Pharmacokinetics, Efficacy, and Safety of the Preservative-free Fixed Combination of Tafluprost 0.0015 % and Timolol 0.5 % in Healthy Volunteers: A Phase I Comparison vs. the Corresponding Preservative-free Monotherapies

Aim: To demonstrate biosimilarity as evidenced by the pharmacokinetic (PK), pharmacodynamics (PD), efficacy and safety comparability of AccofilR/GrastofilR (filgrastim), a recombinant human granulocyte colony-stimulating factor, and the reference product, NeupogenR. Patients and methods: Four phase I studies were conducted to demonstrate the comparative efficacy of Accofil/Grastofil and Neupogen. PD and PK parameters of Accofil/Grastofil (filgrastim) at and around the main clinical dose (5 μg/kg), using both the intravenous (IV) and subcutaneous (SC) routes of administration, were compared with Neupogen (EU) in healthy volunteers in three phase I clinical studies in a single-dose setting and following multiple-dose administration. An additional phase I PK/PD study was performed to compare Accofil/ Grastofil (filgrastim) to both EU-approved Neupogen and US-licensed Neupogen following the administration of a fixed SC dose of 300 μg. The efficacy and safety of Accofil/Grastofil was also evaluated in chemotherapy-naive women with stage IIA, IIB and IIIA breast cancer receiving docetaxel, doxorubicin, cyclophosphamide (TAC) chemotherapy. No comparator arm was included in this study so the efficacy and safety comparison was made with published data for the reference product, Neupogen. Results: A total of 235 healthy subjects were enrolled in the phase I studies and 120 patients in the phase III study. The PK and PD data demonstrated high comparability of the Accofil/ Grastofil and Neupogen products, with the 90 % confidence interval (CI) for primary PK parameters and 95 % CI for primary PD parameters falling within the pre-defined equivalence limits. In the phase III study, Accofil/Grastofil (filgrastim) demonstrated a safety and efficacy profile that was similar to the published data for the reference product Neupogen for the reduction of the duration of neutropenia in patients with breast cancer who were undergoing chemotherapy. Conclusion: Lack of clinically meaningful differences was convincingly demonstrated between Accofil/Grastofil (filgrastim) and the reference product, Neupogen.

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Efficacy and safety of preoperative IOP reduction using a preservative-free fixed combination of dorzolamide/timolol eye drops versus oral acetazolamide and dexamethasone eye drops and assessment of the clinical outcome of trabeculectomy in glaucoma

PLoS ONE ◽

10.1371/journal.pone.0171636 ◽

2017 ◽

Vol 12 (2) ◽

pp. e0171636 ◽

Cited By ~ 6

Author(s):

Katrin Lorenz ◽

Joanna Wasielica-Poslednik ◽

Katharina Bell ◽

Giulia Renieri ◽

Alexander Keicher ◽

...

Keyword(s):

Clinical Outcome ◽

Fixed Combination ◽

Eye Drops ◽

Efficacy And Safety ◽

Preservative Free

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The Efficacy and Safety of Preservative-containing and Preservative-free Brimonidine-Timolol Fixed Combination in Normal Tension Glaucoma

Journal of the Korean Ophthalmological Society ◽

10.3341/jkos.2021.62.10.1407 ◽

2021 ◽

Vol 62 (10) ◽

pp. 1407-1414

Author(s):

Bo Kyung Kim ◽

Si Nae Kim ◽

Joon Mo Kim

Keyword(s):

Intraocular Pressure ◽

Adverse Effects ◽

Fixed Combination ◽

Normal Tension Glaucoma ◽

Eye Drops ◽

Efficacy And Safety ◽

Timolol Maleate ◽

Combination Drug ◽

Brimonidine Tartrate ◽

Preservative Free

Purpose: To analyze the efficacy and safety of preservative-containing and preservative-free 0.2% brimonidine tartrate and 0.5% timolol maleate fixed combination drug in normal tension glaucoma.Methods: Fifty-one patients (84 eyes) who were diagnosed with normal tension glaucoma and with preservative-containing or preservative-free brimonidine-timolol fixed combinations alone were analyzed retrospectively from January 2017 to February 2020. Intraocular pressure (IOP) was measured four times a day (9 a.m., 11 a.m., 2 p.m., and 4 p.m.) before and at 6 months after applying eye drops. We analyzed and compared the effect of lowering IOP and the occurrence of intra or extra-ocular adverse effects.Results: A significant mean IOP reduction was shown in both groups: -1.95 ± 2.50 mmHg (-12.26 ± 15.87%) in the preservative-containing group and -1.60 ± 2.06 mmHg (-10.54 ± 13.94%) in the preservative-free group at 6 months after eyedrop instillation. The IOP was lowest in both groups at 11 a.m. There were no significant differences between the two groups in lowering IOP. Serious adverse effects causing discontinuation of the eye drops were not observed.Conclusions: Both preservative-containing and preservative-free brimonidine-timolol fixed combinations are effective in lowering IOP in normal tension glaucoma patients and are considered to be effective as eye drops without serious adverse effects.

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Efficacy and Safety of Netilmycin/Dexamethasone Preservative-Free and Tobramycin/Dexamethasone-Preserved Fixed Combination in Patients After Cataract Surgery

Journal of Ocular Pharmacology and Therapeutics ◽

10.1089/jop.2010.0050 ◽

2010 ◽

Vol 26 (6) ◽

pp. 617-621 ◽

Cited By ~ 11

Author(s):

Veronica Pianini ◽

Andrea Passani ◽

Gemma C.M. Rossi ◽

Franco Passani

Keyword(s):

Cataract Surgery ◽

Fixed Combination ◽

Efficacy And Safety ◽

Preservative Free

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Comparison of Ocular Surface Cytological Appearance in Glaucoma Patient Treated with Timolol Maleat 0,5% Latanoprost 0,005% and Timolol-Latanoprost Fixed Combination Preservative Free Eye Drop

Ophthalmologica Indonesiana ◽

10.35749/journal.v44i2.167 ◽

2019 ◽

Vol 44 (2) ◽

pp. 82

Author(s):

Maretha Amrayni ◽

Elsa Gustianty ◽

Susi Heryati ◽

Andika Prahasta ◽

Maula Rifada ◽

...

Keyword(s):

Epithelial Cells ◽

Cell Density ◽

Goblet Cell ◽

Ocular Surface ◽

Fixed Combination ◽

Cell Contact ◽

Corneal Epithelial ◽

Preservative Free ◽

Goblet Cell Density ◽

Epithelial Metaplasia

Introduction : The longterm use of topical antiglaucoma might cause ocular surface instability due to active substance or preservative used. Impression cytology examination may reveal superficial epithelial cells on conjunctiva and cornea, including goblet cells. Goblet cell density decrease is the most important parameter on evaluation of ocular surface disorder. Objective : This study was to understand ocular surface remodeling due to active substance of topical antiglaucoma with impression cytology examination among the patient prior and 3 months after therapy. Methods : This was a randomized controlled trial study with single blind masking. A total of 45 eyes from 31 patients were used as subject and distributed onto three groups treatment, which were timolol maleat 0.5%, latanoprost 0.005%, and latanoprost-timolol maleat fixed combination. All topical antiglaucoma in this study were preservative free. Result : There were differences between 3 groups in goblet cells density after 3 months therapy (p=0,030). Goblet cell density in timolol group was lower than latanoprost (p=0,041) and fixed combination (p=0,045). There was no significantly difference between 3 groups in conjunctival epithelial metaplasia degree (p=0,706) and cell to cell contact degree in corneal epithelial cells (p=0.66) after 3 months therapy. Conjunctival epithelial metaplasia degree were increased among group of timolol (p=0,008) and fixed combination (p=0,046). Conclusion : Timolol maleat 0,5% caused lower goblet cell density after 3 months therapy compare with latanoprost and fixed combination. There was no significantly difference in conjunctival epithelial metaplasia and cell to cell contact degree in corneal epithelial cells among these glaucoma treatment groups.

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