Clinical trial NCT02002403 (phase 2, status: completed)
Conditions: diabetic macular edema
ICD codes: E10.311, E10.319, E11.311, E11.319, E13.311, E13.319, E10.3513
Drugs: danazol
SMILES: [H][C@@]12CC[C@@](O)(C#C)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CCC2=CC3=C(C[C@]12C)C=NO3
Eligibility criteria:

        Inclusion Criteria:

          1. Patient has provided informed consent

          2. Male or female 18 years or older with Type 1 or 2 diabetes mellitus [defined as a
             selfreport of diabetes accompanied by treatment (insulin or diet) or a history of
             fasting plasma glucose ≥ 7.0mmo/l (126mg/dl) or 2-hr plasma glucose ≥11.1mmo/l
             (200mg/dl)]

          3. 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: subjects 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.

          4. Enrollment in this study is contraindicated for pregnant or lactating women. Thus,
             female subjects 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.

          5. At least one eye meets the study eye criteria for inclusion in the study (see Study
             Eye Inclusion Criteria, below)

          6. HbA1c less than or equal to 10%

          7. 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)

          8. Blood pressure ≤160/90 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)

        Study Eye Inclusion Criteria:

          1. Best corrected Early Treatment Retinopathy Study (ETDRS) visual acuity letter score of
             ≥24 (i.e., 20/320 or better) and ≤78 (i.e., 20/32 or worse) within 28 days of
             randomization

          2. Definite retinal thickening due to diabetic macular edema involving the center of the
             macula on clinical exam in the opinion of the Investigator

          3. Spectral-domain optical coherence tomography (OCT) central subfield ≥300 microns
             within 28 days of randomization

          4. Media clarity, pupillary dilation, and subject cooperation sufficient for adequate
             fundus photographs

          5. Assessment by the treating ophthalmologist that focal photocoagulation can be deferred
             safely for 16 weeks

          6. Fellow eyes meeting these criteria at enrollment may also be designated "study eyes";
             thus, some patients will have two study eyes and other patients will only have one
             study eye

        Exclusion Criteria:

        Study level exclusions:

          1. Known allergy to any danazol (Cyclomen® or Danocrine®, Sanofi-Aventis) or any other
             non-medicinal component of the danazol test drug (cornstarch, red iron oxide, black
             iron oxide, gelatin, lactose, magnesium stearate, talc and titanium dioxide). Note:
             lactose intolerance is not a contraindication to ingesting the small amount of lactose
             contained in oral medications.

          2. History of systemic (e.g., oral, intra-venous, intra-muscular, sub-cutaneous,
             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 an
             exclusion.

          3. Carcinoma of the breast

          4. Prostate cancer

          5. Androgen-dependent tumor

          6. Undiagnosed abnormal genital bleeding

          7. Genital neoplasia

          8. Currently taking warfarin (coumadin), carbamazepine, phenytoin, phenobarbital
             cyclosporin or tacrolimus

          9. Females who are pregnant or planning pregnancy in the 6 month period after
             randomization. [Note: Enrollment in this study is contraindicated for pregnant or
             lactating women]

         10. Females breast feeding or breast feeding in the 90 days prior to randomization [Note:
             Enrollment in this study is contraindicated for pregnant or lactating women]

         11. Use of any hormonal therapies including Hormone Replacement Therapy and contraceptive
             medications that contain progesterone within 3 months before randomization (NOTE:
             patients on pure estrogen or estradiol replacement therapy can be enrolled in the
             study)

         12. Unstable cardiovascular disease or a history of significant heart disease (including
             unstable angina, acute coronary syndrome, myocardial infarction, or history of
             coronary revascularization procedure) within 6 months before randomization

         13. Any condition that, in the opinion of the investigator, would preclude participation
             in the study (e.g., unstable medical status including blood pressure and glycemic
             control). Patients in poor glycemic control who, within the last 3 months, using a new
             type of insulin (for example, changing to or adding a short acting insulin from a
             longer-acting insulin), or increased the daily dose ≥50%, initiated intensive insulin
             treatment such as an insulin pump or additional daily injections or plan to do so in
             the next 3 months should not be enrolled

         14. Significant hepatic disease (defined as aspartate aminotransferase, alanine
             aminotransferase or alkaline phosphatase, more than twice the upper limit of normal)

         15. Renal disease (defined as serum creatinine ≥2.5 mg/dl, history of renal transplant, or
             undergoing dialysis at screening)

         16. Changes in anti-hypertensive medication within 3 months before randomization (except
             for dosage adjustments that are considered minor in the opinion of the Investigator)

         17. Major surgery (e.g. head and neck, chest, abdomen, gastrointestinal, genitourinary or
             central nervous system) within past 28 days or anticipated in the next 6 months

         18. History of acute intermittent porphyria, any thrombosis or thromboembolic disease or
             pseudotumor cerebri

         19. Participation in an investigational trial within 30 days of study entry that involved
             treatment with any drug that has not received regulatory approval at the time of study
             entry

         20. Patient is expecting to move out of the area of the clinical center during the next 6
             months

        Study eye exclusions:

          1. Macular edema considered to be due to a cause other than diabetic macular edema, e.g.,
             cataract extraction, vitreous-retinal interface disease (a taut posterior hyaloid or
             epiretinal membrane)

          2. An ocular condition is present such that, in the opinion of the investigator, visual
             acuity would not improve from resolution of macular edema (e.g., foveal atrophy,
             closure of juxtafoveal capillaries, dense subfoveal hard exudates)

          3. An ocular condition (other than diabetic retinopathy) that, in the opinion of the
             investigator, might affect macular edema or alter visual acuity during the course of
             the study, e.g., vein occlusion, uveitis or other ocular inflammatory disease,
             Irvine-Gass Syndrome, etc.

          4. Substantial cataract that, in the opinion of the investigator, is likely to interfere
             with ocular measurements or evaluations during this study

          5. History of treatment for DME at any time in the past 3 months (such as focal/grid
             macular photocoagulation, intravitreal or peribulbar corticosteroids, anti-vascular
             endothelial growth factor (VEGF) drugs, or any other treatment)

          6. History of panretinal scatter photocoagulation (PRP) within 4 months prior to
             randomization or anticipated need for PRP in the 6 months following randomization

          7. History of major ocular surgery (including cataract extraction, scleral buckle, any
             intraocular surgery, etc.) within prior 6 months or anticipated within the next 6
             months following randomization

          8. History of yttrium argon yttrium aluminum garnet (YAG) capsulotomy performed within 2
             months prior to randomization

          9. Uncontrolled glaucoma (in investigator's judgment) in the study eye

         10. Aphakia