Vitrectomy
Conditions
Brief summary
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)
Detailed description
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.
Interventions
DRUGocriplasmin
125µg ocriplasmin intravitreal injection
Sponsors
ThromboGenics
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female subjects aged ≥ 18 * Eye disease for which a primary vitrectomy is indicated * Best Corrected Visual Acuity (BCVA) of 20/800 or better in the non-study eye * Written informed consent obtained from the subject prior to inclusion in the trial
Exclusion criteria
* Proliferative diabetic retinopathy. * Subjects with any vitreous hemorrhage or any other vitreous opacification which precludes either of the following: visualization of the posterior pole by visual inspection OR adequate assessment of the macula by either Optical Coherence Tomography (OCT) and/or fluorescein angiogram in the study eye * Aphakia in the study eye * High myopia (more than 8D) in study eye (unless prior cataract extraction or refractive surgery that makes refraction assessment unreliable for myopia severity approximation, in which case axial length \>28 mm is an exclusion). * Subjects with history of rhegmatogenous retinal detachment in the either eye * Subjects who have had ocular surgery, laser photocoagulation treatment, or intravitreal injection(s) in the study eye in the prior three months * Subjects who have had laser photocoagulation to the macula in the study eye at any time * Subjects with uncontrolled glaucoma in the study eye (defined as intraocular pressure ≥ 26 mm Hg in spite of treatment with anti-glaucoma medication) * Subjects with a history of uveitis in either eye. * Subjects who are pregnant or of child-bearing potential not utilizing an acceptable form of contraception. Acceptable methods of birth control include intrauterine device, oral, implanted, or injected contraceptives, and barrier methods with spermicide. * Subjects who, in the Investigators view, will not complete all visits and investigations * Subjects who have participated in an investigational drug trial within the past 30 days * Subjects who have previously participated in this trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ocriplasmin Activity Levels in Vitreous Samples Obtained at the Beginning of Vitrectomy. | 5-30 minutes, 31-60 minutes, 2-4 hours, 1 day, or 7 days after ocriplasmin injection | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Time Necessary to Remove the Vitreous From the Eye | From first start of vitrectomy cutter till the end of core vitrectomy phase | 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. |
Countries
Belgium
Participant flow
Recruitment details
The first subject was enroled on 15 Jul 2010 and the last patient completed the study opn 30 Nov 2010.
Pre-assignment details
38 subjects were enrolled into the study. However, the vitreous samples for 2 subjects were excluded from the analysis: * The vitreous sample for Subject 101106 was contaminated during vitrectomy. * Subject 101202 (Group 2) had a previous vitrectomy and retinal detachment in the study eye (exclusion criteria violation).
Participants by arm
| Arm | Count |
|---|---|
| PPV 5-30 Minutes After Injection Primary Pars Plana Vitrectomy 5 to 30 minutes after 125ug of ocriplasmin intravitreal injection | 9 |
| PPV 31-60 Minutes After Injection Primary Pars Plana Vitrectomy 31 to 60 minutes after 125ug of ocriplasmin intravitreal injection | 9 |
| PPV 2-4 Hours After Injection Primary Pars Plana Vitrectomy 2 to 4 hours after 125ug of ocriplasmin intravitreal injection | 8 |
| PPV 24 Hours (+2 Hours) After Injection Primary Pars Plana Vitrectomy 24 hours (+2 hours)after 125ug of ocriplasmin intravitreal injection | 4 |
| PPV 7 Days (+1 Day) After Injection Primary Pars Plana Vitrectomy 7 days (+1 day)after 125ug of ocriplasmin intravitreal injection | 4 |
| PPV Without Injection Control Arm, no ocriplasmin intravitreal injection | 4 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | PPV 5-30 Minutes After Injection | PPV 31-60 Minutes After Injection | PPV 2-4 Hours After Injection | PPV 24 Hours (+2 Hours) After Injection | PPV 7 Days (+1 Day) After Injection | PPV Without Injection | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 71.3 years STANDARD_DEVIATION 8.56 | 65.6 years STANDARD_DEVIATION 13.5 | 63.8 years STANDARD_DEVIATION 9.38 | 62.5 years STANDARD_DEVIATION 8.66 | 59.3 years STANDARD_DEVIATION 11.87 | 69.8 years STANDARD_DEVIATION 7.8 | 66.0 years STANDARD_DEVIATION 10.5 |
| Sex: Female, Male Female | 7 Participants | 6 Participants | 6 Participants | 3 Participants | 1 Participants | 3 Participants | 26 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 2 Participants | 1 Participants | 3 Participants | 1 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 9 | 5 / 9 | 5 / 8 | 4 / 4 | 4 / 4 | 3 / 4 |
| serious Total, serious adverse events | 1 / 9 | 0 / 9 | 0 / 8 | 0 / 4 | 1 / 4 | 2 / 4 |
Outcome results
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.
Time frame: 5-30 minutes, 31-60 minutes, 2-4 hours, 1 day, or 7 days after ocriplasmin injection
Population: 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)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PPV 5-30 Minutes After Injection | Ocriplasmin Activity Levels in Vitreous Samples Obtained at the Beginning of Vitrectomy. | 11597.711 ng/mL | Standard Deviation 7637.4103 |
| PPV 31-60 Minutes After Injection | Ocriplasmin Activity Levels in Vitreous Samples Obtained at the Beginning of Vitrectomy. | 8108.726 ng/mL | Standard Deviation 5181.8506 |
| PPV 2-4 Hours After Injection | Ocriplasmin Activity Levels in Vitreous Samples Obtained at the Beginning of Vitrectomy. | 2610.563 ng/mL | Standard Deviation 1608.266 |
| PPV 24 Hours (+2 Hours) After Injection | Ocriplasmin Activity Levels in Vitreous Samples Obtained at the Beginning of Vitrectomy. | 496.473 ng/mL | Standard Deviation 288.2498 |
| PPV 7 Days (+1 Day) After Injection | Ocriplasmin Activity Levels in Vitreous Samples Obtained at the Beginning of Vitrectomy. | 272.370 ng/mL | Standard Deviation 0 |
| PPV Without Injection | Ocriplasmin Activity Levels in Vitreous Samples Obtained at the Beginning of Vitrectomy. | 272.370 ng/mL | Standard Deviation 0 |
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.
Time frame: From first start of vitrectomy cutter till the end of core vitrectomy phase
Population: Safety Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PPV 5-30 Minutes After Injection | Time Necessary to Remove the Vitreous From the Eye | 4.2 Minutes | Standard Deviation 3.07 |
| PPV 31-60 Minutes After Injection | Time Necessary to Remove the Vitreous From the Eye | 3.7 Minutes | Standard Deviation 2.88 |
| PPV 2-4 Hours After Injection | Time Necessary to Remove the Vitreous From the Eye | 5.1 Minutes | Standard Deviation 1.86 |
| PPV 24 Hours (+2 Hours) After Injection | Time Necessary to Remove the Vitreous From the Eye | 4.5 Minutes | Standard Deviation 2.12 |
| PPV 7 Days (+1 Day) After Injection | Time Necessary to Remove the Vitreous From the Eye | 4.0 Minutes | Standard Deviation 1.41 |
| PPV Without Injection | Time Necessary to Remove the Vitreous From the Eye | 4.8 Minutes | Standard Deviation 2.06 |