Study to investigate safety and efficacy study of SPARC1412 in subjects with glaucoma

Phase 1

• Conditions: Open-angle glaucoma, chronic angle closure glaucoma with patent iridotomy, pseudoexfoliation, pigment dispersion, or ocular hypertension; MedDRA version: 19.1Level: PTClassification code 10018304Term: GlaucomaSystem Organ Class: 10015919 - Eye disorders; Therapeutic area: Diseases [C] - Eye Diseases [C11]

• Registration Number: EUCTR2015-005540-34-BG
• Lead Sponsor: Sun Pharma Advanced Research Company, Ltd. (SPARC)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-06-03
• Last Update Posted: 24 July 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Be male or female, at least 18 years of age
2. Have glaucoma (chronic open angle glaucoma, chronic angle closure glaucoma with patent iridotomy/iridectomy, pseudo exfoliation, pigment dispersion) or ocular hypertension in both eyes and likely to be controlled on monotherapy.
3. Provide signed and dated written informed consent in accordance with GCP and local legislation prior to any study procedures.
4. Have a baseline (Visit 2/Day -1/8:00 AM) unmedicated IOP = 22 mm Hg and = 34 mm Hg in at least 1 eye, and asymmetry of IOP between
eyes must not exceed 5 mmHg
5. Have a best spectacle-corrected visual acuity (BSCVA) score of 0.8 logarithm of the minimum angle of resolution (logMAR) or better in each eye as assessed with the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at the Screening visit.
6. (If female of childbearing potential) agree to have a urine pregnancy test at Screening (Visit 1) and Baseline (Visit 2) (both must be negative) and Visits 7, 8 and 13. A female is considered of childbearing potential if she has had her first menses and she is either:
· not postmenopausal for at least 12 consecutive months prior to enrollment; or
· not surgically sterilized by bilateral tubal ligation, or bilateral oophorectomy, or hysterectomy; or
· not practicing an acceptable method of birth control as judged by the investigator(s) (such as condoms, foams, jellies, diaphragm,
intrauterine device [IUD], oral or long acting injected contraceptives) from at least 2 months prior to study entry and through the duration of the study; or
· not sexually abstinent through the duration of the study
7. Be able and willing to follow study instructions and complete all required visits
8. At Baseline (Visit 2/Day -1), have 1 reliable visual field on file before dosing (the visual field can be performed at Visit 1 or within 6 months of the Visit 2/Day -1 visit).
9. Adequate washout period prior to baseline (Visit 2/Day -1) of any ocular hypotensive medication. In order to minimize potential risk to
patients due to intraocular pressure (IOP) elevations during the washout period, investigator may choose to substitute a parasympathomimetic or carbonic anhydrase inhibitor in place of a
sympathomimetic, alpha-agonist, beta-adrenergic blocking agent, or prostaglandin; however, all patients must have discontinued all ocular
hypotensive medications for the minimum washout period provided in Table below.

Medication Minimum washout period

Parasympathomimetics [eg, pilocarpine (Isopto® Carpine), carbachol (Isopto® Carbachol)]4 days

Carbonic anhydrase inhibitors (systemic or topical) [eg, acetazolamide (Diamox®), dorzolamide hydrochloride (Trusopt®), brinzolamide (Azopt®)]4 days

Sympathomimetics [eg, dipivefrin (Propine®), epinephrine (Epifrin®)]14 days

Alpha-agonists [eg, apraclonidine (Iopidine®), brimonidine tartrate
(Alphagan®, Alphagan® P), brimonidine tartrate and brinzolamide (Simbrinza®)]14 days

Beta-adrenergic blocking agents [eg, timolol (Timoptic®, Betimol®, Timoptic XE®, Istatol®), timolol maleate, and
dorzolamide hydrochloride (Cosopt®)28 days

timolol maleate and brimonidine tartrate
(Combigan®), levobunolol (Akbeta®, Betagan®), betaxolol (Betoptic®, Betopic- S®), metipranolol (Opti-Pranolol®), carteolol (Ocupress®)] 28 days

Prostaglandin analogs (eg, latanoprost (Xalatan®), travoprost (Travatan®), bimatoprost (Lumigan®), tafluprost (Zioptan™)]28 days

Are the trial

Exclusion Criteria

1. Have occludable angle on gonioscopy without a patent iridotomy
2. Have uncontrolled systemic disease (eg, diabetes) which might interfere with the study
3. Current or history of severe hepatic or renal impairment. Have severe cardiovascular disease unless his/her disease is controlled and clearance has been obtained from the treating primary care physician or cardiologist
4. Subjects with depression, cerebral or active coronary insufficiency or orthostatic hypotension.
5. (If female of childbearing potential) Be pregnant, nursing, or planning a pregnancy during study entry and through the duration of the study.
6. Have clinically relevant, abnormally low or high blood pressure or pulse rate (normal ranges: systolic: 90-160 mm Hg; diastolic: 55-90 mm
Hg; pulse rate: 50-100 bpm)
7. Have central corneal thickness > 600 µm
8. Have any known allergy or sensitivity to the study medications or their components (brimonidine tartrate, amberlite IRP 69, hypromellose, povidone, carbopol, edetate disodium, n-lauroyl sarcosine, sodium, tromethamine, benzalkonium chloride, sodium
carboxymethylcellulose, sodium borate, boric acid, sodium chloride, potassium chloride, calcium chloride, magnesium chloride, Purite® -
preservative).
9. Have intermittently used oral or topical ophthalmic steroids within 30 days prior to the baseline (Visit 2/Day -1), or anticipate use during the study, or have any previous use of an intraocular sustained-release steroid implant; or use within 6 months prior to baseline
(Visit 2/Day -1) of intraocular or subtenon injection of Corticosteroid. Use of topical dermal steroids (except on the face) is allowed.
10. Use of flucinolone (Iluvien) within 24 months of baseline (Visit 2/Day -1)
11. Require the use of any ocular medications during the study other than the study medications; occasional use of artificial tears for mild dry eye or lid scrubs for mild blepharitis is allowed. [Note: If subject uses artificial tears or lib scrubs, the treatment must be administered at least 30 minutes prior to study medication instillation].
12. Have any contraindications to brimonidine therapy
13. Have known lack of ocular hypotensive response to alpha adrenergic receptor agonist.
14. Have concurrent use of monoamine oxidase (MAO) inhibitor therapy within 1 month prior to baseline (Visit 2/Day -1)
15. Have recent (within 30 days of baseline [Visit 2/Day -1]) or anticipate alteration of existing chronic systemic treatment or introduction of treatment with agents which could have a substantial effect on IOP (including, but not necessarily limited to, systemic adrenergic agents including betaadrenergic blocking agents [eg, propranolol, metoprolol, nadolol, timolol, and atenolol])
16. Have recent (within 30 days of baseline [Visit 2/Day -1]) or concurrent use, or anticipate treatment with digoxin, antidepressants which affect noradrenergic transmissions (eg, tricyclic antidepressants, mianserin), or adrenergicaugmenting psychotropic drugs (eg, desipramine, amitriptyline)
17. Have any active ocular disease other than glaucoma that requires treatment or may affect the safety or efficacy of the study medication, in the opinion of the investigator. Please note, artificial tears for mild dry eye and lid scrubs for mild blepharitis are allowed.
18. Have any abnormalities that would preclude accurate readings with an applanation tonometer
19. Have any opacity or subject uncooperativeness that restricts adequate examination of the ocular fundus or an

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Evaluate the safety and diurnal IOP efficacy of once daily (QD) dosing with brimonidine tartrate 0.35% ophthalmic suspension compared with brimonidine tartrate 0.1% dosed 3 times a day (TID) in subjects with chronic open-angle glaucoma, chronic angle closure glaucoma with patent iridotomy/iridectomy, pseudoexfoliation, pigment dispersion, or ocular hypertension.;Secondary Objective: Not applicable;Primary end point(s): Mean IOP (study eye) at each of the 4 time points (8:00 AM, 10:00 AM, 3:00 PM, 5:00 PM) on Day 84 (Visits 7, 13).;Timepoint(s) of evaluation of this end point: 8:00 AM, 10:00 AM, 3:00 PM, 5:00 PM on Day 84 (Visits 7, 13)