A Safety and Efficacy Study of Oral Danazol (a Previously Approved Drug) in the Treatment of Diabetic Macular Edema.

Study Level Inclusion Criteria:

• Subject is willing and able to provide informed consent for study participation
• Male or female 18 years or older with Type 1 or 2 diabetes mellitus [defined as a self-report of diabetes accompanied by treatment (insulin or diet) or a history of fasting plasma glucose ≥ 7.0 mmo/l (126 mg/dl) or 2-hr plasma glucose ≥ 11.1 mmo/l (200 mg/dl)]
• Female subjects of childbearing potential must have a negative pregnancy test within 7 days prior to randomization and must agree to utilize a reliable form of effective contraception (hormonal or barrier method; abstinence) throughout the study and for 90 days after the last dose of study medication. Childbearing potential is defined as women who have had menses within the past 12 months, who have not had tubal ligation or bilateral oophorectomy [Note: patients using contraceptive methods containing progesterone (including a progesterone IUD) for 90 days prior to randomization or planning to use progesterone contraceptive methods (including a progesterone IUD) during the study drug treatment period are not eligible for enrollment.] Should a woman become pregnant or suspect that she is pregnant while participating in this study, she should inform her treating physician immediately
• Enrollment in this study is contraindicated for pregnant or lactating women. Thus, female patients who are postmenopausal without a menstrual period for ≥ 12 months, surgical sterility, not pregnant and not breast feeding for 90 days prior to randomization can be enrolled
• At least one eye meets the study eye criteria for inclusion in the study (see Study Eye Inclusion Criteria, below)
• Stable diabetic and metabolic control (no major changes in diabetic or lipid reducing medications for 3 months prior to start of this study as determined by the Investigator)

Study Eye Inclusion Criteria (if both eyes meet criteria, both eyes will be study eyes)

• Change in VA within previous 12 months reasonably believed to be associated with diabetic macular edema (DME) in the opinion of the Investigator
• Best-corrected visual acuity (BCVA) in accordance with early treatment diabetic retinopathy study (ETDRS) letter score of ≥24 (e.g., 20/320 or better) and ≤78 (e.g., 20/32 or worse)
• Definite retinal thickening ≥275 microns on spectral-domain optical coherence tomography (OCT) due to DME involving the center of the macula on clinical exam in the opinion of the Investigator
• Media clarity, pupillary dilation, and patient cooperation sufficient for adequate fundus photographs
• Assessment by the Investigator that focal photocoagulation can be deferred safely for 16 weeks

Study Level Exclusion Criteria:

• Known allergy to any danazol (Cyclomen® or Danocrine®) or any other non-medicinal component of the danazol test drug (cornstarch, lactose, magnesium stearate, gelatin, and talc) (Note: Lactose intolerance is not a contraindication to ingesting the small amount of lactose contained in oral medications)
• Known allergy to any component of the placebo test drug (lactose, magnesium stearate, and gelatin)
• History of systemic (e.g., oral, intravenous, intramuscular, subcutaneous, intra-uterine, epidural, bursal, or implanted) androgens, progesterone or corticosteroids (including topical ophthalmic corticosteroids preparations within 4 months prior to randomization (topical non-ophthalmic corticosteroids are not excluded)
• Blood pressure >180/110 mm Hg (in cases where either or both of the systolic or diastolic limits are exceeded, blood pressure can be re-measured after 10 minutes rest period for inclusion in the study)
• HbA1c greater than 11% or consistent HbA1c values in a similar range for the last 6 months.
• Carcinoma of the breast
• Prostate cancer
• Androgen-dependent tumor
• Undiagnosed abnormal genital bleeding
• Genital neoplasia
• Currently taking warfarin (coumadin), carbamazepine, phenytoin, phenobarbital cyclosporin or tacrolimus
• Females who ar