| CTRI Number |
CTRI/2012/09/003018 [Registered on: 25/09/2012] Trial Registered Prospectively |
| Last Modified On: |
25/10/2013 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
A clinical trial to study the safety and ocular hypotensive efficacy of AR-12286 in patients with High tension glaucoma |
|
Scientific Title of Study
|
A phase 2b double-masked, randomized, active-controlled, dose-response study assessing the safety and ocular hypotensive efficacy of AR-12286 in patients with elevated intraocular pressure for 3 months |
| Trial Acronym |
Nil |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| AR-12286-CS206, Version: 09 May 2012 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Ramanjit Sihota |
| Designation |
Professor of Ophthalmology |
| Affiliation |
All India Institute of Medical Sciences |
| Address |
Room No. 495, 4th Floor,
Administrative block,
Dr. Rajendra Prasad Centre for Ophthalmic Sciences,
All India Institute of Medical Sciences,
Ansari Nagar
South
DELHI
110029
India |
| Phone |
91-9899806749 |
| Fax |
|
| Email |
rjsihota@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Sumbul Siddiqui |
| Designation |
Medical Monitor |
| Affiliation |
Max Neeman International |
| Address |
Max Neeman International
Max House,1st Floor, 1 Dr. Jha Marg, Okhla Phase-III
South
DELHI
110020
India |
| Phone |
91-11-40772100 |
| Fax |
91-11-41001945 |
| Email |
ssiddiqui@neemanasia.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Shariq Anwar |
| Designation |
Director Operations |
| Affiliation |
Max Neeman International |
| Address |
Max Neeman International
Max House, 1st Floor, 1 Dr. Jha Marg, Okhla Phase-III
South
DELHI
110020
India |
| Phone |
91-11-40772100 |
| Fax |
91-11-40548168 |
| Email |
sanwar@neemanasia.com |
|
|
Source of Monetary or Material Support
|
| Aerie Pharmaceuticals, Inc.
135 US Highway 206, Suite 15
Bedminster, NJ- 07921 United States of America |
|
|
Primary Sponsor
|
| Name |
Aerie Pharmaceuticals Inc |
| Address |
135 US Highway 206, Suite 15
Bedminster, NJ- 07921 United States of America |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| Max Neeman International |
Max House,1st Floor, 1 Dr. Jha Marg, Okhla Phase-III
New Delhi - 110020 India |
|
|
Countries of Recruitment
|
United States of America
India |
Sites of Study
Modification(s)
|
| No of Sites = 8 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr George Varghese Puthuran |
Aravind Eye Hospital |
Room no 11, 1st floor, Paying section ,
1,ANNA Nagar, 625020, India
Madurai
TAMIL NADU |
91-4502356100
91-452-2530984
george@aravind.org |
| Dr R Ramakrishnan |
Aravind Eye Hospital |
Room no. 16, ground floor, Swany Nellaiappar High Road, 627001, , India
Tirunelveli
TAMIL NADU |
91-9443112853
91-462-2331633
drrk@tvl.aravind.org |
| Dr Sathyan Parthasarthi |
Aravind Eye Hospital and Post Graduate Institute of Ophthalmology |
Room no. 28, Basement, Avinashi Road-641014,India
Coimbatore
TAMIL NADU |
91-9443259148
91-422-2593030
dr.sathyan.p@gmail.com |
| Dr Rupali Chopra |
Christian Medical College and Hospital |
Department of Ophthalmology, Room no. 3 ground floor,141008, India
Ludhiana
PUNJAB |
91-9872899124
91-161-2610708
rupalichopra@gmail.com |
| Dr Suneeta Dubey |
Dr. Shroffs Charity Eye Hospital |
5027, Kedar Nath road, Daryaganj110002, India
Central
DELHI |
91-9818224290
dubeysuneeta@hotmail.com |
| Dr Ramgopal B |
Narayana Nethralaya Super Speciality Eye Hospital |
2nd floor
121/C Chord Road,
1st ‘R Block, Rajaji Nagar, Bangalore, Karnataka-560010, India
Bangalore
KARNATAKA |
91-9845233717
91-80-23377329
dr_ramgopal@yahoo.com |
| Dr Sushma Tejwani |
Narayana Nethralaya Super Speciality Eye Hospital |
ground floor, #258/A, Bommasandra, Hosur road560099, India
Bangalore
KARNATAKA |
91-9902287370
91-80-23377329
sushmatej@gmail.com |
| Dr Gowri J Murthy |
Vittala International Institute of Ophthalmology |
C. A., Site No. 1, 2nd Cross, 2nd Main, 7th Block, Hosakerehalli, Banashankari, 3rd stage, 560085, India
Bangalore
KARNATAKA |
91-9886840172
91-80-26722219
gowrijmurthy@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 8 |
| Name of Committee |
Approval Status |
| Dr. Shroffs Charity Eye Hospital Ethics Committee 5027, Kedar Nath road, Daryaganj, New Delhi- 110002, India |
Submittted/Under Review |
| Institutional Ethics committee Deenanath Mangeshkar Hospital & Research Centre,6th Floor,Erandwane,Pune-411004,Maharashtra,India |
Submittted/Under Review |
| Institutional Review Board Aravind Eye Care System, No. 1 Anna Nagar Madurai-625020 Tamil Nadu, India |
Submittted/Under Review |
| Institutional Review Board Aravind Eye Care System, No. 1 Anna Nagar Madurai-625020 Tamil Nadu, India |
Submittted/Under Review |
| Institutional Review Board Aravind Eye Care System, No. 1 Anna Nagar Madurai-625020 Tamil Nadu, India |
Submittted/Under Review |
| Narayana Nethralaya Ethics Committee 121/C, Chord Road 1st R block Rajajinagar, Bangalore-560010, Karnataka, India |
Approved |
| Narayana Nethralaya Ethics Committee 121/C, Chord Road 1st R block Rajajinagar, Bangalore-560010, Karnataka, India |
Approved |
| Science for health, C/O Jnana Sanjeevini Medical center 2,1A Cross, Marenahali, 2nd phase Bangalore, Karnataka, India |
Submittted/Under Review |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
High Tension Glaucoma, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
AR-12286 Ophthalmic Solution 0.5% or 0.7% |
AR-12286 Ophthalmic Solution 0.5% or 0.7% (q.d., PM) will be administered to both eyes for 3 months. |
| Comparator Agent |
Timolol maleate Ophthalmic Solution, 0.5% |
Timolol maleate Ophthalmic Solution, 0.5% (b.i.d.) will be administered to both eyes for 3 months. |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Both |
| Details |
1.18 year of age or greater.
2.Diagnosis of open angle glaucoma (OAG) or ocular hypertension (OHT).
3.Unmedicated (post-washout) IOP greater than or equal to 24 mm Hg at 2 eligibility visits (0800 hr), 2-7 days apart, and greater than or equal to 22 mm Hg at 1000 and 1600 hrs at the second qualification visit. If only one eye meets the IOP criteria it must be the same eye that met the criteria at all the qualification timepoints.
4.Corrected visual acuity in each eye +1.0 logMAR or better by ETDRS in each eye (equivalent to 20/200).
5.Able and willing to give signed informed consent and follow study instructions.
|
|
| ExclusionCriteria |
| Details |
Ophthalmic
1.Glaucoma: pseudoexfoliation or pigment dispersion component, history of angle closure or narrow angles. Note: Previous laser peripheral iridotomy is NOT acceptable.
2.IOP greater than 36 mm Hg
3.Current use of more than 1 ocular hypotensive medications (Note: fixed dose combinations are considered multiple medications).
4.Known hypersensitivity to any component of the formulation (benzalkonium chloride, etc.), or to topical anesthetics.
5.Previous glaucoma intraocular surgery or glaucoma laser procedures in study eye(s).
6.Refractive surgery in study eye(s) (e.g., radial keratotomy, PRK, LASIK, etc.).
7.Ocular trauma within the past six months, or ocular surgery or laser treatment within the past three months.
8.Evidence of ocular infection, inflammation, clinically significant blepharitis or conjunctivitis at baseline (Visit 1), or a history of herpes simplex keratitis
9.Ocular medication of any kind within 30 days of Visit 1, with the exception of a) ocular hypotensive medications (which must be washed out according to the provided schedule), b) lid scrubs (which may be used prior to, but not after Visit 1) or c) lubricating drops for dry eye (which may be used throughout the study).
10.Clinically significant ocular disease (e.g. uveitis, severe keratoconjunctivitis sicca) which might interfere with the study, including glaucomatous damage so severe that washout of ocular hypotensive medications for one month is not judged safe.
11.Central corneal thickness greater than 600 µm.
12.Any abnormality preventing reliable applanation tonometry of either eye.
Systemic:
13.Clinically significant abnormalities (as determined by the treating physician) in laboratory tests at screening.
14.Known hypersensitivity or contraindication to Beta adrenoceptor antagonists including chronic obstructive pulmonary disease or bronchial asthma; abnormally low blood pressure or heart rate; second or third degree heart block or congestive heart failure; severe diabetes).
15.Clinically significant systemic disease (e.g., myasthenia gravis, hepatic, renal, endocrine or cardiovascular disorders) which might interfere with the study.
16.Participation in any investigational study within the past 30 days.
17.Changes of systemic medication that could have a substantial effect on IOP within 30 days prior to screening, or anticipated during the study.
18.Due to the current status of the preclinical safety program, women of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control. An adult woman is considered to be of childbearing potential unless she is one year post-menopausal or three months post-surgical sterilization. All females of childbearing potential must have a negative urine pregnancy test result at the screening examination and must not intend to become pregnant during the study.
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Participant, Investigator and Outcome Assessor Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
The primary efficacy outcome will be the mean IOP across subjects within treatment group.
|
Timepoints of measuring primary outcome is post dose time point (Day 15, Day 30, Day 60 and Day 90). |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| Mean change from diurnally adjusted baseline IOP at each post-dose timepoint of month 3 |
Timepoints of measuring secondary outcome is post dose time point (Day 15, Day 30, Day 60 and Day 90).
|
| Mean percent change from diurnally adjusted baseline IOP at each post-dose timepoint of month 3 |
Timepoints of measuring secondary outcome is post dose time point (Day 15, Day 30, Day 60 and Day 90). |
| Mean diurnal IOP on month 3. |
Timepoints of measuring secondary outcome is post dose time point (Day 15, Day 30, Day 60 and Day 90). |
| Mean change from the baseline mean diurnal IOP on month 3 |
Timepoints of measuring secondary outcome is post dose time point (Day 15, Day 30, Day 60 and Day 90).
|
| An additional analysis of within treatment group paired tests with baseline will be performed using a paired t-test at each post-dose timepoint |
Timepoints of measuring secondary outcome is post dose time point (Day 15, Day 30, Day 60 and Day 90).
|
|
|
Target Sample Size
|
Total Sample Size="195"
Sample Size from India="97"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 2 |
|
Date of First Enrollment (India)
|
27/09/2012 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
15/10/2012 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="0"
Months="8"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Closed to Recruitment of Participants |
| Recruitment Status of Trial (India) |
Closed to Recruitment of Participants |
|
Publication Details
|
None as yet |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
Title of the study: A phase 2b double-masked, randomized, active-controlled, dose-response study assessing the safety and ocular hypotensive efficacy of AR-12286 in patients with elevated intraocular pressure for 3 months.
Research Hypothesis: AR-12286 Ophthalmic Solution 0.5%, or 0.7% (q.d., PM) or timolol maleate Ophthalmic Solution, 0.5% (b.i.d.) will be administered to both eyes for 3 months. The null hypothesis is that the ocular hypotensive efficacy of each concentration of AR-12286 ophthalmic solution is inferior to that of a positive control. The alternative hypothesis is that the ocular hypotensive efficacy of each concentration of AR-12286 is not inferior to that of a positive control, using a non-inferiority limit of -1.5mm Hg. With a sample size of 65-70 in each group, each pair wise comparison of test to control will have >80% power to conclude non-inferiority assuming a common standard deviation of 3.5 mm Hg and using one-sided 95% confidence interval around the difference (control – test) in IOP.
Primary objective:
To evaluate the ocular hypotensive efficacy of 2 doses of AR-12286.
Secondary Objective: To evaluate the ocular and systemic safety of 2 doses of AR-12286. |