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

NCT01821677 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: AP-05-002
• Study Type: interventional
• Target: 354
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Diabetic Macular Edema

Keywords

macular edema; diabetic

Outcome Measures

Primary Outcomes (1)

• Change in Best Corrected Visual Acuity (BCVA)

  Change from baseline score to the week 12 score in the number of letters read on an eye chart in accordance with Early Treatment Diabetic Retinopathy Study (ETDRS) of the Intent to Treat (ITT) population of all treated subjects. A positive number indicates more letters could be read.

  Determined at Baseline and Week 12

Secondary Outcomes (1)

• Change in Central Macular Thickness (CMT)

  Determined at Baseline and Week 12

Study Arms (3)

Low Dose Danazol

EXPERIMENTAL

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.

Drug: Danazol Capsules

High Dose Danazol

EXPERIMENTAL

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.

Drug: Danazol Capsules

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Danazol Capsules DRUG

Also known as: Optina, Cyclomen, Danocrine

High Dose Danazol; Low Dose Danazol

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)
• 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

You may not qualify if:

• 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)
• 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 are pregnant or planning pregnancy in the 6-month period after randomization (Note: Enrollment in this study is contraindicated for pregnant or lactating women)
• 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)
• 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)
• 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
• 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.

Sponsors & Collaborators

• Ampio Pharmaceuticals. Inc.: lead

Related Publications (1)

• 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.

  PMID: 27864867 RESULT

MeSH Terms

Conditions

Macular Edema

Interventions

Danazol

Condition Hierarchy (Ancestors)

Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Limitations and Caveats

The study may have been underpowered to detect a difference in certain endpoints in some arms.

Results Point of Contact

• Title: Dr. Howard Levy / Chief Medical Officer
• Organization: Ampio Pharmaceuticals

clinicaltrials@ampiopharma.com

720-437-6500

Study Officials

• Howard Levy, M.D.

  Ampio Pharmaceuticals. Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2013
• First Posted: April 1, 2013
• Study Start: February 26, 2013
• Primary Completion: October 30, 2014
• Study Completion: January 23, 2015
• Last Updated: October 10, 2022
• Results First Posted: October 10, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share