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Biomedical subjects

G D Novack

Publications and source records attributed to G D Novack.

At least 19 recordsLinked to original sources
PubMed1998

Regulatory review intervals for ophthalmic new drug applications at the US Food and Drug Administration.

PURPOSE: To evaluate the regulatory review interval for recent ophthalmic new drug applications (NDAs) at the U.S. Food and Drug Administration (FDA). METHODS: Based on publicly available information regarding submission and approval dates, the timing of FDA review of NDAs of first indications for therapeutic ophthalmic drugs in the 1990s was evaluated. RESULTS: The mean (median) interval of the 19 NDAs from submission to approval decreased from 44 (18) months in 1990 to 11 (10.6) months in 1996. At least nine of these agents had their first worldwide ophthalmic approval in the United States. For 10 of the 19 NDAs, the ophthalmic NDA represented the first US approval of this molecule by any route. CONCLUSIONS: Quality filings currently appear to be reviewed and approved in 1 year or less. Because of the confidential nature of corporate development, no analysis can be made regarding changes in the presubmission costs and timing.

Drug Approval↗
PubMed1998

A randomized, double-masked, placebo-controlled parallel study of 0.2% loteprednol etabonate in patients with seasonal allergic conjunctivitis.

BACKGROUND: Loteprednol etabonate is a site-active corticosteroid with efficacy and safety in treating ocular inflammation at the 0.5% concentration. Evidence from dose-response studies suggested that the 0.2% concentration might be effective in treating ocular allergy. OBJECTIVES: The objective of this study was to evaluate the effects of 0.2% loteprednol etabonate in reducing the signs and symptoms of seasonal allergic conjunctivitis. METHODS: This was a randomized, double-masked, placebo-controlled, parallel-group multicenter study. Patients with signs and symptoms of environmental seasonal allergic conjunctivitis received either loteprednol etabonate or placebo bilaterally four times daily for 42 days. RESULTS: Enrolled were 133 patients (66 receiving loteprednol etahonate; 67 receiving placebo). A reduction in severity was seen in both loteprednol etabonate and placebo groups for bulbar conjunctival injection (1.3 vs 0.9 units on a 0 to 3 scale) and itching (3.5 vs 3.1 units on a 0 to 4 scale) over the first 2 weeks. The treatment effect was -0.5 and -0.6 units in favor of loteprednol etabonate (P < .001). Resolution (the proportion of patients with the sign or symptom no longer present) at visit 4 (day 14) strongly favored loteprednol etabonate-treated patients over placebo-treated patients (31% and 9%, and 54% and 38%, for injection and itching, respectively). Both treatments were well tolerated. No patients in either treatment group (0 for loteprednol etabonate and 0 for vehicle) had an elevation of intraocular pressure of 10 mm Hg or greater during the 6 weeks of treatment. CONCLUSIONS: Loteprenol etabonate (0.2%) was more effective than placebo in the treatment of seasonal allergic conjunctivitis. Loteprednol etabonate (0.2%) had a safety profile comparable to placebo during this 6-week trial.

Adult↗
PubMed1998

Double-masked, placebo-controlled evaluation of loteprednol etabonate 0.5% for postoperative inflammation. Loteprednol Etabonate Post-operative Inflammation Study Group 1.

PURPOSE: To compare the efficacy and safety of loteprednol etabonate 0.5% with those of a placebo (vehicle) in controlling anterior chamber cell and flare reaction in patients having cataract surgery with intraocular lens (IOL) implantation. METHODS: This randomized, double-masked, placebo-controlled, parallel-group multicenter study comprised patients who exhibited a minimum anterior chamber inflammation (ACI) score (sum of cell and flare reaction) of 3 (0 to 9 scale) on the day after cataract removal with posterior chamber IOL implantation. All 227 patients received loteprednol etabonate 0.5% or the placebo 4 times a day in the operated eye for up to 14 days after surgery. Five patients without valid on-treatment follow-up visits were not evaluated for efficacy. RESULTS: By the final visit, the ACI had resolved in 64% (70/109) of patients in the loteprednol etabonate group and 29% (33/113) of those in the placebo group (P < .001). The resolution rate and mean change from baseline of the individual components of ACI (cell and flare), as well as other signs and symptoms, was better in the loteprednol etabonate group. Both treatments were well tolerated. Among the 53 patients who did not complete the study, 34 (29%) were placebo patients discontinued for inadequate anti-inflammatory effect. The treatment failure rate and the time course of failures were lower in the loteprednol etabonate group; the differences were clinically meaningful and statistically significant (P < .001). Three patients in the loteprednol etabonate group had an intraocular pressure elevation of 10 mm Hg or more over the preoperative screening value. CONCLUSION: Loteprednol etabonate 0.5% led to a clinically meaningful reduction in the signs and symptoms of postoperative ACI and had an acceptable safety profile when compared with a placebo.

Adult↗
PubMed1998

Failure to detect systemic levels, and effects of loteprednol etabonate and its metabolite, PJ-91, following chronic ocular administration.

The objective of this study was to determine the systemic exposure to loteprednol etabonate (LE) following its chronic, ocular instillation. This was a randomized, double-masked, placebo controlled, single center trial in 14 normal volunteers. Subjects were randomly assigned to receive either LE (n=10) or placebo (n=4) and instructed to instill one drop into each eye 8 times daily on Days 0 and 1 and four times daily on Days 2 through 42. Blood levels of loteprednol etabonate (LE) and its major metabolite PJ-91 (delta1 cortienic acid etabonate) in plasma, and circulating plasma cortisol levels were measured during the study. Plasma levels of LE or PJ-91 were below the level of quantitation (1 ng/mL) for all subjects in both treatment groups. Plasma cortisol levels were all within the normal range. Chronic exposure to LE at a concentration and frequency equal to or greater than the intended therapeutic dose does not result in detectable systemic levels or hypothalamic pituitary axis suppression.

Adolescent↗
PubMed1998

A single-blind, crossover comparison of the pharmacokinetics and cognitive effects of a new diazepam rectal gel with intravenous diazepam.

PURPOSE: The objective of this study was to compare the pharmacokinetics and cognitive effects of a new diazepam (DZP) rectal gel (Diastat) with intravenously administered DZP. METHODS: Twenty healthy volunteers were enrolled in a single-blind, randomized, double-dummy, two-period, crossover study. Subjects received either 15 mg of DZP rectal gel or 7.5 mg of DZP by intravenous infusion. Blood samples for DZP and desmethyldiazepam analysis were obtained before the dose and from 3 min to 240 h after the dose. Heart rate and blood pressure were measured over the first 24-h period. Subjects also completed five repetitions of a neuropsychological test battery over the first 8-h period. RESULTS: Diazepam rapidly appeared in plasma after rectal administration, exceeding 200 ng/mL within 15 min and reaching an initial maximum of 373 ng/ml at 45 min and a second maximum of 447 +/- 91.1 ng/ml at approximately 70 min. The absolute bioavailability of DZP rectal gel was 90.4%. Subjects receiving intravenous DZP were less alert and performed less efficiently on the WAIS Digit Symbol test 6 min after the dose. Subjects receiving DZP rectal gel performed less well on the WAIS Digit Span test 1 h after the dose and required more time to complete the Letter Cancellation and Grooved Pegboard tests 1 and 2 h after drug administration. CONCLUSIONS: Diastat displayed rapid, consistent absorption and was well tolerated. Alterations in cognition were mild and dissipated within 4 h of drug administration. This new rectal drug-delivery system offers an easy, safe, and bioavailable method to administer DZP.

Administration, Rectal↗
PubMed1998

Change in intraocular pressure during long-term use of loteprednol etabonate.

PURPOSE: Loteprednol etabonate is a novel site-active corticosteroid synthesized through structural modifications of prednisolone-related compounds so that it will undergo a predictable transformation to an inactive metabolite. In double-masked studies, loteprednol etabonate was effective in the treatment of giant papillary conjunctivitis, seasonal allergic conjunctivitis, postoperative inflammation, and uveitis. The objective of this analysis was to determine the incidence of clinically significant elevations in intraocular pressure (IOP) with long-term use of loteprednol etabonate. PATIENTS AND METHODS: All subjects (healthy volunteers or patients with inflammation or allergy) in all sponsored loteprednol etabonate studies in the United States were evaluated. A clinically significant elevation in IOP was defined as > or = 10 mmHg at any visit, and long-term use was defined as > or = 28 days. Of the 2,210 subjects, 1,648 were treated for 28 days or longer with loteprednol etabonate (0.2% or 0.5%), prednisolone acetate 1%, or vehicle. RESULTS: IOP elevation > or = 10 mmHg occurred in 1.7% (15/901) of patients taking long-term loteprednol etabonate, 0.5% (3/583) of those taking vehicle, and 6.7% (11/164) of those taking prednisolone acetate. Excluding patients who wore contact lenses, the incidence was 0.6% (4/624), 1.0% (3/304), and 6.7% (11/164) for loteprednol etabonate, vehicle, and prednisolone acetate, respectively. The incidence of IOP elevations with 0.2% loteprednol etabonate was 0.8% (1/133), similar to that for vehicle (0.7%, 1/135). CONCLUSION: The results of this analysis in a large population of subjects undergoing long-term therapy and of a previously published controlled, double-masked study in corticosteroid responders suggest that loteprednol etabonate has less propensity to cause clinically significant elevations in IOP than prednisolone acetate.

Androstadienes↗
PubMed1997

The role of mitomycin treatment duration and previous intraocular surgery on the success of trabeculectomy surgery.

PURPOSE: This study was performed to determine the effect of duration of mitomycin exposure during trabeculectomy surgery on filtration success in eyes that had and had not been subjected to previous surgery. METHODS: On hundred six eyes of 92 patients were retrospectively reviewed. The effect of previous surgery and exposure duration of mitomycin 0.5 mg/ml on outcomes of trabeculectomy surgery were evaluated. RESULTS: The mean duration of mitomycin exposure was 0.7 +/- 0.02 min (mean +/- SEM) in the eyes that had not been subjected to previous surgery and 1.5 +/- 0.11 min in the eyes that had (p < 0.001). The mean follow-up times were 14 months in both groups. The mean decrease in intraocular pressure was 13.6 +/- 1.25 mm Hg in the group that had not been subjected to previous surgery and 13.9 +/- 1.45 mm Hg in the group that had been subjected to previous surgery. Analysis of variance techniques demonstrated no predictive value of demographics, history of previous surgery, or duration of mitomycin exposure with results of trabeculectomy surgery. Hypotony was the most frequent complication in both the no previous surgery and the previous surgery groups. The incidence of complications was numerically greater in the group that had not been subjected to previous surgery. CONCLUSIONS: The duration of mitomycin exposure and the history of previous surgery did not correlate with postoperative intraocular pressure, medications, or incidence of complications. The exposure duration response curve of mitomycin 0.5 mg/ml in these patients appears to be flat through the time evaluated. Lower concentrations of mitomycin and shorter exposure should be used to maintain efficacy with reduced risk of complications.

Adolescent↗
PubMed1996

A placebo-controlled, double-masked evaluation of mitomycin C in combined glaucoma and cataract procedures.

PURPOSE: This study was performed to determine if adjunctive use of mitomycin C (MMC) would increase the success of combined phacoemulsification, intraocular lens implantation, and trabeculectomy surgery with releasable sutures. METHODS: Seventy-two eyes with cataract and glaucoma, requiring surgery for decreased vision, uncontrolled intraocular pressure, or to obtain a better view of the optic nerve, were randomized to receive a 2.5-minute subconjunctival exposure to either MMC (0.5 mg/ml) or placebo balanced salt solution. Postoperative evaluations at 3, 6, and 12 months were performed by a masked observer who recorded visual acuity, intraocular pressure, glaucoma medications, presence of filtering blebs, and complications. Endothelial cell counts were measured before and 3 months after surgery. RESULTS: The MMC group had significantly greater reduction in mean intraocular pressure through the first 12 months of follow-up (7.05-7.65 mmHg versus 2.62-3.84 mmHg; P = 0.001-0.028). In addition, through the first 6 months of follow-up, the MMC group required significantly fewer medications (0.4-0.5 versus 1.1-1.2; P = 0.002-0.004). Requirements for additional glaucoma surgery were less in the MMC group (4/ 36) than in the placebo group (7/35) (P = 0.301). Filtering blebs were significantly larger at 6 and 12 months (P = 0.002 and P = 0.001, respectively), and would leaks were more common (P = 0.101) in the MMC group. The mean decrease in endothelial cell count at month 3 was slightly, although not significantly, greater in the MMC treatment group (206.9 versus 91.3 cells/mm2* P = 0.377). CONCLUSION: The increased success of the glaucoma procedure in the MMC group together with relatively minor toxicity, suggests its use is beneficial in combined glaucoma-cataract surgery.

Aged↗
PubMed1993

Vitreous surgery for macular holes.

BACKGROUND: To surgically treat patients with macular holes, the authors previously reported both anatomic (re-attachment) and visual success (2 lines of improvement) in a series of 52 eyes. They now have operated on an additional 118 eyes using similar techniques, for a total of 170 eyes. METHODS: After ophthalmologic examination and history, the authors operated on suitable patients. The surgical objectives included relief of all tangential traction and retinal tamponade with intraocular gas. All eyes were followed for at least 6 months postoperatively. RESULTS: In the total population of 170 eyes, anatomic success was achieved in 73% and vision improved at least two lines in 55%. Twenty-nine percent (49/170) of patients had a visual acuity of 20/40 or better at last examination. Patients with symptoms of less than 6 months' duration managed better than those with symptoms of longer duration (P = 0.3001). In the former group of 66 eyes, anatomic success was achieved in 80% (n = 53), whereas visual acuity improved at least two lines in 68% (n = 45) and at least four lines in 55% (n = 36). CONCLUSIONS: The authors suggest that macular hole surgery may provide meaningful improvement in visual acuity in most patients, especially in those whose symptoms are of less than 6 months' duration.

Aged↗
PubMed1993

Flurbiprofen 0.03% for the control of inflammation following cataract extraction by phacoemulsification.

We conducted a double-masked, vehicle-controlled study to evaluate the anti-inflammatory effect of topical flurbiprofen in cataract surgery by phacoemulsification and implantation of a posterior chamber intraocular lens. The 233 patients were randomized to receive either flurbiprofen or vehicle immediately prior to and for two weeks following surgery. No concomitant corticosteroid use was allowed. The flurbiprofen group had significantly less anterior chamber cells and flare at day 7 and significantly less conjunctival erythema, corneal edema, and lid edema at day 14. The investigator's global effectiveness rating was higher in the flurbiprofen group at day 14. Blood-aqueous barrier disruption, as measured by aqueous fluorophotometry, was statistically significantly diminished in the flurbiprofen group. Burning and stinging were rated significantly greater in the flurbiprofen group than in the vehicle group. Foreign-body sensation and photophobia were significantly more severe in the vehicle group than in the flurbiprofen group. Flurbiprofen provided postsurgical anti-inflammatory efficacy in clinical signs of inflammation and in blood-aqueous barrier disruption, and also showed improved subjective signs.

Adult↗
PubMed1992

Memory-enhancing effects of post-training dipivefrin and epinephrine: involvement of peripheral and central adrenergic receptors.

These experiments examined the effects, in mice, of post-training i.p. injections of dipivefrin (DPE), a lipophilic prodrug of epinephrine, and epinephrine (EPI) on 48-h retention assessed in inhibitory avoidance and Y-maze discrimination tasks. DPE, in doses of 0.3-10 micrograms/kg significantly facilitated retention: the effects were approximately 10-fold more potent than those of EPI obtained with similar experimental conditions. The alpha-adrenergic antagonists prazosin (alpha 1; 3.0 mg/kg; i.p.), yohimbine (alpha 2; 3.0 mg/kg; i.p.) and phentolamine (alpha 1 and alpha 2; 3.0 mg/kg; i.p.) did not block the enhancement of retention induced by either DPE (10.0 micrograms/kg; i.p.) or EPI (0.1 mg/kg; i.p.). However, the beta-adrenergic antagonist propranolol (2.0 mg/kg; i.p.) attenuated the effects of both DPE and EPI. Sotalol (2.0 mg/kg; i.p.), a peripherally-acting beta-adrenergic antagonist, attenuated the effects of EPI but not those of DPE. These findings suggest the DPE-induced enhancement of memory involves central beta- but not alpha-adrenergic mechanisms while EPI's effects are initiated by activation of peripheral beta-adrenergic systems.

Adrenergic Antagonists↗
PubMed1992

Once-daily versus twice-daily levobunolol (0.5%) therapy. A crossover study.

The authors executed a two-period, randomized, double-masked, crossover study comparing once-daily to twice-daily levobunolol hydrochloride (0.5%) in 20 patients with elevated intraocular pressure (IOP). Modified diurnal curves were performed at four times for each study arm: baseline, day 1, day 14, and day 28. The mean diurnal corrected decrease in IOP from baseline ranged from 16% +/- 11% to 22% +/- 9% when the subjects were treated twice daily, and from 14% +/- 10% to 18% +/- 8% when the same subjects were treated once daily. At day 1, patients had a significantly greater IOP lowering after twice-daily therapy than after once-daily therapy (P less than 0.05). At 14 and 28 days, there was no clinically significant difference between the two treatment regimens. The results of our crossover study suggest that once-daily treatment with levobunolol (0.5%) is as effective as twice-daily treatment.

Adult↗