摘要:

ObjectiveTo compare the efficacy, tolerability and local tolerance of diclofenac sodium 0.1% containing hydroxypropylgamma cyclodextrin preserved with benzalkonium chloride 0.005% (Voltaren®Ophtha CD),1with that of diclofenac sodium 0.1% preserved with thiomersal 0.004% (Voltaren®Ophtha) in the treatment of inflammation after cataract-intraocular lens surgery.Design and settingRandomised 2:1, double-masked, parallel-group study in six centres in Germany.Study participants299 patients scheduled to undergo phacoemulsification with posterior chamber intraocular lens implantation.InterventionsStudy medications were instilled four times in the 30 minutes before surgery and four times daily from the first postoperative day.Main outcome measuresThe key efficacy variable was the reduction in anterior chamber flare (photons/millisecond) from day 1 to day 6 to 8. Patients underwent comprehensive ocular examinations, including laser flaremetry (KOWA), preoperatively and postoperatively at days 1, 6 to 8 and 24 to 32.Results268 patients (Voltaren®Ophtha CD 177, Voltaren®Ophtha 91) completed the day 6 to 8 visit without any protocol violations. Reduction in the degree of intraocular inflammation with Voltaren®Ophtha CD was equivalent to that achieved with Voltaren®Ophtha at the day 6 to 8 [95% confidence interval (CI) −3.07 to +0.54] and day 24 to 32 (95% CI −1.44 to +1.40) visits. Although there was no significant (p = 0.464) difference between the two study groups in patients’ global assessment of local tolerance at day 24 to 32, ocular discomfort was significantly (p = 0.023) less with Voltaren®Ophtha CD compared with Voltaren®Ophtha.ConclusionsVoltaren®Ophtha CD was as effective and well tolerated but had less ocular discomfort compared with Voltaren®Ophtha in the treatment of ocular inflammation after phacoemulsification with intraocular lens implantation. This new formulation of diclofenac sodium 0.1% may be used as an alternative to the existing formulations of ophthalmic diclofenac sodium 0.1%.

ISSN:1174-5886    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

Oculex Pharmaceuticals has developed a sustained release formulation of dexamethasone using their intraocular drug delivery system, Surodex®.1The product is indicated for use after cataract surgery to treat post-surgical inflammation. Surodex®is placed directly into the anterior chamber of the eye during cataract surgery. The biodegradable drug delivery capsule provides programmed release of dexamethasone in therapeutic, non-fluctuating levels.Surodex®has completed Phase III trials in the USA and Singapore. Bausch & Lomb will market Surodex®in North America and Europe.

ISSN:1174-5886    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

Loteprednol etabonate is a corticosteroid developed by Pharmos as a topical treatment for various ocular inflammatory conditions, particularly contact lens-associated giant papillary conjunctivitis.1It is also being developed for the treatment of allergic rhinitis and bronchial asthma. Loteprednol etabonate is a product of ‘soft drug’ design, which involves synthesis of a compound that undergoes predictable metabolism to inactive metabolites after its therapeutic effects have been expressed at or near the site of application. The aim of such drug development is to enhance efficacy while minimising systemic adverse effects.Agreement with Bausch & Lomb:In October 2001, it was announced that Bausch & Lomb had acquired all rights to the loteprednol eye medication business of Pharmos Corp, including future extensions of loteprednol etabonate formulations. Prior to this, Bausch & Lomb Pharmaceuticals had manufacturing and marketing rights from Pharmos for its ocular medications in the USA, Europe, Canada and other selected countries.Ophthalmic use in the Americas:Bausch & Lomb and Pharmos received an approvable letter from the FDA for ophthalmic use of loteprednol in the USA in September 1997. Pharmos had amended the original NDA submitted in 1995 to obtain marketing approval of Lotemax®for the treatment of both external (post-cataract surgery inflammation and allergic conjunctivitis) and internal (uveitis) ophthalmic inflammatory conditions. In March 1998, loteprednol 0.5% (Lotemax®) was approved by the FDA for inflammatory conditions of the cornea, conjunctiva and anterior segment of the eye, including postoperative ocular inflammation. A lower dose of loteprednol suspension (0.2%) was also approved by the FDA for use as symptomatic relief of seasonal allergic conjunctivitis as Alrex®. Lotemax®is now launched in the US market and has the broadest range of indications of the ophthalmic steroids available in the USA. Lotemax®and Alrex®have been approved in Argentina; Lotemax®was launched in this market in October 2000.Ophthalmic use in Europe:In December 1999, Pharmos Corporation submitted a registration application to the Medicines Control Agency for loteprednol etabonate 0.5% ophthalmic suspension for ophthalmic inflammatory indications in the UK. Upon approval, the product will be submitted by Bausch & Lomb Pharmaceuticals and Pharmos for approval in other European countries through a Mutual Recognition procedure. The product will be marketed as Loterox®in the UK. The European filing of Alrex®for seasonal allergic conjunctivitis is anticipated to occur shortly.Ophthalmic use in Asia and Oceania:In August 2000, Pharmos entered into a licensing agreement with Senju Pharmaceuticals that grants Senju rights to Pharmos’ formulation patent for loteprednol etabonate. Under this agreement, Senju may commercialise loteprednol using Pharmos’ ophthalmic formulation in Japan, Korea and Australia.Respiratory indications:Viatris in Europe is developing a nasal spray formulation of loteprednol in Phase II clinical studies for the treatment of allergic asthma and allergic rhinitis. Viatris is also developing a multidose dry-powder inhaled (MDPI) formulation of loteprednol for the treatment of asthma. The MDPI formulation is in preclinical trials. These formulations were originally developed by ASTA Medica. ASTA Medica was restructured during 2001, with the result that Viatris (formerly ASTA Medica Health Products) is now developing loteprednol.Dermatological indications:In October 2001, IVAX Corporation licensed worldwide rights to develop loteprednol etabonate for topical use in the treatment of dermatological conditions. The company stated at the time that it intended to initiate Phase II trials in the near future.

ISSN:1174-5886    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

ObjectiveThis study was conducted to investigate the effects of policosanol administered for 12 months on the lipid profile of older patients with hypertension and type II hypercholesterolaemia and no history of coronary heart disease (CHD) or cerebrovascular disease.Patients and participants589 older male and female patients with hypertension and type II hypercholesterolaemia and no history of CHD or cerebrovascular disease were included.MethodsThis was a prospective, randomised, double-blind, placebo-controlled study in parallel groups treated with policosanol (5 to 10 mg/day) for 1 year. After 6 weeks on a standard step I cholesterol-lowering diet, 589 patients were randomised to policosanol (5mg) or placebo tablets, to be taken once daily for 12 months. The dosage was doubled to 10 mg/day if total cholesterol values were >6.1 mmol/L after 6 months of therapy.ResultsPolicosanol significantly (p < 0.00001) lowered serum low-density lipoprotein-cholesterol (LDL-C) [20.5%], total cholesterol (TC) [15.4%], triglycerides (11.9%), LDL-C/high-density lipoprotein-cholesterol (HDL-C) ratio [22.2%] and TC/HDL-C ratio (20.1%), and increased (p < 0.0001) HDL-C (12.7%). The frequency of vascular and all-cause serious adverse events (SAEs) was lower (p < 0.05) in the policosanol recipients (two vascular SAEs, 0.7%; five all-cause SAEs, 1.7%) than in the placebo recipients (six vascular SAEs, 2.0%; 12 all-cause SAEs, 4.1%). Similarly, total adverse events (AEs) were less frequent in the policosanol-treated group (29; 9.8%) compared with the placebo group (52; 17.7%) [p < 0.01]. Three placebo recipients and no policosanol recipients died during the study as a result of myocardial infarction (two patients) and sudden cardiac arrest (one). Policosanol was well tolerated, and no drug-related disturbances in safety indicators were found. Policosanol significantly decreased systolic blood pressure (BP) compared with baseline and placebo, which could be an additional advantage in this population at high coronary risk.ConclusionsPolicosanol administered long term is effective in lowering LDL-C and TC as well as increasing HDL-C levels in older patients with hypertension and type II hypercholesterolaemia without a history of CHD or cerebrovascular disease. In addition, policosanol treatment also shows benefits in the occurrence of SAEs of vascular aetiology, on the general AE profile and the reduction of BP in treated patients compared with baseline.

ISSN:1174-5886    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

Avasimibe [CI 1011] is an ACAT inhibitor that was in development with Parke-Davis (Warner-Lambert) in the USA for the treatment of atherosclerosis and hyperlipidaemia.1In June 2000, Warner-Lambert merged with Pfizer and the resulting company retained the Pfizer name. Parke-Davis was integrated into Pfizer Global Research and Development.Pfizer is continuing development and avasimibe is in Phase III studies. Over 1300 patients have been treated for up to 1 year and initial results from these studies were expected mid-2001. However, they have not been reported.

ISSN:1174-5886    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

Pamaqueside [CP 148623] is a novel cholesterol-lowering compound that is in Phase III trials with Pfizer in the USA for the treatment of hypercholesterolaemia.1Pamaqueside is a synthetic saponin that functions by inhibiting intestinal absorption of cholesterol. In June 2000 Pfizer merged with Warner-Lambert. The resulting company retained the Pfizer name.

ISSN:1174-5886    

出版商:ADIS    

年代:2002

数据来源: ADIS

ISSN:1174-5886    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

Adefovir dipivoxil [GS 840, bis-POM PMEA, Piv2PMEA] is an ester prodrug of the nucleoside reverse transcriptase inhibitor adefovir, the prototype compound of the acyclic nucleosides phosphonates (ANP) class.1Unlike other ANP analogues, unmodified adefovir displays poor oral bioavailability, whereas adefovir dipivoxil is rapidly and completely converted to adefovir after oral administration. Gilead Sciences licensed the rights to develop adefovir dipivoxil from the Institute of Organic Chemistry and Biochemistry (IOCB) in the Czech Republic and the REGA Stichting Research Institute (REGA) in Belgium. The licensing agreement was amended in December 2000, and the royalty rate on future sales of adefovir dipivoxil, tenofovir disoproxil fumarate and cidofovir was reduced in return for an upfront payment of $US11.0 million from Gilead.Accelerated approval for adefovir dipivoxil as therapy for HIV infections was granted by the FDA in November 1998; however, nephrotoxicity developing around week 32 of a 48-week Phase II/III pivotal trial delayed completion of an NDA application. Gilead conducted most of the development of adefovir dipivoxil at 120mg but decided to pursue 60mg for marketing when nephrotoxicity was discovered during what was intended to be a pivotal trial. Gilead submitted an NDA for adefovir dipivoxil, the first anti-HIV nucleotide analogue to be reviewed by the FDA, for a recommended dose of 60mg once daily with the advice to reduce to 30mg if toxicity occurred. An additional NDA for an oral suspension formulation of the drug for a paediatric indication was also submitted. In November 1999, concerns about safety at the proposed 60mg dose led an FDA advisory committee to recommend the full agency not grant Gilead Sciences permission to market adefovir dipivoxil. Following this decision, Gilead decided to terminate development of adefovir dipivoxil 60mg for HIV infections stating that resources would be better utilised by being allocated to other development programs in the company pipeline. A Marketing Authorisation Application under the centralised licensing procedure had been made in the EU with Spain and the UK to act as rapporteur and co-rapporteur, respectively.Adefovir dipivoxil was distributed through an expanded access programme in the USA for patients with advanced HIV disease who had failed treatment with at least one protease inhibitor and two nucleosides. Entry criteria were expanded to provide adefovir dipivoxil to HIV-infected patients in need, regardless of CD4 count or HIV RNA level. Following the results of clinical trials demonstrating the effectiveness of 60mg administration, Gilead amended the expanded access protocol so all patients receiving a 120mg dose have their dose reduced to 60mg and all patients subsequently entering the programme started treatment with 60mg. This US-expanded access programme was extended to Europe, Canada and Australia. Following termination of the development programme of adefovir dipivoxil for HIV infections, Gilead stopped new enrolment in its US clinical trials and the expanded access programme. Patients receiving adefovir dipivoxil in US clinical trials have been given the opportunity to enrol in the expanded access programme.A multicentre Phase III trial (CPCRA 039) designed to assess adefovir dipivoxil (120mg once daily) in prolonging the survival of patients with CD4 counts ≥100 cells/mm3, was terminated early on a recommendation from the National Institutes of Health's National Institute of Allergy and Infectious Diseases (NIAID) Data and Safety Monitoring Board. Enrolment would have had to be increased from 2200 to 4000 patients to adequately study the primary endpoints due to the impact of new antiretroviral treatments on survival and disease progression.Gilead is continuing the development of adefovir dipivoxil for the treatment of hepatitis B for which the drug is administered at lower doses compared with HIV infection. Two pivotal Phase III trials are underway to evaluate adefovir dipivoxil monotherapy for this indication. Enrolment of patients has been completed for the study (GS437) investigating adefovir dipivoxil 10mg and 30mg once-daily doses over 48 weeks of treatment and 1 year of follow-up. 515 patients are participating in this study at centres in North America, Australia, Europe and Southeast Asia. The second pivotal Phase III trial (GS438), investigating adefovir dipivoxil 10mg, is being conducted at sites in Australia, France, Israel, Italy, Canada, Greece and South East Asia. The study is evaluating adefovir dipivoxil 10mg for the treatment of patients diagnosed with precore mutant chronic hepatitis B virus (HBV) infection, a strain of the virus that has evolved without the hallmark HBV ‘e’ antigen. Enrolment of 186 patients in this study was completed in June 2000. Due to the growing importance of lamivudine-resistant hepatitis B virus in liver transplant patients, Gilead is conducting an open-label study (GS435) to evaluate adefovir dipivoxil in this patient population in North America, Asia, Australia and Europe. GlaxoSmithKline (formerly Glaxo Wellcome), in collaboration with Gilead, is conducting a study evaluating once daily adefovir dipivoxil 10mg as combination therapy with lamivudine 100mg in chronic hepatitis B patients who have experienced diminished therapeutic response to lamivudine monotherapy. This 52-week trial will enrol 130 patients and is being conducted in the USA, Australia, Canada, France, Hong Kong, Singapore, Spain and the UK. Smaller clinical studies are planned to evaluate adefovir dipivoxil in patients who are beginning therapy compared with those who have received prior treatment for chronic hepatitis B infection. In March 2002, Gilead announced the initiation of an Early Access Programme to provide adefovir dipivoxil 10mg to patients ≥16 years of age with chronic HBV resistant to lamivudine and who are at risk for disease progression. The programme will initially open in the USA, followed by Canada, Australia and Europe as regulatory approval is obtained.[1] On 21 March 2002 Gilead announced the submission of a New Drug Application to the US FDA for marketing approval of adefovir dipivoxil 10mg for the treatment of patients with chronic hepatitis B, including treatment-naïve and treatment-experienced patients. An application for marketing approval of adefovir dipivoxil 10mg in Europe is expected to be filed shortly.In December 2000, Gilead announced that it had received approval for initiation of clinical trials of adefovir dipivoxil in patients with chronic hepatitis B infections in China. A ’class 1’ designation was granted for the agent in China in December 1999, giving 12 years' market exclusivity after approval. Gilead initiated a Phase I trial of adeforvir dipivoxil in China in June 2001. Three Phase I trials will be conducted there (sequentially), as data from overseas studies are not valid under the ‘class 1’ designation. After completion of these studies, the safety and pharmacokinetics of the drug will be evaluated and a report submitted to the Chinese State Drug Administration (SDA) for expedited review. Subject to SDA aproval, a single Phase II/III trial will then be required.Gilead has merged with NeXstar, which was to be responsible for marketing adefovir dipivoxil outside the USA. Gilead is seeking a partner to co-market the drug for hepatitis B in the Asian market while intending to retain commercial rights to the drug in the USA and certain countries in Europe. Gilead dropped the planned trade name, Preveon™, after being informed by the FDA it was in conflict with another approved pharmaceutical product.The antirheumatic efficacy of adefovir dipivoxil was being investigated in the Czech Republic at the preclinical stage; however, no recent development has been reported.Figure. Adefovir Dipivoxil

ISSN:1174-5886    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

Altropane®[O 587] is under Phase III clinical development with Boston Life Sciences as a SPECT imaging agent for detecting neurological signs and symptoms of Parkinson’s disease.1Boston Life Science has completed a Phase III clinical trial with Altropane®in 160 patients at 20 sites in the USA for the diagnosis of Parkinson’s disease. The study data confirmed Altropane®’s ability to differentiate Parkinson’s movement disorders from other movement disorders.Boston Life Sciences has released details of a human clinical study using Altropane®for the diagnosis of attention deficit hyperactivity disorders (ADHD). The study has demonstrated that patients with ADHD have significantly elevated dopamine transporter levels compared with clinically normal age-matched controls. After discussion with the FDA, Boston Life Sciences initiated a Phase II/III clinical trial programme for use of Altropane®to diagnose ADHD. The company plans to submit a Fast Track application for Altropane®for the diagnosis of ADHD. Following successful completion of a Phase II study in adults with ADHD, Boston Life Sciences has initiated a Phase II clinical study in 40 patients aged 8-17 years in two leading paediatric hospitals. The study will enrol 20 patients with diagnosed ADHD and 20 patients with anxiety syndromes (Generalised Anxiety Disorder, Social Phobia, or Separation Anxiety Disorder). The primary objectives of the study are to confirm the findings of a study in adults that children with diagnosed ADHD have elevated numbers of dopamine transporters compared with those of the anxiety group. This will significantly contribute to the diagnosis and treatment of ADHD in both adults and children. The clinical completion of the programme for the ADHD indication is scheduled for late 2002.In August 2000, Boston Life Sciences announced that it had entered a supply agreement with the Canadian company, MDS Nordion. The company will supply Altropane®for Boston Life Sciences’ regulatory filing for the drug as a diagnostic agent for Parkinson’s disease. Boston Life Sciences has completed in February 2002 chemical and bioequivalence testing of the commercially supplied Altropane®. These studies were necessitated by the change of manufacturer and the process from clinical trials to full cGNP scale. No differences were found between the two sources of material. The results were incorporated in the pre-NDA briefing document to the FDA.Boston Life Sciences holds the exclusive licences of patents and patent applications of Harvard University covering compositions of matter of Altropane®, fluoratec and related compounds, use of these compounds, and the use of any DAT ligand for the diagnosis of ADHD.

ISSN:1174-5886    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

Clevidipine, a dihydropyridine derivative, is an ultra−short-acting calcium channel antagonist that was developed by Astra as an antihypertensive agent.1Clevidipine has high vascularvsmyocardial selectivity, and is rapidly metabolised to the corresponding inactive acid. The agent was undergoing Phase I clinical studies in Sweden for the potential use in perioperative and postoperative hypertension; however, AstraZeneca suspended its development for clevidipine In March 2002, the Medicines Company entered into an agreement with AstraZeneca for the licensing, development and commercialisation of clevidipine. The Medicines Company will develop clevidipine in Phase III trials for the short-term control of high blood pressure in a hospital setting. The agreement covers all worldwide territories except Japan. The Medicines Company will perform further clinical development and has the right to commercialise the product in all other territories worldwide, including the USA.Figure. Clevidipine

ISSN:1174-5886    

出版商:ADIS    

年代:2002

数据来源: ADIS