Slightly more patients in the latanoprost plus timolol group (33% right eye, 32% left eye) had OHT compared with the fixed-dose combination group (25% right eye, 27% left eye), latanoprost group (20% right eye, 19% left eye), and timolol group (22% for each eye). end points were assessed at three time points on visits at weeks 1, 2, 4, and 6 versus baseline. Results The IOP-lowering efficacy of the fixed-dose combination of latanoprost/timolol was similar to that of latanoprost plus timolol administered concomitantly at all time points (mean IOP difference and 95% Quinestrol confidence interval within 1.5 mmHg; test for ordinal variables. All tests were two-tailed, with a significance level of 0.05. Repeated-measures analysis of variance was used for the primary end point (change in IOP from baseline). All statistical analyses were performed using SAS? software version 9.1.3 (SAS Institute Inc., Cary, NC, USA). Results Patients A total of 300 patients were screened at 17 sites in India. Of these, 227 patients met the eligibility criteria and were randomized to one of the four treatment groups: a fixed-dose combination of latanoprost/timolol (n=56), concomitant latanoprost plus timolol (58 patients), latanoprost alone (n=55), and timolol by itself (n=58). Individual disposition is proven in Amount 1. Of the sufferers, 216 (95.2%) completed the analysis. Of the rest of the eleven (4.8%) sufferers who discontinued from the analysis, the reason why were shed to follow-up (latanoprost/timolol, n=2; latanoprost, n=1), main process violation (latanoprost plus timolol, n=1; latanoprost, n=1), drawback of consent (latanoprost plus timolol, n=1; latanoprost, n=1), undesirable occasions (latanoprost, n=1 [corneal disorder]; timolol, n=1 [bradycardia]), individual non-compliance (latanoprost plus timolol, n=1), and failing of study medicine (timolol, n=1). All 227 sufferers randomized to get treatment were regarded as the basic safety people. The intent-to-treat people (efficacy evaluation people) contains 221 sufferers, as well as the per-protocol people contains 215 sufferers. Open in another window Amount 1 Individual disposition. Records: aThe 227 randomized sufferers represented the basic safety people, including all sufferers who received at least one dosage of study medicine. bITT people (efficacy evaluation people) included all sufferers with baseline go to evaluation who received at least one dosage of study medicine with least one on-therapy efficiency evaluation. Missing data had been treated by last observation transported forward. cPP people included sufferers with at least one on-therapy efficiency assessment no main process violation. Abbreviations: ITT, objective to take care of; PP, per process; N/n, number. Individual demographics, baseline features, and baseline IOP from the intent-to-treat people are proven in Desk 1. The entire mean people age group was 55.013.53 (range 20C83) years within this exclusively Asian individual population, and nearly all sufferers were male (67.0%). Significantly, there is no statistically factor in baseline IOP beliefs between your four treatment groupings, including a mean baseline IOP selection of 25.792.84 mmHg to 26.863.50 mmHg. Furthermore, there have been no statistically significant distinctions in the amount of sufferers with a brief history of OAG between your treatment groupings. Slightly more sufferers in the latanoprost plus timolol group (33% correct eye, 32% still left eye) acquired OHT weighed against the fixed-dose mixture group (25% correct eye, 27% still left eyes), latanoprost group (20% correct eye, 19% still left eyes), and timolol group (22% for every eye). This variation in OHT between your combined groups had not been thought to Rabbit Polyclonal to GANP be getting statistically significant. Table 1 Individual demographic and baseline features (ITT people)* thead th align=”still left” valign=”best” rowspan=”2″ colspan=”1″ Category /th th colspan=”12″ align=”still left” valign=”best” rowspan=”1″ Treatment group hr / /th th align=”still left” valign=”best” rowspan=”2″ colspan=”1″ General (n=221) /th th colspan=”3″ align=”still left” valign=”best” rowspan=”1″ Latanoprost/timolol fixed-dose mixture (n =55) /th th colspan=”3″ align=”still left” valign=”best” rowspan=”1″ Latanoprost + timolol (n=56) /th th colspan=”3″ align=”still left” valign=”best” rowspan=”1″ Latanoprost (n=54) /th th colspan=”3″ align=”still left” valign=”best” rowspan=”1″ Timolol (n=56) /th /thead Sex, n (%)?Man39 (70.9)38 (67.9)36 (66.7)35 (62.5)148 (67.0)?Feminine16 (29.1)18 (32.1)18 (33.3)21 (37.5)73 (33.0)Age (years)?Mean56.353.556.254.055.0?SD14.3012.5914.3812.9313.53?Range24C8322C7220C7823C7720C83Iris color, n (%)?Dark brown55 (100.0)56 (100.0)53 (98.1)56 (100.0)220 (99.5)?Hazel001 (1.9)01 (0.5)Mean baseline IOP (mmHg)a9 am11 am5 pm9 am11 am5 pm9 am11 am5 pm9 am11 am5 pm?Mean26.3826.4825.9326.8126.2226.1626.2526.5925.7926.8626.4326.20?SD2.803.133.192.422.672.812.693.112.843.503.612.98?Range20.33C35.0020.00C37.6619.33C36.0019.67C33.3319.33C32.3320.00C34.0020.66C34.0018.00C36.0018.33C34.0019.66C39.0016.00C37.0019.33C35.00? em P /em -valueb0.39420.64580.68700.79830.84820.81260.43180.93750.6403?Difference?0.420.25?0.230.13?0.110.14?0.480.05?0.27?95% CI?1.41 to 0.56?0.84 to at least one 1.35?1.36 to 0.90?0.91 to at least one 1.18?1.30 to at least one 1.07?1.01 to at least one 1.28?1.67.cPP population included individuals with at least 1 on-therapy efficacy assessment no main protocol violation. Abbreviations: ITT, objective to take care of; PP, per process; N/n, number. Individual demographics, baseline features, and baseline IOP from the intent-to-treat population are shown in Desk 1. time factors (mean IOP difference and 95% self-confidence period within 1.5 mmHg; check for ordinal factors. All tests had been two-tailed, using a significance degree of 0.05. Repeated-measures evaluation of variance was employed for the principal end stage (transformation in IOP from baseline). All statistical analyses had been performed using SAS? software program edition 9.1.3 (SAS Institute Inc., Cary, NC, USA). Outcomes Patients A complete of 300 sufferers had been screened at 17 sites in India. Of the, 227 sufferers fulfilled the eligibility requirements and had been randomized to 1 from the four treatment groupings: a fixed-dose mix of latanoprost/timolol (n=56), concomitant latanoprost plus timolol (58 sufferers), latanoprost by itself (n=55), and timolol by itself (n=58). Individual disposition is proven in Amount 1. Of the sufferers, 216 (95.2%) completed the analysis. Of the rest of the eleven (4.8%) sufferers who discontinued from the analysis, the reason why were shed to follow-up (latanoprost/timolol, n=2; latanoprost, n=1), main process violation (latanoprost plus timolol, n=1; latanoprost, n=1), drawback of consent (latanoprost plus timolol, n=1; latanoprost, n=1), undesirable occasions (latanoprost, n=1 [corneal disorder]; timolol, n=1 [bradycardia]), individual non-compliance (latanoprost plus timolol, n=1), and failing of study medicine (timolol, n=1). All 227 sufferers randomized to get treatment were regarded as the basic safety people. The intent-to-treat people (efficacy evaluation people) contains 221 sufferers, as well as the per-protocol people contains 215 sufferers. Open in another window Amount 1 Individual disposition. Records: aThe 227 randomized sufferers represented the safety populace, which included all patients who received at least one dose of study medication. bITT populace (efficacy analysis populace) included all patients with baseline visit assessment who received at least one dose of study medication and at least one on-therapy efficacy assessment. Quinestrol Missing data were treated by last observation carried forward. cPP Quinestrol populace included patients with at least one on-therapy efficacy assessment and no major protocol violation. Abbreviations: ITT, Quinestrol intent to treat; PP, per protocol; N/n, number. Patient demographics, baseline characteristics, and baseline IOP of the intent-to-treat populace are shown in Table 1. The overall mean populace age was 55.013.53 (range 20C83) years in this exclusively Asian patient population, and the majority of patients were male (67.0%). Importantly, there was no statistically significant difference in baseline IOP values between the four treatment groups, which included a mean baseline IOP range of 25.792.84 mmHg to 26.863.50 mmHg. In addition, there were no statistically significant differences in the number of patients with a history of OAG between the treatment groups. Slightly more patients in the latanoprost plus timolol group (33% right eye, 32% left eye) had OHT compared with the fixed-dose combination group (25% right eye, 27% left vision), latanoprost group (20% right eye, 19% left vision), and timolol group (22% for each vision). This variation in OHT between the groups was not regarded as being statistically significant. Table 1 Patient demographic and baseline characteristics (ITT populace)* thead th align=”left” valign=”top” rowspan=”2″ colspan=”1″ Category /th th colspan=”12″ align=”left” valign=”top” rowspan=”1″ Treatment group hr / /th th align=”left” valign=”top” rowspan=”2″ colspan=”1″ Overall (n=221) /th th colspan=”3″ align=”left” valign=”top” rowspan=”1″ Latanoprost/timolol fixed-dose combination (n =55) /th th colspan=”3″ align=”left” valign=”top” rowspan=”1″ Latanoprost + timolol (n=56) /th th colspan=”3″ align=”left” valign=”top” rowspan=”1″ Latanoprost (n=54) /th th colspan=”3″ align=”left” valign=”top” rowspan=”1″ Timolol (n=56) /th /thead Sex, n (%)?Male39 (70.9)38 (67.9)36 (66.7)35 (62.5)148 (67.0)?Female16 (29.1)18 (32.1)18 (33.3)21 (37.5)73 (33.0)Age (years)?Mean56.353.556.254.055.0?SD14.3012.5914.3812.9313.53?Range24C8322C7220C7823C7720C83Iris color, n (%)?Brown55 (100.0)56 (100.0)53 (98.1)56 (100.0)220 (99.5)?Hazel001 (1.9)01 (0.5)Mean baseline IOP (mmHg)a9 am11 am5 pm9 am11 am5 pm9 am11 am5 pm9 am11 am5 pm?Mean26.3826.4825.9326.8126.2226.1626.2526.5925.7926.8626.4326.20?SD2.803.133.192.422.672.812.693.112.843.503.612.98?Range20.33C35.0020.00C37.6619.33C36.0019.67C33.3319.33C32.3320.00C34.0020.66C34.0018.00C36.0018.33C34.0019.66C39.0016.00C37.0019.33C35.00? em P /em -valueb0.39420.64580.68700.79830.84820.81260.43180.93750.6403?Difference?0.420.25?0.230.13?0.110.14?0.480.05?0.27?95% CI?1.41 to 0.56?0.84 to 1 1.35?1.36 to 0.90?0.91 to 1 1.18?1.30 to 1 1.07?1.01 to 1 1.28?1.67 to 0.72?1.22 to 1 1.32?1.43 to 0.89 Open in a separate window Notes: *Data shown are for the efficacy analysis (ITT) population. aMean IOP at baseline is for the study vision only. b em P /em -value was calculated for each group compared with latanoprost/timolol fixed-dose combination at the corresponding time point, using unpaired Students em t /em -test. Abbreviations: CI, confidence interval; IOP, intraocular pressure; ITT,.Administration of therapies with simple regimens is critical in encouraging long-term use of an effective ocular hypotensive agent that might delay or prevent glaucomatous damage.46 The evidence suggests that poor adherence is an issue in patients treated with complex medication regimens for glaucoma.47C51 This finding is supported by studies in patients with other chronic conditions (human immunodeficiency virus, diabetes, hypertension) that suggest adherence to medical therapy is higher in patients receiving fixed-dose combination regimens versus those receiving unfixed concomitant therapies.21 Similar advantages of topical fixed combinations might be expected in the treatment of glaucoma. time points (mean IOP difference and 95% confidence interval within 1.5 mmHg; test for ordinal variables. All tests were two-tailed, with a significance level of 0.05. Repeated-measures analysis of variance was used for the primary end point (change in IOP from baseline). All statistical analyses were performed using SAS? software version 9.1.3 (SAS Institute Inc., Cary, NC, USA). Results Patients A total of 300 patients were screened at 17 sites in India. Of these, 227 patients met the eligibility criteria and were randomized to one of the four treatment groups: a fixed-dose combination of latanoprost/timolol (n=56), concomitant latanoprost plus timolol (58 patients), latanoprost alone (n=55), and timolol alone (n=58). Patient disposition is shown in Physique 1. Of these patients, 216 (95.2%) completed the study. Of the remaining eleven (4.8%) patients who discontinued from the study, the reasons were lost to follow-up (latanoprost/timolol, n=2; latanoprost, n=1), major protocol violation (latanoprost plus timolol, n=1; latanoprost, n=1), withdrawal of consent (latanoprost plus timolol, n=1; latanoprost, n=1), adverse events (latanoprost, n=1 [corneal disorder]; timolol, n=1 [bradycardia]), patient noncompliance (latanoprost plus timolol, n=1), and failure of study medication (timolol, n=1). All 227 patients randomized to receive treatment were considered as the safety populace. The intent-to-treat populace (efficacy analysis populace) consisted of 221 patients, and the per-protocol populace consisted of 215 patients. Open in a separate window Physique 1 Patient disposition. Notes: aThe 227 randomized patients represented the safety populace, which included all patients who received at least one dose of study medication. bITT populace (efficacy analysis populace) included all patients with baseline visit assessment who received at least one dose of study medication and at least one on-therapy efficacy assessment. Missing data were treated by last observation carried forward. cPP populace included individuals with at least one on-therapy effectiveness assessment no main process violation. Abbreviations: ITT, purpose to take care of; PP, per process; N/n, number. Individual demographics, baseline features, and baseline IOP from the intent-to-treat human population are demonstrated in Desk 1. The entire mean human population age group was 55.013.53 (range 20C83) years with this exclusively Asian individual population, and nearly all individuals were male (67.0%). Significantly, there is no statistically factor in baseline IOP ideals between your four treatment organizations, including a mean baseline IOP selection of 25.792.84 mmHg to 26.863.50 mmHg. Furthermore, there have been no statistically significant variations in the amount of individuals with a brief history of OAG between your treatment organizations. Slightly more individuals in the latanoprost plus timolol group (33% correct eye, 32% remaining eye) got OHT weighed against the fixed-dose mixture group (25% correct eye, 27% remaining attention), latanoprost group (20% correct eye, 19% remaining attention), and timolol group (22% for every attention). This variant in OHT between your organizations was not thought to be becoming statistically significant. Desk 1 Individual demographic and baseline features (ITT human population)* thead th align=”remaining” valign=”best” rowspan=”2″ colspan=”1″ Category /th th colspan=”12″ align=”remaining” valign=”best” rowspan=”1″ Treatment group hr / /th th align=”remaining” valign=”best” rowspan=”2″ colspan=”1″ General (n=221) /th th colspan=”3″ align=”remaining” valign=”best” rowspan=”1″ Latanoprost/timolol fixed-dose mixture (n =55) /th th colspan=”3″ align=”remaining” valign=”best” rowspan=”1″ Latanoprost + timolol (n=56) /th th colspan=”3″ align=”remaining” valign=”best” rowspan=”1″ Latanoprost (n=54) /th th colspan=”3″ align=”remaining” valign=”best” rowspan=”1″ Timolol (n=56) /th /thead Sex, n (%)?Man39 (70.9)38 (67.9)36 (66.7)35 (62.5)148 (67.0)?Woman16 (29.1)18 (32.1)18 (33.3)21 (37.5)73 (33.0)Age (years)?Mean56.353.556.254.055.0?SD14.3012.5914.3812.9313.53?Range24C8322C7220C7823C7720C83Iris color, n (%)?Dark brown55 (100.0)56 (100.0)53 (98.1)56 (100.0)220 (99.5)?Hazel001 (1.9)01 (0.5)Mean baseline IOP (mmHg)a9 am11 am5 pm9 am11 am5 pm9 am11 am5 pm9 am11 am5 pm?Mean26.3826.4825.9326.8126.2226.1626.2526.5925.7926.8626.4326.20?SD2.803.133.192.422.672.812.693.112.843.503.612.98?Range20.33C35.0020.00C37.6619.33C36.0019.67C33.3319.33C32.3320.00C34.0020.66C34.0018.00C36.0018.33C34.0019.66C39.0016.00C37.0019.33C35.00? em P /em -valueb0.39420.64580.68700.79830.84820.81260.43180.93750.6403?Difference?0.420.25?0.230.13?0.110.14?0.480.05?0.27?95% CI?1.41 to 0.56?0.84 to at least one 1.35?1.36 to 0.90?0.91 to at least one 1.18?1.30 to at least one 1.07?1.01 to at least one 1.28?1.67 to 0.72?1.22 to at least one 1.32?1.43 to 0.89 Open up in another window Records: *Data demonstrated are for the efficacy analysis (ITT) population. aMean IOP at baseline is perfect for the study attention just. b em P /em -worth was calculated for every group weighed against latanoprost/timolol fixed-dose mixture at the related time stage, using unpaired College students em t /em -check. Abbreviations: CI, self-confidence period; IOP, intraocular pressure; ITT, purpose to take care of; SD, regular deviation. IOP assessments between treatment organizations Significant reductions in IOP from baseline had been seen in all treatment organizations at all period points on the 6-week treatment period (Shape 2). The IOP reduction using the fixed-dose mix of latanoprost/timolol was similar compared to that with concomitant timolol plus latanoprost. Mean IOP in.