Recommended Topic Related To:

Izba

"Glaucoma is a group of diseases that damage the optic nerve, a cable at the back of each eye that connects it to the brain. It affects more than 2.7 million people in the United States and more than 60 million worldwide. There are many forms of t"...

Izba

CLINICAL PHARMACOLOGY

Mechanism Of Action

Travoprost free acid, a prostaglandin analog is a selective FP prostanoid receptor agonist which is believed to reduce intraocular pressure by increasing uveoscleral outflow. The exact mechanism of action is unknown at this time.

Pharmacokinetics

Travoprost is absorbed through the cornea and is hydrolyzed to the active free acid. Data from four multiple dose pharmacokinetic studies using travoprost ophthalmic solution, 0.004% (totaling 107 subjects) have shown that plasma concentrations of the free acid are below 0.01 ng/mL (the quantitation limit of the assay) in two-thirds of the subjects. In those individuals with quantifiable plasma concentrations (N=38), the mean plasma Cmax was 0.018 ± 0.007 ng/mL (ranged 0.01 to 0.052 ng/mL) and was reached within 30 minutes. From these studies, travoprost is estimated to have a plasma half-life of 45 minutes. There was no difference in plasma concentrations between Days 1 and 7, indicating steady-state was reached early and that there was no significant accumulation.

Travoprost, an isopropyl ester prodrug, is hydrolyzed by esterases in the cornea to its biologically active free acid. Systemically, travoprost free acid is metabolized to inactive metabolites via beta-oxidation of the α(carboxylic acid) chain to give the 1,2-dinor and 1,2,3,4-tetranor analogs, via oxidation of the 15-hydroxyl moiety, as well as via reduction of the 13,14 double bond.

The elimination of travoprost free acid from plasma was rapid and levels were generally below the limit of quantification within one hour after dosing. The terminal elimination half-life of travoprost free acid was estimated from fourteen subjects and ranged from 17 minutes to 86 minutes with the mean half-life of 45 minutes. Less than 2% of the topical ocular dose of travoprost was excreted in the urine within 4 hours as the travoprost free acid.

Clinical Studies

A single clinical trial of 3 months duration was conducted to compare the IOP-lowering effect of IZBA (travoprost ophthalmic solution) 0.003% to TRAVATAN (travoprost ophthalmic solution) 0.004% , with both dosed once daily in the evening in adult patients with open angle glaucoma or ocular hypertension. Patient age ranged from 21 to 92 years, with a mean age of 65 years. A total of 864 patients (IZBA, 442 patients; TRAVATAN, 422 patients) were enrolled, with 840 (97%) completing through Month 3.

Analysis was based on the intent-to-treat (ITT) population defined as all patients who received study drug and completed at least one scheduled on-therapy study visit.

The least squares mean IOP (mmHg), the difference in mean IOP (IZBA minus TRAVATAN), and the 95% CI for the treatment difference in mean IOP at visit and time point are presented in Table 1. The differences in the mean IOP at all visits and time points were within ±1 mmHg, demonstrating equivalence of IZBA to TRAVATAN in lowering intraocular pressure.

Table 2 presents the mean IOP change from baseline at Week 2, Week 6, and at Month 3. IZBA demonstrated comparable IOP reductions at all on-therapy visits and time points; the mean IOP reduction from baseline in the IZBA group ranged from 7.1 to 8.2 mmHg and in the TRAVATAN group ranged from 7.1 to 8.4 mmHg. In both treatment groups, the greatest mean IOP reduction was observed at the 8 AM assessment time point.

Table 1 : Mean IOP (mmHg) by Treatment Group and Treatment Difference in Mean IOP

Visit/ Time Point IZBA (Travoprost 0.003%) TRAVATAN (Travoprost 0.004%) Difference
Mean (SE) Mean (SE) Mean (95% CI) *
Baseline (N= 442) (N= 418)
  8 AM 26.9 (0.12) 27.1 (0.14) -0.2 (-0.5, 0.2)
  10 AM 25.4 (0.13) 25.6 (0.15) -0.2 (-0.6, 0.2)
  4 PM 24.6 (0.14) 24.8 (0.16) -0.2 (-0.6, 0.2)
Week 2 (N= 442) (N= 416)
  8 AM 19.4 (0.16) 19.5 (0.17) -0.1 (-0.5, 0.3)
  10 AM 18.6 (0.16) 18.6 (0.16) -0.0 (-0.4, 0.4)
  4 PM 18.0 (0.16) 18.3 (0.16) -0.3 (-0.7, 0.1)
Week 6 (N= 440**) (N= 413)
  8 AM 19.3 (0.16) 19.3 (0.17) -0.0 (-0.4, 0.4)
  10 AM 18.5 (0.16) 18.6 (0.17) -0.1 (-0.5, 0.3)
  4 PM 18.0 (0.16) 18.1 (0.17) -0.2 (-0.6, 0.2)
Month 3 (N= 432**) (N= 408)
  8 AM 19.2 (0.17) 19.3 (0.18) -0.1 (-0.5, 0.3)
  10 AM 18.3 (0.17) 18.6 (0.18) -0.3 (-0.7, 0.1)
  4 PM 18.0 (0.16) 18.0 (0.17) 0.0 (-0.4, 0.4)
SE = Standard Error; CI = Confidence Interval * Estimates for Week 2, Week 6, and Month 3 are based on least squares means derived from a statistical model that accounts for correlated IOP measurements within patient where site and 8 AM baseline IOP stratum are in the model; estimates for Baseline visit at each time point are based on a two sample independent t-test procedure. **One subject had missing data at 8 AM at Week 6; one subject had missing data at 4 PM at Month 3.

Table 2: IOP Change from Baseline (mmHg)

Visit   IZBA RAVATAN
N 8 AM 10 AM 4 PM N 8 AM 10 AM 4 PM
Week 2 Mean
95% CI
442 -8.0
(-8.3, -7.7)
-7.3
(-7.6, -7.0)
-7.1
(-7.4, -6.8)
416 -8.1
(-8.4, -7.8)
-7.5
(-7.8, -7.2)
-7.1
(-7.4, -6.8)
Week 6 Mean
95% CI
440* -8.1
(-8.4, -7.9)
-7.4
(-7.6, -7.1)
-7.2
(-7.5, -6.9)
413 -8.3
(-8.7, -8.0)
-7.5
(-7.9, -7.2)
-7.2
(-7.5, -6.9)
Month 3 Mean
95% CI
432* -8.2
(-8.6, -7.9)
-7.5
(-7.9, -7.2)
-7.1
(-7.4, -6.8)
408 -8.4
(-8.7, -8.1)
-7.6
(-7.9, -7.2)
-7.3
(-7.7, -7.0)
*One subject had missing data at 8 AM at Week 6; one subject had missing data at 4 PM at Month 3.

Last reviewed on RxList: 5/29/2014
This monograph has been modified to include the generic and brand name in many instances.

A A A

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


WebMD Daily

Get breaking medical news.

Health Resources
advertisement
advertisement
Use Pill Finder Find it Now See Interactions

Pill Identifier on RxList

  • quick, easy,
    pill identification

Find a Local Pharmacy

  • including 24 hour, pharmacies

Interaction Checker

  • Check potential drug interactions
Search the Medical Dictionary for Health Definitions & Medical Abbreviations