Squalamine Lactate Eye Drops in Combination With Ranibizumab in Patients With Diabetic Macular Edema (DME)

A randomized, controlled study of the safety and efficacy of Squalamine Lactate eye drops in
combination with Ranibizumab intravitreal injections in patients with diabetic macular
edema. Subjects will be randomized to one of the following treatment arms:

1. Squalamine Lactate Ophthalmic Solution administered twice a day for 52 weeks in
combination with monthly injections of ranibizumab from baseline through week 20 and
ranibizumab as needed from week 24 through week 52.

2. Vehicle Ophthalmic Solution administered twice a day for 52 weeks in combination with
monthly injection of ranibizumab from baseline through week 20 and ranibizumab as
needed from week 24 through week 52.

3. Squalamine Lactate Ophthalmic Solution administered four times a day for 52 weeks in
combination with monthly injections of ranibizumab from baseline through week 20 and
ranibizumab as needed from week 24 through week 52.

4. Vehicle Ophthalmic Solution administered four times a day for 52 weeks in combination
with monthly injection of ranibizumab from baseline through week 20 and ranibizumab as
needed from week 24 through week 52.

Inclusion Criteria:

- Subjects will have clinically significant diabetic macular edema of ≥ 300 microns
with central involvement using the Heidelberg or Cirrus machine

- Best corrected visual acuity of 20/32 to 20/320 inclusive in the study eye

- Adults ≥ 18 years of age with type 1 or 2 diabetes mellitus with diabetic macular
edema

Exclusion Criteria:

- History of vitreoretinal surgery in the study eye

- Panretinal laser photocoagulation or macular laser photocoagulation in the study eye
within 3 months of screening

- Any prior laser in study eye

- Previous use of intraocular or periocular corticosteroids in the study eye within 6
months of screening

- Previous treatment with anti-angiogenic drugs in either eye within 3 months of
screening

- Uncontrolled diabetes mellitus with HbA1c levels greater than 12

- Ocular disorders in the study eye, other than diabetic macular edema, that my
confound interpretation of study results