel, Joerg ; Singer, Carlos ; Khanna, Sarita ; Rubens, Robert ; Kell, Sherron ; Modi, Nishit B. ; Gupta, Suneel. / Conversion to IPX066 from standard levodopa formulations in advanced Parkinson's disease : experience in clinical trials. In: Journal of Parkinson's Disease. 2015 ; Vol. 5, No. 4. pp. 837-845.
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abstract = "Background: Due to the short half-life of levodopa, immediate-release carbidopa-levodopa (IR CD-LD) produces fluctuating LD concentrations, contributing to a risk of eventual motor complications. IPX066 was designed to rapidly attain therapeutic LD concentrations and maintain them to allow a dosing interval of ∼6 hours. Objective: To extensively analyze the dosing data collected in IPX066 studies during open-label conversions from IR CD-LD alone or with entacapone (CLE) and identify patterns relevant for managing conversion in the clinical setting. Methods: Patients had ≥2.5 hours/day of off time despite a stable IR or CLE regimen. Suggested initial dosing conversion tables based on prior LD daily dosage were provided. Results: Of 450 patients previously treated with IR CD-LD and 110 with CLE, 87.3{\%} and 82.7{\%} completed conversion to IPX066, respectively. At the end of conversion, average IPX066 LD daily dosages were higher than pre-conversion dosages, with a mean conversion ratio of 2.1±0.6 for IR CD-LD and 2.8±0.8 for CLE; >90{\%} of patients took IPX066 3 or 4 times/day, compared with a median of 5 times/day at baseline in both studies. After conversion, daily off time significantly decreased, with no significant increase in troublesome dyskinesia. The most common adverse event reported during conversion was nausea, with an incidence of 5.3{\%} for conversion from IR and 7.3{\%} from CLE. Conclusions: Among PD patients with substantial off time, a majority were safely converted to IPX066. The sustained LD profile from the IPX066 formulation allowed an increase in LD dose accompanied by improved motor functions, without increased troublesome dyskinesia.",
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AU - Hsu, Ann

AU - Elmer, Lawrence

AU - Gil, Ramon A.

AU - Spiegel, Joerg

AU - Singer, Carlos

AU - Khanna, Sarita

AU - Rubens, Robert

AU - Kell, Sherron

AU - Modi, Nishit B.

AU - Gupta, Suneel

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AB - Background: Due to the short half-life of levodopa, immediate-release carbidopa-levodopa (IR CD-LD) produces fluctuating LD concentrations, contributing to a risk of eventual motor complications. IPX066 was designed to rapidly attain therapeutic LD concentrations and maintain them to allow a dosing interval of ∼6 hours. Objective: To extensively analyze the dosing data collected in IPX066 studies during open-label conversions from IR CD-LD alone or with entacapone (CLE) and identify patterns relevant for managing conversion in the clinical setting. Methods: Patients had ≥2.5 hours/day of off time despite a stable IR or CLE regimen. Suggested initial dosing conversion tables based on prior LD daily dosage were provided. Results: Of 450 patients previously treated with IR CD-LD and 110 with CLE, 87.3% and 82.7% completed conversion to IPX066, respectively. At the end of conversion, average IPX066 LD daily dosages were higher than pre-conversion dosages, with a mean conversion ratio of 2.1±0.6 for IR CD-LD and 2.8±0.8 for CLE; >90% of patients took IPX066 3 or 4 times/day, compared with a median of 5 times/day at baseline in both studies. After conversion, daily off time significantly decreased, with no significant increase in troublesome dyskinesia. The most common adverse event reported during conversion was nausea, with an incidence of 5.3% for conversion from IR and 7.3% from CLE. Conclusions: Among PD patients with substantial off time, a majority were safely converted to IPX066. The sustained LD profile from the IPX066 formulation allowed an increase in LD dose accompanied by improved motor functions, without increased troublesome dyskinesia.

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