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Nitisinone for Type 1B Oculocutaneous Albinism

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ClinicalTrials.gov Identifier: NCT01838655
Recruitment Status : Completed
First Posted : April 24, 2013
Results First Posted : November 17, 2017
Last Update Posted : November 17, 2017
Sponsor:
Collaborator:
National Human Genome Research Institute (NHGRI)
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Eye Institute (NEI) )

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Albinism
Vision Loss
Intervention Drug: Nitisinone
Enrollment 5

Recruitment Details Five participants with OCA1B will be enrolled initially. However, up to an additional three participants may be enrolled to account for participants who withdraw from the study for any reason before the Month 12 visit.
Pre-assignment Details  
Arm/Group Title Nitisinone
Hide Arm/Group Description

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Period Title: Overall Study
Started 5
Completed 5
Not Completed 0
Arm/Group Title Nitisinone
Hide Arm/Group Description

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Baseline Participants 5
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants
<=18 years
0
   0.0%
Between 18 and 65 years
5
 100.0%
>=65 years
0
   0.0%
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 5 participants
38.8
(24 to 52)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants
Female
3
  60.0%
Male
2
  40.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
4
  80.0%
Unknown or Not Reported
1
  20.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
4
  80.0%
More than one race
0
   0.0%
Unknown or Not Reported
1
  20.0%
1.Primary Outcome
Title Absolute Mean Change in Iris Pigmentation on an 8-point Iris Transillumination Scale at 12 Months as Compared to Baseline. Participants Left and Right Eyes Will be Analyzed.
Hide Description High-resolution (2544x1696) digital images of the anterior segment of both eyes were captured prior to pupil dilation using diffuse illumination and iris transillumination. An independent reviewer selected two transillumination images from each eye of each participant for each visit according to preset quality criteria. Images were coded, randomized and presented to a panel of 18 graders on a SHARP 90” HD LED TV. After instruction and a practice dataset, graders scored each image using an 8-point scale. Graders could score images with a single decimal place if they felt an image fell in between two of the standards. The iris transillumination scale ranged from 0 to 8, with lower scores reflective of greater iris pigmentation (melanin content). The mean across all graders and the two images for each participant's eye at baseline and 12 months was calculated; these mean grades were then used to calculate absolute change from baseline at 12 months.
Time Frame Baseline and 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Right (OD) and left (OS) eyes
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
10
Mean (Standard Deviation)
Unit of Measure: scores on a scale
OD Number Analyzed 5 eyes
1.2  (1.68)
OS Number Analyzed 5 eyes
0.9  (1.52)
2.Secondary Outcome
Title Absolute Mean Change in Iris Pigmentation on an 8-point Iris Transillumination Scale at 3 Months as Compared to Baseline. Participants Left and Right Eyes Will be Analyzed.
Hide Description High-resolution (2544x1696) digital images of the anterior segment of both eyes were captured prior to pupil dilation using diffuse illumination and iris transillumination. An independent reviewer selected two transillumination images from each eye of each participant for each visit according to preset quality criteria. Images were coded, randomized and presented to a panel of 18 graders on a SHARP 90” HD LED TV. After instruction and a practice dataset, graders scored each image using an 8-point scale. Graders could score images with a single decimal place if they felt an image fell in between two of the standards. The iris transillumination scale ranged from 0 to 8, with lower scores reflective of greater iris pigmentation (melanin content). The mean across all graders and the two images for each participant's eye at baseline and 3 months was calculated; these mean grades were then used to calculate absolute change from baseline at 3 months.
Time Frame Baseline and 3 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Right (OD) and left (OS) eyes
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
10
Mean (Standard Deviation)
Unit of Measure: scores on a scale
OD Number Analyzed 5 eyes
0.8  (1.04)
OS Number Analyzed 5 eyes
0.9  (1.23)
3.Secondary Outcome
Title Absolute Mean Change in Iris Pigmentation on an 8-point Iris Transillumination Scale at 6 Months as Compared to Baseline. Participants Left and Right Eyes Will be Analyzed.
Hide Description High-resolution (2544x1696) digital images of the anterior segment of both eyes were captured prior to pupil dilation using diffuse illumination and iris transillumination. An independent reviewer selected two transillumination images from each eye of each participant for each visit according to preset quality criteria. Images were coded, randomized and presented to a panel of 18 graders on a SHARP 90” HD LED TV. After instruction and a practice dataset, graders scored each image using an 8-point scale. Graders could score images with a single decimal place if they felt an image fell in between two of the standards. The iris transillumination scale ranged from 0 to 8, with lower scores reflective of greater iris pigmentation (melanin content). The mean across all graders and the two images for each participant's eye at baseline and 6 months was calculated; these mean grades were then used to calculate absolute change from baseline at 6 months.
Time Frame Baseline and 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Right (OD) and left (OS) eyes
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
10
Mean (Standard Deviation)
Unit of Measure: scores on a scale
OD Number Analyzed 5 eyes
0.6  (0.39)
OS Number Analyzed 5 eyes
0.4  (0.31)
4.Secondary Outcome
Title Absolute Mean Change in Iris Pigmentation on an 8-point Iris Transillumination Scale at 9 Months as Compared to Baseline. Participants Left and Right Eyes Will be Analyzed.
Hide Description High-resolution (2544x1696) digital images of the anterior segment of both eyes were captured prior to pupil dilation using diffuse illumination and iris transillumination. An independent reviewer selected two transillumination images from each eye of each participant for each visit according to preset quality criteria. Images were coded, randomized and presented to a panel of 18 graders on a SHARP 90” HD LED TV. After instruction and a practice dataset, graders scored each image using an 8-point scale. Graders could score images with a single decimal place if they felt an image fell in between two of the standards. The iris transillumination scale ranged from 0 to 8, with lower scores reflective of greater iris pigmentation (melanin content). The mean across all graders and the two images for each participant's eye at baseline and 9 months was calculated; these mean grades were then used to calculate absolute change from baseline at 9 months.
Time Frame Baseline and 9 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Right (OD) and left (OS) eyes
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
10
Mean (Standard Deviation)
Unit of Measure: scores on a scale
OD Number Analyzed 5 eyes
0.9  (1.06)
OS Number Analyzed 5 eyes
0.6  (0.60)
5.Secondary Outcome
Title Absolute Change in Semi-quantitative Iris Pigmentation for Each Eye at 3 Months as Compared to Baseline
Hide Description In Adobe Photoshop 7.0 the high resolution slit lamp image was divided into 4 quadrants with vertical and horizontal lines transecting the center of the iris. Using the elliptical marquee tool, a circle, approximately 0.25 times the diameter of the iris, was drawn in the center of each quadrant. Gaussian blur with radius of 50 was applied to the area enclosed in the 4 circles. With the dropper tool, the red pigment value corresponding to the degree of iris transillumination was sampled at the center of each circle. The 4 values were averaged to yield a composite transillumination score for each subject. Quantified values were then correlated to a scale score from 1 to 8 to generate an 8-point iris transillumination scale, with lower scores reflective of greater iris pigmentation (melanin content). The mean score across the 2 images for each participant's eye was calculated at baseline and 3 months; these mean grades were then used to calculate absolute change from baseline.
Time Frame Baseline and 3 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Right (OD) and left (OS) eyes
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
10
Mean (Standard Deviation)
Unit of Measure: scores on a scale
OD Number Analyzed 5 eyes
1.2  (1.04)
OS Number Analyzed 5 eyes
0.6  (0.82)
6.Secondary Outcome
Title Absolute Change in Semi-quantitative Iris Pigmentation for Each Eye at 6 Months as Compared to Baseline
Hide Description In Adobe Photoshop 7.0 the high resolution slit lamp image was divided into 4 quadrants with vertical and horizontal lines transecting the center of the iris. Using the elliptical marquee tool, a circle, approximately 0.25 times the diameter of the iris, was drawn in the center of each quadrant. Gaussian blur with radius of 50 was applied to the area enclosed in the 4 circles. With the dropper tool, the red pigment value corresponding to the degree of iris transillumination was sampled at the center of each circle. The 4 values were averaged to yield a composite transillumination score for each subject. Quantified values were then correlated to a scale score from 1 to 8 to generate an 8-point iris transillumination scale, with lower scores reflective of greater iris pigmentation (melanin content). The mean score across the 2 images for each participant's eye was calculated at baseline and 6 months; these mean grades were then used to calculate absolute change from baseline.
Time Frame Baseline and 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Right (OD) and left (OS) eyes
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
10
Mean (Standard Deviation)
Unit of Measure: scores on a scale
OD Number Analyzed 5 eyes
0.4  (0.55)
OS Number Analyzed 5 eyes
0.1  (0.22)
7.Secondary Outcome
Title Absolute Change in Semi-quantitative Iris Pigmentation for Each Eye at 9 Months as Compared to Baseline
Hide Description In Adobe Photoshop 7.0 the high resolution slit lamp image was divided into 4 quadrants with vertical and horizontal lines transecting the center of the iris. Using the elliptical marquee tool, a circle, approximately 0.25 times the diameter of the iris, was drawn in the center of each quadrant. Gaussian blur with radius of 50 was applied to the area enclosed in the 4 circles. With the dropper tool, the red pigment value corresponding to the degree of iris transillumination was sampled at the center of each circle. The 4 values were averaged to yield a composite transillumination score for each subject. Quantified values were then correlated to a scale score from 1 to 8 to generate an 8-point iris transillumination scale, with lower scores reflective of greater iris pigmentation (melanin content). The mean score across the 2 images for each participant's eye was calculated at baseline and 9 months; these mean grades were then used to calculate absolute change from baseline.
Time Frame Baseline and 9 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Right (OD) and left (OS) eyes
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
10
Mean (Standard Deviation)
Unit of Measure: scores on a scale
OD Number Analyzed 5 eyes
0.8  (0.76)
OS Number Analyzed 5 eyes
0.7  (0.84)
8.Secondary Outcome
Title Absolute Change in Semi-quantitative Iris Pigmentation for Each Eye at 12 Months as Compared to Baseline
Hide Description In Adobe Photoshop 7.0 the high resolution slit lamp image was divided into 4 quadrants with vertical and horizontal lines transecting the center of the iris. Using the elliptical marquee tool, a circle, approximately 0.25 times the diameter of the iris, was drawn in the center of each quadrant. Gaussian blur with radius of 50 was applied to the area enclosed in the 4 circles. With the dropper tool, the red pigment value corresponding to the degree of iris transillumination was sampled at the center of each circle. The 4 values were averaged to yield a composite transillumination score for each subject. Quantified values were then correlated to a scale score from 1 to 8 to generate an 8-point iris transillumination scale, with lower scores reflective of greater iris pigmentation (melanin content). The mean score across the 2 images for each participant's eye was calculated at baseline and 12 months; these mean grades were then used to calculate absolute change from baseline.
Time Frame Baseline and 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Right (OD) and left (OS) eyes
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
10
Mean (Standard Deviation)
Unit of Measure: scores on a scale
OD Number Analyzed 5 eyes
1.4  (1.39)
OS Number Analyzed 5 eyes
1.2  (1.15)
9.Secondary Outcome
Title Percent Change in Semi-quantitative Iris Pigmentation for Each Eye at 3 Months as Compared to Baseline
Hide Description In Adobe Photoshop 7.0 the high resolution slit lamp image was divided into 4 quadrants with vertical and horizontal lines transecting the center of the iris. Using the elliptical marquee tool, a circle, approximately 0.25 times the diameter of the iris, was drawn in the center of each quadrant. Gaussian blur with radius of 50 was applied to the area enclosed in the 4 circles. With the dropper tool, the red pigment value corresponding to the degree of iris transillumination was sampled at the center of each circle. The 4 values were averaged to yield a composite transillumination score for each subject. Quantified values were then correlated to a scale score from 1 to 8 to generate an 8-point iris transillumination scale, with lower scores reflective of greater iris pigmentation (melanin content). The mean score across the 2 images for each participant's eye was calculated at baseline and 3 months; these mean grades were then used to calculate percentage change from baseline.
Time Frame Baseline and 3 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Right (OD) and left (OS) eyes
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
10
Mean (Standard Deviation)
Unit of Measure: percentage change
OD Number Analyzed 5 eyes
66.7  (51.37)
OS Number Analyzed 5 eyes
29.0  (41.29)
10.Secondary Outcome
Title Percent Change in Semi-quantitative Iris Pigmentation for Each Eye at 6 Months as Compared to Baseline
Hide Description In Adobe Photoshop 7.0 the high resolution slit lamp image was divided into 4 quadrants with vertical and horizontal lines transecting the center of the iris. Using the elliptical marquee tool, a circle, approximately 0.25 times the diameter of the iris, was drawn in the center of each quadrant. Gaussian blur with radius of 50 was applied to the area enclosed in the 4 circles. With the dropper tool, the red pigment value corresponding to the degree of iris transillumination was sampled at the center of each circle. The 4 values were averaged to yield a composite transillumination score for each subject. Quantified values were then correlated to a scale score from 1 to 8 to generate an 8-point iris transillumination scale, with lower scores reflective of greater iris pigmentation (melanin content). The mean score across the 2 images for each participant's eye was calculated at baseline and 6 months; these mean grades were then used to calculate percentage change from baseline.
Time Frame Baseline and 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Right (OD) and left (OS) eyes
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
10
Mean (Standard Deviation)
Unit of Measure: percentage change
OD Number Analyzed 5 eyes
23.3  (32.49)
OS Number Analyzed 5 eyes
4.0  (8.94)
11.Secondary Outcome
Title Percent Change in Semi-quantitative Iris Pigmentation for Each Eye at 9 Months as Compared to Baseline
Hide Description In Adobe Photoshop 7.0 the high resolution slit lamp image was divided into 4 quadrants with vertical and horizontal lines transecting the center of the iris. Using the elliptical marquee tool, a circle, approximately 0.25 times the diameter of the iris, was drawn in the center of each quadrant. Gaussian blur with radius of 50 was applied to the area enclosed in the 4 circles. With the dropper tool, the red pigment value corresponding to the degree of iris transillumination was sampled at the center of each circle. The 4 values were averaged to yield a composite transillumination score for each subject. Quantified values were then correlated to a scale score from 1 to 8 to generate an 8-point iris transillumination scale, with lower scores reflective of greater iris pigmentation (melanin content). The mean score across the 2 images for each participant's eye was calculated at baseline and 9 months; these mean grades were then used to calculate percentage change from baseline.
Time Frame Baseline and 9 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Right (OD) and left (OS) eyes
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
10
Mean (Standard Deviation)
Unit of Measure: percentage change
OD Number Analyzed 5 eyes
42.0  (42.66)
OS Number Analyzed 5 eyes
34.0  (42.19)
12.Secondary Outcome
Title Percent Change in Semi-quantitative Iris Pigmentation for Each Eye at 12 Months as Compared to Baseline
Hide Description In Adobe Photoshop 7.0 the high resolution slit lamp image was divided into 4 quadrants with vertical and horizontal lines transecting the center of the iris. Using the elliptical marquee tool, a circle, approximately 0.25 times the diameter of the iris, was drawn in the center of each quadrant. Gaussian blur with radius of 50 was applied to the area enclosed in the 4 circles. With the dropper tool, the red pigment value corresponding to the degree of iris transillumination was sampled at the center of each circle. The 4 values were averaged to yield a composite transillumination score for each subject. Quantified values were then correlated to a scale score from 1 to 8 to generate an 8-point iris transillumination scale, with lower scores reflective of greater iris pigmentation (melanin content). The mean score across the 2 images for each participant's eye was calculated at baseline and 12 months; these mean grades were then used to calculate percentage change from baseline.
Time Frame Baseline and 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Right (OD) and left (OS) eyes
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
10
Mean (Standard Deviation)
Unit of Measure: percentage change
OD Number Analyzed 5 eyes
77.7  (91.94)
OS Number Analyzed 5 eyes
67.0  (59.75)
13.Secondary Outcome
Title Absolute Change in Electronic Visual Acuity at 3 Months Compared to Baseline
Hide Description Visual acuity was measured using the Electronic ETDRS Visual Acuity Testing protocol. Acuity is measured as letters read using an electronic ETDRS program.
Time Frame Baseline and 3 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Right (OD) and Left (OS) eyes
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
10
Mean (Standard Deviation)
Unit of Measure: ETDRS letters
OD Number Analyzed 5 eyes
1.8  (0.84)
OS Number Analyzed 5 eyes
6.0  (3.61)
14.Secondary Outcome
Title Absolute Change in Electronic Visual Acuity at 6 Months Compared to Baseline
Hide Description Visual acuity was measured using the Electronic ETDRS Visual Acuity Testing protocol. Acuity is measured as letters read using an electronic ETDRS program.
Time Frame Baseline and 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Right (OD) and Left (OS) eyes
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
10
Mean (Standard Deviation)
Unit of Measure: ETDRS letters
OD Number Analyzed 5 eyes
4.2  (2.17)
OS Number Analyzed 5 eyes
4.8  (3.42)
15.Secondary Outcome
Title Absolute Change in Electronic Visual Acuity at 9 Months Compared to Baseline
Hide Description Visual acuity was measured using the Electronic ETDRS Visual Acuity Testing protocol. Acuity is measured as letters read using an electronic ETDRS program.
Time Frame Baseline and 9 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Right (OD) and Left (OS) eyes
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
10
Mean (Standard Deviation)
Unit of Measure: ETDRS letters
OD Number Analyzed 5 eyes
2.8  (2.95)
OS Number Analyzed 5 eyes
5.6  (2.51)
16.Secondary Outcome
Title Absolute Change in Electronic Visual Acuity at 12 Months Compared to Baseline
Hide Description Visual acuity was measured using the Electronic ETDRS Visual Acuity Testing protocol. Acuity is measured as letters read using an electronic ETDRS program.
Time Frame Baseline and 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Right (OD) and Left (OS) eyes
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
10
Mean (Standard Deviation)
Unit of Measure: ETDRS letters
OD Number Analyzed 5 eyes
5.4  (3.78)
OS Number Analyzed 5 eyes
5.0  (5.70)
17.Secondary Outcome
Title Absolute Change in Contrast Sensitivity Without Glare at 3 Months Compared to Baseline
Hide Description Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. The minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity without glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 3 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
Time Frame Baseline and 3 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: units
Frequency 1.5 1.6  (1.52)
Frequency 3 0.8  (0.84)
Frequency 6 0.4  (0.55)
Frequency 12 1.2  (2.17)
Frequency 18 0.6  (1.34)
18.Secondary Outcome
Title Absolute Change in Contrast Sensitivity Without Glare at 6 Months Compared to Baseline
Hide Description Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. The minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity without glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 6 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
Time Frame Baseline and 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: units
Frequency 1.5 2.0  (2.83)
Frequency 3 0.2  (0.45)
Frequency 6 1.6  (1.52)
Frequency 12 2.8  (2.95)
Frequency 18 0.0  (0.00)
19.Secondary Outcome
Title Absolute Change in Contrast Sensitivity Without Glare at 9 Months Compared to Baseline
Hide Description Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. The minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity without glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 9 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
Time Frame Baseline and 9 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: units
Frequency 1.5 1.8  (2.49)
Frequency 3 0.6  (0.55)
Frequency 6 1.0  (1.00)
Frequency 12 1.4  (2.19)
Frequency 18 0.0  (0.00)
20.Secondary Outcome
Title Absolute Change in Contrast Sensitivity Without Glare at 12 Months Compared to Baseline
Hide Description Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. The minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity without glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 12 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
Time Frame Baseline and 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: units
Frequency 1.5 2.4  (2.51)
Frequency 3 2.0  (2.55)
Frequency 6 1.8  (1.92)
Frequency 12 1.6  (2.19)
Frequency 18 0.6  (1.34)
21.Secondary Outcome
Title Absolute Change in Contrast Sensitivity With Medium Glare at 3 Months Compared to Baseline
Hide Description Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. Minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity with medium glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 3 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
Time Frame Baseline and 3 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: units
Frequency 1.5 1.4  (1.14)
Frequency 3 0.4  (0.55)
Frequency 6 3.6  (3.78)
Frequency 12 0.2  (0.45)
Frequency 18 0.6  (1.34)
22.Secondary Outcome
Title Absolute Change in Contrast Sensitivity With Medium Glare at 6 Months Compared to Baseline
Hide Description Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. Minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity with medium glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 6 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
Time Frame Baseline and 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: units
Frequency 1.5 2.4  (2.88)
Frequency 3 1.4  (1.67)
Frequency 6 1.8  (1.79)
Frequency 12 0.4  (0.89)
Frequency 18 0.6  (1.34)
23.Secondary Outcome
Title Absolute Change in Contrast Sensitivity With Medium Glare at 9 Months Compared to Baseline
Hide Description Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. Minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity with medium glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 9 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
Time Frame Baseline and 9 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: units
Frequency 1.5 2.0  (2.35)
Frequency 3 1.2  (0.84)
Frequency 6 1.0  (1.00)
Frequency 12 0.6  (1.34)
Frequency 18 0.8  (1.30)
24.Secondary Outcome
Title Absolute Change in Contrast Sensitivity With Medium Glare at 12 Months Compared to Baseline
Hide Description Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. Minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity with medium glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 12 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
Time Frame Baseline and 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: units
Frequency 1.5 1.4  (2.61)
Frequency 3 1.8  (1.79)
Frequency 6 2.6  (2.79)
Frequency 12 0.4  (0.89)
Frequency 18 1.2  (1.64)
25.Secondary Outcome
Title Absolute Change in Contrast Sensitivity With High Glare at 3 Months Compared to Baseline
Hide Description Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. Minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity with high glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 3 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
Time Frame Baseline and 3 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: units
Frequency 1.5 1.2  (1.10)
Frequency 3 1.8  (2.49)
Frequency 6 0.2  (0.45)
Frequency 12 0.2  (0.45)
Frequency 18 0.0  (0.00)
26.Secondary Outcome
Title Absolute Change in Contrast Sensitivity With High Glare at 6 Months Compared to Baseline
Hide Description Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. Minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity with high glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 6 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
Time Frame Baseline and 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: units
Frequency 1.5 1.0  (1.00)
Frequency 3 1.6  (1.67)
Frequency 6 1.2  (2.17)
Frequency 12 0.4  (0.55)
Frequency 18 0.0  (0.00)
27.Secondary Outcome
Title Absolute Change in Contrast Sensitivity With High Glare at 9 Months Compared to Baseline
Hide Description Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. Minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity with high glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 9 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
Time Frame Baseline and 9 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: units
Frequency 1.5 1.4  (0.55)
Frequency 3 0.6  (0.55)
Frequency 6 1.0  (2.24)
Frequency 12 1.6  (2.61)
Frequency 18 0.6  (1.34)
28.Secondary Outcome
Title Absolute Change in Contrast Sensitivity With High Glare at 12 Months Compared to Baseline
Hide Description Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. Minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity with high glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 12 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
Time Frame Baseline and 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: units
Frequency 1.5 1.6  (1.52)
Frequency 3 2.2  (2.28)
Frequency 6 2.6  (3.21)
Frequency 12 1.8  (1.79)
Frequency 18 0.0  (0.00)
29.Secondary Outcome
Title Absolute Change in Adjusted Melanin Index at 3 Months Compared to Baseline
Hide Description Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object’s reflectance to the maximum reflectance possible). Apparent absorbance (AA) at a given wavelength was determined as log10 (PR of blank/PR of object) at that wavelength. Adjusted Melanin (AM) index is calculated as the slope of AA levels from 650 to 700 nm. Lower values of AM index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites: forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Absolute change from baseline was calculated using these mean values.
Time Frame Baseline and 3 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: Adjusted Melanin Index*10^-5
Forehead 16.4  (14.95)
Inner Bicep 4.8  (5.24)
Lower Back 20.9  (18.91)
Inner Forearm 10.7  (5.52)
Outer Forearm 10.6  (5.60)
30.Secondary Outcome
Title Absolute Change in Adjusted Melanin Index at 6 Months Compared to Baseline
Hide Description Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object’s reflectance to the maximum reflectance possible). Apparent absorbance (AA) at a given wavelength was determined as log10 (PR of blank/PR of object) at that wavelength. Adjusted Melanin (AM) index is calculated as the slope of AA levels from 650 to 700 nm. Lower values of AM index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites: forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Absolute change from baseline was calculated using these mean values.
Time Frame Baseline and 6 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participant 005 did not have skin reflectometry measurements for any site at Month 6.
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: Adjusted Melanin Index*10^-5
Forehead 11.8  (4.57)
Inner Bicep 8.2  (6.19)
Lower Back 9.3  (7.60)
Inner Forearm 12.1  (10.59)
Outer Forearm 12.6  (6.71)
31.Secondary Outcome
Title Absolute Change in Adjusted Melanin Index at 9 Months Compared to Baseline
Hide Description Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object’s reflectance to the maximum reflectance possible). Apparent absorbance (AA) at a given wavelength was determined as log10 (PR of blank/PR of object) at that wavelength. Adjusted Melanin (AM) index is calculated as the slope of AA levels from 650 to 700 nm. Lower values of AM index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites: forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Absolute change from baseline was calculated using these mean values.
Time Frame Baseline and 9 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participant 002 did not have any skin reflectometry measurements for any site at Month 9.
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: Adjusted Melanin Index*10^-5
Forehead 10.3  (13.41)
Inner Bicep 9.4  (5.85)
Lower Back 5.5  (4.12)
Inner Forearm 11.6  (7.82)
Outer Forearm 1.5  (0.98)
32.Secondary Outcome
Title Absolute Change in Adjusted Melanin Index at 12 Months Compared to Baseline
Hide Description Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object’s reflectance to the maximum reflectance possible). Apparent absorbance (AA) at a given wavelength was determined as log10 (PR of blank/PR of object) at that wavelength. Adjusted Melanin (AM) index is calculated as the slope of AA levels from 650 to 700 nm. Lower values of AM index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites: forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Absolute change from baseline was calculated using these mean values.
Time Frame Baseline and 12 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: Adjusted Melanin Index*10^-5
Forehead 8.3  (6.89)
Inner Bicep 7.0  (7.74)
Lower Back 4.2  (3.18)
Inner Forearm 6.8  (4.20)
Outer Forearm 8.6  (5.09)
33.Secondary Outcome
Title Percent Change in Adjusted Melanin Index at 3 Months Compared to Baseline
Hide Description Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object’s reflectance to the maximum reflectance possible). Apparent absorbance (AA) at a given wavelength was determined as log10 (PR of blank/PR of object) at that wavelength. Adjusted Melanin (AM) index is calculated as the slope of AA levels from 650 to 700 nm. Lower values of AM index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites: forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Percent change from baseline was calculated using these mean values.
Time Frame Baseline and 3 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: Percentage change
Forehead 50.1  (49.48)
Inner Bicep 40.1  (35.76)
Lower Back 201.0  (321.19)
Inner Forearm 83.3  (70.69)
Outer Forearm 42.1  (22.67)
34.Secondary Outcome
Title Percent Change in Adjusted Melanin Index at 6 Months Compared to Baseline
Hide Description Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object’s reflectance to the maximum reflectance possible). Apparent absorbance (AA) at a given wavelength was determined as log10 (PR of blank/PR of object) at that wavelength. Adjusted Melanin (AM) index is calculated as the slope of AA levels from 650 to 700 nm. Lower values of AM index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites: forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Percent change from baseline was calculated using these mean values.
Time Frame Baseline and 6 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participant 005 did not have skin reflectometry measurements for any site at Month 6.
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: Percentage change
Forehead 35.4  (14.10)
Inner Bicep 123.0  (113.41)
Lower Back 117.4  (120.5)
Inner Forearm 91.1  (116.26)
Outer Forearm 67.9  (56.49)
35.Secondary Outcome
Title Percent Change in Adjusted Melanin Index at 9 Months Compared to Baseline
Hide Description Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object’s reflectance to the maximum reflectance possible). Apparent absorbance (AA) at a given wavelength was determined as log10 (PR of blank/PR of object) at that wavelength. Adjusted Melanin (AM) index is calculated as the slope of AA levels from 650 to 700 nm. Lower values of AM index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites: forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Percent change from baseline was calculated using these mean values.
Time Frame Baseline and 9 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participant 002 did not have skin reflectometry measurements for any site at Month 9.
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: Percentage change
Forehead 33.2  (44.21)
Inner Bicep 94.5  (60.03)
Lower Back 39.6  (42.36)
Inner Forearm 81.0  (93.51)
Outer Forearm 6.0  (5.86)
36.Secondary Outcome
Title Percent Change in Adjusted Melanin Index at 12 Months Compared to Baseline
Hide Description Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object’s reflectance to the maximum reflectance possible). Apparent absorbance (AA) at a given wavelength was determined as log10 (PR of blank/PR of object) at that wavelength. Adjusted Melanin (AM) index is calculated as the slope of AA levels from 650 to 700 nm. Lower values of AM index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites: forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Percent change from baseline was calculated using these mean values.
Time Frame Baseline and 12 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: Percentage change
Forehead 24.7  (21.76)
Inner Bicep 104.5  (132.61)
Lower Back 32.7  (31.81)
Inner Forearm 47.4  (48.10)
Outer Forearm 30.5  (7.60)
37.Secondary Outcome
Title Absolute Change in Melanin Index at 3 Months Compared to Baseline
Hide Description

Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object’s reflectance to the maximum reflectance possible). Melanin (M) index was calculated as follows:

Eqn 1= [ (PR at 650nm + PR at 660nm + 0.5*PR at 640nm + 0.5*PR at 670nm)/3 ]/100; M index = 100*log (1/Eqn 1) Higher values of M index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites:forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Absolute change from baseline was calculated using these mean values.

Time Frame Baseline and 3 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: Melanin Index
Forehead 3.8  (3.02)
Inner Bicep 1.4  (0.69)
Lower Back 0.6  (0.63)
Inner Forearm 1.8  (1.12)
Outer Forearm 4.5  (4.45)
38.Secondary Outcome
Title Absolute Change in Melanin Index at 6 Months Compared to Baseline
Hide Description

Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object’s reflectance to the maximum reflectance possible). Melanin (M) index was calculated as follows:

Eqn 1= [ (PR at 650nm + PR at 660nm + 0.5*PR at 640nm + 0.5*PR at 670nm)/3 ]/100; M index = 100*log (1/Eqn 1) Higher values of M index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites:forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Absolute change from baseline was calculated using these mean values.

Time Frame Baseline and 6 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participant 005 did not have skin reflectometry measurements for any site at Month 6.
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: Melanin Index
Forehead 2.2  (1.29)
Inner Bicep 2.7  (1.68)
Lower Back 3.3  (3.72)
Inner Forearm 2.1  (1.43)
Outer Forearm 4.4  (5.80)
39.Secondary Outcome
Title Absolute Change in Melanin Index at 9 Months Compared to Baseline
Hide Description

Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object’s reflectance to the maximum reflectance possible). Melanin (M) index was calculated as follows:

Eqn 1= [ (PR at 650nm + PR at 660nm + 0.5*PR at 640nm + 0.5*PR at 670nm)/3 ]/100; M index = 100*log (1/Eqn 1) Higher values of M index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites:forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Absolute change from baseline was calculated using these mean values.

Time Frame Baseline and 9 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participant 002 did not have skin reflectometry measurements for any site at Month 9.
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: Melanin Index
Forehead 2.4  (1.98)
Inner Bicep 1.9  (1.60)
Lower Back 3.2  (3.23)
Inner Forearm 2.1  (1.33)
Outer Forearm 2.2  (2.48)
40.Secondary Outcome
Title Absolute Change in Melanin Index at 12 Months Compared to Baseline
Hide Description

Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object’s reflectance to the maximum reflectance possible). Melanin (M) index was calculated as follows:

Eqn 1= [ (PR at 650nm + PR at 660nm + 0.5*PR at 640nm + 0.5*PR at 670nm)/3 ]/100; M index = 100*log (1/Eqn 1) Higher values of M index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites:forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Absolute change from baseline was calculated using these mean values.

Time Frame Baseline and 12 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: Melanin Index
Forehead 3.7  (3.29)
Inner Bicep 2.3  (1.90)
Lower Back 2.0  (1.55)
Inner Forearm 2.2  (1.96)
Outer Forearm 3.4  (3.38)
41.Secondary Outcome
Title Percent Change in Melanin Index at 3 Months Compared to Baseline
Hide Description

Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object’s reflectance to the maximum reflectance possible). Melanin (M) index was calculated as follows:

Eqn 1= [ (PR at 650nm + PR at 660nm + 0.5*PR at 640nm + 0.5*PR at 670nm)/3 ]/100; M index = 100*log (1/Eqn 1) Higher values of M index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites:forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Percent change from baseline was calculated using these mean values.

Time Frame Baseline and 3 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: Percentage change
Forehead 15.0  (12.90)
Inner Bicep 6.7  (3.50)
Lower Back 2.8  (3.34)
Inner Forearm 8.6  (5.84)
Outer Forearm 18.9  (19.90)
42.Secondary Outcome
Title Percent Change in Melanin Index at 6 Months Compared to Baseline
Hide Description

Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object’s reflectance to the maximum reflectance possible). Melanin (M) index was calculated as follows:

Eqn 1= [ (PR at 650nm + PR at 660nm + 0.5*PR at 640nm + 0.5*PR at 670nm)/3 ]/100; M index = 100*log (1/Eqn 1) Higher values of M index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites:forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Percent change from baseline was calculated using these mean values.

Time Frame Baseline and 6 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participant 005 did not have skin reflectometry measurements for any site at Month 6.
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: Percentage change
Forehead 8.4  (4.62)
Inner Bicep 12.7  (8.31)
Lower Back 17.0  (19.52)
Inner Forearm 10.2  (7.50)
Outer Forearm 19.2  (24.93)
43.Secondary Outcome
Title Percent Change in Melanin Index at 9 Months Compared to Baseline
Hide Description

Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object’s reflectance to the maximum reflectance possible). Melanin (M) index was calculated as follows:

Eqn 1= [ (PR at 650nm + PR at 660nm + 0.5*PR at 640nm + 0.5*PR at 670nm)/3 ]/100; M index = 100*log (1/Eqn 1) Higher values of M index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites:forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Percent change from baseline was calculated using these mean values.

Time Frame Baseline and 9 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participant 002 did not have skin reflectometry measurements for any site at Month 9.
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: Percentage change
Forehead 9.2  (7.30)
Inner Bicep 8.9  (7.89)
Lower Back 15.8  (16.17)
Inner Forearm 9.5  (6.15)
Outer Forearm 8.8  (10.63)
44.Secondary Outcome
Title Percent Change in Melanin Index at 12 Months Compared to Baseline
Hide Description

Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object’s reflectance to the maximum reflectance possible). Melanin (M) index was calculated as follows:

Eqn 1= [ (PR at 650nm + PR at 660nm + 0.5*PR at 640nm + 0.5*PR at 670nm)/3 ]/100; M index = 100*log (1/Eqn 1) Higher values of M index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites:forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Percent change from baseline was calculated using these mean values.

Time Frame Baseline and 12 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: Percentage change
Forehead 14.7  (14.11)
Inner Bicep 10.9  (9.43)
Lower Back 10.2  (7.92)
Inner Forearm 10.4  (10.19)
Outer Forearm 13.3  (13.44)
45.Secondary Outcome
Title Absolute Change in Electroretinogram (ERG) at Month 6 as Compared to Baseline.
Hide Description Amplitude for the ERG parameter, Dark Adaptation (DA) Comb B, was measured at each visit. Participants left and right eye will be analyzed.
Time Frame Baseline and 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Right eyes (OD) and left eyes (OS)
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
10
Mean (Standard Deviation)
Unit of Measure: µV
OD Number Analyzed 5 eyes
38.6  (27.93)
OS Number Analyzed 5 eyes
76.2  (29.06)
46.Secondary Outcome
Title Absolute Change in Electroretinogram (ERG) at Month 12 as Compared to Baseline.
Hide Description Amplitude for the ERG parameter, Dark Adaptation (DA) Comb B, was measured at each visit. Participants left and right eye will be analyzed.
Time Frame Baseline and 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Right eyes (OD) and left eyes (OS)
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
10
Mean (Standard Deviation)
Unit of Measure: µV
OD Number Analyzed 5 eyes
27.8  (16.66)
OS Number Analyzed 5 eyes
85.8  (83.83)
47.Secondary Outcome
Title Qualitative Change in Hair Pigmentation at 3 Months Compared to Previous Visit.
Hide Description Qualitative change in hair pigmentation was measured as a binary endpoint (no change vs. increase) at Month 3 compared to previous visit.
Time Frame Baseline and 3 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Measure Type: Count of Participants
Unit of Measure: Participants
No change in hair pigmentation
1
  20.0%
Increase in hair pigmentation
4
  80.0%
48.Secondary Outcome
Title Qualitative Change in Hair Pigmentation at 6 Months Compared to Previous Visit.
Hide Description Qualitative change in hair pigmentation was measured as a binary endpoint (no change vs. increase) at Month 6 compared to Month 3
Time Frame 3 Months and 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Measure Type: Count of Participants
Unit of Measure: Participants
No change in hair pigmentation
3
  60.0%
Increase in hair pigmentation
2
  40.0%
49.Secondary Outcome
Title Qualitative Change in Hair Pigmentation at 9 Months Compared to Previous Visit.
Hide Description Qualitative change in hair pigmentation was measured as a binary endpoint (no change vs. increase) at Month 9 compared to Month 6
Time Frame 6 Months and 9 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Measure Type: Count of Participants
Unit of Measure: Participants
No change in hair pigmentation
4
  80.0%
Increase in hair pigmentation
1
  20.0%
50.Secondary Outcome
Title Qualitative Change in Hair Pigmentation at 12 Months Compared to Previous Visit.
Hide Description Qualitative change in hair pigmentation was measured as a binary endpoint (no change vs. increase) at Month 12 compared to Month 9
Time Frame 9 Months and 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Measure Type: Count of Participants
Unit of Measure: Participants
No change in hair pigmentation
5
 100.0%
Increase in hair pigmentation
0
   0.0%
51.Secondary Outcome
Title Qualitative Change in Skin Pigmentation at 3 Months Compared to Previous Visit.
Hide Description Qualitative change in skin pigmentation was measured as a binary endpoint (no change vs. increase) at Month 3 compared to previous visit.
Time Frame Baseline and 3 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Measure Type: Count of Participants
Unit of Measure: Participants
No change in skin pigmentation
4
  80.0%
Increase in skin pigmentation
1
  20.0%
52.Secondary Outcome
Title Qualitative Change in Skin Pigmentation at 6 Months Compared to Previous Visit.
Hide Description Qualitative change in skin pigmentation was measured as a binary endpoint (no change vs. increase) at Month 6 compared to Month 3
Time Frame 3 Months and 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Measure Type: Count of Participants
Unit of Measure: Participants
No change in skin pigmentation
5
 100.0%
Increase in skin pigmentation
0
   0.0%
53.Secondary Outcome
Title Qualitative Change in Skin Pigmentation at 9 Months Compared to Previous Visit.
Hide Description Qualitative change in skin pigmentation was measured as a binary endpoint (no change vs. increase) at Month 9 compared to Month 6
Time Frame 6 Months and 9 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Measure Type: Count of Participants
Unit of Measure: Participants
No change in skin pigmentation
5
 100.0%
Increase in skin pigmentation
0
   0.0%
54.Secondary Outcome
Title Qualitative Change in Skin Pigmentation at 12 Months Compared to Previous Visit.
Hide Description Qualitative change in skin pigmentation was measured as a binary endpoint (no change vs. increase) at Month 12 compared to Month 9
Time Frame 9 Months and 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Measure Type: Count of Participants
Unit of Measure: Participants
No change in skin pigmentation
5
 100.0%
Increase in skin pigmentation
0
   0.0%
55.Secondary Outcome
Title Qualitative Change in Fundus Pigmentation at 3 Months Compared to Previous Visit.
Hide Description Qualitative change in fundus pigmentation was measured as a binary endpoint (no change vs. increase) at Month 3 compared to previous visit.
Time Frame Baseline and 3 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Measure Type: Count of Participants
Unit of Measure: Participants
No change in fundus pigmentation
5
 100.0%
Increase in fundus pigmentation
0
   0.0%
56.Secondary Outcome
Title Qualitative Change in Fundus Pigmentation at 6 Months Compared to Previous Visit.
Hide Description Qualitative change in fundus pigmentation was measured as a binary endpoint (no change vs. increase) at Month 6 compared to Month 3
Time Frame 3 Months and 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Measure Type: Count of Participants
Unit of Measure: Participants
No change in fundus pigmentation
5
 100.0%
Increase in fundus pigmentation
0
   0.0%
57.Secondary Outcome
Title Qualitative Change in Fundus Pigmentation at 9 Months Compared to Previous Visit.
Hide Description Qualitative change in fundus pigmentation was measured as a binary endpoint (no change vs. increase) at Month 9 compared to Month 6
Time Frame 6 Months and 9 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Measure Type: Count of Participants
Unit of Measure: Participants
No change in fundus pigmentation
5
 100.0%
Increase in fundus pigmentation
0
   0.0%
58.Secondary Outcome
Title Qualitative Change in Fundus Pigmentation at 12 Months Compared to Previous Visit.
Hide Description Qualitative change in fundus pigmentation was measured as a binary endpoint (no change vs. increase) at Month 12 compared to Month 9
Time Frame 9 Months and 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Measure Type: Count of Participants
Unit of Measure: Participants
No change in fundus pigmentation
5
 100.0%
Increase in fundus pigmentation
0
   0.0%
59.Secondary Outcome
Title Absolute Change in Hair Melanin at 12 Months Compared to Baseline
Hide Description Hair melanin was assessed using pyrrole-2,3,5-tricarboxylic acid (PTCA), a marker of eumelanin and 4-amino-3-hydroxyphenylalanine (4-AHP), a marker of pheomelanin.
Time Frame Baseline and 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: ng/mg
PTCA 8.38  (5.11)
4-AHP 5.92  (11.68)
60.Secondary Outcome
Title Percent Change in Hair Melanin at 12 Months Compared to Baseline
Hide Description Hair melanin was assessed using pyrrole-2,3,5-tricarboxylic acid (PTCA), a marker of eumelanin and 4-amino-3-hydroxyphenylalanine (4-AHP), a marker of pheomelanin.
Time Frame Baseline and 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: percentage change
PTCA 50.30  (45.92)
4-AHP 27.23  (23.22)
61.Other Pre-specified Outcome
Title Number of Ocular Adverse Events
Hide Description [Not Specified]
Time Frame Study duration, up to 18 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Measure Type: Number
Unit of Measure: ocular adverse events
0
62.Other Pre-specified Outcome
Title Number of Non-ocular Adverse Events
Hide Description [Not Specified]
Time Frame Study duration, up to 18 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Measure Type: Number
Unit of Measure: non-ocular adverse events
10
63.Other Pre-specified Outcome
Title Severity of Adverse Events
Hide Description [Not Specified]
Time Frame Study duration, up to 18 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Measure Type: Number
Unit of Measure: adverse events
Mild 9
Moderate 1
64.Other Pre-specified Outcome
Title Number of Adverse Events Related to Investigational Product (IP)
Hide Description [Not Specified]
Time Frame Study duration, up to 18 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Measure Type: Number
Unit of Measure: adverse events related to IP
0
65.Other Pre-specified Outcome
Title Number of Participants Withdrawn From Investigational Product (IP) Due to Safety and Abnormal Laboratory Results
Hide Description [Not Specified]
Time Frame Study duration, up to 18 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitisinone
Hide Arm/Group Description:

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

Overall Number of Participants Analyzed 5
Measure Type: Number
Unit of Measure: participant withdrawals
0
Time Frame Up to 18 months
Adverse Event Reporting Description Adverse events were collected on and after the baseline visit, and when investigational product (IP) began.
 
Arm/Group Title Nitisinone
Hide Arm/Group Description

Oral administration of nitisinone

Nitisinone: Oral dose of 2mg daily for 12 months.

All-Cause Mortality
Nitisinone
Affected / at Risk (%)
Total   0/5 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Nitisinone
Affected / at Risk (%) # Events
Total   0/5 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Nitisinone
Affected / at Risk (%) # Events
Total   5/5 (100.00%)    
Blood and lymphatic system disorders   
Anaemia  1  1/5 (20.00%)  1
Cardiac disorders   
Palpitations  1  1/5 (20.00%)  1
Chest pain  1  1/5 (20.00%)  1
Gastrointestinal disorders   
Dyspepsia  1  1/5 (20.00%)  1
Gastrooesophageal reflux disease  1  1/5 (20.00%)  1
General disorders   
Dizziness  1  1/5 (20.00%)  1
Investigations   
Neurological examination abnormal  1  1/5 (20.00%)  1
Musculoskeletal and connective tissue disorders   
Pain in extremity  1  1/5 (20.00%)  1
Respiratory, thoracic and mediastinal disorders   
Bronchitis  1  1/5 (20.00%)  1
Vascular disorders   
Haemangioma  1  1/5 (20.00%)  1
1
Term from vocabulary, MedDRA (19.0)
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Brian Brooks, MD, PhD, Principal Investigator, NEI
Organization: National Institutes of Health
Phone: 301-451-2238
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Eye Institute (NEI) )
ClinicalTrials.gov Identifier: NCT01838655     History of Changes
Other Study ID Numbers: 130124
13-EI-0124 ( Other Identifier: NIH Combined NeuroScience Institutional Review Board )
First Submitted: April 20, 2013
First Posted: April 24, 2013
Results First Submitted: August 21, 2017
Results First Posted: November 17, 2017
Last Update Posted: November 17, 2017