Age-related Macular Degeneration
Conditions
Keywords
First in human, Safety, Tolerability, Serum PK, Intravitreal (IVT), Age-related macular degeneration, AMD, Geographic Atrophy, Choroidal neovascularization
Brief summary
The purpose of this study is to evaluate the safety, tolerability, and serum pharmacokinetics of CLG561 in subjects with advanced age-related macular degeneration (AMD).
Detailed description
Subjects were divided into 5 cohorts, with the subjects in each cohort being administered a single IVT dose of CLG561 in 1 of 5 concentration levels A-E, where A=lowest and E=highest. All subjects received active CLG561. Progress from one cohort to the next was time-lagged to allow for safety review. Dosing was also time-lagged within each cohort. Only one eye (designated as the study eye) was dosed per subject. Post-dose safety assessments and ocular examination occurred immediately after the IVT injection and continued throughout the outpatient visits at pre-determined timepoints. Collection of post-injection blood samples began after the IVT injection at pre-determined timepoints. Subjects were followed for up to 84 days.
Interventions
DRUGCLG561
Administered by intravitreal injection, Day 1
Sponsors
Alcon Research
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of age-related macular degeneration in study eye, as specified in protocol. * Poor visual acuity in study eye, as specified in protocol. * Willing to receive meningitis and pneumonia vaccinations at least 2 weeks prior to study treatment. * Females must be post-menopausal and/or surgically sterile. * Other protocol-defined inclusion criteria may apply.
Exclusion criteria
* Treatments to the study eye within 28 days prior to study treatment, as specified in protocol. * Any disease or medication expected to cause systemic or ocular immunosuppression. * Participation in another interventional clinical study or use of any experimental treatment for AMD within 12 weeks prior to study treatment. * Other protocol-defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Baseline, Day 2, Day 4, Day 15, Day 29, Day 57, Day 85 | BCVA (with spectacles or other visual corrective devices) using Early Treatment Diabetic Retinopathy Study (ETDRS) testing was reported in letters read correctly. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. One eye (study eye) contributed to the analysis. |
| Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Baseline, Day 1, Day 2, Day 4, Day 15, Day 29, Day 57, Day 85 | IOP was measured by Goldmann applanation tonometry or tonopen, at the discretion of the Investigator, and reported in mmHg (millimeters of mercury). A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). One eye (study eye) contributed to the analysis. |
| Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Baseline, Day 2, Day 4, Day 8, Day 15, Day 29, Day 57, Day 85 | A dilated fundus examination was performed to evaluate the health of the retina, macula, choroid, and optic nerve. Subjects having a normal baseline evaluation were examined at subsequent visits, and any change from normal to abnormal was recorded. Criteria for reclassifying from normal to abnormal were left to the opinion of the investigators. One eye (study eye) contributed to the analysis. None of the abnormalities were deemed related to the study medication. |
| Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Baseline, Day 2, Day 4, Day 8, Day 15, Day 29, Day 57, Day 85 | A slit-lamp biomicroscopy examination was performed to evaluate the anterior segment of the eye. Subjects having a normal baseline evaluation were examined at subsequent visits, and any change from normal to abnormal was recorded. Criteria for reclassifying from normal to abnormal were left to the opinion of the investigators. One eye (study eye) contributed to the analysis. None of the abnormalities were deemed related to the study medication. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose-normalized Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-last)/D] | Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85 | Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental PK method. |
| Area Under the Serum Concentration-time Curve From Time Zero to Time t Where t is a Defined Time Point After Administration [AUC(0-t)] | Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85 | Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. |
| Area Under the Serum Concentration-time Curve (AUC) From Time Zero to All [AUC(0-all)] | Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85 | Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental pharmacokinetic (PK) method. |
| The Apparent Volume of Distribution During the Terminal Elimination Phase Following Extravascular Administration (Vz/F) | Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85 | Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. |
| Apparent Systemic (or Total Body) Clearance From Serum Following Extravascular Administration (CL/F) | Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85 | Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. |
| Terminal Elimination Half-life (T½) | Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85 | Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. |
| Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-last)] | Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85 | Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental PK method. |
| Time to Reach the Maximum Serum Concentration After Drug Administration (Tmax) | Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85 | Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental PK method. |
| Dose Normalized Observed Maximum Serum Concentration Following Drug Administration (Cmax/D) | Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85 | Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental PK method. |
Participant flow
Recruitment details
Subjects were recruited from 4 investigational centers located in the US.
Pre-assignment details
Of the 50 enrolled,19 subjects were exited as screen failures prior to randomization. This reporting group includes all assigned subjects (31).
Participants by arm
| Arm | Count |
|---|---|
| CLG561, Level A Single 50 μL intravitreal injection of CLG561, Dose Level A | 6 |
| CLG561, Level B Single 50 μL intravitreal injection of CLG561, Dose Level B | 6 |
| CLG561, Level C Single 50 μL intravitreal injection of CLG561, Dose Level C | 7 |
| CLG561, Level D Single 50 μL intravitreal injection of CLG561, Dose Level D | 6 |
| CLG561, Level E Single 100 μL intravitreal injection of CLG561, Dose Level E | 6 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | CLG561, Level A | CLG561, Level B | CLG561, Level C | CLG561, Level D | CLG561, Level E | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 74.2 years STANDARD_DEVIATION 6.82 | 76.2 years STANDARD_DEVIATION 8.8 | 76.1 years STANDARD_DEVIATION 6.69 | 73.3 years STANDARD_DEVIATION 9.52 | 76.5 years STANDARD_DEVIATION 10.86 | 75.3 years STANDARD_DEVIATION 8.12 |
| Primary Diagnosis Exudative macular degeneration | 6 participants | 4 participants | 5 participants | 5 participants | 4 participants | 24 participants |
| Primary Diagnosis Geographic atrophy | 0 participants | 2 participants | 2 participants | 1 participants | 2 participants | 7 participants |
| Sex: Female, Male Female | 6 Participants | 1 Participants | 4 Participants | 5 Participants | 3 Participants | 19 Participants |
| Sex: Female, Male Male | 0 Participants | 5 Participants | 3 Participants | 1 Participants | 3 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 | 5 / 6 | 3 / 6 | 6 / 7 | 2 / 6 | 3 / 6 | 0 / 50 |
| serious Total, serious adverse events | 1 / 6 | 0 / 6 | 1 / 7 | 0 / 6 | 0 / 6 | 0 / 50 |
Outcome results
Primary
Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye
BCVA (with spectacles or other visual corrective devices) using Early Treatment Diabetic Retinopathy Study (ETDRS) testing was reported in letters read correctly. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. One eye (study eye) contributed to the analysis.
Time frame: Baseline, Day 2, Day 4, Day 15, Day 29, Day 57, Day 85
Population: This analysis population includes all enrolled subjects who received investigational product. Here, n is the number of subjects with non-missing values at the specific time point for each arm group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CLG561, Level A | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Change from Baseline, Day 29, n=6,5,6,6,6 | 2.2 letters | Standard Deviation 5.85 |
| CLG561, Level A | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Change from Baseline, Day 15, n=6,6,6,6,6 | 2.7 letters | Standard Deviation 7.99 |
| CLG561, Level A | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Change from Baseline, Day 2, n=6,6,7,6,6 | 0.7 letters | Standard Deviation 8.24 |
| CLG561, Level A | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Change from Baseline, Day 57, n=6,5,6,6,6 | 4.7 letters | Standard Deviation 11.09 |
| CLG561, Level A | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Change from Baseline, Day 4, n=6,6,7,6,6 | 3.5 letters | Standard Deviation 8.53 |
| CLG561, Level A | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Change from Baseline, Day 85, n=6,6,6,6,6 | 3.8 letters | Standard Deviation 9.43 |
| CLG561, Level A | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Baseline, n=6,6,7,6,6 | 23.7 letters | Standard Deviation 16.55 |
| CLG561, Level B | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Change from Baseline, Day 2, n=6,6,7,6,6 | 2.5 letters | Standard Deviation 5.24 |
| CLG561, Level B | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Change from Baseline, Day 29, n=6,5,6,6,6 | 4.8 letters | Standard Deviation 5.02 |
| CLG561, Level B | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Change from Baseline, Day 57, n=6,5,6,6,6 | 2.0 letters | Standard Deviation 3.24 |
| CLG561, Level B | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Baseline, n=6,6,7,6,6 | 25.7 letters | Standard Deviation 15.2 |
| CLG561, Level B | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Change from Baseline, Day 15, n=6,6,6,6,6 | 3.7 letters | Standard Deviation 4.5 |
| CLG561, Level B | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Change from Baseline, Day 85, n=6,6,6,6,6 | 3.0 letters | Standard Deviation 4.86 |
| CLG561, Level B | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Change from Baseline, Day 4, n=6,6,7,6,6 | 4.8 letters | Standard Deviation 4.67 |
| CLG561, Level C | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Change from Baseline, Day 2, n=6,6,7,6,6 | 1.1 letters | Standard Deviation 3.02 |
| CLG561, Level C | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Change from Baseline, Day 15, n=6,6,6,6,6 | 2.0 letters | Standard Deviation 4.73 |
| CLG561, Level C | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Change from Baseline, Day 4, n=6,6,7,6,6 | 1.7 letters | Standard Deviation 3.04 |
| CLG561, Level C | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Baseline, n=6,6,7,6,6 | 27.6 letters | Standard Deviation 17.67 |
| CLG561, Level C | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Change from Baseline, Day 57, n=6,5,6,6,6 | 2.5 letters | Standard Deviation 5.75 |
| CLG561, Level C | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Change from Baseline, Day 29, n=6,5,6,6,6 | 1.3 letters | Standard Deviation 5.28 |
| CLG561, Level C | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Change from Baseline, Day 85, n=6,6,6,6,6 | 2.2 letters | Standard Deviation 5.12 |
| CLG561, Level D | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Change from Baseline, Day 4, n=6,6,7,6,6 | 1.8 letters | Standard Deviation 5.19 |
| CLG561, Level D | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Baseline, n=6,6,7,6,6 | 41.5 letters | Standard Deviation 20.42 |
| CLG561, Level D | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Change from Baseline, Day 2, n=6,6,7,6,6 | 0.0 letters | Standard Deviation 5.73 |
| CLG561, Level D | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Change from Baseline, Day 15, n=6,6,6,6,6 | 3.5 letters | Standard Deviation 8.26 |
| CLG561, Level D | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Change from Baseline, Day 29, n=6,5,6,6,6 | 2.0 letters | Standard Deviation 6.84 |
| CLG561, Level D | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Change from Baseline, Day 57, n=6,5,6,6,6 | 4.2 letters | Standard Deviation 11.09 |
| CLG561, Level D | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Change from Baseline, Day 85, n=6,6,6,6,6 | 2.2 letters | Standard Deviation 5.12 |
| CLG561, Level E | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Change from Baseline, Day 85, n=6,6,6,6,6 | 3.2 letters | Standard Deviation 5.12 |
| CLG561, Level E | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Change from Baseline, Day 57, n=6,5,6,6,6 | 2.3 letters | Standard Deviation 2.94 |
| CLG561, Level E | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Change from Baseline, Day 2, n=6,6,7,6,6 | -1.0 letters | Standard Deviation 10.02 |
| CLG561, Level E | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Baseline, n=6,6,7,6,6 | 38.0 letters | Standard Deviation 11.75 |
| CLG561, Level E | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Change from Baseline, Day 15, n=6,6,6,6,6 | 5.2 letters | Standard Deviation 8.06 |
| CLG561, Level E | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Change from Baseline, Day 29, n=6,5,6,6,6 | 1.5 letters | Standard Deviation 4.51 |
| CLG561, Level E | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye | Change from Baseline, Day 4, n=6,6,7,6,6 | 3.3 letters | Standard Deviation 7.87 |
Primary
Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye
IOP was measured by Goldmann applanation tonometry or tonopen, at the discretion of the Investigator, and reported in mmHg (millimeters of mercury). A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). One eye (study eye) contributed to the analysis.
Time frame: Baseline, Day 1, Day 2, Day 4, Day 15, Day 29, Day 57, Day 85
Population: This analysis population includes all enrolled subjects who received investigational product. Here, n is the number of subjects with non-missing values at the specific time point for each arm group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CLG561, Level A | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 1, n=6,6,7,6,6 | 16.3 mmHg | Standard Deviation 3.72 |
| CLG561, Level A | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 2, n=6,6,7,6,6 | 16.0 mmHg | Standard Deviation 1.79 |
| CLG561, Level A | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 57, n=6,5,6,6,6 | 17.7 mmHg | Standard Deviation 2.94 |
| CLG561, Level A | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 15, n=6,6,6,6,6 | 14.0 mmHg | Standard Deviation 1.67 |
| CLG561, Level A | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 85, n=6,6,6,6,6 | 16.5 mmHg | Standard Deviation 2.07 |
| CLG561, Level A | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 29, n=6,5,6,6,6 | 16.8 mmHg | Standard Deviation 3.19 |
| CLG561, Level A | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Baseline, n=6,6,7,6,6 | 14.7 mmHg | Standard Deviation 2.16 |
| CLG561, Level A | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 4, n=6,6,7,6,6 | 16.2 mmHg | Standard Deviation 2.32 |
| CLG561, Level B | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 15, n=6,6,6,6,6 | 15.5 mmHg | Standard Deviation 2.81 |
| CLG561, Level B | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 1, n=6,6,7,6,6 | 20.2 mmHg | Standard Deviation 8.01 |
| CLG561, Level B | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 4, n=6,6,7,6,6 | 14.5 mmHg | Standard Deviation 3.99 |
| CLG561, Level B | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 2, n=6,6,7,6,6 | 14.5 mmHg | Standard Deviation 1.05 |
| CLG561, Level B | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 85, n=6,6,6,6,6 | 15.5 mmHg | Standard Deviation 5.24 |
| CLG561, Level B | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 57, n=6,5,6,6,6 | 15.6 mmHg | Standard Deviation 5.32 |
| CLG561, Level B | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 29, n=6,5,6,6,6 | 16.8 mmHg | Standard Deviation 4.6 |
| CLG561, Level B | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Baseline, n=6,6,7,6,6 | 14.3 mmHg | Standard Deviation 2.42 |
| CLG561, Level C | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 57, n=6,5,6,6,6 | 16.3 mmHg | Standard Deviation 3.27 |
| CLG561, Level C | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 85, n=6,6,6,6,6 | 16.7 mmHg | Standard Deviation 4.27 |
| CLG561, Level C | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Baseline, n=6,6,7,6,6 | 15.7 mmHg | Standard Deviation 3.86 |
| CLG561, Level C | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 15, n=6,6,6,6,6 | 16.2 mmHg | Standard Deviation 6.21 |
| CLG561, Level C | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 1, n=6,6,7,6,6 | 16.6 mmHg | Standard Deviation 6.24 |
| CLG561, Level C | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 4, n=6,6,7,6,6 | 15.1 mmHg | Standard Deviation 4.74 |
| CLG561, Level C | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 29, n=6,5,6,6,6 | 16.0 mmHg | Standard Deviation 4.94 |
| CLG561, Level C | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 2, n=6,6,7,6,6 | 14.3 mmHg | Standard Deviation 3.15 |
| CLG561, Level D | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 4, n=6,6,7,6,6 | 14.7 mmHg | Standard Deviation 4.23 |
| CLG561, Level D | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 15, n=6,6,6,6,6 | 16.2 mmHg | Standard Deviation 3.76 |
| CLG561, Level D | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 85, n=6,6,6,6,6 | 16.2 mmHg | Standard Deviation 4.07 |
| CLG561, Level D | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 2, n=6,6,7,6,6 | 14.0 mmHg | Standard Deviation 4 |
| CLG561, Level D | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 29, n=6,5,6,6,6 | 16.8 mmHg | Standard Deviation 4.26 |
| CLG561, Level D | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 1, n=6,6,7,6,6 | 22.3 mmHg | Standard Deviation 3.5 |
| CLG561, Level D | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Baseline, n=6,6,7,6,6 | 15.2 mmHg | Standard Deviation 3.06 |
| CLG561, Level D | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 57, n=6,5,6,6,6 | 16.3 mmHg | Standard Deviation 2.25 |
| CLG561, Level E | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 85, n=6,6,6,6,6 | 16.2 mmHg | Standard Deviation 4.26 |
| CLG561, Level E | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 4, n=6,6,7,6,6 | 15.3 mmHg | Standard Deviation 3.93 |
| CLG561, Level E | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 15, n=6,6,6,6,6 | 16.5 mmHg | Standard Deviation 4.09 |
| CLG561, Level E | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Baseline, n=6,6,7,6,6 | 16.5 mmHg | Standard Deviation 3.67 |
| CLG561, Level E | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 1, n=6,6,7,6,6 | 20.2 mmHg | Standard Deviation 3.97 |
| CLG561, Level E | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 2, n=6,6,7,6,6 | 15.0 mmHg | Standard Deviation 3.1 |
| CLG561, Level E | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 29, n=6,5,6,6,6 | 16.2 mmHg | Standard Deviation 4.67 |
| CLG561, Level E | Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye | Day 57, n=6,5,6,6,6 | 15.8 mmHg | Standard Deviation 3.13 |
Primary
Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment
A slit-lamp biomicroscopy examination was performed to evaluate the anterior segment of the eye. Subjects having a normal baseline evaluation were examined at subsequent visits, and any change from normal to abnormal was recorded. Criteria for reclassifying from normal to abnormal were left to the opinion of the investigators. One eye (study eye) contributed to the analysis. None of the abnormalities were deemed related to the study medication.
Time frame: Baseline, Day 2, Day 4, Day 8, Day 15, Day 29, Day 57, Day 85
Population: This analysis population includes all enrolled subjects who received investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CLG561, Level A | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Iris: Change from Normal to Abnormal | 0 participants |
| CLG561, Level A | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Conjunctiva: Baseline Normal | 5 participants |
| CLG561, Level A | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Conjunctiva: Change from Normal to Abnormal | 2 participants |
| CLG561, Level A | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Cornea: Change from Normal to Abnormal | 0 participants |
| CLG561, Level A | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Iris: Baseline Normal | 6 participants |
| CLG561, Level A | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Lids/Lashes: Baseline Normal | 5 participants |
| CLG561, Level A | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Lids/Lashes: Change from Normal to Abnormal | 0 participants |
| CLG561, Level A | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Cornea: Baseline Normal | 6 participants |
| CLG561, Level B | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Iris: Baseline Normal | 6 participants |
| CLG561, Level B | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Conjunctiva: Baseline Normal | 4 participants |
| CLG561, Level B | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Cornea: Baseline Normal | 5 participants |
| CLG561, Level B | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Lids/Lashes: Baseline Normal | 4 participants |
| CLG561, Level B | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Iris: Change from Normal to Abnormal | 0 participants |
| CLG561, Level B | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Cornea: Change from Normal to Abnormal | 0 participants |
| CLG561, Level B | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Conjunctiva: Change from Normal to Abnormal | 1 participants |
| CLG561, Level B | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Lids/Lashes: Change from Normal to Abnormal | 1 participants |
| CLG561, Level C | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Cornea: Baseline Normal | 6 participants |
| CLG561, Level C | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Conjunctiva: Change from Normal to Abnormal | 4 participants |
| CLG561, Level C | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Conjunctiva: Baseline Normal | 6 participants |
| CLG561, Level C | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Iris: Baseline Normal | 6 participants |
| CLG561, Level C | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Cornea: Change from Normal to Abnormal | 2 participants |
| CLG561, Level C | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Lids/Lashes: Change from Normal to Abnormal | 1 participants |
| CLG561, Level C | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Lids/Lashes: Baseline Normal | 5 participants |
| CLG561, Level C | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Iris: Change from Normal to Abnormal | 0 participants |
| CLG561, Level D | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Conjunctiva: Change from Normal to Abnormal | 0 participants |
| CLG561, Level D | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Cornea: Change from Normal to Abnormal | 0 participants |
| CLG561, Level D | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Iris: Change from Normal to Abnormal | 0 participants |
| CLG561, Level D | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Iris: Baseline Normal | 6 participants |
| CLG561, Level D | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Lids/Lashes: Change from Normal to Abnormal | 0 participants |
| CLG561, Level D | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Conjunctiva: Baseline Normal | 5 participants |
| CLG561, Level D | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Cornea: Baseline Normal | 6 participants |
| CLG561, Level D | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Lids/Lashes: Baseline Normal | 6 participants |
| CLG561, Level E | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Lids/Lashes: Baseline Normal | 6 participants |
| CLG561, Level E | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Iris: Baseline Normal | 6 participants |
| CLG561, Level E | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Iris: Change from Normal to Abnormal | 0 participants |
| CLG561, Level E | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Cornea: Baseline Normal | 5 participants |
| CLG561, Level E | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Conjunctiva: Baseline Normal | 5 participants |
| CLG561, Level E | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Cornea: Change from Normal to Abnormal | 1 participants |
| CLG561, Level E | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Conjunctiva: Change from Normal to Abnormal | 2 participants |
| CLG561, Level E | Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment | Lids/Lashes: Change from Normal to Abnormal | 1 participants |
Primary
Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment
A dilated fundus examination was performed to evaluate the health of the retina, macula, choroid, and optic nerve. Subjects having a normal baseline evaluation were examined at subsequent visits, and any change from normal to abnormal was recorded. Criteria for reclassifying from normal to abnormal were left to the opinion of the investigators. One eye (study eye) contributed to the analysis. None of the abnormalities were deemed related to the study medication.
Time frame: Baseline, Day 2, Day 4, Day 8, Day 15, Day 29, Day 57, Day 85
Population: This analysis population includes all enrolled subjects who received investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CLG561, Level A | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Choroid: Change from Normal to Abnormal | 0 participants |
| CLG561, Level A | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Retina: Baseline Normal | 5 participants |
| CLG561, Level A | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Retina: Change from Normal to Abnormal | 1 participants |
| CLG561, Level A | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Optic Nerve: Baseline Normal | 6 participants |
| CLG561, Level A | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Macula: Change from Normal to Abnormal | 0 participants |
| CLG561, Level A | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Optic Nerve: Change from Normal to Abnormal | 1 participants |
| CLG561, Level A | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Macula: Baseline Normal | 6 participants |
| CLG561, Level A | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Choroid: Baseline Normal | 6 participants |
| CLG561, Level B | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Retina: Baseline Normal | 4 participants |
| CLG561, Level B | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Choroid: Baseline Normal | 6 participants |
| CLG561, Level B | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Optic Nerve: Change from Normal to Abnormal | 0 participants |
| CLG561, Level B | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Choroid: Change from Normal to Abnormal | 0 participants |
| CLG561, Level B | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Macula: Baseline Normal | 6 participants |
| CLG561, Level B | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Optic Nerve: Baseline Normal | 3 participants |
| CLG561, Level B | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Macula: Change from Normal to Abnormal | 0 participants |
| CLG561, Level B | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Retina: Change from Normal to Abnormal | 0 participants |
| CLG561, Level C | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Retina: Change from Normal to Abnormal | 0 participants |
| CLG561, Level C | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Optic Nerve: Baseline Normal | 5 participants |
| CLG561, Level C | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Macula: Baseline Normal | 6 participants |
| CLG561, Level C | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Retina: Baseline Normal | 4 participants |
| CLG561, Level C | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Macula: Change from Normal to Abnormal | 0 participants |
| CLG561, Level C | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Choroid: Baseline Normal | 6 participants |
| CLG561, Level C | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Choroid: Change from Normal to Abnormal | 0 participants |
| CLG561, Level C | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Optic Nerve: Change from Normal to Abnormal | 2 participants |
| CLG561, Level D | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Retina: Baseline Normal | 6 participants |
| CLG561, Level D | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Retina: Change from Normal to Abnormal | 0 participants |
| CLG561, Level D | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Macula: Baseline Normal | 6 participants |
| CLG561, Level D | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Macula: Change from Normal to Abnormal | 0 participants |
| CLG561, Level D | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Choroid: Change from Normal to Abnormal | 0 participants |
| CLG561, Level D | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Optic Nerve: Baseline Normal | 6 participants |
| CLG561, Level D | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Optic Nerve: Change from Normal to Abnormal | 0 participants |
| CLG561, Level D | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Choroid: Baseline Normal | 6 participants |
| CLG561, Level E | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Retina: Baseline Normal | 5 participants |
| CLG561, Level E | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Choroid: Baseline Normal | 6 participants |
| CLG561, Level E | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Macula: Change from Normal to Abnormal | 1 participants |
| CLG561, Level E | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Macula: Baseline Normal | 6 participants |
| CLG561, Level E | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Retina: Change from Normal to Abnormal | 1 participants |
| CLG561, Level E | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Optic Nerve: Change from Normal to Abnormal | 0 participants |
| CLG561, Level E | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Optic Nerve: Baseline Normal | 5 participants |
| CLG561, Level E | Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment | Choroid: Change from Normal to Abnormal | 0 participants |
Secondary
Apparent Systemic (or Total Body) Clearance From Serum Following Extravascular Administration (CL/F)
Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method.
Time frame: Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85
Population: This parameter was not calculated as AUClast and AUCall were considered sufficient to characterize the systemic exposure to CLG561.
Secondary
Area Under the Serum Concentration-time Curve (AUC) From Time Zero to All [AUC(0-all)]
Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental pharmacokinetic (PK) method.
Time frame: Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85
Population: This analysis population includes all subjects who received investigational product, completed at least 1 post-injection study visit and for whom serum concentration-time data is available, provided no collection or analytical deviations which would affect the integrity of the data occurred.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CLG561, Level A | Area Under the Serum Concentration-time Curve (AUC) From Time Zero to All [AUC(0-all)] | NA hr*ng/mL | — |
| CLG561, Level B | Area Under the Serum Concentration-time Curve (AUC) From Time Zero to All [AUC(0-all)] | NA hr*ng/mL | — |
| CLG561, Level C | Area Under the Serum Concentration-time Curve (AUC) From Time Zero to All [AUC(0-all)] | NA hr*ng/mL | — |
| CLG561, Level D | Area Under the Serum Concentration-time Curve (AUC) From Time Zero to All [AUC(0-all)] | 238000 hr*ng/mL | Standard Deviation 81800 |
| CLG561, Level E | Area Under the Serum Concentration-time Curve (AUC) From Time Zero to All [AUC(0-all)] | 373000 hr*ng/mL | Standard Deviation 160000 |
Secondary
Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-last)]
Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental PK method.
Time frame: Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85
Population: This analysis population includes all subjects who received investigational product, completed at least 1 post-injection study visit and for whom serum concentration-time data is available, provided no collection or analytical deviations which would affect the integrity of the data occurred.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CLG561, Level A | Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-last)] | NA hr*ng/mL | — |
| CLG561, Level B | Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-last)] | NA hr*ng/mL | — |
| CLG561, Level C | Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-last)] | NA hr*ng/mL | — |
| CLG561, Level D | Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-last)] | 195000 hr*ng/mL | Standard Deviation 78300 |
| CLG561, Level E | Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-last)] | 304000 hr*ng/mL | Standard Deviation 148000 |
Secondary
Area Under the Serum Concentration-time Curve From Time Zero to Time t Where t is a Defined Time Point After Administration [AUC(0-t)]
Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method.
Time frame: Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85
Population: This parameter was not calculated as AUClast and AUCall were considered sufficient to characterize the systemic exposure to CLG561.
Secondary
Dose-normalized Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-last)/D]
Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental PK method.
Time frame: Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85
Population: This analysis population includes all subjects who received investigational product, completed at least 1 post-injection study visit and for whom serum concentration-time data is available, provided no collection or analytical deviations which would affect the integrity of the data occurred.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CLG561, Level A | Dose-normalized Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-last)/D] | NA hr*ng/mL/mg | — |
| CLG561, Level B | Dose-normalized Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-last)/D] | NA hr*ng/mL/mg | — |
| CLG561, Level C | Dose-normalized Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-last)/D] | NA hr*ng/mL/mg | — |
| CLG561, Level D | Dose-normalized Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-last)/D] | 38900 hr*ng/mL/mg | Standard Deviation 15700 |
| CLG561, Level E | Dose-normalized Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-last)/D] | 30400 hr*ng/mL/mg | Standard Deviation 14800 |
Secondary
Dose Normalized Observed Maximum Serum Concentration Following Drug Administration (Cmax/D)
Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental PK method.
Time frame: Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85
Population: This analysis population includes all subjects who received investigational product, completed at least 1 post-injection study visit and for whom serum concentration-time data is available, provided no collection or analytical deviations which would affect the integrity of the data occurred.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CLG561, Level A | Dose Normalized Observed Maximum Serum Concentration Following Drug Administration (Cmax/D) | NA ng/mL/mg | — |
| CLG561, Level B | Dose Normalized Observed Maximum Serum Concentration Following Drug Administration (Cmax/D) | NA ng/mL/mg | — |
| CLG561, Level C | Dose Normalized Observed Maximum Serum Concentration Following Drug Administration (Cmax/D) | NA ng/mL/mg | — |
| CLG561, Level D | Dose Normalized Observed Maximum Serum Concentration Following Drug Administration (Cmax/D) | 102 ng/mL/mg | Standard Deviation 30 |
| CLG561, Level E | Dose Normalized Observed Maximum Serum Concentration Following Drug Administration (Cmax/D) | 75.8 ng/mL/mg | Standard Deviation 30.9 |
Secondary
Terminal Elimination Half-life (T½)
Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method.
Time frame: Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85
Population: This parameter was not calculated as AUClast and AUCall were considered sufficient to characterize the systemic exposure to CLG561.
Secondary
The Apparent Volume of Distribution During the Terminal Elimination Phase Following Extravascular Administration (Vz/F)
Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method.
Time frame: Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85
Population: This parameter was not calculated as AUClast and AUCall were considered sufficient to characterize the systemic exposure to CLG561.
Secondary
Time to Reach the Maximum Serum Concentration After Drug Administration (Tmax)
Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental PK method.
Time frame: Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85
Population: This analysis population includes all subjects who received investigational product, completed at least 1 post-injection study visit and for whom serum concentration-time data is available, provided no collection or analytical deviations which would affect the integrity of the data occurred.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CLG561, Level A | Time to Reach the Maximum Serum Concentration After Drug Administration (Tmax) | NA hours | — |
| CLG561, Level B | Time to Reach the Maximum Serum Concentration After Drug Administration (Tmax) | NA hours | — |
| CLG561, Level C | Time to Reach the Maximum Serum Concentration After Drug Administration (Tmax) | NA hours | — |
| CLG561, Level D | Time to Reach the Maximum Serum Concentration After Drug Administration (Tmax) | 144 hours | Standard Deviation 62.7 |
| CLG561, Level E | Time to Reach the Maximum Serum Concentration After Drug Administration (Tmax) | 187 hours | Standard Deviation 79.8 |