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A Three Part Study of MGV354 in Ocular Hypertension or Glaucoma

Primary Purpose

Ocular Hypertension, Open-Angle Glaucoma

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
MGV354 ophthalmic suspension
MGV354 placebo
Sponsored by
Alcon Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Ocular Hypertension focused on measuring Ocular Hypertension, Open-Angle Glaucoma, POAG, Glaucoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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 exclusion criteria may apply.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    MGV354

    Placebo

    Arm Description

    Part 3: MGV354 ophthalmic suspension, 1 drop in both eyes once per day for 7 days

    Part 3: MGV354 placebo, 1 drop in both eyes once per day for 7 days

    Outcomes

    Primary Outcome Measures

    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.
    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.

    Secondary Outcome Measures

    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.

    Full Information

    First Posted
    April 14, 2016
    Last Updated
    May 31, 2018
    Sponsor
    Alcon Research
    Collaborators
    Novartis Institute for BioMedical Research
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02743780
    Brief Title
    A Three Part Study of MGV354 in Ocular Hypertension or Glaucoma
    Official Title
    A Three Part, First-in-human, Randomized, Double-masked, Placebo-Controlled, Safety, Tolerability and Early Efficacy Study of MGV354 in Healthy Subjects and in Patients With Ocular Hypertension or Glaucoma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2017
    Overall Recruitment Status
    Completed
    Study Start Date
    March 2, 2016 (Actual)
    Primary Completion Date
    September 20, 2016 (Actual)
    Study Completion Date
    September 20, 2016 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Alcon Research
    Collaborators
    Novartis Institute for BioMedical Research

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Ocular Hypertension, Open-Angle Glaucoma
    Keywords
    Ocular Hypertension, Open-Angle Glaucoma, POAG, Glaucoma

    7. Study Design

    Primary Purpose
    Other
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    191 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    MGV354
    Arm Type
    Experimental
    Arm Description
    Part 3: MGV354 ophthalmic suspension, 1 drop in both eyes once per day for 7 days
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Part 3: MGV354 placebo, 1 drop in both eyes once per day for 7 days
    Intervention Type
    Drug
    Intervention Name(s)
    MGV354 ophthalmic suspension
    Intervention Type
    Drug
    Intervention Name(s)
    MGV354 placebo
    Intervention Description
    Inactive ingredients used as placebo comparator
    Primary Outcome Measure Information:
    Title
    Part 3: Change in Diurnal IOP (Averaged Over 8 AM, 10 AM, Noon, 4 PM, and 8 PM) From Baseline to Day 8
    Description
    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
    Title
    Part 3: Change in IOP From Baseline to Day 8 at 8 AM, 10 AM, Noon, 4 PM, and 8 PM
    Description
    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
    Secondary Outcome Measure Information:
    Title
    Part 3: Change From Baseline in IOP at 36 Hours and 48 Hours Post Day 7 Administration
    Description
    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
    Title
    Part 1: Maximum Observed Concentration [Cmax (ng/mL)]
    Description
    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
    Title
    Part 1: Time to Reach Maximum Concentration [Tmax (h)]
    Description
    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
    Title
    Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUClast (ng*h/mL)]
    Description
    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
    Title
    Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to 120 Hours Post Dose [AUC0-120 (ng*h/mL)]
    Description
    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
    Title
    Part 1: Area Under the Concentration-time Curve From 0 to Infinity [AUCinf (ng*h/mL)]
    Description
    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
    Title
    Part 1: Terminal Elimination Half-life [t1/2 (h)]
    Description
    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
    Title
    Part 2: Maximum Observed Concentration [Cmax (ng/mL)]
    Description
    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
    Title
    Part 2: Time to Reach Maximum Concentration [Tmax (h)]
    Description
    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
    Title
    Part 2: Area Under the Concentration-time Curve From 0 to the End of the Dosing Interval Tau [AUCtau (ng*h/mL)]
    Description
    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
    Title
    Part 2: Accumulation Ratio (Racc)
    Description
    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
    Title
    Part 3: Observed Concentration at 12 Hours Following Drug Administration [C12 (ng/mL)]
    Description
    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

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    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 exclusion criteria may apply.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Clinical Science Expert, NIBR
    Organizational Affiliation
    Novartis Institute for BioMedical Research
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    29802818
    Citation
    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.
    Results Reference
    derived

    Learn more about this trial

    A Three Part Study of MGV354 in Ocular Hypertension or Glaucoma

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