RESUMO
PURPOSE: The safety and intraocular pressure (IOP)-lowering efficacy of brimonidine tartrate 0.15% preserved with polyquaternium-1 were evaluated and compared with brimonidine tartrate 0.15% preserved with chlorine dioxide in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). DESIGN: Randomized, double-masked, parallel group, multicenter equivalence study. PARTICIPANTS: Eight hundred forty-two patients randomized to the study treatments. METHODS: Patients with OAG or OHT and with qualifying IOP (22-36 mmHg at 8 am on 2 eligibility visits after an appropriate washout period from previous treatment) were assigned randomly to either brimonidine tartrate 0.15% preserved with polyquaternium-1 (brimonidine PQ) or brimonidine tartrate 0.15% preserved with chlorine dioxide (brimonidine P) dosed 3 times daily and were followed up for 6 months. Approximately one half of the study sites continued to follow up their patients for an additional 6 months to obtain longer-term safety data. RESULTS: Brimonidine PQ produced statistically significant and clinically relevant reductions from baseline ranging from 4.3 to 6.5 mmHg, which were statistically and clinically equivalent to brimonidine P at all 18 visit days and times. No safety concerns were identified based on an assessment of ocular and cardiovascular parameters. Patient discontinuations resulting from adverse events were similar for both groups and most of these were a result of signs or symptoms of ocular allergic reaction. CONCLUSIONS: Brimonidine PQ is equivalent in IOP-lowering efficacy and safety to brimonidine P.
Assuntos
Agonistas alfa-Adrenérgicos/uso terapêutico , Glaucoma de Ângulo Aberto/tratamento farmacológico , Pressão Intraocular/efeitos dos fármacos , Hipertensão Ocular/tratamento farmacológico , Quinoxalinas/uso terapêutico , Agonistas alfa-Adrenérgicos/efeitos adversos , Agonistas alfa-Adrenérgicos/farmacocinética , Idoso , Tartarato de Brimonidina , Compostos Clorados/efeitos adversos , Compostos Clorados/farmacocinética , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Hipertensão Ocular/fisiopatologia , Óxidos/efeitos adversos , Óxidos/farmacocinética , Polímeros/efeitos adversos , Polímeros/farmacocinética , Conservantes Farmacêuticos/efeitos adversos , Conservantes Farmacêuticos/farmacocinética , Quinoxalinas/efeitos adversos , Quinoxalinas/farmacocinética , Equivalência TerapêuticaRESUMO
BACKGROUND: A nasal spray containing the antiallergy agent olopatadine hydrochloride is being developed for the treatment of seasonal allergic rhinitis (SAR) to mountain cedar. OBJECTIVE: To evaluate the safety and efficacy of 2 concentrations of olopatadine nasal spray vs placebo nasal spray in patients with SAR to mountain cedar. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study. After a 3- to 21-day placebo run-in, 677 patients aged 12 to 81 years were randomized to receive 0.4% or 0.6% olopatadine or placebo, 2 sprays per nostril twice daily for 2 weeks. Patients evaluated morning and evening reflective and instantaneous nasal symptoms (sneezing, stuffy nose, runny nose, and itchy nose, which compose the total nasal symptom score [TNSS]) and ocular symptoms. RESULTS: Olopatadine spray (0.4% and 0.6%) was statistically significantly superior to placebo for percentage change from baseline in overall reflective and instantaneous TNSSs. Also, 0.6% olopatadine was statistically significantly superior to placebo for reducing the reflective and instantaneous assessments of sneezing, runny nose, itchy nose, stuffy nose, itchy eyes, and watery eyes. Olopatadine spray exhibited a safety profile comparable with that of placebo. CONCLUSIONS: Olopatadine nasal spray (0.4% and 0.6%) provided statistically significant improvements in allergic rhinitis symptoms compared with placebo regarding TNSSs and individual symptoms, including congestion, itchy and runny nose, sneezing, and itchy and watery eyes, in patients with SAR to mountain cedar. Olopatadine nasal spray administered twice daily was safe and well tolerated in adolescents and adults.
Assuntos
Administração por Inalação , Dibenzoxepinas/uso terapêutico , Juniperus/imunologia , Rinite Alérgica Sazonal/tratamento farmacológico , Resultado do Tratamento , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antialérgicos/efeitos adversos , Antialérgicos/uso terapêutico , Criança , Demografia , Dibenzoxepinas/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cloridrato de OlopatadinaRESUMO
Five independent, multicentered, double-masked, parallel, controlled studies were conducted to determine the safety of moxifloxacin ophthalmic solution 0.5% (VIGAMOX) in pediatric and nonpediatric patients with bacterial conjunctivitis. Patients were randomized into one of two treatment groups in each study and received either moxifloxacin ophthalmic solution 0.5% b.i.d. or t.i.d. or a comparator. A total of 1,978 patients (918 pediatric and 1,060 nonpediatric) was evaluable for safety. The most frequent adverse event in the overall safety population was transient ocular discomfort, occurring at an incidence of 2.8%, which was similar to that observed with the vehicle. No treatment-related changes in ocular signs or visual acuity were observed with moxifloxacin ophthalmic solution 0.5%, except for one clinically relevant change in visual acuity. Thus, based upon a review of adverse events and an assessment of ocular parameters, moxifloxacin ophthalmic solution 0.5% formulated without the preservative, benzalkonium chloride, is safe and well tolerated in pediatric (3 days-17 years of age) and nonpediatric (18-93 years) patients with bacterial conjunctivitis.
Assuntos
Compostos Aza/administração & dosagem , Compostos Aza/efeitos adversos , Conjuntivite Bacteriana/tratamento farmacológico , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Adulto , Criança , Pré-Escolar , Ensaios Clínicos como Assunto , Fluoroquinolonas , Humanos , Lactente , Moxifloxacina , Soluções Oftálmicas/administração & dosagem , Soluções Oftálmicas/efeitos adversosRESUMO
BACKGROUND: A nasal spray containing the antiallergy agent olopatadine hydrochloride is being developed for the treatment of seasonal allergic rhinitis (SAR). OBJECTIVE: To evaluate the safety and efficacy of 2 concentrations of olopatadine nasal spray vs placebo in patients with SAR. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study. After a 3- to 21-day placebo run-in, 565 patients aged 12 to 80 years were randomized to receive 0.4% or 0.6% olopatadine or placebo, 2 sprays per nostril twice daily for 2 weeks. Patients evaluated morning and evening reflective and instantaneous nasal symptoms (sneezing, stuffy nose, runny nose, and itchy nose, which compose the total nasal symptom score [TNSS]) and ocular symptoms and completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). RESULTS: Olopatadine spray (0.4% and 0.6%) was significantly superior to placebo for percentage change from baseline in overall reflective (P = .004 and P < .001, respectively) and instantaneous (P = .02 and P = .003, respectively) TNSSs. Also, 0.6% olopatadine was significantly superior to placebo for reducing the reflective and instantaneous assessments of sneezing, runny and itchy nose, and itchy eyes; the instantaneous assessments of watery eyes; and the overall and all 7 domain scores of the RQLQ (P < .05). Olopatadine spray exhibited a safety profile comparable with that of placebo. CONCLUSIONS: Olopatadine nasal spray (0.4% and 0.6%) provided statistically significant improvements in allergic rhinitis symptoms compared with placebo regarding TNSSs (reflective and instantaneous) and in quality-of-life variables in patients with SAR. Olopatadine nasal spray administered twice daily was safe and well tolerated in adolescents and adults.
Assuntos
Dibenzoxepinas/efeitos adversos , Dibenzoxepinas/uso terapêutico , Antagonistas dos Receptores Histamínicos H1/efeitos adversos , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Administração Intranasal , Adolescente , Adulto , Idoso , Antialérgicos/administração & dosagem , Antialérgicos/efeitos adversos , Antialérgicos/uso terapêutico , Criança , Dibenzoxepinas/administração & dosagem , Método Duplo-Cego , Feminino , Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Cloridrato de Olopatadina , Qualidade de Vida , Inquéritos e Questionários , Resultado do TratamentoRESUMO
BACKGROUND: Prostaglandin analogues are effective ocular hypotensive agents and are being used increasingly in the treatment of elevated intraocular pressure (IOP). These agents are typically dosed once daily. OBJECTIVES: A pilot study was conducted to evaluate the duration of travoprost's IOP-lowering efficacy up to 84 hours after the final dose in patients with open-angle glaucoma. A follow-up study was conducted to compare diurnal IOP control with travoprost and latanoprost over a 44-hour period. METHODS: In the open label pilot study, patients received 0.004% travoprost in both eyes at 8 pm daily for 2 weeks. After 2 weeks, IOP was measured before administration of the last daily dose, every 4 hours thereafter for 36 hours, and 60 and 84 hours after the last dose, with no additional ocular hypotensive medication given. In the controlled, double-masked, parallel-group, follow-up study, patients were randomized to self-administer 1 drop of the marketed doses of 0.004% travoprost or 0.005% latanoprost in both eyes at 8 pm daily for 2 weeks. At the end of this period, patients returned to the facility at approximately 8 pm for IOP measurement and administration of the final dose of study medication. IOP was then measured at 4-hour intervals for 44 hours after the last dose, with no additional ocular hypotensive medication given. RESULTS: The pilot study included 21 patients (67% female, 33% male; age range, 35-81 years) with open-angle glaucoma. IOP values were significantly below baseline at all time points up to 84 hours after the final dose of travoprost ( P<0.001). The follow-up study enrolled 35 patients, 1 of whom was excluded for missing data; thus, the intent-to-treat analysis included 34 patients (68% female, 32% male; age range, 36-72 years). At the unmedicated eligibility visit, mean IOP over 24 hours ranged from 21 to 26 mm Hg in each treatment group. After 2 weeks of treatment and 24 hours after the last dose, mean (SD) IOP was 13.1 (2.1) mm Hg (change from eligibility visit, -10.4 [2.7] mm Hg) in the travoprost group and 16.0 (3.1) mm Hg (change from eligibility visit, -7.1 [2.4] mm Hg) in the latanoprost group. The difference in change from baseline was statistically significant between treatment groups (P=0.006). Travoprost lowered IOP significantly at all time points throughout the 44-hour period after the last dose (mean IOP, Assuntos
Anti-Hipertensivos/administração & dosagem
, Ritmo Circadiano
, Cloprostenol/análogos & derivados
, Cloprostenol/administração & dosagem
, Glaucoma de Ângulo Aberto/tratamento farmacológico
, Prostaglandinas F Sintéticas/administração & dosagem
, Adulto
, Idoso
, Idoso de 80 Anos ou mais
, Anti-Hipertensivos/farmacologia
, Anti-Hipertensivos/uso terapêutico
, Cloprostenol/farmacologia
, Cloprostenol/uso terapêutico
, Método Duplo-Cego
, Feminino
, Seguimentos
, Glaucoma de Ângulo Aberto/patologia
, Humanos
, Latanoprosta
, Masculino
, Pessoa de Meia-Idade
, Projetos Piloto
, Prostaglandinas F Sintéticas/farmacologia
, Prostaglandinas F Sintéticas/uso terapêutico
, Travoprost
RESUMO
Two prospective, controlled, multicenter, double-masked studies--one lasting 6 months (n=594) and the other, 12 months (n=787)--examined the intraocular pressure (IOP)-lowering efficacy of travoprost in 1381 black and nonblack patients with open-angle glaucoma or ocular hypertension. Investigated regimens were travoprost 0.004% once daily, latanoprost 0.005% once daily, and timolol 0:5% twice daily. In both studies, mean IOP was significantly lower in blacks treated with travoprost. The IOP reduction was also significantly greater in blacks after adjustments for age, sex, iris color, diagnosis, and corneal thickness. Timolol lowered mean IOP to a greater extent in nonblack patients. The significantly larger IOP reduction with travoprost compared with timolol in both racial groups was more pronounced in blacks. Travoprost also was superior to latanoprost in blacks. Mean changes from baseline generally were greater for black than for nonblack patients, although the differences did not achieve statistical significance. The response rate to travoprost was higher in blacks. The most common adverse effect was hyperemia.
Assuntos
População Negra , Cloprostenol/análogos & derivados , Cloprostenol/uso terapêutico , Glaucoma de Ângulo Aberto/tratamento farmacológico , Hipertensão Ocular/tratamento farmacológico , População Branca , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Criança , Córnea/fisiopatologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Glaucoma de Ângulo Aberto/etnologia , Humanos , Pressão Intraocular/efeitos dos fármacos , Latanoprosta , Masculino , Pessoa de Meia-Idade , Hipertensão Ocular/etnologia , Estudos Prospectivos , Prostaglandinas F Sintéticas/uso terapêutico , Fatores de Tempo , Timolol/uso terapêutico , Travoprost , Resultado do TratamentoRESUMO
The structure-activity studies that led to the identification of travoprost, a highly selective and potent FP prostaglandin analog, and AL-6598, a DP prostaglandin analog, are detailed. In both series, the 1-alcohol analogs are very effective and are thought to be acting as prodrugs for the biologically active carboxylic acids. The efficacy of amide prodrugs depends on the degree of substitution and the size of the substituents. Selected compounds are profiled in vitro and in vivo preclinically. Clinical studies show that travoprost 0.004% (isopropyl ester) provided intraocular pressure control superior to timolol 0.5% when used as monotherapy in patients with open-angle glaucoma or ocular hypertension. In clinical studies, AL-6598 0.01% provided a sustained intraocular pressure reduction with q.d. application; b.i.d. provided greater intraocular pressure control. The acute and, apparently, conjunctival hyperemia associated with topical ocular AL-6598 can be attenuated while maintaining intraocular pressure-lowering efficacy by formulating with brimonidine.
Assuntos
Anti-Hipertensivos/uso terapêutico , Cloprostenol/análogos & derivados , Cloprostenol/uso terapêutico , Dinoprosta/uso terapêutico , Glaucoma de Ângulo Aberto/tratamento farmacológico , Pressão Intraocular/efeitos dos fármacos , Receptores de Prostaglandina/agonistas , Animais , Anti-Hipertensivos/química , Anti-Hipertensivos/farmacologia , Humor Aquoso/efeitos dos fármacos , Gatos , Cloprostenol/química , Cloprostenol/farmacologia , Dinoprosta/análogos & derivados , Dinoprosta/química , Dinoprosta/farmacologia , Relação Dose-Resposta a Droga , Feminino , Cobaias , Humanos , Macaca fascicularis , Masculino , Hipertensão Ocular/tratamento farmacológico , Coelhos , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores Imunológicos , Segurança , Relação Estrutura-Atividade , Timolol/uso terapêutico , TravoprostRESUMO
OBJECTIVE: To compare the safety and intraocular pressure (IOP)-lowering efficacy of once-daily travoprost (0.0015% and 0.004%) to twice-daily timolol 0.5%. DESIGN: Prospective, 6-month, randomized, controlled, multicenter, double-masked, phase III study. PARTICIPANTS: Six hundred five patients with open-angle glaucoma or ocular hypertension. METHODS: Patients with an 8 AM IOP between 24 to 36 mmHg in at least one eye (the same eye) at two eligibility visits received either travoprost 0.0015%, travoprost 0.004% (dosed every day), or timolol 0.5% (dosed twice daily). MAIN OUTCOME MEASURES: Mean IOP at 8 AM, 10 AM, and 4 PM in the patient's eye with the higher baseline IOP. RESULTS: The mean IOP was significantly lower for both concentrations of travoprost compared with timolol. Travoprost was statistically superior to timolol at 9 of 13 visits, with differences in IOP reductions ranging from 0.9 to 1.8 mmHg (0.0015%) and 10 of 13 visits with differences in IOP reductions from 0.9 to 2.4 mmHg (0.004%). Mean IOP changes from baseline ranged from -6.0 to -7.5 mmHg (0.0015%), -6.5 to -8.0 mmHg (0.004%), and -5.2 to -7.0 mmHg for timolol. Hyperemia was experienced at rates of 29.2% (59 of 202) for travoprost 0.0015%, 42.8% (86 of 201) for travoprost 0.004%, and 8.9% (18 of 202) for timolol. Iris pigmentation changes were observed in 1.0% (2 of 200) of patients receiving travoprost 0.004% with no changes noted in the travoprost 0.0015% group or the timolol group. A decrease in pulse and systolic blood pressure was observed in the timolol group. There were no other clinically relevant or statistically significant changes from baseline in ocular signs or laboratory values, and no serious, related, unexpected adverse events were reported for any group. CONCLUSIONS: Travoprost (0.0015% and 0.004%), dosed once daily in the evening, is statistically superior or equal to timolol 0.5% dosed twice daily at all treatment visits during this 6-month study. IOP reductions of up to 2.0 mmHg greater than timolol were found in the travoprost 0.004% pooled data group. Travoprost is safe and well tolerated in patients with open-angle glaucoma or ocular hypertension.