PMID- 15189751
OWN - NLM
STAT- MEDLINE
DCOM- 20040629
LR  - 20190922
IS  - 0149-2918 (Print)
IS  - 0149-2918 (Linking)
VI  - 26
IP  - 4
DP  - 2004 Apr
TI  - A 12-month, multicenter, randomized, double-masked, parallel-group comparison of 
      timolol-LA once daily and timolol maleate ophthalmic solution twice daily in the 
      treatment of adults with glaucoma or ocular hypertension.
PG  - 541-51
AB  - BACKGROUND: Timolol maleate, a nonselective beta-adrenoceptor antagonist applied 
      topically to the eye as a solution, is well known for its ocular hypotensive 
      efficacy. A gellan formulation of timolol maleate is given once daily and has 
      been shown to be as effective as timolol maleate solution, but is associated with 
      ocular symptoms that may limit its utility. A new timolol maleate solution has 
      been formulated that contains potassium sorbate (timolol-LA [TLA; Istalol(R)]) to 
      enhance the ocular bioavailability of timolol instilled into the eye, as well as 
      half the benzalkonium chloride preservative found in timolol maleate. OBJECTIVE: 
      The objective of this trial was to assess the ocular hypotensive efficacy and 
      safety profile of TLA 0.5% solution once daily with those of timolol maleate 
      ophthalmic solution (TIM) 0.5% twice daily in patients with open-angle glaucoma 
      (OAG) or ocular hypertension (OHT). METHODS: This multicenter, prospective, 
      randomized, double-masked, parallel-group clinical trial was conducted at 21 
      participating private practices across the United States. Patients aged > or =18 
      years with OAG or OHT in 1 or both eyes and an unmedicated intraocular pressure 
      (IOP) of > or =22 mm Hg were randomized to receive either TLA once daily or TIM 
      twice daily bilaterally for 12 months. The primary outcome measure was IOP (95% 
      CIs) on treatment difference at each visit (ie, equivalence analysis). The safety 
      profile was assessed based on biomicroscopic and ophthalmoscopic examination and 
      patient symptoms. RESULTS: A total of 332 patients (203 women, 129 men; mean 
      [SEM] age, 64.6 [11.8] years [range, 29-92 years]) entered the study. Of these, 
      290 patients (87.3%) completed it. At none of the visits did the 95% CIs for 
      between-treatment comparisons exceed 1.5 mm Hg and, at most of the visits, these 
      intervals did not exceed 1.0 mm Hg. Mean baseline IOP was approximately 25 mm Hg 
      in both groups. IOP was reduced at all posttreatment visits to 18 to 19 mm Hg at 
      peak and to approximately 19 to 20 mm Hg at trough drug level in both treatment 
      groups. Mean reductions from baseline were 6 to 7 mm Hg at peak and 5 to 6 mm Hg 
      at trough (25.5%-28.7% and 20.8%-24.7%, respectively). Seventeen patients (5.1%) 
      withdrew due to adverse events (AEs) (10 patients [6.0%] and 7 patients [4.2%] in 
      the TLA and TIM groups, respectively). Based on biomicroscopic and 
      ophthalmoscopic examination and volunteered symptoms, the safety profile was 
      similar between the 2 treatments, except for burning and stinging on 
      instillation, with an incidence of 41.6% in the TLA group and 22.9% in the TIM 
      group (P = 0.001). Nearly all cases of burning and stinging were mild (94.2% [65 
      events] with TLA and 90.0% [36 events] with TIM), and none of the patients 
      discontinued treatment due to this AE. CONCLUSIONS: TLA solution, a nonselective 
      beta-adrenoceptor antagonist, given once daily in the morning, was found to be 
      statistically equivalent in ocular hypotensive efficacy (as defined a priori) 
      compared with TIM, given twice daily, and with an acceptable safety profile in 
      this study population of adult patients.
FAU - Mundorf, Thomas K
AU  - Mundorf TK
AD  - Senju Pharmaceutical Co. Ltd., Osaka, Japan.
FAU - Ogawa, Takahiro
AU  - Ogawa T
FAU - Naka, Hiroaki
AU  - Naka H
FAU - Novack, Gary D
AU  - Novack GD
FAU - Crockett, R Stephens
AU  - Crockett RS
CN  - US Istalol Study Group
LA  - eng
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Ophthalmic Solutions)
RN  - 817W3C6175 (Timolol)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Delayed-Action Preparations/*administration & dosage/therapeutic use
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Female
MH  - Glaucoma, Open-Angle/*drug therapy
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Ocular Hypertension/*drug therapy
MH  - Ophthalmic Solutions
MH  - Prospective Studies
MH  - Timolol/*administration & dosage/therapeutic use
MH  - Treatment Outcome
EDAT- 2004/06/11 05:00
MHDA- 2004/06/30 05:00
CRDT- 2004/06/11 05:00
PHST- 2004/02/10 00:00 [accepted]
PHST- 2004/06/11 05:00 [pubmed]
PHST- 2004/06/30 05:00 [medline]
PHST- 2004/06/11 05:00 [entrez]
AID - S0149291804900562 [pii]
AID - 10.1016/s0149-2918(04)90056-2 [doi]
PST - ppublish
SO  - Clin Ther. 2004 Apr;26(4):541-51. doi: 10.1016/s0149-2918(04)90056-2.