Ocular Hypertension, Open-Angle Glaucoma
Conditions
Keywords
Ocular Hypertension, Open-Angle Glaucoma, POAG, Glaucoma
Brief summary
The purpose of this study is to determine if the clinical profile of topical-ocular MGV354 merits further development for the indication of lowering intraocular pressure (IOP).
Detailed description
Part 1 will evaluate the safety and tolerability of single ascending doses of MGV354 compared to placebo in healthy male and female subjects. Part 2 will evaluate the safety and tolerability of MGV354 in a multiple ascending dose design (two highest tolerated doses from Part 1) compared to placebo when administered for 7 days to patients with ocular hypertension or glaucoma. Part 3 will explore the safety, tolerability and efficacy of a single dose level of MGV354 (maximum tolerated dose) compared to placebo when administered for 7 days in patients with ocular hypertension or glaucoma.
Interventions
DRUGMGV354 ophthalmic suspension
DRUGMGV354 placebo
Inactive ingredients used as placebo comparator
Sponsors
Novartis Institute for BioMedical Research
Alcon Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Documented informed consent. * Part 1: 18 to 70 years of age; * Parts 2 and 3: 18 years of age or older; * Able to communicate well with the investigator and understand and comply with the requirements of the study; * Body Mass Index (BMI) between 18 and 39; * In case of contact lens wear, willing to remove lenses 30 minutes before the first assessment until the end of the study. Corrective spectacles may be worn as needed. * Sitting vital signs (systolic and diastolic blood pressure and pulse rate) within normal ranges as specified in the protocol; * Part 1 (Healthy Volunteers): In good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening. * Parts 2 and 3 (Patients): Diagnosed with open-angle glaucoma or confirmed ocular hypertension; mean IOP measurements in at least one eye after washout as specified in the protocol * Other protocol-specified inclusion criteria may apply.
Exclusion criteria
* History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes; * History of or current presence of clinically significant ECG abnormalities or arrhythmias; * History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in-situ cervical or breast cancer), treated or untreated, within the past 5 years; * Known clinical history of heart failure, myocardial infarction, or stroke; * Exposure during the four weeks preceding the Screening visit to any topical, inhaled, or systemic corticosteroids; * Angle grade less than Grade 2 in either eye; * Any abnormality, including corneal thickness \> 620 microns, preventing reliable applanation tonometry; * Pregnant or lactating women and women of child-bearing potential; * Sexually active males must agree to use a condom during intercourse while taking drug and for 6 days after stopping MGV354 medication and should not father a child in this period; * Positive HIV, Hepatitis B Ag or Hepatitis C Ab test result at Screening; * Abnormal liver function tests; * History or presence of impaired renal function; * Part 1 (Healthy Volunteers): Use of any NEW prescription drugs or herbal supplements within four (4) weeks prior to initial dosing, and/or NEW over-the-counter (OTC) medication, dietary supplements (vitamins included) within two (2) weeks prior to initial dosing. * Parts 2 and 3 (Patients): Patients with related disease condition(s) including any form of glaucoma other than open-angle glaucoma and pseudoexfoliation and/or pigment dispersion components; patients who cannot safely discontinue use of all topical ocular and/or systemic IOP-lowering medication according to protocol-specified Washout Schedule; patients with ocular diseases or conditions as specified in the protocol; patients taking certain medications as specified in the protocol; * Other protocol-specified
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 3: Change in Diurnal IOP (Averaged Over 8 AM, 10 AM, Noon, 4 PM, and 8 PM) From Baseline to Day 8 | Baseline, Day 8 | IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in mmHg. Diurnal IOP was defined as the average of the five time points measured (8 AM, 10 AM, noon, 4 PM, and 8 PM). Baseline diurnal IOP was the average of IOP measurements obtained at the 2 eligibility visits. Change from baseline was calculated by taking the change at each time point from baseline to Day 8 and averaging the available changes. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. Only one eye (study eye) contributed to the analysis. |
| Part 3: Change in IOP From Baseline to Day 8 at 8 AM, 10 AM, Noon, 4 PM, and 8 PM | Baseline, Day 8 | IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in mmHg. Baseline IOP was the average of IOP measurements obtained at the 2 eligibility visits. Change from baseline was calculated by taking the change at each time point from baseline to Day 8. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. Only one eye (study eye) contributed to the analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Time to Reach Maximum Concentration [Tmax (h)] | Pre-dose, .5, 2, 4, 6, 12, 24, 48, 72, 96, 120 hours post-dose, and Day 7 post-dose | Based on plasma samples collected at pre-determined nominal time points, dependent on observed concentrations. Approximately 2 mL of venous blood was collected at each time point. |
| Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUClast (ng*h/mL)] | Pre-dose, .5, 2, 4, 6, 12, 24, 48, 72, 96, 120 hours post-dose, and Day 7 post-dose | Based on plasma samples collected at pre-determined nominal time points, dependent on observed concentrations. Approximately 2 mL of venous blood was collected at each time point. AUClast is reported as mass\*time/volume. |
| Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to 120 Hours Post Dose [AUC0-120 (ng*h/mL)] | Pre-dose to 120 hours post-dose | Based on plasma samples collected at pre-determined nominal time points, dependent on observed concentrations. Approximately 2 mL of venous blood was to be collected at each time point. |
| Part 1: Area Under the Concentration-time Curve From 0 to Infinity [AUCinf (ng*h/mL)] | Pre-dose to 120 hours post-dose | Based on plasma samples collected at pre-determined nominal time points, dependent on observed concentrations. Approximately 2 mL of venous blood was to be collected at each time point. |
| Part 1: Terminal Elimination Half-life [t1/2 (h)] | Pre-dose to 120 hours post-dose | Based on plasma samples collected at pre-determined nominal time points, dependent on observed concentrations. Approximately 2 mL of venous blood was to be collected at each time point. |
| Part 3: Change From Baseline in IOP at 36 Hours and 48 Hours Post Day 7 Administration | Baseline, up to Day 9 | IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in mmHg. Baseline IOP was the average of IOP measurements obtained at the 2 eligibility visits. Change from baseline was calculated by taking the change at each time point from baseline to Day 8 and averaging the available changes. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. Only one eye (study eye) contributed to the analysis. |
| Part 2: Time to Reach Maximum Concentration [Tmax (h)] | Up to Day 7 | Based on plasma samples collected at pre-determined nominal time points, dependent on observed concentrations. Approximately 2 mL of venous blood was collected at each time point. |
| Part 2: Area Under the Concentration-time Curve From 0 to the End of the Dosing Interval Tau [AUCtau (ng*h/mL)] | Up to Day 7 | Based on plasma samples collected at pre-determined nominal time points, dependent on observed concentrations. Approximately 2 mL of venous blood was collected at each time point. AUCtau is reported as mass\*time/volume. |
| Part 2: Accumulation Ratio (Racc) | Day 7 | Accumulation Ratio was derived using Cmax on Day 7 versus Cmax on Day 1. Approximately 2 mL of venous blood was collected at each time point. |
| Part 3: Observed Concentration at 12 Hours Following Drug Administration [C12 (ng/mL)] | Up to Day 8 | Based on plasma samples collected at pre-determined nominal time points, dependent on observed concentrations. Approximately 2 mL of venous blood was collected at each time point. C12 is reported as mass/volume. |
| Part 2: Maximum Observed Concentration [Cmax (ng/mL)] | Up to Day 7 | Based on plasma samples collected at pre-determined nominal time points, dependent on observed concentrations. Approximately 2 mL of venous blood was collected at each time point. Cmax is reported as mass/volume. |
| Part 1: Maximum Observed Concentration [Cmax (ng/mL)] | Pre-dose, .5, 2, 4, 6, 12, 24, 48, 72, 96, 120 hours post-dose, and Day 7 post-dose | Based on plasma samples collected at pre-determined nominal time points, dependent on observed concentrations. Approximately 2 mL of venous blood was collected at each time point. Cmax is reported as mass/volume. |
Participant flow
Recruitment details
Subjects were recruited from 5 study centers located in the US.
Pre-assignment details
This study was conducted in 3 parts. A separate cohort of subjects was enrolled for each part. Of the 191 subjects enrolled (Part 1, 2, and 3 combined), 79 were exited as screen failures and 14 were discontinued prior to randomization. This reporting group includes all randomized subjects. A zero indicates no intended subjects.
Participants by arm
| Arm | Count |
|---|---|
| MGV354 0.01% MGV354 ophthalmic suspension 0.01%, 1 drop in the study eye (Part 1) | 6 |
| MGV354 0.03% MGV354 ophthalmic suspension 0.03%, 1 drop in the study eye (Part 1) or 1 drop in each eye for 7 days (Part 2) | 12 |
| MGV354 0.1% MGV354 ophthalmic suspension 0.1%, 1 drop in the study eye (Part 1) or 1 drop in each eye for 7 days (Part 2 and Part 3) | 36 |
| MGV354 0.3% MGV354 ophthalmic suspension 0.3%, 1 drop in the study eye (Part 1) | 6 |
| Placebo Placebo, 1 drop in the study eye (Part 1); 1 drop in each eye for 7 days (Part 2 and Part 3) | 37 |
| Total | 97 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Part 3 (7 Days) | Adverse Event | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | MGV354 0.01% | MGV354 0.03% | MGV354 0.1% | MGV354 0.3% | Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Customized Part 1 | 31.2 years STANDARD_DEVIATION 13.61 | 51.7 years STANDARD_DEVIATION 15.77 | 48.5 years STANDARD_DEVIATION 17.55 | 62.7 years STANDARD_DEVIATION 7.74 | 50.1 years STANDARD_DEVIATION 7.51 | 48.9 years STANDARD_DEVIATION 15.54 |
| Age, Customized Part 2 | — | 59.2 years STANDARD_DEVIATION 7.52 | 63.3 years STANDARD_DEVIATION 7.79 | — | 63.3 years STANDARD_DEVIATION 6.7 | 61.8 years STANDARD_DEVIATION 7.23 |
| Age, Customized Part 3 | — | — | 65.5 years STANDARD_DEVIATION 8.17 | — | 64.8 years STANDARD_DEVIATION 9.92 | 65.2 years STANDARD_DEVIATION 9.02 |
| Intraocular Pressure (IOP) 10 AM IOP | — | — | 24.68 mmHg STANDARD_DEVIATION 2.571 | — | 24.77 mmHg STANDARD_DEVIATION 1.976 | 24.72 mmHg STANDARD_DEVIATION 2.263 |
| Intraocular Pressure (IOP) 4 PM IOP | — | — | 24.39 mmHg STANDARD_DEVIATION 2.521 | — | 24.21 mmHg STANDARD_DEVIATION 1.939 | 24.30 mmHg STANDARD_DEVIATION 2.221 |
| Intraocular Pressure (IOP) 8 AM IOP | — | — | 26.60 mmHg STANDARD_DEVIATION 2.289 | — | 27.33 mmHg STANDARD_DEVIATION 3.3 | 26.97 mmHg STANDARD_DEVIATION 2.844 |
| Intraocular Pressure (IOP) 8 PM IOP | — | — | 23.34 mmHg STANDARD_DEVIATION 2.998 | — | 22.64 mmHg STANDARD_DEVIATION 2.344 | 22.98 mmHg STANDARD_DEVIATION 2.68 |
| Intraocular Pressure (IOP) Diurnal IOP | — | — | 24.69 mmHg STANDARD_DEVIATION 2.475 | — | 24.63 mmHg STANDARD_DEVIATION 2.119 | 24.66 mmHg STANDARD_DEVIATION 2.276 |
| Intraocular Pressure (IOP) Noon IOP | — | — | 24.46 mmHg STANDARD_DEVIATION 2.842 | — | 24.21 mmHg STANDARD_DEVIATION 2.046 | 24.33 mmHg STANDARD_DEVIATION 2.445 |
| Sex/Gender, Customized Female, Part 1 | 0 participants | 5 participants | 4 participants | 6 participants | 5 participants | 20 participants |
| Sex/Gender, Customized Female, Part 2 | — | 4 participants | 3 participants | — | 2 participants | 9 participants |
| Sex/Gender, Customized Female, Part 3 | — | — | 17 participants | — | 17 participants | 34 participants |
| Sex/Gender, Customized Male, Part 1 | 6 participants | 1 participants | 2 participants | 0 participants | 3 participants | 12 participants |
| Sex/Gender, Customized Male, Part 2 | — | 2 participants | 3 participants | — | 2 participants | 7 participants |
| Sex/Gender, Customized Male, Part 3 | — | — | 7 participants | — | 8 participants | 15 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 | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 4 | 0 / 25 | 0 / 25 |
| other Total, other adverse events | 0 / 6 | 0 / 6 | 3 / 6 | 6 / 6 | 0 / 8 | 6 / 6 | 6 / 6 | 1 / 4 | 23 / 25 | 5 / 25 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 4 | 0 / 25 | 0 / 25 |
Outcome results
Primary
Part 3: Change in Diurnal IOP (Averaged Over 8 AM, 10 AM, Noon, 4 PM, and 8 PM) From Baseline to Day 8
IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in mmHg. Diurnal IOP was defined as the average of the five time points measured (8 AM, 10 AM, noon, 4 PM, and 8 PM). Baseline diurnal IOP was the average of IOP measurements obtained at the 2 eligibility visits. Change from baseline was calculated by taking the change at each time point from baseline to Day 8 and averaging the available changes. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. Only one eye (study eye) contributed to the analysis.
Time frame: Baseline, Day 8
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MGV354 0.1% | Part 3: Change in Diurnal IOP (Averaged Over 8 AM, 10 AM, Noon, 4 PM, and 8 PM) From Baseline to Day 8 | -0.6 mmHg | Standard Error 0.43 |
| Placebo | Part 3: Change in Diurnal IOP (Averaged Over 8 AM, 10 AM, Noon, 4 PM, and 8 PM) From Baseline to Day 8 | -1.1 mmHg | Standard Error 0.42 |
Primary
Part 3: Change in IOP From Baseline to Day 8 at 8 AM, 10 AM, Noon, 4 PM, and 8 PM
IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in mmHg. Baseline IOP was the average of IOP measurements obtained at the 2 eligibility visits. Change from baseline was calculated by taking the change at each time point from baseline to Day 8. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. Only one eye (study eye) contributed to the analysis.
Time frame: Baseline, Day 8
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| MGV354 0.1% | Part 3: Change in IOP From Baseline to Day 8 at 8 AM, 10 AM, Noon, 4 PM, and 8 PM | Change from BL at 10 AM | -0.4 mmHg | Standard Error 0.57 |
| MGV354 0.1% | Part 3: Change in IOP From Baseline to Day 8 at 8 AM, 10 AM, Noon, 4 PM, and 8 PM | Change from BL at 4 PM | -1.2 mmHg | Standard Error 0.57 |
| MGV354 0.1% | Part 3: Change in IOP From Baseline to Day 8 at 8 AM, 10 AM, Noon, 4 PM, and 8 PM | Change from BL at noon | -0.2 mmHg | Standard Error 0.57 |
| MGV354 0.1% | Part 3: Change in IOP From Baseline to Day 8 at 8 AM, 10 AM, Noon, 4 PM, and 8 PM | Change from BL at 8 PM | -1.1 mmHg | Standard Error 0.57 |
| MGV354 0.1% | Part 3: Change in IOP From Baseline to Day 8 at 8 AM, 10 AM, Noon, 4 PM, and 8 PM | Change from Baseline (BL) at 8 AM | 0.1 mmHg | Standard Error 0.57 |
| Placebo | Part 3: Change in IOP From Baseline to Day 8 at 8 AM, 10 AM, Noon, 4 PM, and 8 PM | Change from BL at 8 PM | -0.7 mmHg | Standard Error 0.56 |
| Placebo | Part 3: Change in IOP From Baseline to Day 8 at 8 AM, 10 AM, Noon, 4 PM, and 8 PM | Change from Baseline (BL) at 8 AM | -1.5 mmHg | Standard Error 0.56 |
| Placebo | Part 3: Change in IOP From Baseline to Day 8 at 8 AM, 10 AM, Noon, 4 PM, and 8 PM | Change from BL at 10 AM | -1.5 mmHg | Standard Error 0.56 |
| Placebo | Part 3: Change in IOP From Baseline to Day 8 at 8 AM, 10 AM, Noon, 4 PM, and 8 PM | Change from BL at noon | -0.2 mmHg | Standard Error 0.56 |
| Placebo | Part 3: Change in IOP From Baseline to Day 8 at 8 AM, 10 AM, Noon, 4 PM, and 8 PM | Change from BL at 4 PM | -1.4 mmHg | Standard Error 0.56 |
Secondary
Part 1: Area Under the Concentration-time Curve From 0 to Infinity [AUCinf (ng*h/mL)]
Based on plasma samples collected at pre-determined nominal time points, dependent on observed concentrations. Approximately 2 mL of venous blood was to be collected at each time point.
Time frame: Pre-dose to 120 hours post-dose
Population: Due to the low exposure and the limit of LLOQ (0.05 ng/mL), none of the observed individual profiles could generate valid AUCinf.
Secondary
Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to 120 Hours Post Dose [AUC0-120 (ng*h/mL)]
Based on plasma samples collected at pre-determined nominal time points, dependent on observed concentrations. Approximately 2 mL of venous blood was to be collected at each time point.
Time frame: Pre-dose to 120 hours post-dose
Population: Due to the low exposure and the limit of the lower limit of quantitation (LLOQ) (0.05 ng/mL), none of the observed individual profiles could generate valid AUC0-120.
Secondary
Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUClast (ng*h/mL)]
Based on plasma samples collected at pre-determined nominal time points, dependent on observed concentrations. Approximately 2 mL of venous blood was collected at each time point. AUClast is reported as mass\*time/volume.
Time frame: Pre-dose, .5, 2, 4, 6, 12, 24, 48, 72, 96, 120 hours post-dose, and Day 7 post-dose
Population: PK Analysis Set. Number Analyzed is the number of subjects with data at visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MGV354 0.1% | Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUClast (ng*h/mL)] | 0.213 ng*h/mL | Standard Deviation 0.336 |
| Placebo | Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUClast (ng*h/mL)] | 0.157 ng*h/mL | Standard Deviation 0.043 |
| MGV354 0.3% | Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUClast (ng*h/mL)] | 1.611 ng*h/mL | Standard Deviation 1.484 |
Secondary
Part 1: Maximum Observed Concentration [Cmax (ng/mL)]
Based on plasma samples collected at pre-determined nominal time points, dependent on observed concentrations. Approximately 2 mL of venous blood was collected at each time point. Cmax is reported as mass/volume.
Time frame: Pre-dose, .5, 2, 4, 6, 12, 24, 48, 72, 96, 120 hours post-dose, and Day 7 post-dose
Population: This analysis population includes all subjects who received IP, had at least 1 plasma sample following exposure to non-placebo IP and had no known specimen collection or analytical deviations which would affect the integrity of the data (Pharmacokinetic (PK) Analysis Set). Number Analyzed is the number of subjects with data at visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MGV354 0.1% | Part 1: Maximum Observed Concentration [Cmax (ng/mL)] | 0.073 ng/mL | Standard Deviation 0.013 |
| Placebo | Part 1: Maximum Observed Concentration [Cmax (ng/mL)] | 0.098 ng/mL | Standard Deviation 0.032 |
| MGV354 0.3% | Part 1: Maximum Observed Concentration [Cmax (ng/mL)] | 0.327 ng/mL | Standard Deviation 0.178 |
Secondary
Part 1: Terminal Elimination Half-life [t1/2 (h)]
Based on plasma samples collected at pre-determined nominal time points, dependent on observed concentrations. Approximately 2 mL of venous blood was to be collected at each time point.
Time frame: Pre-dose to 120 hours post-dose
Population: Due to the low exposure and the limit of LLOQ (0.05 ng/mL), none of the observed individual profiles could generate valid t1/2.
Secondary
Part 1: Time to Reach Maximum Concentration [Tmax (h)]
Based on plasma samples collected at pre-determined nominal time points, dependent on observed concentrations. Approximately 2 mL of venous blood was collected at each time point.
Time frame: Pre-dose, .5, 2, 4, 6, 12, 24, 48, 72, 96, 120 hours post-dose, and Day 7 post-dose
Population: PK Analysis Set. Number Analyzed is the number of subjects with data at visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MGV354 0.1% | Part 1: Time to Reach Maximum Concentration [Tmax (h)] | 0.483 hours |
| Placebo | Part 1: Time to Reach Maximum Concentration [Tmax (h)] | 0.559 hours |
| MGV354 0.3% | Part 1: Time to Reach Maximum Concentration [Tmax (h)] | 0.575 hours |
Secondary
Part 2: Accumulation Ratio (Racc)
Accumulation Ratio was derived using Cmax on Day 7 versus Cmax on Day 1. Approximately 2 mL of venous blood was collected at each time point.
Time frame: Day 7
Population: PK Analysis Set. Number Analyzed is the number of subjects with data at visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MGV354 0.1% | Part 2: Accumulation Ratio (Racc) | 1.893 ng/mL | Standard Deviation 1.038 |
| Placebo | Part 2: Accumulation Ratio (Racc) | 1.391 ng/mL | Standard Deviation 0.366 |
Secondary
Part 2: Area Under the Concentration-time Curve From 0 to the End of the Dosing Interval Tau [AUCtau (ng*h/mL)]
Based on plasma samples collected at pre-determined nominal time points, dependent on observed concentrations. Approximately 2 mL of venous blood was collected at each time point. AUCtau is reported as mass\*time/volume.
Time frame: Up to Day 7
Population: PK Analysis Set. Number Analyzed is the number of subjects with data at visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MGV354 0.1% | Part 2: Area Under the Concentration-time Curve From 0 to the End of the Dosing Interval Tau [AUCtau (ng*h/mL)] | Day 7 | 0.392 ng*h/mL | Standard Deviation 0.444 |
| Placebo | Part 2: Area Under the Concentration-time Curve From 0 to the End of the Dosing Interval Tau [AUCtau (ng*h/mL)] | Day 1 | 0.723 ng*h/mL | — |
| Placebo | Part 2: Area Under the Concentration-time Curve From 0 to the End of the Dosing Interval Tau [AUCtau (ng*h/mL)] | Day 7 | 1.461 ng*h/mL | Standard Deviation 1.043 |
Secondary
Part 2: Maximum Observed Concentration [Cmax (ng/mL)]
Based on plasma samples collected at pre-determined nominal time points, dependent on observed concentrations. Approximately 2 mL of venous blood was collected at each time point. Cmax is reported as mass/volume.
Time frame: Up to Day 7
Population: PK Analysis Set. Number Analyzed is the number of subjects with data at visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MGV354 0.1% | Part 2: Maximum Observed Concentration [Cmax (ng/mL)] | Day 1 | 0.077 ng/mL | Standard Deviation 0.026 |
| MGV354 0.1% | Part 2: Maximum Observed Concentration [Cmax (ng/mL)] | Day 7 | 0.132 ng/mL | Standard Deviation 0.054 |
| Placebo | Part 2: Maximum Observed Concentration [Cmax (ng/mL)] | Day 1 | 0.139 ng/mL | Standard Deviation 0.034 |
| Placebo | Part 2: Maximum Observed Concentration [Cmax (ng/mL)] | Day 7 | 0.188 ng/mL | Standard Deviation 0.07 |
Secondary
Part 2: Time to Reach Maximum Concentration [Tmax (h)]
Based on plasma samples collected at pre-determined nominal time points, dependent on observed concentrations. Approximately 2 mL of venous blood was collected at each time point.
Time frame: Up to Day 7
Population: PK Analysis Set. Number Analyzed is the number of subjects with data at visit.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| MGV354 0.1% | Part 2: Time to Reach Maximum Concentration [Tmax (h)] | Day 1 | 0.533 hours |
| MGV354 0.1% | Part 2: Time to Reach Maximum Concentration [Tmax (h)] | Day 7 | 0.550 hours |
| Placebo | Part 2: Time to Reach Maximum Concentration [Tmax (h)] | Day 1 | 0.567 hours |
| Placebo | Part 2: Time to Reach Maximum Concentration [Tmax (h)] | Day 7 | 0.533 hours |
Secondary
Part 3: Change From Baseline in IOP at 36 Hours and 48 Hours Post Day 7 Administration
IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in mmHg. Baseline IOP was the average of IOP measurements obtained at the 2 eligibility visits. Change from baseline was calculated by taking the change at each time point from baseline to Day 8 and averaging the available changes. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. Only one eye (study eye) contributed to the analysis.
Time frame: Baseline, up to Day 9
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MGV354 0.1% | Part 3: Change From Baseline in IOP at 36 Hours and 48 Hours Post Day 7 Administration | Change from Baseline at 36 hours post Day 7 dose | -1.58 mmHg | Standard Deviation 3.574 |
| MGV354 0.1% | Part 3: Change From Baseline in IOP at 36 Hours and 48 Hours Post Day 7 Administration | Change from Baseline at 48 hours post Day 7 dose | -1.39 mmHg | Standard Deviation 3.282 |
| Placebo | Part 3: Change From Baseline in IOP at 36 Hours and 48 Hours Post Day 7 Administration | Change from Baseline at 36 hours post Day 7 dose | -1.09 mmHg | Standard Deviation 2.209 |
| Placebo | Part 3: Change From Baseline in IOP at 36 Hours and 48 Hours Post Day 7 Administration | Change from Baseline at 48 hours post Day 7 dose | -0.12 mmHg | Standard Deviation 2.541 |
Secondary
Part 3: Observed Concentration at 12 Hours Following Drug Administration [C12 (ng/mL)]
Based on plasma samples collected at pre-determined nominal time points, dependent on observed concentrations. Approximately 2 mL of venous blood was collected at each time point. C12 is reported as mass/volume.
Time frame: Up to Day 8
Population: PK Analysis Set. Number Analyzed is the number of subjects with data at visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MGV354 0.1% | Part 3: Observed Concentration at 12 Hours Following Drug Administration [C12 (ng/mL)] | Day 2 | 0.0881 ng/mL | Standard Deviation 0.03964 |
| MGV354 0.1% | Part 3: Observed Concentration at 12 Hours Following Drug Administration [C12 (ng/mL)] | Day 8 | 0.1488 ng/mL | Standard Deviation 0.11026 |