Trial Outcomes & Findings for A Safety and Efficacy Study of Oral Danazol (a Previously Approved Drug) in the Treatment of Diabetic Macular Edema. (NCT NCT01821677)

Last Updated: 2022-10-10

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

354 participants

Primary outcome timeframe

Determined at Baseline and Week 12

Results posted on

2022-10-10

Participant Flow

Subjects were recruited for study enrollment from a population of subjects being seen by clinicians participating in the investigational trial. Recruitment occurred from February 2013 to June 2014.

Standard of care treatment for diabetes will not be withheld during the study.

Unit of analysis: Eyes

Participant milestones

Participant milestones
Measure	Low Dose Danazol Low Dose Danazol 0.5 mg / BMI administered as 2 capsules twice daily (total of 4 capsules/day) for 12 weeks.	High Dose Danazol High Dose Danazol 1.0 mg / BMI administered as 2 capsules twice daily (total of 4 capsules/day) for 12 weeks.	Placebo Placebo (lactose and magnesium stearate) administered as 2 capsules twice daily (total of 4 capsules/day) for 12 weeks.
Overall Study STARTED	117 141	117 142	120 142
Overall Study COMPLETED	94 114	102 126	105 124
Overall Study NOT COMPLETED	23 27	15 16	15 18

Reasons for withdrawal

Reasons for withdrawal
Measure	Low Dose Danazol Low Dose Danazol 0.5 mg / BMI administered as 2 capsules twice daily (total of 4 capsules/day) for 12 weeks.	High Dose Danazol High Dose Danazol 1.0 mg / BMI administered as 2 capsules twice daily (total of 4 capsules/day) for 12 weeks.	Placebo Placebo (lactose and magnesium stearate) administered as 2 capsules twice daily (total of 4 capsules/day) for 12 weeks.
Overall Study Adverse Event	4	6	5
Overall Study Physician Decision	1	4	1
Overall Study Non-compliance	0	1	2
Overall Study Lost to Follow-up	2	1	3
Overall Study Protocol Violation	0	0	2
Overall Study Withdrawal by Subject	7	3	2
Overall Study Other	9	0	0

Baseline Characteristics

Number of eyes analyzed differs from overall population

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Low Dose Danazol n=141 Eyes 0.5 mg/BMI/day of Danazol administered as 2 capsules twice daily (total of 4 capsules/day) for 12 weeks.	High Dose Danazol n=142 Eyes 1.0 mg/BMI/day of Danazol administered as 2 capsules twice daily (total of 4 capsules/day) for 12 weeks.	Placebo n=142 Eyes Placebo capsules administered as 2 capsules twice daily (total of 4 capsules/day) for 12 weeks.	Total n=425 Eyes Total of all reporting groups
Age, Continuous	64.2 Years STANDARD_DEVIATION 11.2 • n=93 Participants	62.7 Years STANDARD_DEVIATION 8.8 • n=4 Participants	62.4 Years STANDARD_DEVIATION 10.6 • n=27 Participants	63.1 Years STANDARD_DEVIATION 10.3 • n=483 Participants
Sex: Female, Male Female	58 Participants n=93 Participants	51 Participants n=4 Participants	68 Participants n=27 Participants	177 Participants n=483 Participants
Sex: Female, Male Male	59 Participants n=93 Participants	66 Participants n=4 Participants	52 Participants n=27 Participants	177 Participants n=483 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	28 Participants n=93 Participants	27 Participants n=4 Participants	31 Participants n=27 Participants	86 Participants n=483 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	89 Participants n=93 Participants	90 Participants n=4 Participants	89 Participants n=27 Participants	268 Participants n=483 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=93 Participants	2 Participants n=4 Participants	0 Participants n=27 Participants	3 Participants n=483 Participants
Race (NIH/OMB) Asian	2 Participants n=93 Participants	2 Participants n=4 Participants	3 Participants n=27 Participants	7 Participants n=483 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	3 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	4 Participants n=483 Participants
Race (NIH/OMB) Black or African American	13 Participants n=93 Participants	10 Participants n=4 Participants	7 Participants n=27 Participants	30 Participants n=483 Participants
Race (NIH/OMB) White	97 Participants n=93 Participants	102 Participants n=4 Participants	109 Participants n=27 Participants	308 Participants n=483 Participants
Race (NIH/OMB) More than one race	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	2 Participants n=483 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Region of Enrollment United States	117 participants n=93 Participants	117 participants n=4 Participants	120 participants n=27 Participants	354 participants n=483 Participants
Body Mass Index (BMI)	32.3 kg/m^2 STANDARD_DEVIATION 7.1 • n=93 Participants	32.2 kg/m^2 STANDARD_DEVIATION 6.9 • n=4 Participants	32.3 kg/m^2 STANDARD_DEVIATION 6.8 • n=27 Participants	32.3 kg/m^2 STANDARD_DEVIATION 6.9 • n=483 Participants
Best Corrected Visual Acuity (BCVA)	63.8 Letters Correctly Read STANDARD_DEVIATION 11.2 • n=14 Eyes	63.6 Letters Correctly Read STANDARD_DEVIATION 10.2 • n=23 Eyes	62.7 Letters Correctly Read STANDARD_DEVIATION 11.6 • n=50 Eyes	63.4 Letters Correctly Read STANDARD_DEVIATION 11.0 • n=50 Eyes
Central Macular Thickness	438.6 micrometers (μm) STANDARD_DEVIATION 132.8 • n=14 Eyes • Number of eyes analyzed differs from overall population	423.3 micrometers (μm) STANDARD_DEVIATION 120.8 • n=23 Eyes • Number of eyes analyzed differs from overall population	426.8 micrometers (μm) STANDARD_DEVIATION 126.9 • n=50 Eyes • Number of eyes analyzed differs from overall population	430.1 micrometers (μm) STANDARD_DEVIATION 127.6 • n=50 Eyes • Number of eyes analyzed differs from overall population

PRIMARY outcome

Timeframe: Determined at Baseline and Week 12

Population: Intent to Treat (ITT)

Outcome measures

Outcome measures
Measure	Low Dose Danazol n=141 Eyes Low Dose Danazol 0.5 mg / BMI administered as 2 capsules twice daily (total of 4 capsules/day) for 12 weeks.	High Dose Danazol n=142 Eyes High Dose Danazol 1.0 mg / BMI administered as 2 capsules twice daily (total of 4 capsules/day) for 12 weeks.	Danazol Combined (0.5 mg / BMI and 1.0 mg / BMI Dose) n=283 Eyes Combined Results of 0.5 mg / BMI (Low) and 1.0 mg / BMI (High) Dose administered as 2 capsules twice daily (total of 4 capsules/day) for 12 weeks.	Placebo n=142 Eyes Placebo (lactose and magnesium stearate) administered as 2 capsules twice daily (total of 4 capsules/day) for 12 weeks.
Change in Best Corrected Visual Acuity (BCVA)	1.0 Letters Correctly Read Interval -0.3 to 2.4	0.8 Letters Correctly Read Interval -0.4 to 2.0	0.9 Letters Correctly Read Interval 0.0 to 1.8	2.5 Letters Correctly Read Interval 1.5 to 3.5

SECONDARY outcome

Timeframe: Determined at Baseline and Week 12

Population: Intent to Treat (ITT)

A measured change from baseline to week 12 of central macular thickness of the Intent to Treat population of all treated subjects. A negative difference in Central Macular Thickness constitutes a reduction in retinal thickness. Increase in Central Macular Thickness is caused by diabetic macular edema. A greater negative value indicates a greater reduction in swelling.

Outcome measures

Outcome measures
Measure	Low Dose Danazol n=117 Participants Low Dose Danazol 0.5 mg / BMI administered as 2 capsules twice daily (total of 4 capsules/day) for 12 weeks.	High Dose Danazol n=117 Participants High Dose Danazol 1.0 mg / BMI administered as 2 capsules twice daily (total of 4 capsules/day) for 12 weeks.	Danazol Combined (0.5 mg / BMI and 1.0 mg / BMI Dose) n=234 Participants Combined Results of 0.5 mg / BMI (Low) and 1.0 mg / BMI (High) Dose administered as 2 capsules twice daily (total of 4 capsules/day) for 12 weeks.	Placebo n=120 Participants Placebo (lactose and magnesium stearate) administered as 2 capsules twice daily (total of 4 capsules/day) for 12 weeks.
Change in Central Macular Thickness (CMT)	-6.0 micrometers (μm) Interval -20.5 to 8.6	-2.8 micrometers (μm) Interval -17.6 to 12.0	-4.4 micrometers (μm) Interval -14.7 to 5.9	-17.5 micrometers (μm) Interval -33.1 to -2.0

Adverse Events

Low Dose Danazol

Serious events: 14 serious events

Other events: 32 other events

Deaths: 1 deaths

High Dose Danazol

Serious events: 7 serious events

Other events: 34 other events

Deaths: 0 deaths

Placebo

Serious events: 12 serious events

Other events: 48 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Low Dose Danazol n=117 participants at risk Low Dose Danazol 0.5 mg / BMI	High Dose Danazol n=117 participants at risk High Dose Danazol 1.0 mg / BMI	Placebo n=120 participants at risk Placebo (lactose and magnesium stearate)
Eye disorders Vitreous Haemorrhage	6.0% 7/117 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).	4.3% 5/117 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).	6.7% 8/120 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).
Eye disorders Diabetic Retinal Oedema	1.7% 2/117 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).	6.0% 7/117 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).	4.2% 5/120 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).
Vascular disorders Hypertension	4.3% 5/117 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).	3.4% 4/117 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).	4.2% 5/120 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).
Gastrointestinal disorders Nausea	2.6% 3/117 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).	1.7% 2/117 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).	3.3% 4/120 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).
Gastrointestinal disorders Diarrhoea	0.00% 0/117 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).	1.7% 2/117 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).	4.2% 5/120 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).
Eye disorders Eye Pain	1.7% 2/117 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).	1.7% 2/117 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).	2.5% 3/120 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).
Nervous system disorders Headache	1.7% 2/117 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).	3.4% 4/117 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).	0.83% 1/120 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).
Infections and infestations Nasopharyngitis	2.6% 3/117 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).	1.7% 2/117 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).	1.7% 2/120 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).
General disorders Oedema Peripheral	2.6% 3/117 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).	0.85% 1/117 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).	2.5% 3/120 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).
Infections and infestations Urinary Tract Infection	0.85% 1/117 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).	0.85% 1/117 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).	4.2% 5/120 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).
Infections and infestations Sinusitis	3.4% 4/117 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).	0.85% 1/117 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).	0.83% 1/120 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).
Eye disorders Vitreous Detachment	0.00% 0/117 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).	1.7% 2/117 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).	2.5% 3/120 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).
Eye disorders Dry Eye	0.00% 0/117 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).	0.85% 1/117 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).	2.5% 3/120 • 16 weeks Patients will be followed for all adverse events (AEs) until 30 days after the last dose of study medication. All AEs considered to be possibly related to Optina™ will be followed until the event resolves or stabilized without further change. Adverse events were assessed by participant level not eyes (units analyzed).

Additional Information

Dr. Howard Levy / Chief Medical Officer

Ampio Pharmaceuticals

Phone: 720-437-6500

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place