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

NCT ID: NCT01821677

Last Updated: 2022-10-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 354 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-26
• Study Completion Date: 2015-01-23

Brief Summary

This study will evaluate the efficacy of ultra low dose danazol (Optina™) for the treatment of diabetic macular edema.

Detailed Description

A Randomized, Placebo-Controlled, Parallel, Double-Masked Study to Evaluate the Efficacy and Safety of Two Doses of Oral Optina™ in Adult Patients With Diabetic Macular Edema.

The primary trial objective is to evaluate the efficacy of two oral BMI-related doses (0.5 mg per body mass index (BMI), 1.0 mg per BMI per day) of Optina™ in improving visual acuity (VA) compared to placebo.

The secondary objectives are to evaluate the efficacy of two oral BMI-related doses of Optina™ on change in central macular thickness (CMT) and VA responder status compared to placebo, and to assess the safety and tolerability of two oral BMI-related doses of Optina™ compared to placebo.

Conditions

Diabetic Macular Edema

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Low Dose Danazol

Capsules, 0.5 mg/BMI Danazol with dose determined by subject's BMI at baseline, 2 capsules (5 mg, 7.5 mg, or 10 mg) twice daily, for 12 weeks.

Group Type: EXPERIMENTAL

Danazol Capsules

Intervention Type: DRUG

High Dose Danazol

Capsules, 1.0 mg/BMI Danazol with dose determined by subject's BMI at baseline, 2 capsules (5 mg, 7.5 mg, or 10 mg) twice daily, for 12 weeks.

Group Type: EXPERIMENTAL

Danazol Capsules

Intervention Type: DRUG

Placebo

Gelatin capsules, identical in appearance to the active capsules, filled with pharmaceutical grade lactose and magnesium stearate.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

Danazol Capsules

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

Optina; Cyclomen; Danocrine

Eligibility Criteria

Inclusion Criteria

1. Subject is willing and able to provide informed consent for study participation

2. 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)]

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: 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

4. 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

6. 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)

1. Change in VA within previous 12 months reasonably believed to be associated with diabetic macular edema (DME) in the opinion of the Investigator

2. 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)

3. 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

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

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

Exclusion Criteria

1. 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)

2. Known allergy to any component of the placebo test drug (lactose, magnesium stearate, and gelatin)

3. 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)

4. 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)

5. HbA1c greater than 11% or consistent HbA1c values in a similar range for the last 6 months.

6. Carcinoma of the breast

7. Prostate cancer

8. Androgen-dependent tumor

9. Undiagnosed abnormal genital bleeding

10. Genital neoplasia

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

12. 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)

13. 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)

14. Use of any hormonal therapies including hormone replacement therapy (HRT) 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)

15. 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

16. 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.

17. Significant hepatic disease (defined as aspartate aminotransferase, alanine aminotransferase or alkaline phosphatase [ALP], more than twice the upper limit of normal) where, in the opinion of the Investigator, danazol might be contraindicated

18. Significant renal disease (defined as serum creatinine ≥ 2.5 mg/dl, history of renal transplant, or undergoing dialysis at screening) where, in the opinion of the Investigator, danazol might be contraindicated

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

20. 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

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

22. 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

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

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

2. An ocular condition is present such that, in the opinion of the Investigator, VA 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 VA 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 8 weeks (such as focal/grid macular photocoagulation, intravitreal or peribulbar corticosteroids, anti-vascular endothelial growth factor [VEGF drugs], or any other treatment). Note, the 28-day screening period allows subjects to be screened at 4 weeks post DME treatment and have a baseline visit 28 days later.

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 aluminum garnet (YAG) capsulotomy performed within 2 months prior to randomization

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

10. Aphakia

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Ampio Pharmaceuticals. Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Howard Levy, M.D.

Role: STUDY_DIRECTOR

Ampio Pharmaceuticals. Inc.

References

Bar-Or D, Orlando A, Singer M; danazol study group. Potential beneficial effect of low-dose danazol in combination with renin-angiotensin system inhibitors in diabetic macular oedema. Acta Ophthalmol. 2017 Nov;95(7):e665-e667. doi: 10.1111/aos.13318. Epub 2016 Nov 19. No abstract available.

Reference Type: RESULT

PMID: 27864867 (View on PubMed)

Other Identifiers

AP-05-002

Identifier Type: -

Identifier Source: org_study_id