Non-inferiority study between two formulations Brimonidine 0.2%/Timolol 0.5% eye drops solution

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Becro (Cyprus) Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

31 May 2024 → 6 Feb 2025

Decision date (initial)

2024-03-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

BECRO (Cyprus) Ltd

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To confirm the clinical non-inferiority of a fixed-Combination Generic Formulation of Brimonidine0.2%/Timolol 0.5% eye drops, solution in single-dose container with the marketed preservative-containing Combigan® eye drops, solution in patients with open angle glaucoma, or ocular hypertension (IOP≥22 mmHg) by examining the change of IOP at 08:00 from end of study to baseline

Conditions and MedDRA coding

Open angle glaucoma is characterized by increased intraocular pressure, resulting in pathological changes in the optic disk and typical visual field defects,and eventually blindness

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Male or female, of any race and ≥18 years of age.
2. Diagnosed of unilateral or bilateral open angle glaucoma or ocular hypertension
3. Average IOP ≥ 22 mmHg and ≤ 35 mmHg measured at 08:00, 12:00 and 16:00 hours pre-treatment in at least one eye at day 0.
4. Without treatment for open-angle glaucoma with IOP-lowering drugs, for at least 4 weeks.
5. Best-corrected visual acuity ≥20 of 100 (Snellen) corresponding to logMAR of ≤0.7.
6. No new systemic medication that may alter IOP in the previous 30 days (e.g. beta-blockers, Ca-channel-blockers, ACE-inhibitors, prostaglandins, etc.), or expected to continue the current treatment with these medicinal products on stable regimen for 30 days prior to the study and during the study.
7. Patients with controlled arterial blood pressure according to the investigator’s opinion.
8. Females who participate in the study are either unable to gestate [i.e. post-menopausal (absence of menses for 12 months prior to drug administration), hysterectomy, bilateral oophorectomy, tubal ligation at least 6 months prior to drug administration] or at reproductive age; Females of reproductive age if sexually active, must be practicing an effective method of birth control throughout the study; Reliable contraception methods are considered the following: • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal or transdermal • progestogen-only hormonal contraception associated with inhibition of ovulation oral, implantable or injectable • intrauterine device (IUD) • intrauterine hormone-releasing system (IUS) • bilateral tubal occlusion • vasectomised partner • sexual abstinence
9. Expected by the Investigator that IOP will remain controlled with the new treatment without optic nerve damage or progression of visual field loss;
10. Able to understand the requirements of the clinical trial and to agree to return for the required follow-up visits;
11. Willing to provide voluntary written informed consent and data protection declaration before any clinical trial related procedure is performed.

Exclusion criteria 27

1. Ηistory of chronic or recurrent inflammatory eye disease (i.e. scleritis, uveitis, herpes keratitis), ocular trauma within the past 6 months or ocular inflammation within the past 3 months or infections;
2. History of anterior chamber lens, torn posterior lens capsule, aphakia or any known risk factor for cystoid macular edema
3. Narrow-angle/angle-closure glaucoma;
4. Corneal abnormalities that will preclude accurate IOP reading with an aplanation tonometer
5. Clinically significant or progressive retinal disease (e.g. retinal degeneration, diabetic retinopathy, retinal detachment);
6. Intraocular surgery within the past 3 months;
7. Ocular laser surgery within the past 1 months;
8. Best-corrected visual acuity < 20 of 100 (Snellen), corresponding to worse than 0.7 logarithm of minimal angle of resolution (logMAR) score;
9. Cup/disk ratio >0.8;
10. Current use of topical, ocular, nonsteroidal anti-inflammatory drugs
11. Ocular treatment with any prostamide, prostaglandin, carbonic anhydrase inhibitor and pilocarpine
12. Treatment with local or systemic corticosteroids;
13. History of reactive airway disease including bronchial asthma or a history of bronchial asthma, severe chronic obstructive pulmonary disease;
14. History of sinus bradycardia, sick sinus syndrome, sino-atrial block, second or third degree atrioventricular block not controlled with pace-maker, overt cardiac failure, cardiogenic shock
15. History of severe or unstable and uncontrolled cardiovascular disease;
16. History of depression, cerebral or coronary insufficiency, Raynaud's phenomenon, orthostatic hypotension or thromboangiitis obliterans
17. Treatment with monoamine oxidase (MAO) inhibitor therapy or discontinuation of the treatment less than 15 days before randomization;
18. Treatment with adrenergic augmenting psychotropic drugs/antidepressants which affect noradrenergic transmission (e.g. tricyclic antidepressants and mianserin);
19. Any change in any systemic medication that affects IOP within the last 30 days (e.g. clonidine, etc.);
20. Treatment with oral carbonic anhydrase inhibitors (e.g. acetazolamide, methazolamide, topiramate, sultiame, zonisamide);
21. A history of allergic hypersensitivity or poor tolerance to any component of the eye drop solution used in this clinical trial
22. Pregnancy or breast-feeding or childbearing potential not protected by a highly effective contraceptive method of birth control;
23. Current participation or not yet completed period of at least 30 days since ending other investigational device or drug trial(s);
24. Unwillingness or inability to comply with the clinical trial procedures;
25. Unwillingness to consent to storage, saving and transmission of pseudonymous medical data for clinical trial reasons;
26. Who are legally incapacitated
27. Who are legally detained in an official institute

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in IOP at 08:00 in study eye from end of treatment (week 12) to baseline (week 0) in subjects treated with the test product as compared to subjects treated with the reference product

Secondary endpoints 7

1. Change in IOP at 12:00 and 16:00 in study eye from end of treatment (week 12) to baseline (week 0) in subjects treated with the test product as compared to subjects treated with the reference product.
2. Change in IOP at 08:00, 12:00 and 16:00 in study eye from week 2 to baseline (week 0) in subjects treated with the test product as compared to subjects treated with the reference product.
3. Change in IOP at 08:00, 12:00 and 16:00 in study eye from week 6 to baseline (week 0) in subjects treated with the test product as compared to subjects treated with the reference product
4. Average diurnal IOP change from baseline to end of week 12
5. Average decrease of diurnal IOP measured between baseline and week 2.
6. Average decrease of diurnal IOP measured between baseline and week 6
7. Proportion of withdrawals for therapeutic failure (diurnal IOP ≥22 mmHg) at any time point during or at the end of week 12.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Becro (Cyprus) Limited

Sponsor organisation

Becro (Cyprus) Limited

Address

Chanteclair Building 1st Floor, Office 108, Sofouli 16 Office 108 Sofouli 16

City

Nicosia

Postcode

1096

Country

Cyprus

Scientific contact point

Organisation

Becro (Cyprus) Limited

Contact name

BECRO M.E.P.E

Public contact point

Organisation

Becro (Cyprus) Limited

Contact name

BECRO M.E.P.E

Third parties 1

Locations

1 EU/EEA country · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications