Introduction: Carbidopa-levodopa extended-release capsules (ER CD-LD, IPX066) significantly improve motor symptoms and activities of daily living in early and advanced Parkinson’s disease (PD). ER CD-LD produces an initial peak in plasma levodopa concentrations at about one hour, which are maintained for about 4–5 hours before declining. Methods: ER CD-LD was studied in three Phase 3 controlled trials, one in early PD vs. placebo and two in advanced PD: one vs. immediate-release (IR) CD-LD and one vs. IR CD-LD+entacapone (CLE). For each study, adverse events (AEs) were collected at each visit and comparative summaries were examined in patients categorized by age groups of <65, 65–74, and ≥75 years old. Results: Of the 849 patients treated with ER CD-LD in controlled trials, 431 (50.8%) were of age <65, 310 (36.5%) were 65–74, and 108 (12.7%) were ≥75 years old. The percent of patients reporting ≥1 AE in each age group (<65, 65–74, ≥75 years) were 54.1%, 60.0%, and 64.8%, respectively. AEs reported by ≥5% in any age group (<65, 65–74, ≥75 years) were nausea (9.7%, 11.0%, 11.1%), headache (7.9%, 7.1%, 3.7%), dizziness (6.0%, 9.4%, 8.3%), dyskinesia (5.8%, 4.8%, 5.6%), insomnia (5.3%, 3.5%, 3.7%), and constipation (2.3%, 1.6%, 7.4%). Conclusions: In this population of PD patients treated with ER CD-LD in the Phase 3 clinical studies, the number of patients reporting ≥1 AE increased with increasing age. Of the most frequent AEs, headache decreased with increasing age, but no clear pattern of AE frequency emerged for nausea, dizziness, dyskinesia, insomnia or constipation.

Introduction: Carbidopa-levodopa extended-release capsules (ER CD-LD, IPX066) significantly improves motor symptoms and activities of daily living in early and advanced Parkinson’s disease (PD). ER CD-LD produces an initial peak in plasma levodopa concentrations at about one hour, which are maintained for about 4–5 hours before declining. Methods: The safety and efficacy of ER CD-LD vs. immediate-release (IR) CD-LD was examined in a randomized, double-blind, active-controlled, Phase 3 study. Efficacy measures (PD diary and Unified PD Rating Scale [UPDRS] Parts II [activities of daily living] + III [motor score]) were analyzed to evaluate the effect of concomitant use or non-use of dopamine agonists (DA), monoamine oxidase-B (MAO-B) inhibitors, or amantadine on the response to ER CD-LD. Results: In the overall study (N=393), ER CD-LD improved “off” time (P<.0001), “on” time without troublesome dyskinesia (P=.0002), and UPDRS Parts II+III scores (P<.0001) vs. IR CD-LD. Numerical improvements from baseline in PD diary measures and UPDRS Parts II+III were seen with ER CD-LD vs. IR CD-LD in each subgroup. Improvements in “off” time and “on” time without troublesome dyskinesia were significant (P<.05) for ER CD-LD vs. IR in each subgroup, except for the group using concomitant amantadine (P>.50). ER CD-LD did not significantly worsen “on” time with troublesome dyskinesia vs. IR in any subgroup (P>.11). The most frequent adverse events were similarly reported across subgroups. Conclusions: The concomitant use or non-use of adjunctive PD medications did not affect the efficacy or degree of troublesome dyskinesias when ER CD-LD was compared to IR CD-LD.

IPX066, an extended-release capsule formulation of carbidopa-levodopa (CD-LD), is designed to produce a rapid increase in plasma levodopa concentrations similar to immediate-release CD-LD (IR), but with sustained plasma levels allowing dosing every 6 hours. This post hoc analysis investigated whether baseline Parkinson’s disease (PD) severity influenced the patient reported efficacy of IPX066 vs. IR in advanced PD patients. IPX066 was evaluated in a randomized, double-blind, Phase 3 study vs. IR CD-LD for 13 weeks (N=393). Patients were split into subgroups of higher and lower disease severity based on median baseline “off” time (5.67 hr) and Unified Parkinson’s Disease Rating Scale (UPDRS) Parts II+III (score: 32). Patient Global Impression (PGI), and the change from baseline in “off” time and “on” time with troublesome dyskinesia by PD diary were analyzed for each subgroup. IPX066 significantly improved PGI (P<.0001) and “off” time (P<.0001) compared with IR CD-LD in the overall randomized population. IPX066 significantly improved PGI scores compared with IR CD-LD in both higher severity subgroups (P<.001) and lower severity subgroups (P<.02). Numerical improvements from baseline in “off” time were seen with IPX066 vs. IR CD-LD in each disease severity subgroup. The improvements in “off” time were significantly greater for IPX066 vs. IR CD-LD in the higher severity “off” (P<.0001) and in both the higher (P=.02) and lower severity (P=.0001) UPDRS subgroups. The improvement by IPX066 compared to IR CD-LD in the lower severity “off” subgroup did not reach significance (P=.11), possibly due to a floor effect. IPX066 did not significantly worsen “on” time with troublesome dyskinesia compared to IR CD-LD in any subgroup (P>.14). Advanced PD patients reported higher global impression of change and greater improvements in “off” time without worsening troublesome dyskinesia after treatment with IPX066 compared with IR CD-LD, regardless of disease severity subgroup.

European Journal of Pain SupplementsVolume 5, Issue S1 p. 277-277 S625 A PHARMACOKINETIC AND PHARMACODYNAMIC STUDY OF A PERIPHERAL κ-OPIOID RECEPTOR AGONIST CR665 AND OXYCODONE A.E. Olesen, A.E. Olesen Dept. of Gastroenterology, Mech-Sense, Aalborg Hospital, Aarhus University Hospital, Aalborg, DenmarkSearch for more papers by this authorK. Kristensen, K. Kristensen Department of Clinical Pharmacolgy & DMPK, AstraZeneca, Lund, Sweden; Aalborg University, Aalborg, DenmarkSearch for more papers by this authorC. Staahl, C. Staahl R & D, Grünenthal GmbH, Aachen, Germany; Aalborg University, Aalborg, DenmarkSearch for more papers by this authorF. Menzaghi, F. Menzaghi Research Development, Cara Therapeutics Inc., Shelton, CT, Aalborg University, Aalborg, DenmarkSearch for more papers by this authorS. Kell, S. Kell Impax Pharmaceuticals, Hayward, Aalborg University, Aalborg, Denmark ALZA Corporation, Mountain View, CA, USA; Aalborg University, Aalborg, DenmarkSearch for more papers by this authorG.Y. Wong, G.Y. Wong Impax Pharmaceuticals, Hayward, Aalborg University, Aalborg, Denmark ALZA Corporation, Mountain View, CA, USA; Aalborg University, Aalborg, DenmarkSearch for more papers by this authorA.M. Drewes, A.M. Drewes Dept. of Gastroenterology, Mech-Sense, Aalborg Hospital, Aarhus University Hospital, Aalborg, DenmarkSearch for more papers by this authorL. Arendt-Nielsen, L. Arendt-Nielsen Center for Sensory-Motor Interaction, Department of Health Science and Technology, Aalborg University, Aalborg, DenmarkSearch for more papers by this author A.E. Olesen, A.E. Olesen Dept. of Gastroenterology, Mech-Sense, Aalborg Hospital, Aarhus University Hospital, Aalborg, DenmarkSearch for more papers by this authorK. Kristensen, K. Kristensen Department of Clinical Pharmacolgy & DMPK, AstraZeneca, Lund, Sweden; Aalborg University, Aalborg, DenmarkSearch for more papers by this authorC. Staahl, C. Staahl R & D, Grünenthal GmbH, Aachen, Germany; Aalborg University, Aalborg, DenmarkSearch for more papers by this authorF. Menzaghi, F. Menzaghi Research Development, Cara Therapeutics Inc., Shelton, CT, Aalborg University, Aalborg, DenmarkSearch for more papers by this authorS. Kell, S. Kell Impax Pharmaceuticals, Hayward, Aalborg University, Aalborg, Denmark ALZA Corporation, Mountain View, CA, USA; Aalborg University, Aalborg, DenmarkSearch for more papers by this authorG.Y. Wong, G.Y. Wong Impax Pharmaceuticals, Hayward, Aalborg University, Aalborg, Denmark ALZA Corporation, Mountain View, CA, USA; Aalborg University, Aalborg, DenmarkSearch for more papers by this authorA.M. Drewes, A.M. Drewes Dept. of Gastroenterology, Mech-Sense, Aalborg Hospital, Aarhus University Hospital, Aalborg, DenmarkSearch for more papers by this authorL. Arendt-Nielsen, L. Arendt-Nielsen Center for Sensory-Motor Interaction, Department of Health Science and Technology, Aalborg University, Aalborg, DenmarkSearch for more papers by this author First published: 30 January 2012 https://doi.org/10.1016/S1754-3207(11)70955-5Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume5, IssueS1September 2011Pages 277-277 RelatedInformation

Kappa-opioid receptors are located on visceral pain fibres. JNJ-38488502 is a highly selective tetrapeptide kappa-opioid agonist with little access to the central nervous system and low risk of central nervous system side effects. The aim of the study was to evaluate the effects of i.v. JNJ-38488502 on sensations, including pain, during colonic distension. In a single-centre study, 23 healthy adult males underwent a single-dose, randomized, double-blind crossover study of JNJ-38488502 (0.42 mg kg(-1) i.v. infusion) vs placebo on left colon compliance, sensory thresholds and ratings during standard distensions. One participant could not undergo sensation studies. In the other 22, JNJ-38488502 increased colonic compliance (pressure at half-maximum volume 17.9 +/- 0.8 mmHg) compared to placebo (21.6 +/- 0.9 mmHg, P = 0.007). There was no significant effect on sensory thresholds which, however, were not reached by 44 mmHg in >50% of participants in both treatment phases. There were no significant treatment effects on sensory ratings to distensions at 8, 16, 24, 32 and 36 mmHg above baseline operating pressure. JNJ-38488502 was associated with increased urine output and plasma prolactin, consistent with kappa-opioid receptor activation. This study concluded that i.v. JNJ-38488502 induced kappa-opioid effects, but did not attenuate colonic sensations following random order colonic distension. Further studies of effects on pain sensations in health and disease are required.

The tolerability of dapoxetine, a short‐acting selective serotonin reuptake inhibitor being developed for premature ejaculation, was evaluated when coadministered with tamsulosin. Adult men on a stable dose of tamsulosin were randomized to also receive dapoxetine 30 or 60 mg, or placebo, in a crossover design. Supine and standing vital signs were measured on days 1 and 7. Plasma samples were collected for measurement of tamsulosin, dapoxetine, and dapoxetine metabolites. Coadministration of dapoxetine with tamsulosin did not alter orthostatic profiles or affect the incidence of orthostatic hypotension. Tamsulosin and dapoxetine pharmacokinetics were not altered. Adverse events were reported by 5.4%, 10.9%, and 23.2% of participants receiving tamsulosin with placebo, dapoxetine 30 mg, and dapoxetine 60 mg, respectively. The most common adverse events were diarrhea, dizziness, headache, and nausea. Therefore, dapoxetine had no clinically important effects on the pharmacokinetics or orthostatic profile of tamsulosin in men on a stable tamsulosin regimen.

OBJECTIVE:To investigate the efficacy and adverse effects of dapoxetine in the treatment of premature ejaculation. METHODS:We randomly assigned outpatients with premature ejaculation in the proportion of 2:1 to receive 30 mg dapoxetine on demand (n =78) or 50 mg sertraline qd for one month (n = 39). Follow-up was accomplished in 95 cases, 63 in the dapoxetine group and 32 in the sertraline group. We recorded the intravaginal ejaculatory latency time (IELT), clinical global impression of change (CGIC) score, and adverse reactions of the patients and compared them between the two groups. RESULTS:IELT was significantly increased in both the dapoxetine (from [0.87 ± 0.31] to [2.84 ± 0.68] min, P < 0.05) and the sertraline group (from [0.84 ± 0.28] to [2.71 ± 0.92] min, P < 0.05) after medication. Based on the CGIC scores in premature ejaculation, the rate of excellence or effectiveness was 36.5% in the dapoxetine and 37. 5% in the sertraline group, and the rate of improvement was 63.5% in the former and 71.9% in the latter. The incidence rates of dizziness, nausea, headache, and diarrhea were slightly higher (P > 0.05) while those of fatigue, somnolence, and dry mouth significantly higher (P < 0.05) in the sertraline than in the dapoxetine group. CONCLUSION:On-demand oral medication of dapoxetine is effective and well-tolerated for the treatment of premature ejaculation.

You have accessJournal of UrologyPodium, Monday, May 23, 2005, 1:00 - 3:00 pm1 Apr 2005877: Dapoxetine for the Treatment of Men with Premature Ejaculation (PE): Dose-Finding Analysis Wayne J.G. Hellstrom, Stanley E. Althof, Marc Gittelman, Christopher Steidle, Kai-Fai Ho, Sherron Kell, and Anders Nilsson-Neijber Wayne J.G. HellstromWayne J.G. Hellstrom , Stanley E. AlthofStanley E. Althof , Marc GittelmanMarc Gittelman , Christopher SteidleChristopher Steidle , Kai-Fai HoKai-Fai Ho , Sherron KellSherron Kell , and Anders Nilsson-NeijberAnders Nilsson-Neijber View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)35046-8AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "877: Dapoxetine for the Treatment of Men with Premature Ejaculation (PE): Dose-Finding Analysis." The Journal of Urology, 173(4S), p. 238 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 173Issue 4SApril 2005Page: 238 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Wayne J.G. Hellstrom More articles by this author Stanley E. Althof More articles by this author Marc Gittelman More articles by this author Christopher Steidle More articles by this author Kai-Fai Ho More articles by this author Sherron Kell More articles by this author Anders Nilsson-Neijber More articles by this author Expand All Advertisement PDF DownloadLoading ...