| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Open-Angle Glaucoma
or Ocular Hypertension |
|
| E.1.1.1 | Medical condition in easily understood language |
Open-Angle Glaucoma
or Ocular Hypertension |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
The primary objective is to demonstrate that the mean intraocular
pressure (IOP) reduction after 3 months (90 days) of treatment with
BOL-303259-X 0.024% (latanoprostene bunod) once daily (QD) is
non-inferior to timolol maleate 0.5% twice daily (BID). |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objective is to demonstrate the superiority of
BOL-303259-X 0.024% QD to timolol maleate 0.5% BID. This
assessment will be performed if the non-inferiority of
BOL-303259-X 0.024% QD to timolol maleate 0.5% BID is determined. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subjects must be of legal age (at least 18 years) on the date the
Informed Consent Form (ICF) is signed and with the capacity to
provide voluntary informed consent.
2. Subjects must be able to read, understand, and provide written
informed consent on the Institutional Review Board/Ethics
Committee-approved ICF and provide authorization as appropriate
for local privacy regulations.
3. Subjects who are able and willing to comply with all treatment and
follow-up/study procedures.
4. Subjects who are not of childbearing potential or female subjects
who have a negative urine pregnancy test result at Visit 1
(Screening) and Visit 3 (Eligibility, Day 0).
5. Female subjects of childbearing potential are eligible for the study
but should be willing to use adequate (at least 1 form of)
contraceptive methods as described below during the study treatment
period plus 7 days (starting from the first dose of study drug and
ending 7 days after the last dose of study drug).
Male subjects with partners of childbearing potential must agree to
use adequate (at least 1 form of) contraception as described below
during the study treatment period plus 7 days (starting from the first
dose of study drug and ending 7 days after the last dose of study
drug).
- Acceptable contraceptive methods for female subjects (need at
least one):
o Hormonal methods of contraception (including oral and
transdermal contraceptives, injectable progesterone,
progestin subdermal implants, progesterone-releasing
intrauterine devices [IUDs]) initiated at least 14 days prior
to the first dose of study drug
o Abstinence
o Placement of a copper-containing IUD
o Condom with spermicidal foam/gel/film/cream/suppository
o Postmenopausal at least 12 months (365 days) prior to the
first dose of study drug or permanently sterilized (eg, tubal
occlusion, hysterectomy, bilateral salpingectomy)
o Male partner who has had a vasectomy for at least 3 months
(90 days) prior to the first dose of study drug or is
surgically sterile
- Acceptable contraceptive methods for male subjects with
partners of childbearing potential (need at least one):
o Abstinence
o Vasectomy for at least 3 months (90 days) prior to the first
dose of study drug or surgically sterile
o Without a vasectomy, must use a condom with spermicidal
foam/gel/film/cream/suppository
Ocular Inclusion Criteria
6. Subjects must have a diagnosis of OAG (including pigmentary or
pseudoexfoliative) or OHT in 1 or both eyes.
7. Subjects must meet the following IOP requirements at Visit 3
(Eligibility, Day 0 [after washout for the subjects currently under
treatment with an IOP-lowering medication]):
- mean/median IOP ≥ 26 mmHg at a minimum of 1 time point,
≥ 24 mmHg at a minimum of 1 time point, and ≥ 22 mmHg at
1 time point in the same eye, and
- IOP ≤ 36 mmHg at all 3 measurement time points in both eyes.
8. Subjects with a best-corrected visual acuity (BCVA), using the Early
Treatment of Diabetic Retinopathy Study (ETDRS) protocol, of
+0.7 logMAR units (Snellen equivalent of approximately 20/100) or
better in either eye. |
|
| E.4 | Principal exclusion criteria |
1. Subjects participating in any drug or device clinical investigation
within 30 days prior to Visit 1 (Screening) for subjects who require a
washout period or 30 days prior to Visit 3 (Eligibility, Day 0) for
subjects who do not require a washout period.
2. Subjects who are known to have been exposed to BOL-303259-X
(formerly identified as NCX 116 and PF 03187207) in any previous
clinical investigation prior to Visit 1 (Screening).
3. Subjects who anticipate participating in any other drug or device
clinical investigation within the duration of this study.
4. Female subjects who are pregnant or breastfeeding.
5. Subjects with a history or presence of any of the following:
− Severe dysfunction of the liver or the kidneys
− Wasting disease
− Angina pectoris not controlled by medical or surgical treatment
− Severe asthma
− Hematological diseases such as aplastic anemia, pancytopenia,
or hemolytic icterus
− Severe chronic obstructive pulmonary disease
− Second or third degree atrioventricular block
− Overt cardiac failure
− Cardiogenic shock
6. Subjects with a current diagnosis of cancer.
7. Subjects with a history or presence of chronic generalized systemic
disease that the Investigator feels might increase the risk to the
subject or confound the results of the study.
8. Subjects with known or suspected drug or alcohol abuse.
Drug Therapies
9. Subjects with an anticipated need to initiate or modify medication
(systemic or topical) that is known to affect IOP (eg, beta-adrenergic
antagonists, alpha-adrenergic agonists, calcium channel blockers,
angiotensin-converting enzyme [ACE] inhibitors, and angiotensin II
receptor blockers) during the first 3 months (90 days) of study
treatment.
10. Subjects for whom concomitant use of medications may interact
with the safety or efficacy of a nitric oxide (NO)-donating compound
(eg, vasodilators such as Isordil® and BiDil®).
11. Subjects with known hypersensitivity or contraindications to
latanoprost, NO treatment, or any of the ingredients in the study
drugs.
12. Subjects with known hypersensitivity or contraindications to timolol
maleate, other beta-adrenergic receptor antagonists, or any of the
ingredients in the study drugs.
13. Subjects who are expected to require treatment with ocular or
systemic corticosteroids during the study duration.
14. Subjects who are currently taking diclofenac (oral or topical) or who
are expected to require treatment with diclofenac (oral or topical)
during the study duration.
15. Subjects who are in need of or expected to require any other topical
or systemic treatment of OAG or OHT during the study duration.
Ocular exclusion criteria:
16. Subjects who are unable to discontinue contact lens use during and
for 15 minutes following instillation of study drug and during study
visits.
17. Subjects who are unable to discontinue other eye drop medications
such as artificial tears for 15 minutes prior to and 15 minutes after
instillation of study drug.
18. Subjects with a central corneal thickness greater than 600 μm in
either eye.
19. Subjects with any condition that prevents reliable applanation
tonometry (eg, significant corneal surface abnormalities) in either
eye.
20. Subjects with advanced glaucoma with a cup/disc ratio greater than
0.8, a history of split fixation, or a field loss threatening fixation in
either eye.
21. Subjects with any condition that prevents clear visualization of the
fundus in either eye.
22. Subjects who are monocular (fellow eye is absent).
23. Subjects who do not have an intact posterior capsule in either eye.
24. Subjects with aphakia in either eye.
25. Subjects with previous or active corneal disease in either eye.
26. Subjects with current or a history of severe dry eye in either eye.
27. Subjects with current or a history of optic disc hemorrhage in either
eye.
28. Subjects with current or a history of central/branch retinal vein or
artery occlusion in either eye.
29. Subjects with current or a history of macular edema in either eye.
30. Subjects with very narrow angles (3 quadrants with less than
Grade 2 according to Shaffer's anterior chamber angle grading
system) and subjects with angle closure, congenital, and secondary
glaucoma, and subjects with history of angle closure in either eye.
31. Subjects with a diagnosis of a clinically significant or progressive
retinal disease (eg, diabetic retinopathy, macular degeneration) in
either eye.
32. Subjects with any intraocular infection or inflammation in either eye
within 3 months (90 days) prior to Visit 1 (Screening).
Surgery
33. Subjects with a history of ocular laser surgery in either eye within
the 3 months (90 days) prior to Visit 1 (Screening).
34. Subjects with a history of incisional ocular surgery or severe trauma
in either eye within 3 months (90 days) prior to Visit 1 (Screening). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the IOP in subjects’ study eye measured
at the specified time points: 8 AM, 12 PM, and 4 PM at Visit 4 (Week 2),
Visit 5 (Week 6), and Visit 6 (Month 3). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Efficacy evaluations will be made at Visit 4 (Week 2), Visit 5 (Week 6),
and Visit 6 (Month 3), with ongoing safety evaluations made at Visit 7
(Month 6). |
|
| E.5.2 | Secondary end point(s) |
Key Secondary Efficacy Endpoints
• Proportion of subjects with IOP ≤ 1 8 m mHg consistently at all
9 time points in the first 3 months
• Proportion of subjects with IOP reduction ≥ 25% consistently at all
9 time points in the first 3 months
Additional Secondary Efficacy Endpoints
• Change from baseline (CFB) in IOP at specified time points (8 AM,
12 PM, and 4 PM) at Visits 4, 5, and 6 (Week 2, Week 6, and Month
3, respectively)
• Absolute and CFB in diurnal IOP at each post-randomization visit
(Visits 4, 5, 6, and 7 [Week 2, Week 6, Month 3, and Month 6,
respectively])
• Absolute and CFB in IOP at the specified time points: 8 AM, 12 PM,
and 4 PM at Visit 7 (Month 6)
• Standardized IOP area under the curve (AUC) (the AUC divided by
the time period that the subject was observed) by treatment group
from 8 AM at Visit 4 (Week 2) to 4 PM at the following visits: Visit 4
(Week 2), Visit 5 (Week 6), Visit 6 (Month 3), and Visit 7
(Month 6)
• For the timolol maleate 0.5% BID group (ie, the group of subjects
randomized to timolol maleate 0.5% BID at Visit 3 [Eligibility,
Day 0]), change in IOP from Visit 6 (Month 3) at each time point at
Visit 7 (Month 6)
• For the timolol maleate 0.5% BID group (ie, the group of subjects
randomized to timolol maleate 0.5% BID at Visit 3 [Eligibility,
Day 0]), change in diurnal IOP from Visit 6 (Month 3) to Visit 7
(Month 6).
Safety Endpoint
The safety endpoint of this study is the incidence of ocular and systemic
adverse events (AEs). |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy evaluations will be made at Visit 4 (Week 2), Visit 5 (Week 6),
and Visit 6 (Month 3), with ongoing safety evaluations made at Visit 7
(Month 6). |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 9 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
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