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To evaluate the pharmacokinetic properties of intravitreal ocriplasmin 125 µg dose when administered at different time-points prior to planned primary pars plana vitrectomy (PPV)
Open-label, ascending-exposure-time, single center trial in which a total of 36 subjects will be enrolled. The time to remove the vitreous will be recorded and a vitreous sample will be obtained at the beginning of vitrectomy for determination of ocriplasmin activity; 32 subjects will receive 125 μg ocriplasmin intravitreal injection prior to vitrectomy and 4 subjects will not receive ocriplasmin intravitreal injection prior to vitrectomy (control arm).
Study drug will be administered in the mid-vitreous by injection. The study eye will be examined after study drug injection to exclude retinal non-perfusion or other complications.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PPV 5-30 minutes after injection | Experimental | Primary Pars Plana Vitrectomy 5 to 30 minutes after 125µg of ocriplasmin intravitreal injection |
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| PPV 31-60 minutes after injection | Experimental | Primary Pars Plana Vitrectomy 31 to 60 minutes after 125µg of ocriplasmin intravitreal injection |
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| PPV 2-4 hours after injection | Experimental | Primary Pars Plana Vitrectomy 2 to 4 hours after 125µg of ocriplasmin intravitreal injection |
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| PPV 24 hours (+2 hours) after injection | Experimental | Primary Pars Plana Vitrectomy 24 hours (+2 hours)after 125µg of ocriplasmin intravitreal injection |
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| PPV 7 days (+1 day) after injection | Experimental | Primary Pars Plana Vitrectomy 7 days (+1 day)after 125µg of ocriplasmin intravitreal injection |
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| PPV without injection |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ocriplasmin | Drug | 125µg ocriplasmin intravitreal injection |
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| Measure | Description | Time Frame |
|---|---|---|
| Ocriplasmin Activity Levels in Vitreous Samples Obtained at the Beginning of Vitrectomy. | Vitreous samples were obtained at the beginning of vitrectomy in subjects at various times relative to ocriplasmin injection (post-injection), for the determination of ocriplasmin activity (Group 1 [5-30 minutes]; Group 2 [31-60 minutes]; Group 3 [2-4 hours]; Group 4 [24 hours ±2 hours]; Group 5 [7 days ±1 day]. Subjects in Group 6 (control) did not receive the ocriplasmin injection. | 5-30 minutes, 31-60 minutes, 2-4 hours, 1 day, or 7 days after ocriplasmin injection |
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| Measure | Description | Time Frame |
|---|---|---|
| Time Necessary to Remove the Vitreous From the Eye | PPV was performed in all subjects. The time necessary to remove the vitreous from the eye, measured from first start of vitrectomy cutter till end of core vitrectomy phase, was calculated. | From first start of vitrectomy cutter till the end of core vitrectomy phase |
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Leuven | Leuven | B-3000 | Belgium |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23982845 | Derived | Stalmans P, Girach A. Vitreous levels of active ocriplasmin following intravitreal injection: results of an ascending exposure trial. Invest Ophthalmol Vis Sci. 2013 Oct 9;54(10):6620-7. doi: 10.1167/iovs.13-11811. |
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38 subjects were enrolled into the study. However, the vitreous samples for 2 subjects were excluded from the analysis:
The first subject was enroled on 15 Jul 2010 and the last patient completed the study opn 30 Nov 2010.
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| ID | Title | Description |
|---|---|---|
| FG000 | PPV 5-30 Minutes After Injection | Primary Pars Plana Vitrectomy 5 to 30 minutes after 125ug of ocriplasmin intravitreal injection |
| FG001 | PPV 31-60 Minutes After Injection | Primary Pars Plana Vitrectomy 31 to 60 minutes after 125ug of ocriplasmin intravitreal injection |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| No Intervention |
Control Arm, no ocriplasmin intravitreal injection |
| ocriplasmin | Drug | 125µg ocriplasmin intravitreal injection |
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| ocriplasmin | Drug | 125µg ocriplasmin intravitreal injection |
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| ocriplasmin | Drug | 125µg ocriplasmin intravitreal injection |
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| ocriplasmin | Drug | 125µg ocriplasmin intravitreal injection |
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| FG002 | PPV 2-4 Hours After Injection | Primary Pars Plana Vitrectomy 2 to 4 hours after 125ug of ocriplasmin intravitreal injection |
| FG003 | PPV 24 Hours (+2 Hours) After Injection | Primary Pars Plana Vitrectomy 24 hours (+2 hours)after 125ug of ocriplasmin intravitreal injection |
| FG004 | PPV 7 Days (+1 Day) After Injection | Primary Pars Plana Vitrectomy 7 days (+1 day)after 125ug of ocriplasmin intravitreal injection |
| FG005 | PPV Without Injection | Control Arm, no ocriplasmin intravitreal injection |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | PPV 5-30 Minutes After Injection | Primary Pars Plana Vitrectomy 5 to 30 minutes after 125ug of ocriplasmin intravitreal injection |
| BG001 | PPV 31-60 Minutes After Injection | Primary Pars Plana Vitrectomy 31 to 60 minutes after 125ug of ocriplasmin intravitreal injection |
| BG002 | PPV 2-4 Hours After Injection | Primary Pars Plana Vitrectomy 2 to 4 hours after 125ug of ocriplasmin intravitreal injection |
| BG003 | PPV 24 Hours (+2 Hours) After Injection | Primary Pars Plana Vitrectomy 24 hours (+2 hours)after 125ug of ocriplasmin intravitreal injection |
| BG004 | PPV 7 Days (+1 Day) After Injection | Primary Pars Plana Vitrectomy 7 days (+1 day)after 125ug of ocriplasmin intravitreal injection |
| BG005 | PPV Without Injection | Control Arm, no ocriplasmin intravitreal injection |
| BG006 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Ocriplasmin Activity Levels in Vitreous Samples Obtained at the Beginning of Vitrectomy. | Vitreous samples were obtained at the beginning of vitrectomy in subjects at various times relative to ocriplasmin injection (post-injection), for the determination of ocriplasmin activity (Group 1 [5-30 minutes]; Group 2 [31-60 minutes]; Group 3 [2-4 hours]; Group 4 [24 hours ±2 hours]; Group 5 [7 days ±1 day]. Subjects in Group 6 (control) did not receive the ocriplasmin injection. | Safety Set. Values for the PPV 7 days (+1 day) after injection and for PPV without injection treatment groups were all < Lower Limit of Quantification (LLOQ) | Posted | Mean | Standard Deviation | ng/mL | 5-30 minutes, 31-60 minutes, 2-4 hours, 1 day, or 7 days after ocriplasmin injection |
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| Other Pre-specified | Time Necessary to Remove the Vitreous From the Eye | PPV was performed in all subjects. The time necessary to remove the vitreous from the eye, measured from first start of vitrectomy cutter till end of core vitrectomy phase, was calculated. | Safety Set | Posted | Mean | Standard Deviation | Minutes | From first start of vitrectomy cutter till the end of core vitrectomy phase |
|
Adverse Events (AEs) were collected from study drug administration through last subject follow-up visit (42 days (+ 3 days) post-surgery).
Only treatment emergent AEs, defined as events with an onset on or after the date of study drug injection were included in the AE summaries. For the control arm (Group 6), AEs on or after the Baseline visit were considered treatment emergent in order to compare with the treatment groups.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | PPV 5-30 Minutes After Injection | Primary Pars Plana Vitrectomy 5 to 30 minutes after 125ug of ocriplasmin intravitreal injection | 1 | 9 | 2 | 9 | ||
| EG001 | PPV 31-60 Minutes After Injection | Primary Pars Plana Vitrectomy 31 to 60 minutes after 125ug of ocriplasmin intravitreal injection | 0 | 9 | 5 | 9 | ||
| EG002 | PPV 2-4 Hours After Injection | Primary Pars Plana Vitrectomy 2 to 4 hours after 125ug of ocriplasmin intravitreal injection | 0 | 8 | 5 | 8 | ||
| EG003 | PPV 24 Hours (+2 Hours) After Injection | Primary Pars Plana Vitrectomy 24 hours (+2 hours)after 125ug of ocriplasmin intravitreal injection | 0 | 4 | 4 | 4 | ||
| EG004 | PPV 7 Days (+1 Day) After Injection | Primary Pars Plana Vitrectomy 7 days (+1 day)after 125ug of ocriplasmin intravitreal injection | 1 | 4 | 4 | 4 | ||
| EG005 | PPV Without Injection | Control Arm, no ocriplasmin intravitreal injection | 2 | 4 | 3 | 4 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Choroidal Hemorrhage | Eye disorders | MedDRA 13.1 | Systematic Assessment |
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| Hypaema | Eye disorders | MedDRA 13.1 | Systematic Assessment |
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| Vitreous Hemorrhage | Eye disorders | MedDRA 13.1 | Systematic Assessment |
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| Cardiac failure congestive | Cardiac disorders | MedDRA 13.1 | Systematic Assessment |
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| Paraneoplastic syndrome | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 13.1 | Systematic Assessment |
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| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Photopsia | Eye disorders | MedDRA 13.1 | Systematic Assessment |
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| Visual acuity reduced | Eye disorders | MedDRA 13.1 | Systematic Assessment |
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| Vitreous floaters | Eye disorders | MedDRA 13.1 | Systematic Assessment |
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| Chromatopsia | Eye disorders | MedDRA 13.1 | Systematic Assessment |
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| Cataract cortical | Eye disorders | MedDRA 13.1 | Systematic Assessment |
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| Conjunctival haemorrhage | Eye disorders | MedDRA 13.1 | Systematic Assessment |
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| Corneal erosion | Eye disorders | MedDRA 13.1 | Systematic Assessment |
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| Eye pain | Eye disorders | MedDRA 13.1 | Systematic Assessment |
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| Hypotony of eye | Eye disorders | MedDRA 13.1 | Systematic Assessment |
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| Macular oedema | Eye disorders | MedDRA 13.1 | Systematic Assessment |
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| Metamorphosia | Eye disorders | MedDRA 13.1 | Systematic Assessment |
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| Photophobia | Eye disorders | MedDRA 13.1 | Systematic Assessment |
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| Pupillary deformity | Eye disorders | MedDRA 13.1 | Systematic Assessment |
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| Retinal artery occlusion | Eye disorders | MedDRA 13.1 | Systematic Assessment |
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| Retinal oedema | Eye disorders | MedDRA 13.1 | Systematic Assessment |
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| Retinal tear | Eye disorders | MedDRA 13.1 | Systematic Assessment |
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| Blepharitis | Eye disorders | MedDRA 13.1 | Systematic Assessment |
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| Dry eye | Eye disorders | MedDRA 13.1 | Systematic Assessment |
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| Eye irritation | Eye disorders | MedDRA 13.1 | Systematic Assessment |
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| Lens dislocation | Eye disorders | MedDRA 13.1 | Systematic Assessment |
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| Intraocular pressure increased | Investigations | MedDRA 13.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Eye infection | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
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| Dacryocistitis | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
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| Procedural pain | Injury, poisoning and procedural complications | MedDRA 13.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Petra Kozma-Wiebe | ThromboGenics | +32 16751310 | Petra.kozma@thrombogenics.com |
| ID | Term |
|---|---|
| C054561 | microplasmin |
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| Male |
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| OG004 | PPV 7 Days (+1 Day) After Injection | Primary Pars Plana Vitrectomy 7 days (+1 day)after 125ug of ocriplasmin intravitreal injection |
| OG005 | PPV Without Injection | Control Arm, no ocriplasmin intravitreal injection |
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