A Three Part Study of MGV354 in Ocular Hypertension or Glaucoma

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.

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.