ATS17: Levodopa for the Treatment of Residual Amblyopia

• Sponsor: Jaeb Center for Health Research (Other)
• Overall Status: Completed
• CT.gov ID: NCT01190813
• Collaborator: National Eye Institute (NEI) (NIH)
• Enrollment: 139
• Location: 1
• Arms: 2
• Duration (Months): 43
• Patients Per Site Per Month: 3.2

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of oral levodopa and patching versus oral placebo and patching as treatment for residual amblyopia in children 7 to <13 years old with visual acuity of 20/50 to 20/400 in the amblyopic eye.

Condition or Disease	Intervention/Treatment	Phase
Amblyopia	Drug: Levodopa/Carbidopa; Drug: Placebo; Other: Patching	Phase 3

Detailed Description

Amblyopia is the most common cause of monocular visual impairment in both children and young and middle-aged adults. Both patching and atropine are accepted treatment modalities for the management of moderate amblyopia in children. Despite best efforts with conventional amblyopia treatment, many older children and teenagers with amblyopia fail to achieve normal visual acuity in the amblyopic eye. In a previous PEDIG study where children 7 to 12 years old were treated with atropine and patching, only 36% of the children with moderate amblyopia and only 23% of the children with severe amblyopia achieved 20/40 or better acuity.

Many clinicians have recognized that conventional therapies with patching and atropine have not been universally successful and have sought alternatives. PEDIG has discussed for several years the problem of residual amblyopia and how the remaining visual acuity deficit could be reduced. A number of research groups have evaluated the short term use of oral levodopa-carbidopa as an adjunct to patching therapy for older children.

Study Design

• Study Type: Interventional
• Actual Enrollment: 139 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized Trial of Levodopa as Treatment for Residual Amblyopia (ATS 17)
• Study Start Date: Sep 1, 2010
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Levodopa/Carbidopa Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid	Drug: Levodopa/Carbidopa; Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid; Other: Patching; Two hours of daily patching
Placebo Comparator: Placebo Oral placebo tid	Drug: Placebo; Oral placebo tid; Other: Patching; Two hours of daily patching

Outcome Measures

Primary Outcome Measures

1. Distribution of Amblyopic Eye Visual Acuity Change From Baseline [18 weeks after enrollment]

   The primary outcome is the amblyopic eye visual acuity letter score measured at the 18-week primary outcome visit following a rapid taper of study medicine beginning at week 16. The primary analytic approach will be a treatment group comparison of the mean amblyopic eye visual acuity adjusted for baseline acuity. Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.

2. Mean Amblyopic Eye Visual Acuity Change From Baseline [18 weeks after enrollment]

   The primary outcome is the amblyopic eye visual acuity letter score measured at the 18-week primary outcome visit following a rapid taper of study medicine beginning at week 16. The primary analytic approach will be a treatment group comparison of the mean amblyopic eye visual acuity adjusted for baseline acuity. Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.

Secondary Outcome Measures

1. Amblyopic Eye Visual Acuity Improvement Treatment Group Comparison at 18 Weeks [18 weeks after enrollment]

   Treatment group comparisons of the proportion of subjects who have improved from baseline by 10 or more letters.

2. Distribution of Amblyopic Eye Visual Acuity at 18 Weeks [18 weeks after enrollment]

3. Mean Amblyopic Eye Visual Acuity at 18 Weeks [18 weeks after enrollment]

   Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.

4. Amblyopic Eye Visual Acuity Improvement Treatment Group Comparison at 4 Weeks [4 weeks after enrollment]

   Treatment group comparisons adjusted for baseline acuity scores using logistic regression of the proportion of subjects who have improved from baseline by 10 or more letters.

5. Amblyopic Eye Visual Acuity Improvement Treatment Group Comparison at 10 Weeks [10 weeks after enrollment]

   Treatment group comparisons of the proportion of subjects who have improved from baseline by 10 or more letters.

6. Amblyopic Eye Visual Acuity Improvement Treatment Group Comparison at 16 Weeks [16 weeks after enrollment]

   Treatment group comparisons of the proportion of subjects who have improved from baseline by 10 or more letters.

7. Amblyopic Eye Visual Acuity Improvement Treatment Group Comparison at 26 Weeks [26 weeks after enrollment]

   Treatment group comparisons adjusted for baseline acuity scores using logistic regression of the proportion of subjects who have improved from baseline by 10 or more letters.

8. Amblyopia Resolutionat 4 Weeks [4 weeks after enrollment]

   Treatment group comparisons adjusted for baseline acuity scores using logistic regression of the proportion of subjects with 20/25 or better visual acuity.

9. Amblyopia Resolution at 10 Weeks [10 weeks after enrollment]

   Treatment group comparisons adjusted for baseline acuity scores using logistic regression of the proportion of subjects with 20/25 or better visual acuity.

10. Amblyopia Resolution at 16 Weeks [16 weeks after enrollment]

    Treatment group comparisons adjusted for baseline acuity scores using logistic regression of the proportion of subjects with 20/25 or better visual acuity.

11. Amblyopia Resolution at 18 Weeks [18 weeks after enrollment]

    Treatment group comparisons adjusted for baseline acuity scores using logistic regression of the proportion of subjects with 20/25 or better visual acuity.

12. Amblyopia Resolution at 26 Weeks [26 weeks after enrollment]

    Treatment group comparisons adjusted for baseline acuity scores using logistic regression of the proportion of subjects with 20/25 or better visual acuity.

13. Distribution of Amblyopic Eye Visual Acuity Change From Baseline at 4 Weeks [4 weeks after enrollment]

    Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.

14. Mean Change in Amblyopic Eye Visual Acuity From Baseline at 4 Weeks [4 weeks after enrollment]

    A treatment group comparison of the mean amblyopic eye visual acuity at 4 weeks after enrollment, adjusted for baseline acuity.

15. Distribution of Amblyopic Eye Visual Acuity Change From Baseline at 10 Weeks [10 weeks after enrollment]

    Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.

16. Mean Change in Amblyopic Eye Visual Acuity From Baseline at 10 Weeks [10 weeks after enrollment]

    A treatment group comparison of the mean amblyopic eye visual acuity at 10 weeks after enrollment, adjusted for baseline acuity. Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.

17. Distribution of Amblyopic Eye Visual Acuity Change From Baseline at 16 Weeks [16 weeks after enrollment]

    Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.

18. Mean Change in Amblyopic Eye Visual Acuity From Baseline at 16 Weeks [16 weeks after enrollment]

    A treatment group comparison of the mean amblyopic eye visual acuity at 16 weeks after enrollment, adjusted for baseline acuity. Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.

19. Distribution of Amblyopic Eye Visual Acuity Change From Baseline at 26 Weeks [26 weeks after enrollment]

    Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.

20. Mean Change in Amblyopic Eye Visual Acuity From Baseline at 26 Weeks [26 weeks after enrollment]

    A treatment group comparison of the mean amblyopic eye visual acuity at 26 weeks after enrollment, adjusted for baseline acuity. Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.

21. Distribution of Fellow Eye Visual Acuity at 18 Weeks [18 weeks after enrollment]

    Similar to the analysis for the amblyopic eye, the fellow eye visual acuity will be evaluated to determine if study treatment had an adverse effect on the occluded eye. The analysis will be a treatment group comparison of the mean fellow eye visual acuity at 18 weeks after enrollment, adjusted for baseline acuity.

22. Mean Fellow Eye Visual Acuity at 18 Weeks [18 weeks after enrollment]

    Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.

23. Distribution of Fellow Eye Visual Acuity Change From Baseline at 18 Weeks [18 weeks after enrollment]

    Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.

24. Mean Fellow Eye Visual Acuity Change From Baseline at 18 Weeks [18 weeks after enrollment]

    Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.

25. Mean Child Symptom Survey Score at Enrollment [At enrollment]

    A treatment group comparison of symptom survey scores at enrollment. The average of the overall item responses will be calculated and compared by treatment group with a t-test for difference in means. A higher number reflects a more negative response (5=always, 4=often, 3=sometimes, 2=rarely, 1=never).

26. Mean Child Symptom Survey Score at 4 Weeks [4 weeks after enrollment]

    A treatment group comparison of symptom survey scores at the 4 week visit. The average of the overall item responses will be calculated and compared by treatment group with a t-test for difference in means. A higher number reflects a more negative response (5=always, 4=often, 3=sometimes, 2=rarely, 1=never).

27. Mean Child Symptom Survey Score at 10 Weeks [10 weeks after enrollment]

    A treatment group comparison of symptom survey scores at the 10 week visit. The average of the overall item responses will be calculated and compared by treatment group with a t-test for difference in means. A higher number reflects a more negative response (5=always, 4=often, 3=sometimes, 2=rarely, 1=never).

28. Mean Child Symptom Survey Score at 16 Weeks [16 weeks after enrollment]

    A treatment group comparison of symptom survey scores at the 16 week visit. The average of the overall item responses will be calculated and compared by treatment group with a t-test for difference in means. A higher number reflects a more negative response (5=always, 4=often, 3=sometimes, 2=rarely, 1=never).

29. Mean Child Symptom Survey Score at 18 Weeks [18 weeks after enrollment]

    A treatment group comparison of symptom survey scores at the primary outcome (18 week) visit. The average of the overall item responses will be calculated and compared by treatment group with a t-test for difference in means. A higher number reflects a more negative response (5=always, 4=often, 3=sometimes, 2=rarely, 1=never).

30. Mean Child Symptom Survey Score at 26 Weeks [26 weeks after enrollment]

    A treatment group comparison of symptom survey scores at the 26 week visit. The average of the overall item responses will be calculated and compared by treatment group with a t-test for difference in means. A higher number reflects a more negative response (5=always, 4=often, 3=sometimes, 2=rarely, 1=never).

31. Mean Parent Symptom Survey Score at Enrollment [At enrollment]

    A treatment group comparison of symptom survey scores at enrollment. The average of the overall item responses will be calculated and compared by treatment group with a t-test for difference in means. A higher number reflects a more negative response (5=always, 4=often, 3=sometimes, 2=rarely, 1=never).

32. Mean Parent Symptom Survey Score at 4 Weeks [4 weeks after enrollment]

    A treatment group comparison of symptom survey scores at the 4 week visit. The average of the overall item responses will be calculated and compared by treatment group with a t-test for difference in means. A higher number reflects a more negative response (5=always, 4=often, 3=sometimes, 2=rarely, 1=never).

33. Mean Parent Symptom Survey Score at 10 Weeks [10 weeks after enrollment]

    A treatment group comparison of symptom survey scores at the 10 week visit. The average of the overall item responses will be calculated and compared by treatment group with a t-test for difference in means. A higher number reflects a more negative response (5=always, 4=often, 3=sometimes, 2=rarely, 1=never).

34. Mean Parent Symptom Survey Score at 16 Weeks [16 weeks after enrollment]

    A treatment group comparison of symptom survey scores at the 16 week visit. The average of the overall item responses will be calculated and compared by treatment group with a t-test for difference in means. A higher number reflects a more negative response (5=always, 4=often, 3=sometimes, 2=rarely, 1=never).

35. Mean Parent Symptom Survey Score at 18 Weeks [18 weeks after enrollment]

    A treatment group comparison of symptom survey scores at the primary outcome (18 week) visit. The average of the overall item responses will be calculated and compared by treatment group with a t-test for difference in means. A higher number reflects a more negative response (5=always, 4=often, 3=sometimes, 2=rarely, 1=never).

36. Mean Parent Symptom Survey Score at 26 Weeks [26 weeks after enrollment]

    A treatment group comparison of symptom survey scores at the 26 week visit. The average of the overall item responses will be calculated and compared by treatment group with a t-test for difference in means. A higher number reflects a more negative response (5=always, 4=often, 3=sometimes, 2=rarely, 1=never).

37. Mean Systemic Adverse Events [Enrollment through 26 weeks]

38. Distribution of Fellow Eye Visual Acuity at 26 Weeks [26 weeks after enrollment]

    Similar to the analysis for the amblyopic eye, the fellow eye visual acuity will be evaluated to determine if study treatment had an adverse effect on the occluded eye. The analysis will be a treatment group comparison of the mean fellow eye visual acuity at 26 weeks after enrollment, adjusted for baseline acuity.

39. Mean Fellow Eye Visual Acuity at 26 Weeks [26 weeks after enrollment]

    Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.

40. Distribution of Fellow Eye Visual Acuity Change From Baseline at 26 Weeks [26 weeks after enrollment]

    Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.

41. Mean Fellow Eye Visual Acuity Change From Baseline at 26 Weeks [26 weeks after enrollment]

    Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 7 Years to 12 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age 7 to 12

2. Amblyopia associated with strabismus, anisometropia, or both

• Criteria for strabismus: One of the following criteria must be met: Heterotropia at distance and/or near fixation on examination (with or without spectacles); History of strabismus surgery; Documented history of strabismus which is no longer present (which in the judgment of the investigator could have caused amblyopia)

• Criteria for anisometropia: One of the following criteria must be met: ≥0.50 D difference between eyes in spherical equivalent; ≥1.50 D difference between eyes in astigmatism in any meridian

1. Visual acuity, measured in each eye (amblyopic eye without cycloplegia) within 7 days prior to enrollment using the E-ETDRS protocol by a study certified visual acuity tester as follows:

• Visual acuity in the amblyopic eye 18 to 67 letters inclusive (20/50 to 20/400)

• Visual acuity in the fellow eye ≥78 letters (20/25 or better)

1. Current amblyopia treatment (other than spectacles)

• 12 weeks of at least 2 hours of occlusion per day prescribed for the fellow eye during the immediate pre-enrollment period.

• While on current treatment, visual acuity has not improved one line (5 letters) or more since a non-study visit at least 6 weeks ago. Both acuity measurements to define no improvement must have been done using the same testing method.

• Treatment with atropine at any time during this pre-enrollment period is not allowed.

• Any treatment prior to the current patching episode with stable acuity is acceptable.

1. Spectacle correction (if applicable) for measurement of enrollment visual acuity must meet the following criteria and be based on a cycloplegic refraction that is no more than 6 months old:

2. Requirements for spectacle correction:

• Spherical equivalent must be within 0.50 D of fully correcting the anisometropia.

• Hypermetropia of 3.00D or more must be corrected.

• Hypermetropia must not be under corrected by more than 1.50 D spherical equivalent, and reduction in plus sphere must be symmetric in the two eyes.

• Cylinder power in both eyes must be within 0.50 D of fully correcting the astigmatism.

• Cylinder axis in both eyes is within 6 degrees of the axis in the spectacles when cylinder power is ≥1.00 D.

• Myopia of amblyopic eye greater than 0.50 D by spherical equivalent must be corrected, and the glasses must not under correct the myopia by more than 0.25 D or overcorrect it by more than 0.50 D.

1. Spectacles meeting above criteria must be worn :until visual acuity in amblyopic eye is stable (defined as 2 consecutive visual acuity measurements by the same testing method at least 4 weeks apart with no improvement of one line (5 letters) or more.

2. Eye examination within 6 months prior to enrollment

3. Parent available for at least one year of follow-up, has access to phone), and willing to be contacted by clinical site and Jaeb Center staff

4. In the investigator's judgment, the subject is likely to comply with prescribed treatment (e.g., no history of poor compliance with patching treatment) and unlikely to continue to improve by using 2 hours of patching per day alone.

Exclusion Criteria:

1. Myopia more than -6.00 D (spherical equivalent) in either eye.

2. Current vision therapy or orthoptics

3. Ocular cause for reduced visual acuity

• nystagmus per se does not exclude the subject if the above visual acuity criteria are met

1. Prior intraocular or refractive surgery

2. History of narrow-angle glaucoma

3. Bronchial asthma or severe pulmonary disease

4. Strabismus surgery planned within 26 weeks

5. Known allergy to levodopa or carbidopa

6. History of dystonic reactions

7. Current use of oral iron supplements including multivitamins containing iron during treatment with levodopa-carbidopa

8. Current use of antihypertensive, anti-depressant medications, phenothiazines, butyrophenones, risperidone and isoniazid, non-specific monoamine oxidase inhibitors, or medication for the treatment of attention deficit hyperactivity disorder

9. Known liver disease

10. History of melanoma

11. Known psychological problems

12. Known skin reactions to patch or bandage adhesives

13. Prior levodopa treatment

14. Treatment with topical ophthalmic atropine within the past 12 weeks

15. A physician-prescribed diet high in protein

16. Females who are pregnant, lactating, or intend to become pregnant within the next 34 weeks.

• A negative urine pregnancy test will be required for all females who have experienced menarche.

• Requirements regarding pregnancy testing prior to enrollment may be further defined by each individual Institutional Review Board.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wilmer Eye Institute	Baltimore	Maryland	United States	21287

Sponsors and Collaborators

• Jaeb Center for Health Research
• National Eye Institute (NEI)

Investigators

• Study Chair: Michael X Repka, MD, Jaeb Center for Health Research

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• PubMed abstract
• PubMed Central HHS Public Access - Full Text

Publications

None provided.

• Responsible Party: Jaeb Center for Health Research
• ClinicalTrials.gov Identifier: NCT01190813
• Other Study ID Numbers: ATS 17; 2U10EY011751
• First Posted: Aug 30, 2010
• Last Update Posted: Jun 2, 2016
• Last Verified: May 1, 2016

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Jaeb Center for Health Research: amblyopia, levodopa
• Additional relevant MeSH terms: Amblyopia; Levodopa; Carbidopa

Study Results

Participant Flow

Recruitment Details	Between September 2010 and October 2013, 139 participants from 27 sites were randomly assigned to levodopa (n=90) or placebo (n=49).

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Period Title: Overall Study
STARTED	90	49
2-week Phone Call	87	48
4-week Visit	88	47
7-week Phone Call	85	46
10-week Visit	88	48
13-week Phone Call	82	48
16-week Visit	87	46
18-week Visit (Masked Primary)	87	45
23-week Phone Call	82	41
26-week Visit	86	45
COMPLETED	86	45
NOT COMPLETED	4	4

Baseline Characteristics

Arm/Group Title	Levodopa/Carbidopa	Placebo	Total
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching	Total of all reporting groups
Overall Participants	90	49	139
Age (Count of Participants)
<=18 years	90 100%	49 100%	139 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	9.4 (1.8)	9.5 (1.7)	9.5 (1.7)
Age, Customized (participants) [Number]
7 to <9 years	39 43.3%	21 42.9%	60 43.2%
9 to <11 years	33 36.7%	14 28.6%	47 33.8%
11 to <13 years	18 20%	14 28.6%	32 23%
Sex: Female, Male (Count of Participants)
Female	40 44.4%	24 49%	64 46%
Male	50 55.6%	25 51%	75 54%
Race/Ethnicity, Customized (participants) [Number]
Asian	2 2.2%	1 2%	3 2.2%
Black/African American	1 1.1%	1 2%	2 1.4%
Hispanic or Latino	5 5.6%	2 4.1%	7 5%
White	77 85.6%	44 89.8%	121 87.1%
Unknown/Not Reported	5 5.6%	1 2%	6 4.3%
Region of Enrollment (participants) [Number]
United States	90 100%	49 100%	139 100%
Cause of Amblyopia (participants) [Number]
Strabismus	22 24.4%	5 10.2%	27 19.4%
Anisometropia	20 22.2%	16 32.7%	36 25.9%
Combined Mechanism	48 53.3%	28 57.1%	76 54.7%
Patching Duration at Randomization (participants) [Number]
2 hours per day	81 90%	43 87.8%	124 89.2%
>= 3 hours per day	9 10%	6 12.2%	15 10.8%
Visual Acuity in the Amblyopic Eye at Randomization (participants) [Number]
20/200 or worse (<=37 letters)	7 7.8%	9 18.4%	16 11.5%
20/100 to <20/200 (38-52 letters)	34 37.8%	13 26.5%	47 33.8%
20/80 (53-57 letters)	15 16.7%	8 16.3%	23 16.5%
20/63 (58-62 letters)	20 22.2%	6 12.2%	26 18.7%
20/50 (63-67 letters)	14 15.6%	13 26.5%	27 19.4%
Visual Acuity in the Amblyopic Eye at Randomization (letters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [letters]	52.8 (9.8)	51.7 (11.9)	52.4 (10.5)
Visual Acuity in the Fellow Eye at Randomization (participants) [Number]
20/25 (78-82 letters)	15 16.7%	4 8.2%	19 13.7%
20/20 (83-87 letters)	35 38.9%	20 40.8%	55 39.6%
20/16 (88-92 letters)	34 37.8%	23 46.9%	57 41%
20/12 (93-97 letters)	6 6.7%	2 4.1%	8 5.8%
Visual Acuity in the Fellow Eye at Randomization (letters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [letters]	86.7 (4.1)	87.3 (3.5)	86.9 (3.9)
Intraocular Visual Acuity Difference at Randomization (letters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [letters]	33.9 (10.9)	35.6 (13.1)	34.5 (11.7)
SE Refractive Error in Amblyopic Eye at Randomization (diopters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [diopters]	4.0 (2.6)	4.5 (2.3)	4.2 (2.5)
SE Refractive Error in Fellow Eye at Randomization (diopters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [diopters]	1.9 (2.0)	1.6 (1.7)	1.8 (1.9)
Anisometropia at Randomization (diopters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [diopters]	2.5 (2.1)	3.1 (2.0)	2.7 (2.1)

Outcome Measures

1. Primary Outcome

Title	Distribution of Amblyopic Eye Visual Acuity Change From Baseline
Description	The primary outcome is the amblyopic eye visual acuity letter score measured at the 18-week primary outcome visit following a rapid taper of study medicine beginning at week 16. The primary analytic approach will be a treatment group comparison of the mean amblyopic eye visual acuity adjusted for baseline acuity. Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.
Time Frame	18 weeks after enrollment

Outcome Measure Data

Analysis Population Description

The ITT principle was followed. For subjects with no visit in the +/- 1 wk window for the 18-wk visit, data from a visit 14-27 wks after randomization were used, if available. Multiple imputation by the Monte Carlo Markov Chain method was used for missing 18-wk VA outcomes based on tx group, baseline VA, & VA scores from completed follow-up visits.

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	86	45
10-14 letters worse	0 0%	0 0%
5-9 letters worse	2 2.2%	1 2%
within 4 letters	35 38.9%	23 46.9%
5-9 letters better	36 40%	19 38.8%
10-14 letters better	10 11.1%	1 2%
>= 15 letters better	3 3.3%	1 2%

2. Secondary Outcome

Title	Amblyopic Eye Visual Acuity Improvement Treatment Group Comparison at 18 Weeks
Description	Treatment group comparisons of the proportion of subjects who have improved from baseline by 10 or more letters.
Time Frame	18 weeks after enrollment

Outcome Measure Data

Analysis Population Description

The analysis followed the intent-to-treat principle. For missing primary outcome visits (±1 wk), data from a visit 14-27 wks after randomization were used, if available.Multiple imputation(Monte Carlo Markov Chain method) was used for missing 18-wk VA outcomes based on treatment group, baseline VA, and VA scores from completed follow-up visits

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	86	45
Number [participants]	13 14.4%	2 4.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levodopa/Carbidopa, Placebo
	Comments	A sample size of 129 participants provided 80% power with 1-sided type I error rate of 5% to reject the hypothesis of no difference between groups if the proportion improved was 30% in the levodopa group compared with 10% in the placebo group.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.06
	Comments
	Method	Fisher Exact
	Comments	It was not possible to adjust for baseline VA in these secondary analyses due to the small number of subjects meeting secondary outcome criteria.
Method of Estimation	Estimation Parameter	Percent Difference
	Estimated Value	11
	Confidence Interval	(2-Sided) 95%; -7 to 28
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment group difference calculated as Levodopa - Placebo

3. Secondary Outcome

Title	Distribution of Amblyopic Eye Visual Acuity at 18 Weeks
Time Frame	18 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	86	45
20/25 (78-82 letters)	0 0%	0 0%
20/32 (73-77 letters)	5 5.6%	1 2%
20/40 (68-72 letters)	7 7.8%	6 12.2%
20/50 (63-67 letters)	20 22.2%	5 10.2%
20/63 (58-62 letters)	18 20%	9 18.4%
20/80 (53-57 letters)	12 13.3%	5 10.2%
20/100 (48-52 letters)	17 18.9%	9 18.4%
20/125 (43-47 letters)	4 4.4%	3 6.1%
20/160 or worse (<=42 letters)	3 3.3%	7 14.3%

4. Secondary Outcome

Title	Mean Amblyopic Eye Visual Acuity at 18 Weeks
Description	Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.
Time Frame	18 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	86	45
Mean (Standard Deviation) [letters]	58.7 (8.9)	54.8 (12.3)

5. Secondary Outcome

Title	Amblyopic Eye Visual Acuity Improvement Treatment Group Comparison at 4 Weeks
Description	Treatment group comparisons adjusted for baseline acuity scores using logistic regression of the proportion of subjects who have improved from baseline by 10 or more letters.
Time Frame	4 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	88	47
Improved 10 or more letters	4 4.4%	2 4.1%
Did not improve 10 or more letters	84 93.3%	45 91.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levodopa/Carbidopa, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percent Difference
	Estimated Value	0
	Confidence Interval	(2-Sided) 95%; -17 to 18
	Parameter Dispersion	Type: Value:
	Estimation Comments	Levodopa - Placebo

6. Secondary Outcome

Title	Amblyopic Eye Visual Acuity Improvement Treatment Group Comparison at 10 Weeks
Description	Treatment group comparisons of the proportion of subjects who have improved from baseline by 10 or more letters.
Time Frame	10 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	88	48
Improved 10 or more letters	10 11.1%	9 18.4%
Not improved 10 or more letters	78 86.7%	39 79.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levodopa/Carbidopa, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percent Difference
	Estimated Value	-7
	Confidence Interval	(2-Sided) 95%; -25 to 10
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Amblyopic Eye Visual Acuity Improvement Treatment Group Comparison at 16 Weeks
Description	Treatment group comparisons of the proportion of subjects who have improved from baseline by 10 or more letters.
Time Frame	16 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	87	46
Improved 10 or more letters	15 16.7%	10 20.4%
Not improved 10 or more letters	72 80%	36 73.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levodopa/Carbidopa, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percent Difference
	Estimated Value	-5
	Confidence Interval	(2-Sided) 95%; -22 to 13
	Parameter Dispersion	Type: Value:
	Estimation Comments	Levodopa - Placebo

8. Secondary Outcome

Title	Amblyopic Eye Visual Acuity Improvement Treatment Group Comparison at 26 Weeks
Description	Treatment group comparisons adjusted for baseline acuity scores using logistic regression of the proportion of subjects who have improved from baseline by 10 or more letters.
Time Frame	26 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	86	45
Improved 10 or more letters	17 18.9%	5 10.2%
Not improved 10 or more letters	69 76.7%	40 81.6%

9. Secondary Outcome

Title	Amblyopia Resolutionat 4 Weeks
Description	Treatment group comparisons adjusted for baseline acuity scores using logistic regression of the proportion of subjects with 20/25 or better visual acuity.
Time Frame	4 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	88	47
20/25 or better	0 0%	0 0%
20/32 or worse	88 97.8%	47 95.9%

10. Secondary Outcome

Title	Amblyopia Resolution at 10 Weeks
Description	Treatment group comparisons adjusted for baseline acuity scores using logistic regression of the proportion of subjects with 20/25 or better visual acuity.
Time Frame	10 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	88	48
20/25 or better	0 0%	0 0%
20/32 or worse	88 97.8%	48 98%

11. Secondary Outcome

Title	Amblyopia Resolution at 16 Weeks
Description	Treatment group comparisons adjusted for baseline acuity scores using logistic regression of the proportion of subjects with 20/25 or better visual acuity.
Time Frame	16 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	87	46
20/25 or better	1 1.1%	0 0%
20/32 or worse	86 95.6%	46 93.9%

12. Secondary Outcome

Title	Amblyopia Resolution at 18 Weeks
Description	Treatment group comparisons adjusted for baseline acuity scores using logistic regression of the proportion of subjects with 20/25 or better visual acuity.
Time Frame	18 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	86	45
20/25 or better	0 0%	0 0%
20/32 or worse	86 95.6%	45 91.8%

13. Secondary Outcome

Title	Amblyopia Resolution at 26 Weeks
Description	Treatment group comparisons adjusted for baseline acuity scores using logistic regression of the proportion of subjects with 20/25 or better visual acuity.
Time Frame	26 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	86	45
20/25 or better	0 0%	0 0%
20/32 or worse	86 95.6%	45 91.8%

14. Secondary Outcome

Title	Distribution of Amblyopic Eye Visual Acuity Change From Baseline at 4 Weeks
Description	Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.
Time Frame	4 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	88	47
10-14 letters worse	0 0%	0 0%
5-9 letters worse	6 6.7%	2 4.1%
within 4 letters	55 61.1%	28 57.1%
5-9 letters better	23 25.6%	15 30.6%
10-14 letters better	4 4.4%	1 2%
>= 15 letters better	0 0%	1 2%

15. Secondary Outcome

Title	Mean Change in Amblyopic Eye Visual Acuity From Baseline at 4 Weeks
Description	A treatment group comparison of the mean amblyopic eye visual acuity at 4 weeks after enrollment, adjusted for baseline acuity.
Time Frame	4 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	88	47
Mean (Standard Deviation) [letters]	2.2 (4.1)	2.5 (4.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levodopa/Carbidopa, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.65
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.9 to 1.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated as Levodopa - Placebo

16. Secondary Outcome

Title	Distribution of Amblyopic Eye Visual Acuity Change From Baseline at 10 Weeks
Description	Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.
Time Frame	10 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	88	48
10-14 letters worse	1 1.1%	0 0%
5-9 letters worse	4 4.4%	1 2%
within 4 letters	43 47.8%	30 61.2%
5-9 letters better	30 33.3%	8 16.3%
10-14 letters better	7 7.8%	9 18.4%
>= 15 letters better	3 3.3%	0 0%

17. Secondary Outcome

Title	Mean Change in Amblyopic Eye Visual Acuity From Baseline at 10 Weeks
Description	A treatment group comparison of the mean amblyopic eye visual acuity at 10 weeks after enrollment, adjusted for baseline acuity. Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.
Time Frame	10 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	88	48
Mean (Standard Deviation) [letters]	3.8 (4.9)	3.7 (4.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levodopa/Carbidopa, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.44
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -1.6 to 1.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

18. Secondary Outcome

Title	Distribution of Amblyopic Eye Visual Acuity Change From Baseline at 16 Weeks
Description	Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.
Time Frame	16 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	87	46
10-14 letters worse	0 0%	0 0%
5-9 letters worse	1 1.1%	0 0%
within 4 letters	41 45.6%	26 53.1%
5-9 letters better	30 33.3%	10 20.4%
10-14 letters better	9 10%	10 20.4%
>= 15 letters better	6 6.7%	0 0%

19. Secondary Outcome

Title	Mean Change in Amblyopic Eye Visual Acuity From Baseline at 16 Weeks
Description	A treatment group comparison of the mean amblyopic eye visual acuity at 16 weeks after enrollment, adjusted for baseline acuity. Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.
Time Frame	16 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	87	46
Mean (Standard Deviation) [letters]	5.1 (6.3)	4.2 (4.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levodopa/Carbidopa, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.20
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.9
	Confidence Interval	(2-Sided) 95%; -1.2 to 2.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

20. Secondary Outcome

Title	Distribution of Amblyopic Eye Visual Acuity Change From Baseline at 26 Weeks
Description	Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.
Time Frame	26 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	86	45
5-9 letters worse	3 3.3%	1 2%
within 4 letters	36 40%	23 46.9%
5-9 letters better	30 33.3%	16 32.7%
10-14 letters better	14 15.6%	5 10.2%
>= 15 letters better	3 3.3%	0 0%

21. Secondary Outcome

Title	Mean Change in Amblyopic Eye Visual Acuity From Baseline at 26 Weeks
Description	A treatment group comparison of the mean amblyopic eye visual acuity at 26 weeks after enrollment, adjusted for baseline acuity. Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.
Time Frame	26 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	86	45
Mean (Standard Deviation) [letters]	5.0 (5.7)	4.2 (4.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levodopa/Carbidopa, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.17
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.9
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

22. Secondary Outcome

Title	Distribution of Fellow Eye Visual Acuity at 18 Weeks
Description	Similar to the analysis for the amblyopic eye, the fellow eye visual acuity will be evaluated to determine if study treatment had an adverse effect on the occluded eye. The analysis will be a treatment group comparison of the mean fellow eye visual acuity at 18 weeks after enrollment, adjusted for baseline acuity.
Time Frame	18 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	87	45
20/12 (93-97 letters)	12 13.3%	4 8.2%
20/16 (88-92 letters)	44 48.9%	22 44.9%
20/20 (83-87 letters)	22 24.4%	16 32.7%
20/25 (78-82 letters)	8 8.9%	3 6.1%
20/32 (73-77 letters)	1 1.1%	0 0%

23. Secondary Outcome

Title	Mean Fellow Eye Visual Acuity at 18 Weeks
Description	Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.
Time Frame	18 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	87	45
Mean (Standard Deviation) [letters]	88.1 (4.4)	88.0 (3.2)

24. Secondary Outcome

Title	Distribution of Fellow Eye Visual Acuity Change From Baseline at 18 Weeks
Description	Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.
Time Frame	18 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	87	45
>=15 letters worse	0 0%	0 0%
10-14 letters worse	0 0%	0 0%
5-9 letters worse	4 4.4%	3 6.1%
within 4 letters	68 75.6%	39 79.6%
5-9 letters better	15 16.7%	3 6.1%
10-14 letters better	0 0%	0 0%

25. Primary Outcome

Title	Mean Amblyopic Eye Visual Acuity Change From Baseline
Description	The primary outcome is the amblyopic eye visual acuity letter score measured at the 18-week primary outcome visit following a rapid taper of study medicine beginning at week 16. The primary analytic approach will be a treatment group comparison of the mean amblyopic eye visual acuity adjusted for baseline acuity. Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.
Time Frame	18 weeks after enrollment

Outcome Measure Data

Analysis Population Description

The ITT principle was followed. For subjects with no visit in the +/- 1 wk window for the 18-wk visit, data from a visit 14-27 wks after randomization were used, if available. Multiple imputation by the Monte Carlo Markov Chain method was used for missing 18-wk VA outcomes based on tx group, baseline VA, & VA scores from completed follow-up visits.

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	86	45
Mean (Standard Deviation) [letters]	5.2 (5.3)	3.8 (5.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levodopa/Carbidopa, Placebo
	Comments	With 129 participants, assuming a 1-sided type I error rate of 4.85%, there was 96% power to detect a difference in mean visual acuity between treatment groups at 18 weeks adjusted for baseline and for 1 interim analysis for futility if the true difference was 5 letters with SD of 7 letters and 82% power if the true difference was 3.75 letters
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.06
	Comments	The alpha level was set to 0.0485 for the primary analysis to adjust for alpha spending of 0.015 for one interim analysis for efficacy conducted when outcome data were available for 50% of participants.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95%; -0.4 to 3.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated as Levodopa - Placebo

26. Secondary Outcome

Title	Mean Fellow Eye Visual Acuity Change From Baseline at 18 Weeks
Description	Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.
Time Frame	18 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	87	45
Mean (Standard Deviation) [letters]	1.5 (3.0)	0.5 (3.1)

27. Secondary Outcome

Title	Mean Child Symptom Survey Score at Enrollment
Description	A treatment group comparison of symptom survey scores at enrollment. The average of the overall item responses will be calculated and compared by treatment group with a t-test for difference in means. A higher number reflects a more negative response (5=always, 4=often, 3=sometimes, 2=rarely, 1=never).
Time Frame	At enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	90	49
Mean (Standard Deviation) [units on a scale]	1.60 (0.37)	1.73 (0.45)

28. Secondary Outcome

Title	Mean Child Symptom Survey Score at 4 Weeks
Description	A treatment group comparison of symptom survey scores at the 4 week visit. The average of the overall item responses will be calculated and compared by treatment group with a t-test for difference in means. A higher number reflects a more negative response (5=always, 4=often, 3=sometimes, 2=rarely, 1=never).
Time Frame	4 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	88	47
Mean (Standard Deviation) [units on a scale]	1.42 (0.37)	1.51 (0.42)

29. Secondary Outcome

Title	Mean Child Symptom Survey Score at 10 Weeks
Description	A treatment group comparison of symptom survey scores at the 10 week visit. The average of the overall item responses will be calculated and compared by treatment group with a t-test for difference in means. A higher number reflects a more negative response (5=always, 4=often, 3=sometimes, 2=rarely, 1=never).
Time Frame	10 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	88	47
Mean (Standard Deviation) [units on a scale]	1.33 (0.31)	1.42 (0.37)

30. Secondary Outcome

Title	Mean Child Symptom Survey Score at 16 Weeks
Description	A treatment group comparison of symptom survey scores at the 16 week visit. The average of the overall item responses will be calculated and compared by treatment group with a t-test for difference in means. A higher number reflects a more negative response (5=always, 4=often, 3=sometimes, 2=rarely, 1=never).
Time Frame	16 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	87	46
Mean (Standard Deviation) [units on a scale]	1.25 (0.27)	1.38 (0.36)

31. Secondary Outcome

Title	Mean Child Symptom Survey Score at 18 Weeks
Description	A treatment group comparison of symptom survey scores at the primary outcome (18 week) visit. The average of the overall item responses will be calculated and compared by treatment group with a t-test for difference in means. A higher number reflects a more negative response (5=always, 4=often, 3=sometimes, 2=rarely, 1=never).
Time Frame	18 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	87	45
Mean (Standard Deviation) [units on a scale]	1.17 (0.22)	1.28 (0.32)

32. Secondary Outcome

Title	Mean Child Symptom Survey Score at 26 Weeks
Description	A treatment group comparison of symptom survey scores at the 26 week visit. The average of the overall item responses will be calculated and compared by treatment group with a t-test for difference in means. A higher number reflects a more negative response (5=always, 4=often, 3=sometimes, 2=rarely, 1=never).
Time Frame	26 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	86	45
Mean (Standard Deviation) [units on a scale]	1.23 (0.26)	1.33 (0.32)

33. Secondary Outcome

Title	Mean Parent Symptom Survey Score at Enrollment
Description	A treatment group comparison of symptom survey scores at enrollment. The average of the overall item responses will be calculated and compared by treatment group with a t-test for difference in means. A higher number reflects a more negative response (5=always, 4=often, 3=sometimes, 2=rarely, 1=never).
Time Frame	At enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	90	49
Mean (Standard Deviation) [units on a scale]	1.42 (0.34)	1.44 (0.29)

34. Secondary Outcome

Title	Mean Parent Symptom Survey Score at 4 Weeks
Description	A treatment group comparison of symptom survey scores at the 4 week visit. The average of the overall item responses will be calculated and compared by treatment group with a t-test for difference in means. A higher number reflects a more negative response (5=always, 4=often, 3=sometimes, 2=rarely, 1=never).
Time Frame	4 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	88	47
Mean (Standard Deviation) [units on a scale]	1.29 (0.27)	1.26 (0.27)

35. Secondary Outcome

Title	Mean Parent Symptom Survey Score at 10 Weeks
Description	A treatment group comparison of symptom survey scores at the 10 week visit. The average of the overall item responses will be calculated and compared by treatment group with a t-test for difference in means. A higher number reflects a more negative response (5=always, 4=often, 3=sometimes, 2=rarely, 1=never).
Time Frame	10 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	88	47
Mean (Standard Deviation) [units on a scale]	1.22 (0.22)	1.30 (0.25)

36. Secondary Outcome

Title	Mean Parent Symptom Survey Score at 16 Weeks
Description	A treatment group comparison of symptom survey scores at the 16 week visit. The average of the overall item responses will be calculated and compared by treatment group with a t-test for difference in means. A higher number reflects a more negative response (5=always, 4=often, 3=sometimes, 2=rarely, 1=never).
Time Frame	16 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	87	46
Mean (Standard Deviation) [units on a scale]	1.24 (0.27)	1.25 (0.22)

37. Secondary Outcome

Title	Mean Parent Symptom Survey Score at 18 Weeks
Description	A treatment group comparison of symptom survey scores at the primary outcome (18 week) visit. The average of the overall item responses will be calculated and compared by treatment group with a t-test for difference in means. A higher number reflects a more negative response (5=always, 4=often, 3=sometimes, 2=rarely, 1=never).
Time Frame	18 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	87	45
Mean (Standard Deviation) [units on a scale]	1.17 (0.21)	1.17 (0.20)

38. Secondary Outcome

Title	Mean Parent Symptom Survey Score at 26 Weeks
Description	A treatment group comparison of symptom survey scores at the 26 week visit. The average of the overall item responses will be calculated and compared by treatment group with a t-test for difference in means. A higher number reflects a more negative response (5=always, 4=often, 3=sometimes, 2=rarely, 1=never).
Time Frame	26 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	86	45
Mean (Standard Deviation) [units on a scale]	1.19 (0.24)	1.22 (0.29)

39. Secondary Outcome

Title	Mean Systemic Adverse Events
Time Frame	Enrollment through 26 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	90	49
Mean (Standard Deviation) [events]	1.28 (1.39)	1.55 (1.90)

40. Secondary Outcome

Title	Distribution of Fellow Eye Visual Acuity at 26 Weeks
Description	Similar to the analysis for the amblyopic eye, the fellow eye visual acuity will be evaluated to determine if study treatment had an adverse effect on the occluded eye. The analysis will be a treatment group comparison of the mean fellow eye visual acuity at 26 weeks after enrollment, adjusted for baseline acuity.
Time Frame	26 weeks after enrollment

Outcome Measure Data

Analysis Population Description

All participants continued in the study regardless of whether they continued with study medication after the 18-week visit; 49 participants in the levodopa group and 24 participants in the placebo group continued study medication at the 18-week visit.

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	86	45
20/12 (93-97 letters)	15 16.7%	7 14.3%
20/16 (88-92 letters)	34 37.8%	22 44.9%
20/20 (83-87 letters)	28 31.1%	13 26.5%
20/25 (78-82 letters)	9 10%	2 4.1%
20/32 (73-77 letters)	0 0%	1 2%

41. Secondary Outcome

Title	Mean Fellow Eye Visual Acuity at 26 Weeks
Description	Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.
Time Frame	26 weeks after enrollment

Outcome Measure Data

Analysis Population Description

All participants continued in the study regardless of whether they continued with study medication after the 18-week visit; 49 participants in the levodopa group and 24 participants in the placebo group continued study medication at the 18-week visit.

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	86	45
Mean (Standard Deviation) [letters]	88.0 (4.5)	88.2 (4.1)

42. Secondary Outcome

Title	Distribution of Fellow Eye Visual Acuity Change From Baseline at 26 Weeks
Description	Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.
Time Frame	26 weeks after enrollment

Outcome Measure Data

Analysis Population Description

All participants continued in the study regardless of whether they continued with study medication after the 18-week visit; 49 participants in the levodopa group and 24 participants in the placebo group continued study medication at the 18-week visit.

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	86	45
>=15 letters worse	1 1.1%	0 0%
10-14 letters worse	0 0%	0 0%
5-9 letters worse	2 2.2%	4 8.2%
within 4 letters	74 82.2%	35 71.4%
5-9 letters better	7 7.8%	6 12.2%
10-14 letters better	2 2.2%	0 0%

43. Secondary Outcome

Title	Mean Fellow Eye Visual Acuity Change From Baseline at 26 Weeks
Description	Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.
Time Frame	26 weeks after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levodopa/Carbidopa	Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching	Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
Measure Participants	86	45
Mean (Standard Deviation) [letters]	1.4 (3.6)	0.8 (3.3)

Adverse Events

Time Frame	From enrollment to last follow-up visit (26 weeks)
Arm/Group Title	Levodopa/Carbidopa		Placebo
Arm/Group Description	Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid Levodopa/Carbidopa: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid Patching: Two hours of daily patching		Oral placebo tid Placebo: Oral placebo tid Patching: Two hours of daily patching
All Cause Mortality
	Levodopa/Carbidopa		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Levodopa/Carbidopa		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/90 (0%)		0/49 (0%)
Other (Not Including Serious) Adverse Events
	Levodopa/Carbidopa		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	37/90 (41.1%)		17/49 (34.7%)
Eye disorders
Dry eye	0/90 (0%)	0	4/49 (8.2%)	4
Eye irritation	0/90 (0%)	0	3/49 (6.1%)	3
Gastrointestinal disorders
Gastroenteritis viral	4/90 (4.4%)	5	3/49 (6.1%)	3
General disorders
Headache	18/90 (20%)	23	4/49 (8.2%)	6
Nausea	6/90 (6.7%)	7	6/49 (12.2%)	6
Cough	4/90 (4.4%)	4	3/49 (6.1%)	4
Nasopharyngitis	4/90 (4.4%)	4	4/49 (8.2%)	4
Pharyngitis streptococcal	3/90 (3.3%)	3	3/49 (6.1%)	3
Skin and subcutaneous tissue disorders
Rash	5/90 (5.6%)	6	3/49 (6.1%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.