Phase II 90-Day Study of Emixustat in GA
Appendix. Complete Inclusion and Exclusion Criteria for Phase IIa Emixustat HCl Protocol (Clinicaltrials.gov # NCT01002950)
Inclusion Criteria
1.
Age ≥18 years.
2.
Have a clinical diagnosis of GA, as defined by well demarcated areas of partial or complete retinal pigment epithelium (RPE) depigmentation or loss
confirmed by the Digital Angiography Reading Center (DARC), a central reading center.
3.
Have steady fixation and clear ocular media with adequate pupil dilation to visualize the fundus in each eye.
4.
Have a best-corrected visual acuity (BCVA) by Early Treatment of Diabetic Retinopathy Study (ETDRS) equal to or better than 20/400 in the study eye.
5.
Females will be non-pregnant, non-lactating, and either postmenopausal for at least 1 year, surgically sterile or agree to use a highly effective, medicallyapproved method of contraception (a non-hormonal intrauterine contraceptive device with spermicide, female condom with spermicide, contraceptive
sponge with spermicide, diaphragm with spermicide, cervical cap with spermicide, a male sexual partner who agrees to use a male condom with spermicide
or a sterile sexual partner) for the duration of the study and for 45 days following completion of study.
6.
Males will be either sterile or agree to use a highly effective method of contraception with their partner with child bearing potential (as listed in 6 above) for
the duration of the study and for 45 days after completion of study.
7.
Are able to provide written informed consent.
Exclusion Criteria
1.
Have clinically significant ocular abnormalities in either eye that in the opinion of the investigator or study ophthalmologist would interfere with the study
evaluation.
2.
Have known congenital/inherited color vision abnormalities.
3.
Have active choroidal neovascularization (i.e., ‘wet’, exudative AMD) in the study eye or currently receiving treatment for this condition with intravitreal
therapy (anti-VEGF agents or steroid), photodynamic therapy, or thermal laser photocoagulation in the study eye.
4.
Have GA in either eye associated with ocular disease other than AMD.
5.
Have an active ocular disease that in the opinion of the investigator is significantly affecting visual function, including, but not limited to, uveitis, macular
diseases such as epiretinal membrane or macular hole, retinal dystrophy, central serous retinopathy, diabetic retinopathy, macular edema, and poorly
controlled glaucoma.
6.
Have had cataract or other intraocular surgery within 3 months of study entry in either eye.
7.
Have had LASIK surgery, glaucoma filtration surgery, or corneal transplant within 6 months of study entry in either eye.
8.
Currently receiving or have received chemotherapy, immunotherapy or cytokine therapy within 4 weeks of study entry.
CONFIDENTIAL
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25 September 2013; Revised 28 January 2015
Phase II 90-Day Study of Emixustat in GA
Exclusion Criteria, Continued
9.
Currently receiving or have received CYP3A4 and CYP2D6 inducers and inhibitors and CYP2C19 inducers listed in Appendix 12.3 within 4 weeks of study
entry.
10. Have had a change in a systemic prescription medication within 28 days prior to expected dosing. Exceptions to this exclusion may be allowed on an
individual basis if the medical monitor and investigator agree prior to randomization of the subject.
11. Have had a change in an over-the-counter (OTC) systemic medication within the 7 days prior to randomization. More recent changes or episodic use of
acetaminophen, aspirin up to 81 mg daily, or nonsteroidal anti-inflammatory drug are permitted. OTC medications considered to be dietary supplements are
allowed as long as taken regularly and thus in steady state. Other exceptions to this exclusion may be allowed on an individual basis if the medical monitor
and investigator agree prior to randomization of the subject.
12. Have received treatment with an investigational drug or device which may have a persistent effect for the study period within 30 days prior to
randomization.
13. Have unstable or poorly controlled medical conditions that in the opinion of the investigator might interfere with the safety evaluation of the test article, put
the subject at any clinical risk or jeopardize the subject’s ability to complete the study.
14. History of cancer within the past 5 years except for non-melanoma cutaneous cancer.
15. Any medical condition (e.g., malabsorption, inflammatory bowel disease, hepatic or renal disease) that could alter the absorption, metabolism, or elimination
of drugs.
16. History of myocardial infarction, stroke, or hospitalization for congestive heart failure within the past 6 months.
17. History of uncontrolled cardiac arrhythmias.
18. Any history or current condition including psychiatric illness, alcohol or drug abuse, likely to interfere with the ability to comply with protocol requirements.
19. Have any of the following:
•
Abnormal clinical laboratory test results e.g.:
a. Impaired hepatic function, e.g., AST/ALT > 2 × ULN;
b. Alkaline phosphatase > 2 × ULN
c. Creatinine > 1.5 mg/dL
d. INR, PT or PTT > 1.25 × ULN
e. Impaired hematologic function: hemoglobin <11 g/dL; neutrophil count <2.0 x 109/L; or platelet count <100 x 109/L.
•
Abnormal electrocardiogram (ECG) results that are considered to be clinically significant by the investigator.
CONFIDENTIAL
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25 September 2013; Revised 28 January 2015