Novel drug OMS103HP reduces pain and improves joint motion and function for 90 days after arthroscopic meniscectomy.

PURPOSE: This phase 2 study compared OMS103HP (Omeros, Seattle, WA) with control (lactated Ringer's) irrigation solution in patients undergoing arthroscopic partial meniscectomy. METHODS: This was a prospective, multicenter, double-blind, randomized, vehicle-controlled, parallel-group study. Safety and postoperative pain, range of motion, and self-reported function were evaluated for 90 days. Statistical results were based on univariate analysis of variance and repeated-measures analyses. RESULTS: Mean visual analog scale (VAS) pain scores within 24 hours after discharge from the recovery room showed more pain in the control group beginning at 2 hours and peaking at 8 hours. Univariate analysis of variance of mean VAS scores over the 24-hour period did not meet statistical significance. Repeated-measures analysis yielded a statistically significant difference (P = .004) for time-by-treatment interaction, showing a clear drug benefit over time based on VAS scores. There were statistically significant differences at day 7 between the groups in passive flexion without pain (P = .022). The proportion of patients achieving flexion of 95° or greater, 110°, and 125° was greater for the OMS103HP group. The Knee Injury and Osteoarthritis Outcome Score (KOOS) showed statistically significant differences (P ≤ .05) between the OMS103HP and control groups for 4 of 5 outcomes (symptoms, pain, sport and recreation, and knee-based quality of life but not activities of daily living). All scores showed a treatment effect through day 90. The overall incidence of adverse events and abnormal laboratory values for the OMS103HP and control groups was similar. Serious adverse events occurred in 1 control patient. CONCLUSIONS: In this study of patients with meniscal tears who underwent simple debridement, the use of OMS103HP resulted in reduced acute postoperative pain (measured by VAS over the first 24 hours postoperatively), reduced pain during recovery (measured by the KOOS pain subscale, which measures both background levels of pain and exacerbations caused by movements or activities), improved postoperative knee motion, and improved functional outcomes as assessed with the KOOS Knee Survey. Clinical benefits of OMS103HP were consistent and sustained throughout 90 days of postoperative follow-up. LEVEL OF EVIDENCE: Level I, prospective, randomized, controlled trial.

Intracameral ketorolac and phenylephrine effect on intraoperative pupil diameter and postoperative pain in cataract surgery.

PURPOSE: To evaluate the study drug OMS302 (Omidria [phenylephrine and ketorolac injection 1.0%/0.3%]) compared with a balanced salt solution (vehicle), ketorolac, and phenylephrine on pupil diameter during cataract surgery and early postoperative ocular pain. SETTING: Twenty-three centers in the United States. DESIGN: Randomized clinical trial. METHODS: Patients were randomized (1:1:1:1) to receive vehicle, phenylephrine, ketorolac, or the study drug containing phenylephrine and ketorolac administered intracamerally during surgery. Intraoperative pupil diameter was determined each minute by video capture. Postoperative ocular pain was evaluated for up to 12 hours. RESULTS: The study evaluated 223 patients. The study drug was significantly better than the vehicle and ketorolac in maintaining mydriasis (least-squares mean differences 0.9 ± 0.1 [SEM] and 0.7 ± 0.1 for the study drug versus vehicle and ketorolac, respectively; P < .0001 each). Ocular pain assessed using the Visual Analog Scale was significantly reduced for the study drug compared with the vehicle or phenylephrine (least-squares mean difference -4.6 ± 2.2 and P = .042 and 5.9 ± 2.2 and P = .009, respectively). Significantly fewer patients treated with the study drug (3 [6.1%]) had an intraoperative pupil diameter smaller than 6.0 mm compared with those treated with the vehicle (25 [47.2%]; P < .0001), ketorolac (18 [34.6%]; P = .0004), or phenylephrine (11 [22.4%]; P = .0216). CONCLUSIONS: The study drug was safe and efficacious in maintaining mydriasis and reducing postoperative ocular pain. Both ketorolac and phenylephrine contributed to the therapeutic effects, with the combination showing superiority to either agent alone in maintaining an intraoperative pupil diameter of 6.0 mm or larger.

Semen and sperm reference ranges for men 45 years of age and older.

The most widely used reference values for human semen and sperm variables were developed by the World Health Organization (WHO) to help assess the fertility status of men interested in reproduction (typically a younger population). In this retrospective analysis, data from a large population of men aged 45 years or older were analyzed to derive semen and sperm reference ranges for an older population. Baseline semen samples were obtained from 1174 men with no or mild erectile dysfunction (ED) during the screening phase of two clinical trials evaluating the effects of a drug on human spermatogenesis. The median values and 95% reference ranges for 4 measured semen and sperm parameters (semen volume, sperm concentration, sperm motility, and sperm morphology) and 1 derived parameter (total sperm count) were calculated for the population and by age quartile. These references ranges were compared to established WHO reference values. Associations between the semen and sperm parameters and smoking status, alcohol use, and serum hormone concentrations were also analyzed. The mean age was 52.9 years (range: 45-80). Median semen volume, sperm motility, and sperm morphology parameters declined significantly with age. Only 46% of study subjects had baseline values for semen and sperm parameters that met or surpassed all the WHO reference values. This is the first study to statistically derive semen reference ranges from a large population of men aged 45 years or older. The observation that less than half the men in this study met all 4 WHO reference values for measured semen and sperm parameters underscores the need for age-specific reference ranges.

Intracameral phenylephrine and ketorolac injection (OMS302) for maintenance of intraoperative pupil diameter and reduction of postoperative pain in intraocular lens replacement with phacoemulsification.

BACKGROUND: The purpose of this study was to evaluate the effect of OMS302 on intraoperative pupil diameter and early postoperative ocular pain when administered during intraocular lens replacement surgery. METHODS: Four hundred and six patients (406 study eyes; 202 in the OMS302 group and 204 in the placebo group) were entered into this randomized, double-masked, placebo-controlled, multicenter Phase III study, which was conducted at 15 centers in the USA and the Netherlands. The patients received OMS302 (60.75 mM phenylephrine HCl and 11.25 mM ketorolac tromethamine) or placebo in irrigation solution during intraocular lens replacement. No other changes in procedure were required. Coprimary endpoints were change in pupil diameter over time from surgical baseline to end of procedure and patient-reported ocular pain during the first 12 hours postoperatively. Secondary endpoints included additional measures of pupil diameter and postoperative pain. RESULTS: OMS302 was superior to placebo in maintaining intraoperative mydriasis, preventing miosis, and reducing postoperative pain. The weighted mean (standard error) difference (OMS302 - placebo) in change in the area under the curve from baseline for pupil diameter was 0.590 ([0.049]; 95% confidence interval 0.494 to 0.686; P<0.0001). For ocular pain scores, the weighted mean (standard error) difference was -4.580 ([1.192]; 95% confidence interval -6.917 to 2.244; P=0.0002). All secondary efficacy results favored OMS302. Specifically, analyses supporting prevention of miosis (patients with ≥6 mm pupil diameter at completion of cortical clean-up and those with <6 mm diameter at any time during surgery) were significant for OMS302 (95.9% versus 77.0% and 9.2% versus 38.0%, respectively; P<0.0001 for each endpoint). OMS302 was well tolerated and not associated with any unexpected adverse events. CONCLUSION: OMS302 maintained mydriasis, prevented miosis, and reduced early postoperative pain when administered in irrigation solution during intraocular lens replacement, with a safety profile similar to that of placebo. OMS302 is preservative-free and bisulfite-free, and its administration does not require any modification to the surgical procedure.