摘要:

ObjectiveThe aim of this study was to investigate the analgesic efficacy of Neodolpasse®, a fixed-dose combination of orphenadrine and diclofenac, compared with those of its single active ingredients in a human pain model.MethodsThe study was designed as a randomised, double-blind, placebo-controlled, four-period crossover study. Twenty-four healthy female and male subjects received single infusions of Neodolpasse®, orphenadrine, diclofenac or saline solution over 60 minutes. Infusions were separated by a 1-week washout period. Neurogenic inflammation and hyperalgesia were induced by topical occlusive application of a 1% capsaicin solution for 30 minutes on defined skin areas on the back. The pain response to CO2laser pulses applied to the capsaicin-pretreated skin was measured by event-related vertex EEG recordings. This allowed us to study the influence of a single infusion on the central P2- and peripheral N1-components of laser-induced somatosensory-evoked potentials (LSEP) as a measure of pain response.ResultsAlthough none of the active treatments had a significant effect on the peripheral N1-component, all active treatments reduced the P2-component of the LSEP, reflecting central/spinal analgesic (anti-hyperalgesic) effects. These effects were statistically significant for orphenadrine (p < 0.0001) and for the combination of orphenadrine and diclofenac (p < 0.0013). The single ingredient diclofenac reduced the P2-component by a value just below clinical relevance (p < 0.0848).ConclusionThis study demonstrated the efficacy of Neodolpasse®in a human pain model. The observed effect was mainly caused by central mechanisms and was found to be superior for the fixed-dose combination of orphenadrine and diclofenac compared with the individual ingredients. Both components contributed to the effect of the combination in an additive fashion, which can be explained by the different molecular mechanisms of action of each drug.

ISSN:1174-5886    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

ObjectiveTo investigate the effect of food on the pharmacokinetics of eslicarbazepine acetate (BIA 2-093), a new voltage-gated sodium channel antagonist.Material and methodsSingle-centre, open-label, randomised, two-way crossover study in 12 healthy subjects. The study consisted of two consecutive treatment periods separated by a washout of 14 days or more. In each of the study periods subjects were administered a single dose of eslicarbazepine acetate 800mg following either a standard high-fat content meal or 10 hours of fasting.ResultsEslicarbazepine acetate was rapidly and extensively metabolised to BIA 2-005. Maximum BIA 2-005 plasma concentrations (Cmax) in fed (test) and fasting (reference) conditions were, respectively, 12.8 ± 1.8 µg/mL and 11.3 ± 1.9 µg/mL, and the areas under the plasma concentration time curve from 0 to infinity (AUC∞) were, respectively, 242.5 ± 32.1 µg · h/mL and 243.6 ± 31.1 µg · h/mL (arithmetic mean ± SD). The point estimate (PE) and 90% confidence interval (90% CI) of the test/reference Cmaxgeometric mean ratio were 1.14 and 1.04, 1.25, respectively; for the AUC∞ratio, the PE and 90% CI were 1.00 and 0.95, 1.04, respectively. Bioavailability of eslicarbazepine acetate administered in fed and fasting conditions was similar and bioequivalence is accepted for both AUC∞and Cmaxbecause the 90% CI lies within the acceptance range of 0.80–1.25. No statistically significant differences were found in time of occurrence of Cmax.ConclusionThe presence of food had no significant effect on the pharmacokinetics of eslicarbazepine acetate and therefore this new voltage-gated sodium channel antagonist may be administered without regard to meals.

ISSN:1174-5886    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

BackgroundPolicosanol is a mixture of higher aliphatic primary alcohols purified from sugar-cane wax. The mixture has cholesterol-lowering efficacy, its specific effects being to reduce serum total (TC) and low-density lipoprotein cholesterol (LDL-C), and to increase high-density lipoprotein cholesterol (HDL-C). The effects of policosanol on triglycerides (TG) are modest and inconsistent. Omega-3 fatty acids (FA) from fish oil protect against coronary disease, mainly through antiarrhythmic and antiplatelet effects. Omega-3 FA also have lipid-modifying effects, mostly relating to TG reduction. Thus, potential benefits could be expected from combined therapy with omega-3 FA and policosanol.Four patients (two in the omega-3 FA + placebo group and two in the omega-3 FA + policosanol 10 mg/day group) withdrew from the study; none of these withdrawals was due to AEs. Two patients reported mild AEs, namely nausea/headache (one in the omega-3 FA + placebo group) and heartburn (one in the omega-3 FA + policosanol 5 mg/day group).ObjectiveTo investigate whether combined therapy with omega-3 FA + policosanol offers benefits compared with omega-3 FA + placebo with respect to the lipid profile of patients with type II hypercholesterolaemia.Four patients (two in the omega-3 FA + placebo group and two in the omega-3 FA + policosanol 10 mg/day group) withdrew from the study; none of these withdrawals was due to AEs. Two patients reported mild AEs, namely nausea/headache (one in the omega-3 FA + placebo group) and heartburn (one in the omega-3 FA + policosanol 5 mg/day group).MethodsThis randomised, double-blind study was conducted in 90 patients with type II hypercholesterolaemia. After 5 weeks on a cholesterol-lowering diet, patients were randomised to omega-3 FA + placebo, omega-3 FA + policosanol 5 mg/day or omega-3 FA + policosanol 10 mg/day for 8 weeks. Omega-3 FA was supplied as 1g capsules (two per day); placebo and policosanol were provided in tablet form. Physical signs and laboratory markers were assessed at baseline and after 4 and 8 weeks on therapy. Drug compliance and adverse experiences (AEs) were assessed at weeks 4 and 8. The primary efficacy variable was LDL-C reduction; other lipid profile markers were secondary variables.Four patients (two in the omega-3 FA + placebo group and two in the omega-3 FA + policosanol 10 mg/day group) withdrew from the study; none of these withdrawals was due to AEs. Two patients reported mild AEs, namely nausea/headache (one in the omega-3 FA + placebo group) and heartburn (one in the omega-3 FA + policosanol 5 mg/day group).ResultsAfter 8 weeks, omega-3 FA + policosanol 5 and 10 mg/day, but not omega-3 FA + placebo, significantly reduced LDL-C by 21.1% and 24.4%, respectively (both p < 0.0001). Omega-3 FA + policosanol 5 mg/day also significantly lowered TC (12.7%; p < 0.01) and TG (13.6%; p < 0.05), and significantly increased HDL-C (+14.4%; p < 0.001). Omega-3 FA + policosanol 10 mg/day significantly decreased TC (15.3%; p < 0.001) and TG (14.7%; p < 0.01), and significantly increased HDL-C (+15.5%; p < 0.0001). Omega-3 FA + placebo significantly reduced TG (14.2%; p < 0.05) but had no significant effect on other lipid profile variables. The proportion of randomised patients in the omega-3 FA + policosanol 5 or 10 mg/day groups that achieved LDL-C targets or reductions ≥15% was significantly greater than in the omega-3 FA + placebo group (p < 0.001). Combined therapy with omega-3 FA + policosanol 5 or 10 mg/day resulted in significantly greater changes in LDL-C, TC and HDL-C than treatment with omega-3 FA + placebo, but did not modify the TG response compared with the omega-3 FA + placebo group.Four patients (two in the omega-3 FA + placebo group and two in the omega-3 FA + policosanol 10 mg/day group) withdrew from the study; none of these withdrawals was due to AEs. Two patients reported mild AEs, namely nausea/headache (one in the omega-3 FA + placebo group) and heartburn (one in the omega-3 FA + policosanol 5 mg/day group).ConclusionsPolicosanol 5 or 10 mg/day administered concomitantly with omega-3 FA 1 g/day improved LDL-C, TC and HDL-C, maintained the reduction in TG attributable to omega-3 FA monotherapy, and was well tolerated. Treatment with omega-3 FA + policosanol could be useful for regulating lipid profile in patients with type II hypercholesterolaemia, but further studies involving larger sample sizes are needed before definitive conclusions can be drawn.

ISSN:1174-5886    

出版商:ADIS    

年代:2005

数据来源: ADIS

ISSN:1174-5886    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

Fumapharm AG has developed a second-generation fumarate (fumaric acid) derivative, BG 12 [BG 00012, FAG-201, BG 12/Oral Fumarate], for the oral treatment of psoriasis. Biogen Idec is currently evaluating the product in clinical trials as an oral treatment for multiple sclerosis (phase II) and psoriasis (phase III) trials.BG 12 has an immunomodulatory mechanism of action. It seems that this product has been developed to reduce the adverse effects associated with a first-generation product containing fumaric acid esters (mixed dimethylfumarate and monoethylfumarate salts), Fumaderm®. Fumaderm®was approved in Germany in August 1994 and is currently the leading oral systemic therapy for moderate-to-severe psoriasis in Germany. One of the problems associated with Fumaderm®capsules has been its gastrointestinal adverse effects (including diarrhoea and nausea).In September 2003, Biogen (now Biogen Idec) licensed exclusive worldwide rights (excluding Germany) from Fumapharm to develop and market BG 12. Biogen plans to collaborate with Fumapharm to accelerate phase III development for psoriasis and the registration programme worldwide. Financial terms of the agreement were not disclosed. Development plans for BG 12 include other autoimmune and inflammatory disorders, such as multiple sclerosis.[1,2]In November 2003, Biogen and IDEC Pharmaceuticals merged to form Biogen Idec. Fumapharm completed phase II trials of this second-generation fumarate derivative for psoriasis prior to licensing of the product to Biogen, also with positive results.[1]

ISSN:1174-5886    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

Connetics Corporation (USA) has licensed a first-in-class, dual-action 1% clindamycin/0.025% tretinoin aqueous gel [Clindamycin phosphate/tretinoin gel, Velac®, Velac®Gel] from Yamanouchi Europe BV. The product combines the anti-inflammatory and antibacterial properties of clindamycin with the beneficial effects of tretinoin [all-trans-retinoic acid], and is in phase III trials for the treatment of acne.On 1 April 2005, Yamanouchi merged with Fujisawa to form Astellas Pharma.Connetics has exclusive development and commercialisation rights for clindamycin/tretinoin gel in the US and Canada, and has non-exclusive rights to the product in Mexico. Under the licensing agreement terms, Connetics initially paid Yamanouchi a $US2 million licensing fee, as well as milestone payments and royalties on future products.[1]In the fourth quarter of 2002, a $US2 million milestone payment was made to Yamanouchi following the initiation of pivotal phase III trials in the US and Canada, and in the third quarter of 2004 a $US3 million milestone payment was made to Yamanouchi following the filing of an NDA to the US FDA.In March 2004, Connectics reported that clindamycin/tretinoin is approved in Europe. It appears that this approval was specifically for France.[2,3]In October 2004, Connetics announced that the US FDA has accepted its NDA filing for clindamycin/tretinoin.[4]Two pivotal phase III trials of clindamycin/tretinoin have been conducted in the US and Canada. These trials included 2219 patients with acne who received 12 weeks' treatment in the double-blind, placebo- and active-controlled trials. Results of these trials were reported in March 2004.[2]Connetics anticipates launch of the product during mid-2005. An action date of 25 June 2005 has been given by the FDA for it to respond to the NDA submission.Phase III trials in patients with acne in Europe have shown clindamycin/tretinoin gel to be as effective and safe as other leading topical therapies. Data from a combined analysis of six controlled efficacy and safety trials of clindamycin/tretinoin have been reported.[5]The patent for clindamycin/tretinoin gel is held by Yamanouchi in the US and internationally.Other analysts, at CIBC World Markets, were quoted saying that Evoclin™ represents Connetics' ‘first foray’ into the acne market (followed by others, such as Velac®), a market that has been valued at $US1.7 billion, of which that for topical antibiotics is worth approximately $US500 million.

ISSN:1174-5886    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

Hexyl aminolevulinate [aminolevulinic acid hexyl ester, hexyl 5-aminolevulinate, 5-ALA hexylester, hexaminolevulinate, Hexvix®, Hexvix®PD, Hexvix®PDT, P 1206] is being developed by PhotoCure, a Norwegian company, for the diagnosis and treatment of bladder cancer.The current standard diagnosis of bladder cancer involves cystoscopic examination of urine and bladder washings and is combined with biopsy for better detection of low-grade malignancies. However, the method largely relies on the experience of the surgeon and often results in false negatives especially for low-grade malignancies and pre-cancerous tissues.Photocure believes that imaging with hexyl aminolevulinate (Hexvix®) offers significant advantages over standard diagnostic methods for detection of bladder cancer and also can be used in combination with those to ensure the optimal diagnostic accuracy.PhotoCure's procedure for diagnosis of bladder cancer involves filling of the patient's bladder with hexyl aminolevulinate solution and allowing the active agent to accumulate in the cancerous tissue. Following bladder emptying, blue light illumination is applied to the bladder causing red fluorescence that is clearly visible, thus identifying the cancerous tissue. Imaging with hexyl aminolevulinate improves detection of bladder tumours and also can be used together with transurethral resection to check the completeness of tumour removal.PhotoCure is looking for the opportunity to out-license hexaminolevulinate for all regions except the Nordic regions.PhotoCure has proprietary rights for hexyl aminolevulinate from the Norwegian Radium Hospital. Under the terms of the agreement with the Norwegian Radium Hospital, PhotoCure gains an access to, and an option to acquire, all of the new photodynamic therapy technologies developed by the Norwegian Radium Hospital. For its part, PhotoCure provides research and development funding to the Norwegian Radium Hospital. This 3-year agreement was extended in February 2003 until December 2006.PhotoCure and Karl Storz GmbH of Germany have signed a formal collaboration for the development and marketing of hexyl aminolevulinate (Hexvix®) and Karl Storz's D-light system. The two systems will be used in the diagnosis of bladder cancer. PhotoCure and Karl Storz GmbH will jointly apply for a marketing approval of hexyl aminolevulinate (Hexvix®) and Karl Storz' D-light system in the US for detection of bladder cancer.[1]The D-light system is already approved in Europe.[2]PhotoCure has also formed a collaborative agreement with the Swiss Federal Institute of Lausanne and the Municipal University Hospital in Lausanne. These institutions have conducted preclinical studies and some exploratory clinical research on the active ingredient of Hexvix®in approximately 100 patients.The first MAA for hexyl aminolevulinate fluorescence was filed in Sweden, the reference member state, in December 2002,[3]and was approved in September 2004.[4]PhotoCure plans to launch hexyl aminolevulinate in Sweden in June 2005.[5]Phase II clinical trials were conducted in 52 patients with known or suspected bladder cancer at the university clinics in Switzerland, Germany, Sweden and Norway. Clinical data suggests that hexyl aminolevulinate (Hexvix®) is useful in the early diagnosis of bladder cancers allowing treatment to be performed at an earlier stage and, thus, improve the chance of a successful clinical outcome.The company believes that the data from the US phase III programme at 19 leading urology clinics and two multicentre European trials at 28 leading hospitals across nine countries, will sufficiently support an NDA with the US FDA.The US phase III programme with hexyl aminolevulinate was initiated in December 2001.The results from the first European multicentre study conducted in 19 centres in 286 patients confirmed the advantages of hexaminolevulinate fluorescence cystoscopy over standard white light cystoscopy in the detection of bladder cancer.[6]The second multicentre phase III study at ten centres in Germany and the Netherlands in 146 patients with known or suspected bladder cancer was sucessfully completed in March 2003. The independent blind reviewer acknowledged that imaging with hexyl aminolevulinate would result in better treatment options in every fifth patient compared with standard cystoscopy.[7]Hexaminolevulinate is also undergoing early feasibility studies for the diagnosis and treatment of gynaecological and gastrointestinal conditions.PhotoCure was granted a European patent No. 0820432 covering hexyl aminolevulinate, an active ingredient used in Hexvix®for the diagnosis and treatment of bladder cancer. The company was also granted patents in Australia, China, the Czech Republic, New Zealand, Russia, Singapore, South Korea and the US.

ISSN:1174-5886    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

Icatibant [HOE 140, JE 049] is a potent, specific and selective peptidomimetic bradykinin B2-receptor antagonist. It has a modified peptide structure, and is the first bradykinin receptor antagonist to act on the guinea-pig trachea without demonstrating agonist effects. Icatibant was originated by Hoechst Marion Roussel (now sanofi-aventis).Jerini AG is seeking a worldwide partner for the development and marketing of icatibant for the treatment of refractory ascites in liver cirrhosis and seeking a partner in Asia, North America, South America and Australia for angioedema.In August 2004, Aventis merged with Sanofi-Synthelabo to form sanofi-aventis.Icatibant has shown an excellent safety profile in phase I studies. In December 2003, Jerini demonstrated positive results in the phase IIa study. Results obtained were statistically significant and clinically relevant. At the BIO 2004 International Annual Convention (BIO-2004) [San Francisco, CA, USA; 6–9 June 2004], Jerini reported plans to initiate phase IIb trials in this indication in the second half of 2004.[1]It was announced in September 2004 by Jerini that a pivotal registration study, known as FAST 1 (For Angioedema Subcutaneous Treatment), had been initiated in the US and Canada. The protocol of a European study, known as FAST 2, was submitted to the authorities in September 2004. Jerini is currently conducting pivotal/registration trials for angioedema in the US, Canada and Europe.[2]During the 3rd Annual BioPartnering North America Conference (BPN-2005), Jerini announced that it expects to complete registration trials in the second half of 2005/first half of 2006, with a launch of icatibant for HAE in 2007.[3]The US FDA granted fast-track status to icatibant in July 2004 for the treatment of HAE.[4]Effective December 2003, icatibant gained orphan drug status in the US for the same indication.[5]Previously, in January 2003, the European Agency for the Evaluation of Medicinal Products granted icatibant orphan drug status in Europe for the treatment of angioedema.

ISSN:1174-5886    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

Lubiprostone [RU 0211, SPI 0211] is a bicyclic fatty acid that acts as a chloride channel opener, increasing intestinal water secretion. Lubiprostone, an orally-administered formulation, is one of a series of functional fatty acid compounds discovered by Dr Ryuji Ueno, and is currently undergoing development for the treatment of constipation, constipation-predominant irritable bowel syndrome (IBS-C) and postoperative ileus with Sucampo Pharmaceutical's.Lubiprostone activates a specific chloride channel (CLC2) on cells lining the gut, thereby naturally increasing intestinal fluid secretion. The increased fluid level softens the stool, promotes spontaneous bowel movements, and reduces abdominal discomfort/pain and bloating. The chloride channel is a protein that controls cell membrane transport of chloride ion. Lubiprostone acts on the ClC-2 chloride channel, which is located in the apical intestinal membrane.In November 2004, Takeda Pharmaceuticals entered into a collaboration and licensing agreement for Lubiprostone with Sucampo Pharmaceuticals for the treatment of chronic constipation and constipation-predominant Irritable Bowel Syndrome (c-IBS). Under the terms of the agreement, Takeda received the right to market the product in the US and Canada, while Sucampo reserved the co-promotion rights for these countries. Takeda's wholly-owned US subsidiary, Takeda Pharmaceuticals North America Inc., will sell lubiprostone once the product is approved by the US FDA. Takeda will also receive an option for marketing rights in other territories, including Japan and Europe. Takeda and Sucampo agreed on the exclusive manufacturing and supply of Lubiprostone by R-Tech Ueno, Ltd, a member of the Sucampo Group. Sucampo has the potential to receive up to $US 210 million in initial and milestone payments, some of which are contingent upon the successful achievement of several milestones. Takeda will fund a major part of development costs not only for chronic constipation and c-IBS, but also for other indications in the gastroenterology field. Takeda will make royalty payments to Sucampo after the product is launched.[1]In May 2005, Sucampo received $US 20 million from Takeda Pharmaceutical as payment for achieving a development milestone of initiating a phase III clinical trial of lubiprostone to treat patients with constipation-predominant irritable bowel syndrome.[2]Sucampo Pharmaceuticals submitted a new drug application (NDA) for lubiprostone to the FDA on 31 March 2005 for approval in the treatment of chronic idiopathic constipation (CIC) and associated symptoms in adults.[3]Sucampo completed three long-term, open-label safety studies, which will support the NDA for lubiprostone, in treating constipation. Results from its second open-label safety study with lubiprostone were announced in February 2004, with the first two studies demonstrating long-term safety and sustained effectiveness in constipated subjects. In the US, the final phase III study for chronic constipation was completed in the fourth quarter of 2004.[1]In November 2004, Sucampo announced completing a phase II safety and efficacy study of lubiprostone for the treatment of IBS-C. This study, which was initiated in April 2003, randomised 195 patients with documented IBS into four treatment groups (three doses of SPI 0211 and placebo) from 19 locations throughout the US.[3]

ISSN:1174-5886    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

Rufinamide [E 2080, CGP 33101, RUF 331, Inovelon®, Xilep™] is the lead compound in a series of five-substituted phenylalkyl-3- carbamoyl-4H-1,2,4-triazoles with anticonvulsant activity that was discovered by Novartis AG. Although the precise mechanism of action for rufinamide is unknown, it is known that it limits the firing of sodium-dependent action potentials in neurons, hinting at a membrane-stabilising effect.Rufinamide is under regulatory review in Europe for epilepsy, and phase III trials in the same indication are underway with Eisai in the US.In February 2004, Eisai Co. Ltd announced that it had signed an in-licensing agreement with Novartis Pharma AG for the exclusive worldwide rights to manufacture, develop and market rufinamide for the treatment of epilepsy.[1]Eisai submitted an MAA for rufinamide (Inovelon®) as an adjunct therapy of seizures associated with Lennox-Gastaut Syndrome to the European Medicines Agency through the centralised procedure in March 2005. The drug also received orphan drug designation from the European commission in October 2004 for this indication.[2]Eisai also plans to file for regulatory approval in the US.[1]Rufinamide has demonstrated statistically significant efficacy as an adjunctive therapy in adult patients with epilepsy and in patients with seizures associated with Lennox-Gastaut syndrome.Novartis stated in June 2001, prior to the licensing agreement with Eisai, that it had stopped development of rufinamide in the US, Japan and Europe for neuropathic pain (at phase II) and epilepsy (at phase III).[1]

ISSN:1174-5886    

出版商:ADIS    

年代:2005

数据来源: ADIS