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| Name | Class |
|---|---|
| Novartis Institutes for BioMedical Research | OTHER |
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MGV354 | Experimental | Part 3: MGV354 ophthalmic suspension, 1 drop in both eyes once per day for 7 days |
|
| Placebo | Placebo Comparator | Part 3: MGV354 placebo, 1 drop in both eyes once per day for 7 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MGV354 ophthalmic suspension | Drug |
| ||
| MGV354 placebo |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline, Day 8 |
| 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. | Baseline, Day 8 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Science Expert, NIBR | Novartis Institutes for BioMedical Research | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29802818 | Derived | Stacy R, Huttner K, Watts J, Peace J, Wirta D, Walters T, Sall K, Seaman J, Ni X, Prasanna G, Mogi M, Adams C, Yan JH, Wald M, He Y, Newton R, Kolega R, Grosskreutz C. A Randomized, Controlled Phase I/II Study to Evaluate the Safety and Efficacy of MGV354 for Ocular Hypertension or Glaucoma. Am J Ophthalmol. 2018 Aug;192:113-123. doi: 10.1016/j.ajo.2018.05.015. Epub 2018 May 24. |
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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.
Subjects were recruited from 5 study centers located in the US.
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| ID | Title | Description |
|---|---|---|
| FG000 | MGV354 0.01% | MGV354 ophthalmic suspension 0.01%, 1 drop in the study eye (Part 1) |
| FG001 | 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) |
| FG002 | 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) |
| FG003 | MGV354 0.3% | MGV354 ophthalmic suspension 0.3%, 1 drop in the study eye (Part 1) |
| FG004 | Placebo | Placebo, 1 drop in the study eye (Part 1); 1 drop in each eye for 7 days (Part 2 and Part 3) |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1 (3 Days) |
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| Part 2 (8 Days) |
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| Part 3 (7 Days) |
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This analysis population includes all randomized subjects who received at least one on-treatment measurement of IOP (Full Analysis Set).
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| ID | Title | Description |
|---|---|---|
| BG000 | MGV354 0.01% | MGV354 ophthalmic suspension 0.01%, 1 drop in the study eye (Part 1) |
| BG001 | 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) |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | This study was conducted in 3 parts. |
| 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 | 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. | Full Analysis Set | Posted | Least Squares Mean | Standard Error | mmHg | Baseline, Day 8 |
|
Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (Part 1: up to 37 days, Part 2: up to 50 days, and Part 3: up to 59 days).
AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol. This analysis population includes all subjects exposed to investigational product (Safety Analysis Set).
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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 | MGV354 0.01% Part 1 | 1 drop in the study eye | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Conjunctival hyperaemia | Eye disorders | MedDRA (18.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Translational Medicine Expert II, TM-Ophthalmic | Alcon, A Novartis Division | 1-888-451-3937 | alcon.medinfo@alcon.com |
| ID | Term |
|---|---|
| D009798 | Ocular Hypertension |
| D005902 | Glaucoma, Open-Angle |
| D005901 | Glaucoma |
| ID | Term |
|---|---|
| D005128 | Eye Diseases |
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Inactive ingredients used as placebo comparator |
|
| Baseline, up to Day 9 |
| 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. | Pre-dose, .5, 2, 4, 6, 12, 24, 48, 72, 96, 120 hours post-dose, and Day 7 post-dose |
| 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. | Pre-dose, .5, 2, 4, 6, 12, 24, 48, 72, 96, 120 hours post-dose, and Day 7 post-dose |
| 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. | Pre-dose, .5, 2, 4, 6, 12, 24, 48, 72, 96, 120 hours post-dose, and Day 7 post-dose |
| 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. | Pre-dose to 120 hours post-dose |
| 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. | Pre-dose to 120 hours post-dose |
| 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. | Pre-dose to 120 hours post-dose |
| 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. | Up to Day 7 |
| 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. | Up to Day 7 |
| 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. | Up to Day 7 |
| 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. | Day 7 |
| 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. | Up to Day 8 |
| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| BG002 | 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) |
| BG003 | MGV354 0.3% | MGV354 ophthalmic suspension 0.3%, 1 drop in the study eye (Part 1) |
| BG004 | Placebo | Placebo, 1 drop in the study eye (Part 1); 1 drop in each eye for 7 days (Part 2 and Part 3) |
| BG005 | Total | Total of all reporting groups |
| Mean |
| Standard Deviation |
| years |
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| Sex/Gender, Customized | This study was conducted in 3 parts. | Number | participants |
|
| Intraocular Pressure (IOP) | IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in millimeters mercury (mmHg). Only one eye (study eye) contributed to the analysis. | IOP analysis was pre-specified for Part 3 subjects only. | Mean | Standard Deviation | mmHg |
|
| OG001 | Placebo | Part 3: MGV354 placebo, 1 drop in each eye for 7 days |
|
|
| 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. | Full Analysis Set | Posted | Least Squares Mean | Standard Error | mmHg | Baseline, Day 8 |
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| 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. | Full Analysis Set | Posted | Mean | Standard Deviation | mmHg | Baseline, up to Day 9 |
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| 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. | 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. | Posted | Mean | Standard Deviation | ng/mL | Pre-dose, .5, 2, 4, 6, 12, 24, 48, 72, 96, 120 hours post-dose, and Day 7 post-dose |
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| 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. | PK Analysis Set. Number Analyzed is the number of subjects with data at visit. | Posted | Median | Full Range | hours | Pre-dose, .5, 2, 4, 6, 12, 24, 48, 72, 96, 120 hours post-dose, and Day 7 post-dose |
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| 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. | PK Analysis Set. Number Analyzed is the number of subjects with data at visit. | Posted | Mean | Standard Deviation | ng*h/mL | Pre-dose, .5, 2, 4, 6, 12, 24, 48, 72, 96, 120 hours post-dose, and Day 7 post-dose |
|
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| 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. | 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. | Posted | Pre-dose to 120 hours post-dose |
|
|
| 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. | Due to the low exposure and the limit of LLOQ (0.05 ng/mL), none of the observed individual profiles could generate valid AUCinf. | Posted | Pre-dose to 120 hours post-dose |
|
|
| 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. | 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. | Posted | Pre-dose to 120 hours post-dose |
|
|
| 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. | PK Analysis Set. Number Analyzed is the number of subjects with data at visit. | Posted | Mean | Standard Deviation | ng/mL | Up to Day 7 |
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| 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. | PK Analysis Set. Number Analyzed is the number of subjects with data at visit. | Posted | Median | Full Range | hours | Up to Day 7 |
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| 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. | PK Analysis Set. Number Analyzed is the number of subjects with data at visit. | Posted | Mean | Standard Deviation | ng*h/mL | Up to Day 7 |
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| 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. | PK Analysis Set. Number Analyzed is the number of subjects with data at visit. | Posted | Mean | Standard Deviation | ng/mL | Day 7 |
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| 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. | PK Analysis Set. Number Analyzed is the number of subjects with data at visit. | Posted | Mean | Standard Deviation | ng/mL | Up to Day 8 |
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| 6 |
| 0 |
| 6 |
| 0 |
| 6 |
| EG001 | MGV354 0.03% Part 1 | 1 drop in the study eye | 0 | 6 | 0 | 6 | 0 | 6 |
| EG002 | MGV354 0.1% Part 1 | 1 drop in the study eye | 0 | 6 | 0 | 6 | 3 | 6 |
| EG003 | MGV354 0.3% Part 1 | 1 drop in the study eye | 0 | 6 | 0 | 6 | 6 | 6 |
| EG004 | Placebo Part 1 | 1 drop in the study eye | 0 | 8 | 0 | 8 | 0 | 8 |
| EG005 | MGV354 0.03% Part 2 | 1 drop in each eye for 7 days | 0 | 6 | 0 | 6 | 6 | 6 |
| EG006 | MGV354 0.1% Part 2 | 1 drop in each eye for 7 days | 0 | 6 | 0 | 6 | 6 | 6 |
| EG007 | Placebo Part 2 | 1 drop in each eye for 7 days | 0 | 4 | 0 | 4 | 1 | 4 |
| EG008 | MGV354 0.1% Part 3 | 1 drop in each eye for 7 days | 0 | 25 | 0 | 25 | 23 | 25 |
| EG009 | Placebo Part 3 | 1 drop in each eye for 7 days | 0 | 25 | 0 | 25 | 5 | 25 |
| Conjunctival oedema | Eye disorders | MedDRA (18.0) | Systematic Assessment |
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| Conjunctival cyst | Eye disorders | MedDRA (18.0) | Systematic Assessment |
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| Dry eye | Eye disorders | MedDRA (18.0) | Systematic Assessment |
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| Eye pruritus | Eye disorders | MedDRA (18.0) | Systematic Assessment |
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| Eyelid oedema | Eye disorders | MedDRA (18.0) | Systematic Assessment |
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| Lacrimation increased | Eye disorders | MedDRA (18.0) | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
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| Ocular hyperaemia | Eye disorders | MedDRA (18.0) | Systematic Assessment |
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| Conjunctival haemorrhage | Eye disorders | MedDRA (18.0) | Systematic Assessment |
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| Eye irritation | Eye disorders | MedDRA (18.0) | Systematic Assessment |
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| Ocular discomfort | Eye disorders | MedDRA (18.0) | Systematic Assessment |
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Sponsor reserves the right of prior review of any publication or presentation of information related to the study.
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| Change from BL at noon |
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| Change from BL at 4 PM |
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| Change from BL at 8 PM |
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| Day 7 |
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| Day 7 |
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| Day 7 |
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