Diabetic Macular EdemaPhase 2NCT02002403
Efficacy and Safety Study to Evaluate Two Doses of Oral DMI-5207 in Adult Subjects With Diabetic Macular Edema
A Phase 2 study testing Danazol in people with Diabetic Macular Edema, run by Unity Health Toronto.
Trial summary
The drug being tested in this study is low doses of Optina (formerly known as Danazol) (DMI-5207) that may be an effective treatment for diabetic retinopathy and diabetic macular edema (DME). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Macular Edema
- What is being tested?
- Danazol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 34 participants
- Where
- No sites listed yet
- Study dates
- Jan 2011to Apr 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient has provided informed consent
- 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)]
- 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.
- 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.
- At least one eye meets the study eye criteria for inclusion in the study (see Study Eye Inclusion Criteria, below)
- HbA1c less than or equal to 10%
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- 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)
- 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:
- 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
- Definite retinal thickening due to diabetic macular edema involving the center of the macula on clinical exam in the opinion of the Investigator
- Spectral-domain optical coherence tomography (OCT) central subfield ≥300 microns within 28 days of randomization
- Media clarity, pupillary dilation, and subject cooperation sufficient for adequate fundus photographs
- Assessment by the treating ophthalmologist that focal photocoagulation can be deferred safely for 16 weeks
- 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
Who cannot join
- Study level exclusions:
- 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.
- 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.
- Carcinoma of the breast
- Prostate cancer
- Androgen-dependent tumor
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- 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 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
- Significant hepatic disease (defined as aspartate aminotransferase, alanine aminotransferase or alkaline phosphatase, more than twice the upper limit of normal)
- Renal disease (defined as serum creatinine ≥2.5 mg/dl, history of renal transplant, or undergoing dialysis at screening)
- Changes in anti-hypertensive medication within 3 months before randomization (except for dosage adjustments that are considered minor in the opinion of the Investigator)
- 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
- History of acute intermittent porphyria, any thrombosis or thromboembolic disease or pseudotumor cerebri
- 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
- Patient is expecting to move out of the area of the clinical center during the next 6 months
- Study eye exclusions:
- 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)
- 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)
- 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.
- Substantial cataract that, in the opinion of the investigator, is likely to interfere with ocular measurements or evaluations during this study
- 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)
- History of panretinal scatter photocoagulation (PRP) within 4 months prior to randomization or anticipated need for PRP in the 6 months following randomization
- 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
- History of yttrium argon yttrium aluminum garnet (YAG) capsulotomy performed within 2 months prior to randomization
- Uncontrolled glaucoma (in investigator's judgment) in the study eye
- Aphakia
About this study
Official title: A Randomized, Placebo-Controlled, Parallel Treatment Group, Double-Masked Study to Evaluate the Efficacy and Safety of Two Doses of Oral DMI-5207 in Adult Subjects With Diabetic Macular Edema
The drug being tested in this study is low doses of Optina (formerly known as Danazol) (DMI-5207) that may be an effective treatment for diabetic retinopathy and diabetic macular edema (DME). Laboratory studies have demonstrated that low doses of this drug may treat diabetic retinopathy and diabetic macular edema by two important ways, decreasing blood vessel permeability (related to leaking and edema) and by decreasing the formation of new leaky blood vessels. Optina is not approved by Health Canada for the treatment of diabetic macular edema but higher doses of Optina are approved by Health Canada for treatment of endometriosis (growth of cells similar to those that form inside of the womb that grows outside of the womb) and fibrocystic breast disease (a condition of the breast tissue). Higher doses of Optina have also been approved in the United States and many other countries since the mid-1970s in the treatment of men and women with hereditary angioedema (a disease which causes swelling in parts of the body) in addition to endometriosis and fibrocystic breast disease in women.
All of the Optina doses that will be used in the current study are less than half of the typical starting doses for the approved indications. This can be compared to "high-dose" aspirin that is used to treat, for example, headache, while low-dose "baby aspirin" is used to reduce blood clotting. Similarly, Optina has two different effects at high and low dose. The low doses for this study have been selected based on the laboratory studies mentioned above.
The purpose of this study is to investigate the safety and effectiveness of low doses of Optina in the treatment of macular edema due to diabetes, and also to test if it helps to slow the development of macular edema.
- Conditions
- Diabetic Macular Edema
- Being tested
- Danazol
- Keywords
- Edema, Macular Edema, Retinal Diseases, Eye Diseases, Danazol, Estrogen Antagonists, Estrogen Receptor Modulators, Hormone Antagonists, Hormones, Hormone Substitutes, and Hormone Antagonists, Physiological Effects of Drugs, Pharmacologic Actions
- Medical subject headings
- Edema, Macular Edema, Retinal Diseases, Eye Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DanazolDrug
Also called Optina
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Not described |
| Optina Low Dose | Experimental | Optina, 15 mg orally, twice daily Receives: Drug: Danazol |
| Optina - High Dose | Experimental | Optina, 45 mg orally, twice daily Receives: Drug: Danazol |
What is being measured
The primary outcome is the main question the study is designed to answer.
OCT
Change in Central Macular Thickness (CMT), measured by time-domain optical coherence tomography (OCT), from baseline to study endpoint at 12 weeks of study treatment compared to placebo
Measured: 12 weeks
Secondary outcomes (2)
ETDRS BCVA
Change in Early Treatment Diabetic Retinopathy Study (ETDRS) best corrected visual acuity (BCVA) from baseline to study endpoint after 12 weeks of study treatment compared to placebo
Measured: 12 weeks
Retinal volume
Change in center subfield retinal volume as measured by OCT from baseline to study endpoint after 12 weeks of study treatment compared to placebo.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2013 (estimated)
- Study startJan 2011
- Primary completionApr 2012
- Study completionApr 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetic Macular EdemaStudies of the same condition, open and under way.
- More trials run by Unity Health TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Unity Health Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Shelley R Boyd, MD, FRCSC, Principal investigator, Unity Health Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02002403
- Sponsor's protocol ID
- DMILS-RX09-001
- Status last verified
- Nov 2013
- First submitted
- 29 Nov 2013
- Last updated
- 6 Dec 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Placebo-Controlled, Parallel Treatment Group, Double-Masked Study to Evaluate the Efficacy and Safety of Two Doses of Oral DMI-5207 in Adult Subjects With Diabetic Macular Edema
- ClinicalTrials.gov ID
- NCT02002403
- Acronym / sponsor ID
- DMILS-RX09-001
- Conditions
- Diabetic Macular Edema
- Keywords
- Edema, Macular Edema, Retinal Diseases, Eye Diseases, Danazol, Estrogen Antagonists, Estrogen Receptor Modulators, Hormone Antagonists
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Unity Health TorontoUniversity, hospital or other
- Study start
- Jan 2011
- Primary completion
- Apr 2012 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 5 Dec 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The drug being tested in this study is low doses of Optina (formerly known as Danazol) (DMI-5207) that may be an effective treatment for diabetic retinopathy and diabetic macular edema (DME). Laboratory studies have demonstrated that low doses of this drug may treat diabetic retinopathy and diabetic macular edema by two important ways, decreasing blood vessel permeability (related to leaking and edema) and by decreasing the formation of new leaky blood vessels. Optina is not approved by Health Canada for the treatment of diabetic macular edema but higher doses of Optina are approved by Health Canada for treatment of endometriosis (growth of cells similar to those that form inside of the womb that grows outside of the womb) and fibrocystic breast disease (a condition of the breast tissue). Higher doses of Optina have also been approved in the United States and many other countries since the mid-1970s in the treatment of men and women with hereditary angioedema (a disease which causes swelling in parts of the body) in addition to endometriosis and fibrocystic breast disease in women.
All of the Optina doses that will be used in the current study are less than half of the typical starting doses for the approved indications. This can be compared to "high-dose" aspirin that is used to treat, for example, headache, while low-dose "baby aspirin" is used to reduce blood clotting. Similarly, Optina has two different effects at high and low dose. The low doses for this study have been selected based on the laboratory studies mentioned above.
The purpose of this study is to investigate the safety and effectiveness of low doses of Optina in the treatment of macular edema due to diabetes, and also to test if it helps to slow the development of macular edema.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | – |
| Optina Low Dose | Experimental | Drug: DanazolOptina, 15 mg orally, twice daily |
| Optina - High Dose | Experimental | Drug: DanazolOptina, 45 mg orally, twice daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Patient has provided informed consent
- 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)]
- 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.
- 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.
- At least one eye meets the study eye criteria for inclusion in the study (see Study Eye Inclusion Criteria, below)
Key exclusion criteria (32 listed)
- 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.
- 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.
- Carcinoma of the breast
- Prostate cancer
- Androgen-dependent tumor
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DanazolAlso: Optina | Drug | Optina - High Dose, Optina Low Dose |
Primary outcome
OCT
Time frame: 12 weeks
Change in Central Macular Thickness (CMT), measured by time-domain optical coherence tomography (OCT), from baseline to study endpoint at 12 weeks of study treatment compared to placebo
2 secondary outcomes
ETDRS BCVA
Time frame: 12 weeks
Retinal volume
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shelley R Boyd, MD, FRCSC principal investigator
Unity Health Toronto
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Danazol in people with Diabetic Macular Edema, run by Unity Health Toronto.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
OCT (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2013.