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K-232 phase 3 long-term administration study in patients with primary open-angle glaucoma (POAG), exfoliative glaucoma, pigmentary glaucoma or ocular hypertension (OH)

K-232 phase 3 long-term administration study

200

Cohort 1 (n=48) [Sex] Male: 25 participants (52.1%), Female: 23 participants (47.9%) [Age, Mean (SD)] 59.9 (13.8) years [Diagnosis] POAG (broad definition): 42 participants (87.5%), OH: 6 participants (12.5%) [Baseline IOP, Mean (SD)] before instillation: 17.5 (1.7) mmHg, 2 hours after instillation: 16.5 (2.0) mmHg [Previous treatment <= 2 years before the start of the screening period] presence: 47 participants (97.9%), absense: 1 participant (2.1%) [Received ripasudil or brimonidine during screening period] brimonidine: 2 participants (4.2%), none: 46 participants (95.8%) [History of allergy] presence: 26 participants (54.2%), absence: 22 participants (45.8%) Cohort 2 (n=44) [Sex] Male: 26 participants (59.1%), Female: 18 participants (40.9%) [Age, Mean (SD)] 65.3 (9.5) years [Diagnosis] POAG (broad definition): 34 participants (77.3%), OH: 8 participants (18.2%), Exfoliative glaucoma: 2 participants (4.5%) [Baseline IOP, Mean (SD)] before instillation: 18.8 (3.5) mmHg, 2 hours after instillation: 17.5 (3.3) mmHg [Previous treatment <= 2 years before the start of the screening period] presence: 43 participants (97.7%), absence: 1 participant (2.3%) [Received ripasudil or brimonidine during screening period] brimonidine: 2 participants (4.5%), none: 42 participants (95.5%) [History of allergy] presence: 25 participants (56.8%), absence: 19 participants (43.2%) Cohort 3 (n=41) [Sex] Male: 26 participants (63.4%), Female: 15 participants (36.6%) [Age, Mean (SD)] 63.5 (10.0) years [Diagnosis] POAG (broad definition): 39 participants (95.1%), OH: 2 participants (4.9%) [Baseline IOP, Mean (SD)] before instillation: 17.6 (1.9) mmHg, 2 hours after instillation: 16.0 (2.1) mmHg [Previous treatment <= 2 years before the start of the screening period] presence: 41 participants (100.0%) [Received ripasudil or brimonidine during screening period] ripasudil: 6 participants (14.6%), brimonidine: 4 participants (9.8%), none: 31 participants (75.6%) [History of allergy] presence: 16 participants (39.0%), absence: 25 participants (61.0%) Cohort 4 (n=46) [Sex] Male: 22 participants (47.8%), Female: 24 participants (52.2%) [Age, Mean (SD)] 65.2 (9.1) years [Diagnosis] POAG (broad definition): 36 participants (78.3%), OH: 10 participants (21.7%) [Baseline IOP, Mean (SD)] before instillation: 19.1 (3.3) mmHg, 2 hours after instillation: 17.4 (3.0) mmHg [Previous treatment <= 2 years before the start of the screening period] presence: 37 participants (80.4%), absence: 9 participants (19.6%) [Received ripasudil or brimonidine during screening period] ripasudil: 3 participants (6.5%), brimonidine: 5 participants (10.9%), none: 38 participants (82.6%) [History of allergy] presence: 22 participants (47.8%), absence: 24 participants (52.2%)

Informed Consent Obtained: 200 participants Entered the treatment period: 179 participants (Cohort 1: 48, Cohort 2: 44, Cohort 3: 41, Cohort 4: 46) Completed: 141 participants (Cohort 1: 36, Cohort 2: 36, Cohort 3: 35, Cohort 4: 34) Primary Efficacy Analysis Set: 179 participants (participants who entered the treatment period) Safety Analysis Set: 179 participants (participants who entered the treatment period)

The incidence of adverse events and adverse drug reactions were 92.2% and 76.0% in the total study population, 91.7% and 83.3% in cohort 1, 88.6% and 75.0% in cohort 2, 92.7% and 65.9% in cohort 3, and 95.7% and 78.3% in cohort 4, respectively. The most frequent adverse event and adverse drug reaction in all cohorts was conjunctival hyperemia, which was observed in 58.1% and 58.1% in the total study population, 68.8% and 68.8% in cohort 1, 50.0% and 50.0% in cohort 2, 51.2% and 51.2% in cohort 3, and 60.9% and 60.9% in cohort 4, respectively. Serious adverse events were observed in 1 participant in cohort 1, 1 participant in cohort 3, and 2 participants in cohort 4, but none of these events were considered to be related to the investigational product. No deaths occurred. There were no clinically significant changes in ocular assessments such as corneal thickness, corneal endothelial cell density and morphology.

Mean changes in IOP from baseline at each measurement point were negative in the total study population and each cohort, and significantly reduced from baseline for all participants and cohorts (p<0.05, one-sample t-test), except before instillation on week 36 and week 40 in cohort 3. Mean changes (SD) in IOP at 2 hours after instillation from baseline to weeks 8, 28, and 52 were -3.7 (2.5), -3.6 (2.7), -3.4 (3.1) mmHg in the total study population, -3.8 (2.1), -4.1 (2.5), -3.5 (2.8) mmHg in cohort 1, -3.5 (3.1), -3.5 (2.8), -3.3 (3.4) mmHg in cohort 2, -3.2 (2.3), -3.0 (2.5), -2.7 (3.1) mmHg in cohort 3, and -4.2 (2.5), -3.6 (2.9), -4.1 (3.0) mmHg in cohort 4, respectively. Mean changes (SD) in IOP before instillation from baseline to weeks 8, 28 and 52 were -1.9 (2.4), -1.2 (2.4), -1.4 (2.7) mmHg in the total study population, -2.0, (1.8), -1.0 (1.9), -0.8 (2.2) mmHg in cohort 1, -1.7 (3.2), -1.5 (2.7), -1.8 (2.4) mmHg in cohort 2, -1.7 (2.1), -1.0 (2.5), -1.0 (2.9) mmHg in cohort 3, -2.1 (2.3), -1.2 (2.6), -1.9 (3.0) mmHg in cohort 4.

Mean IOP at each measurement point decreased from baseline values in the total study population and each cohort. Mean IOP (SD) at 2 hours after instillation at weeks 8, 28 and 52 were 16.8 (2.7), 13.2 (2.6), 13.2 (3.1) mmHg for all participants, 12.7 (2.0), 12.4 (2.1), 12.9 (2.9) mmHg in cohort 1, 14.0 (3.0), 14.1 (3.7), 13.8 (3.4) mmHg in cohort 2, 12.8 (2.1), 12.9 (2.1), 13.2 (3.3) mmHg in cohort 3, 13.3 (3.1), 13.7 (3.3), 13.0 (2.9) mmHg in cohort 4. Mean IOP before instillation at weeks 8, 28 and 52 were 16.4 (3.1), 17.2 (3.3), 16.8 (3.2) mmHg for all participants, 15.5 (2.7), 16.6 (2.6), 16.7 (3.0) mmHg in cohort 1, 17.1 (3.2), 17.7 (3.3), 16.7 (3.3) mmHg in cohort 2, 16.0 (2.6), 16.7 (3.1), 16.6 (3.2) mmHg in cohort 3, 17.0 (3.4), 18.0 (4.1), 17.1 (3.6) mmHg in cohort 4.

This study demonstrated the 52-week IOP-lowering efficacy and safety of K-232, both alone and in combination with current ocular IOP-lowering agents, in Japanese patients with POAG, OH or exfoliative glaucoma.

April. 05, 2024

Mar. 02, 2024

https://link.springer.com/article/10.1007/s00417-024-06388-y

No

-

Kowa Company, Ltd.

4-14, Nihonbashi-honcho 3-chome, Chuo-ku, Tokyo

ctrdinfo@kowa.co.jp

Kowa Company, Ltd.

4-14, Nihonbashi-honcho 3-chome, Chuo-ku, Tokyo

+81-3-3279-7454

ctrdinfo@kowa.co.jp

completed

Feb. 19, 2020

Interventional

multicenter, open

treatment purpose

3

1.POAG (broad definition), exfoliative glaucoma, pigmentary glaucoma or OH patients
2.Baseline IOP => 15mmHg

1.Patients whose visual acuity is below 0.3
2.Patients with severe visual field defects
3.Patients thought to wear contact lenses
etc.

Both

primary open-angle glaucoma (broad definition), exfoliative glaucoma, pigmentary glaucoma, ocular hypertension

investigational material(s)
Generic name etc : K-232
INN of investigational material : -
Therapeutic category code : 131 Agents for ophthalmic use
Dosage and Administration for Investigational material : Instill one drop at a time, twice daily.

control material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code :
Dosage and Administration for Investigational material : -

safety
efficacy
Safety :Incidence of adverse event and adverse drug reaction
Efficacy :Mean IOP reduction from baseline at all measurement points

safety
efficacy
Safety :Change from baseline in ophthalmologic examination at 28 weeks and 52 weeks, etc
Efficacy :IOP at all measurement points

+81-6-6395-9000

Feb. 20, 2020