| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
| An eye disorder that occurs if increased pressure of the fluid in the eye builds up causing damage to the optic nerve. This can permanently damage vision and progress to blindness if untreated. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10018304 |
| E.1.2 | Term | Glaucoma |
| E.1.2 | System Organ Class | 10015919 - Eye disorders |
|
| 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 |
| To evaluate the safety and intraocular pressure (IOP)-lowering efficacy of once-daily bimatoprost 0.03% preservative-free (PF) ophthalmic solution compared with twice-daily timolol (0.5% or 0.25%, based on age group) ophthalmic solution for 12 weeks in paediatric patients with glaucoma. |
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male or female patients, 2 months (age adjusted for prematurity, if applicable, for children younger than 1 year postnatal) to < 18 years of age at the baseline (day -1) visit (To adjust for prematurity, subtract the infant’s gestational age in weeks from 40 and then subtract this from the child’s postnatal age in weeks.)
2. Written parental/legal guardian consent and minor assent (if applicable) has been obtained in accordance with any applicable state and local laws/regulations. At IRB/IEC’s discretion, a minor’s oral assent my be obtained in lieu of a written assent.
3. Written documentation for use of health information has been obtained in accordance with the relevant country and local privacy requirements, where applicable (eg, Allergan’s Authorization for Use and Disclosure of Protected Health Information, or its equivalent, and Research Study Information [US sites] and written Data Protection consent [European Union sites]).
4. Good general health as determined by the investigator from medical history and physical examination
5. Patient has been diagnosed by an ophthalmologist to have congenital, juvenile, primary or secondary (except as excluded in Section 4.4 of the protocol), aphakic or pseudophakic glaucoma, requiring IOP lowering therapy in one or both eyes.
6. Based on the patient’s medical history and the investigator’s opinion, IOP is likely to be controlled for the next 12 weeks (after baseline) by a single IOP-lowering topical ophthalmic medication.
7. Patient can go without IOP-lowering therapy from 4 days to 2 weeks, without significant risk to the patient.
8. Ability of patient and/or parent(s)/legal guardian(s) to follow study instructions and willingness to complete all required procedures and visits
9. Baseline: Females of childbearing potential (ie, post-menarche) must have a urine pregnancy test result confirmed as negative prior to the start of treatment on day 1.
10. Baseline: For patients able to perform recognition acuity, a best corrected visual acuity score equivalent to a Snellen acuity of 20/100 or better in each eye, using a logarithmic letter visual acuity chart, LEA symbol chart, or Allen pictures. For preverbal patients or patients who may be unable to be tested using standard methodology, patient must be able to at least fixate on and briefly follow an object
(eg, small toy, “fix and follow”)
11. Baseline (morning): IOP ≥ 22 mm Hg and ≤ 36 mm Hg in one or both eyes
12. Baseline: Patient has been appropriately washed out of all IOP lowering medications in each eye. |
|
| E.4 | Principal exclusion criteria |
1. Uncontrolled systemic disease
2. Contraindications to beta-adrenoceptor antagonist therapy such as chronic obstructive pulmonary disease, bronchial asthma, history of bronchial asthma, sinus bradycardia, second and third degree atrioventricular block, overt cardiac failure or cardiogenic shock or uncontrolled congestive heart failure. Clearance for participation in the study from the patient’s primary paediatrician or primary care physician must be documented for all patients.
3. Clinically relevant low or high blood pressure or pulse rate for age as determined by the investigator
4. Females who are pregnant, nursing, or planning a pregnancy or who are of childbearing potential not using a reliable means of contraception throughout the study
5. Abnormally low body weight for age (below 5th percentile)
6. Patients in whom surgical intervention is indicated or anticipated for IOP lowering within 12 weeks after baseline. Note: Patients with primary congenital glaucoma will be excluded from the study unless surgery has already been performed.
7. Patients with lens-induced glaucoma, steroid-induced glaucoma, or retinoblastoma
8. Patients with secondary angle closure glaucoma due to anatomical abnormalities
9. Patients with secondary glaucoma associated with increased episcleral pressure (eg, Sturge-Weber, cavernous fistula, orbital disease)
10. Any other active or recurrent ocular disease (eg, iritis, uveitis, ocular infection, chronic moderate to severe blepharitis or severe dry eye, ocular seasonal allergies, diabetic retinopathy) in either eye that would interfere with the interpretation of the study data. However, ocular conditions of myopia, hyperopia, and strabismus (excluding cases where surgery is planned within the next 12 weeks) are allowed.
11. History or evidence of severe ocular trauma in either eye
12. Corneal or other ocular abnormalities (eg, bullous keratopathy, refractive surgery, corneal graft) that would preclude accurate readings with either Goldmann applanation tonometer or a hand-held tonometer. Note: A well-healed corneal scar or Haab’s striae will not exclude a patient.
13. Any ocular anterior segment (including glaucoma) surgery in the study eye(s) within 3 months prior to baseline
14. Patients who have had a cyclodestructive procedure
15. Known allergy or sensitivity to the study medication(s) or their components
16. Known allergy or contraindication to use of fluorescein
17. Contraindication to pupil dilation
18. Required chronic use of other ocular medications (post-screening visit) during the study. Note: Occasional use of artificial tear products is allowed but not within 24 hours prior to a scheduled visit through the week 12 visit.
19. Current enrollment in an investigational drug or device study or participation in such a study at or past the screening visit, or within 30 days prior to the baseline (day -1) visit
20. For patients with visual field test records, visual field loss that in the opinion of the investigator is functionally significant, or evidence of progressive visual field loss within the year prior to baseline (day -1)
21. Patient’s IOP was previously uncontrolled on bimatoprost or timolol monotherapy
22. Intermittent use of oral, intramuscular, or intravenous corticosteroids within 21 days prior to baseline or anticipated use within 21 days prior to a postbaseline study visit through the week 12
23. Use of topical ophthalmic corticosteroids from 2 months prior to the screening visit through the week 12 visit
24. Anticipated use of contact lenses during the study through the week 12 visit (use of soft lenses should be discontinued at least 24 hours prior to baseline, and use of rigid gas permeable or hard contact lenses should be discontinued at least 1 week prior to baseline)
25. Introduction or anticipated alteration of existing chronic systemic medications (topical or injection) that may have a substantial effect on IOP from 2 months prior to screening visit through the week 12 visit
26. Use or anticipated use of systemic beta-blocker medication from 2 months prior to screening visit through the week 12 visit
27. Patient has a condition or is in a situation which, in the investigator's opinion, may put the patient at significant risk, may confound the study results, or may interfere significantly with the patient’s participation in the study.
28. In the judgment of the investigator, patient is unwilling or unable to cooperate for study-related procedures, including IOP measurement and biomicroscopic examination. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change from baseline (follow-up minus baseline) in the study eye IOP at week 12 (hour 2) is the primary efficacy variable. Note that a negative change from baseline indicates an IOP-lowering effect. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
| The secondary variable is IOP response. A patient is considered to be an IOP responder if he/she demonstrates at least a 15% reduction from baseline study eye IOP at week 12 (hour 2). Patients who received escape medication for the study eye prior to the week 12 visit will be classified as non-responders. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| 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 | 12 |
| 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 |
| Brazil |
| Canada |
| France |
| Germany |
| Italy |
| Korea, Republic of |
| Philippines |
| Spain |
| Taiwan |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
| Last Patient, Last Visit. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
Print
