STAR: Study of Ataluren in Participants With Nonsense Mutation Aniridia

• Sponsor: PTC Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02647359
• Collaborator: (none)
• Enrollment: 39
• Locations: 3
• Arms: 2
• Actual Duration (Months): 59.7
• Patients Per Site: 13
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study is designed to evaluate the effect of ataluren on Maximum Reading Speed as measured using the Minnesota Low Vision Reading Test (MNREAD) Acuity Charts in participants with nonsense mutation aniridia. This study involves a 4-week screening period, a 144-week treatment period (Stage 1: Weeks 1 to 48 [double-masked treatment] and Stage 2: Weeks 49 to 144 [open label treatment]), an optional 96-week open label extension sub-study, and a 4-week post-treatment follow-up period (either study completion or early termination). Participants that choose not to participate in the sub-study will be required to complete the post-treatment follow-up visit at the end of the Stage 2 open-label extension.

Condition or Disease	Intervention/Treatment	Phase
Aniridia	Drug: Ataluren; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 39 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Multicenter, Randomized, Double-Masked, Placebo-Controlled Study of the Safety and Efficacy of Ataluren (PTC124) for the Treatment of Nonsense Mutation Aniridia
• Actual Study Start Date: Jan 31, 2016
• Actual Primary Completion Date: Jan 22, 2021
• Actual Study Completion Date: Jan 22, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ataluren Participants will receive ataluren orally 3 times a day (TID) at a dose of 10 milligrams per kilogram (mg/kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who complete Stage 2 and agree to continue in open-label sub-study, will continue to receive ataluren treatment at same dose as mentioned above, for 96 weeks or until commercial availability of ataluren for this indication, whichever is first, or until a positive risk-benefit assessment in this indication is not demonstrated.	Drug: Ataluren; Ataluren oral suspension will be administered as per the dose and schedule specified in the respective arms.; Other Names: PTC124 Translarna
Placebo Comparator: Placebo Participants will receive placebo matching to ataluren TID orally in the morning, at midday, and in the evening for 48 weeks in Stage 1 (double-masked period) and ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for additional 96 weeks in Stage 2 (open-label extension period). Participants, who complete Stage 2 and agree to continue in open-label sub-study, will continue to receive ataluren treatment at same dose as mentioned above, for 96 weeks or until commercial availability of ataluren for this indication, whichever is first, or until a positive risk-benefit assessment in this indication is not demonstrated.	Drug: Ataluren; Ataluren oral suspension will be administered as per the dose and schedule specified in the respective arms.; Other Names: PTC124 Translarna ; Drug: Placebo; Placebo will be administered as per the schedule specified in the respective arm.

Outcome Measures

Primary Outcome Measures

1. Percent Change From Baseline in Maximum Reading Speed of Oculus Unitas (OU) (Both Eyes) at Week 48, as Measured Using the Minnesota Low Vision Reading Test (MNREAD) Acuity Charts [Baseline, Week 48]

   MNREAD Acuity Chart can only be used to assess participants ≥8 years old. MNREAD Acuity Chart measures reading speed as a function of print size in participants with normal and low vision. The test consists of short sentences with print size decreasing by 0.1 log unit steps from a maximum of 1.3 logarithm of the minimum angle of resolution (logMAR) (equivalent to 20/400 or 6/120 when viewed at 40 centimeters [cm]) to -0.5 logMAR (equivalent to 20/6 or 6/2). An MNREAD Acuity Chart curve of reading speed vs print size has a typical shape for normally sighted persons and many low-vision individuals. This curve is characterized by 3 summary values. At large print sizes, reading speed remains fairly constant, forming a plateau that represents the maximum reading speed. As the print size decreases, a critical print size (CPS) is reached at which reading speed begins to decline rapidly. Finally, the smallest print size that can be read is defined as the reading acuity (RA).

Secondary Outcome Measures

1. Change From Baseline in Reading Accessibility Index of Both Eyes at Week 48 [Baseline, Week 48]

   Reading Accessibility Index is defined as the mean reading speed in words per minute (wpm) across the 10 largest physical print sizes on the MNREAD Acuity Chart, normalized by the value for a group of normally sighted young adults. For a viewing distance of 40 cm, this range of print sizes corresponds to 0.4 to 1.3 logMAR. This range of print sizes was chosen for 2 reasons. First, it sustains the manifest refraction spherical equivalent (MRS) in normally sighted persons. Second, it covers most contemporary printed text found in everyday life. Because the Reading Accessibility Index is normalized by the value for a group of normally sighted young adults (aged 18 to 39 years), a Reading Accessibility Index of 1.0 represents normal performance for this age group. Values less than 1.0 mean reduced accessibility to printed text within the range of print size encountered in daily life. Missing data was imputed using last observation carried forward (LOCF) method.

2. Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 48 [Baseline, Week 48]

   The BCVA was evaluated using the Early Treatment Diabetic Retinopathy Study (ETDRS) Method. Missing data was imputed using LOCF method.

3. Percent Change From Baseline in Maximum Reading Speed of Oculus Dexter (OD) (Right Eye) and Oculus Sinister (OS) (Left Eye) at Week 48 [Baseline, Week 48]

   Maximum Reading Speed was measured using the MNREAD Acuity Chart, which can only be used to assess participants ≥8 years old. The MNREAD Acuity Chart measures reading speed as a function of print size in participants with normal and low vision. The test consists of short sentences with print size decreasing by 0.1 log unit steps from a maximum of 1.3 logMAR (equivalent to 20/400 or 6/120 when viewed at 40 cm) to -0.5 logMAR (equivalent to 20/6 or 6/2). An MNREAD Acuity Chart curve of reading speed vs print size has a typical shape for normally sighted persons and many low-vision individuals. This curve is characterized by 3 summary values. At large print sizes, reading speed remains fairly constant, forming a plateau that represents the maximum reading speed. As the print size decreases, a CPS is reached at which reading speed begins to decline rapidly. Finally, the smallest print size that can be read is defined as the RA.

4. Change From Baseline in Reading Accessibility Index of Right Eye and Left Eye at Week 48 [Baseline, Week 48]

   Reading Accessibility Index is defined as the mean reading speed in wpm across the 10 largest physical print sizes on the MNREAD Acuity Chart, normalized by the value for a group of normally sighted young adults. For a viewing distance of 40 cm, this range of print sizes corresponds to 0.4 to 1.3 logMAR. This range of print sizes was chosen for 2 reasons. First, it sustains the MRS in normally sighted persons. Second, it covers most contemporary printed text found in everyday life. Because the Reading Accessibility Index is normalized by the value for a group of normally sighted young adults (aged 18 to 39 years), a Reading Accessibility Index of 1.0 represents normal performance for this age group. Values less than 1.0 mean reduced accessibility to printed text within the range of print size encountered in daily life. Missing data was imputed using LOCF method.

5. Change From Baseline in Critical Print Size (CPS) of Both Eyes, Right Eye, and Left Eye at Week 48 [Baseline, Week 48]

   The MNREAD Acuity Chart measures reading speed as a function of print size in participants with normal and low vision. The test consists of short sentences with print size decreasing by 0.1 log unit steps from a maximum of 1.3 logMAR (equivalent to 20/400 or 6/120 when viewed at 40 cm) to -0.5 logMAR (equivalent to 20/6 or 6/2). An MNREAD Acuity Chart curve of reading speed vs print size has a typical shape for normally sighted persons and many low-vision individuals. This curve is characterized by 3 summary values. At large print sizes, reading speed remains fairly constant, forming a plateau that represents the maximum reading speed. As the print size decreases, a CPS is reached at which reading speed begins to decline rapidly. Finally, the smallest print size that can be read is defined as the RA. Missing data was imputed using LOCF method.

6. Change From Baseline in Reading Acuity (RA) of Both Eyes, Right Eye, and Left Eye at Week 48 [Baseline, Week 48]

   The MNREAD Acuity Chart measures reading speed as a function of print size in participants with normal and low vision. The test consists of short sentences with print size decreasing by 0.1 log unit steps from a maximum of 1.3 logMAR (equivalent to 20/400 or 6/120 when viewed at 40 cm) to -0.5 logMAR (equivalent to 20/6 or 6/2). An MNREAD Acuity Chart curve of reading speed vs print size has a typical shape for normally sighted persons and many low-vision individuals. This curve is characterized by 3 summary values. At large print sizes, reading speed remains fairly constant, forming a plateau that represents the maximum reading speed. As the print size decreases, a CPS is reached at which reading speed begins to decline rapidly. Finally, the smallest print size that can be read is defined as the RA. Missing data was imputed using LOCF method.

7. Number of Participants With Change From Baseline in Severity of Corneal Keratopathy at Week 48 [Baseline to Week 48]

   The severity of corneal keratopathy was reported as worsened, not change, or improve. Missing data were imputed using LOCF.

8. Change From Baseline in Iris Area at Week 48 [Baseline, Week 48]

   Missing data were imputed using LOCF.

9. Change From Baseline in BCVA at Week 240 [Baseline, Week 240]

   The BCVA was evaluated using the ETDRS Method. Missing data were imputed using LOCF method.

10. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Baseline up to Week 244]

    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'. AEs were summarized separately for Stage 1 and for the overall ataluren experience, which included all participants who received ataluren throughput the study (Stage 1, open-label extension period [Stage 2], and sub-study).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Evidence of signed and dated informed consent document(s) indicating that the study candidate (and/or a parent/legal guardian) has been informed of all pertinent aspects of the study. Note: If the study candidate is considered a child under local regulation, a parent or legal guardian must provide written consent prior to initiation of study screening procedures and the study candidate may be required to provide written assent. The rules of the responsible institutional review board/independent ethics committee (IRB/IEC) regarding whether 1 or both parents must provide consent and the appropriate ages for obtaining consent and assent from the participant should be followed.

• Body weight greater than or equal to (>=) 12 kg.

• Documentation of the presence of a nonsense mutation in 1 allele of the PAX6 gene as determined by genotyping performed at a laboratory certified by the College of American Pathologists (CAP), or under the Clinical Laboratory Improvement Act/Amendment (CLIA), or by an equivalent organization.

• Clinical diagnosis of aniridia.

• Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, and study restrictions.

• Good general health, as determined at Screening by medical history and physical examination (including vital sign measurements).

• No clinically significant abnormality based upon laboratory assessments at Screening, in the opinion of the investigator.

• Female participants of childbearing potential are eligible for the study but must be willing to use adequate (at least 1 form of) contraceptive methods as described below during the study treatment period (starting from the day of first dose of study drug and ending 60 days after the last dose of study drug). Childbearing potential is defined as participants who have experienced menarche and who are neither postmenopausal nor have been permanently sterilized.

1. Hormonal methods of contraception (including oral and transdermal contraceptives, injectable progesterone, progestin subdermal implants, progesterone-releasing intrauterine devices [IUDs]) initiated at least 14 days prior to the first dose of study drug

2. Abstinence

3. Placement of a copper-containing IUD

4. Condom with spermicidal foam/gel/film/cream/suppository

5. Postmenopausal at least 12 months prior to first dose of study drug or permanently sterilized (for example, tubal occlusion, hysterectomy, bilateral salpingectomy)

6. Male partner who has had a vasectomy for at least 3 months prior to the first dose of study drug

• Male participants with partners of childbearing potential must agree to use adequate (at least 1 form of) contraception as described below during the study treatment period (starting from the day of first dose of study drug and ending 60 days after the last dose of study drug).

1. Abstinence

2. Vasectomy for at least 3 months prior to first dose of study drug or surgically sterile

3. Without a vasectomy, must use a condom with spermicidal foam/gel/film/cream suppository

Exclusion Criteria:

• Participants participating in any drug or device clinical investigation within 90 days prior to Screening or who anticipate participating in any other drug or device clinical investigation within the duration of this study.

• Exposure to ataluren within 90 days prior to Screening.

• Surgery within 30 days prior to enrollment.

• Female participants who are pregnant or breastfeeding. Female participants of childbearing potential must have a negative pregnancy test (beta-human chorionic gonadotropin [beta-HCG]) at screening and must use adequate (at least 1 form of) contraceptive methods.

• Active ocular infection or inflammation.

• Prior or ongoing medical condition (for example, concomitant illness, alcoholism, drug abuse, psychiatric condition), medical history, physical findings, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the participant, makes it unlikely that the course of study drug administration or follow-up would be completed, or could impair the assessment of study results.

• Participants with a positive result for hepatitis B, hepatitis C, or human immunodeficiency virus at Visit 1 (Screening).

• Ongoing warfarin, phenytoin, or tolbutamide therapy.

• Ongoing intravenous (IV) aminoglycoside or IV vancomycin use.

• Ongoing systemic cyclosporine therapy. Note: Topical cyclosporine therapy is permitted.

• Known hypersensitivity to any of the ingredients or excipients of the study drug (polydextrose, polyethylene glycol 3350, poloxamer 407, mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, vanilla, colloidal silica, or magnesium stearate).

• 20/200 or worse visual acuity in the better eye with best correction.

• Participants who are monocular.

• Participants with a history of complications due to ocular surgery that could interfere with the study procedures or assessment of study endpoints.

• Participants with any other significant ocular or systemic disease that the Investigator determines could interfere with the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Casey Eye Institute, Oregon Health & Science University	Portland	Oregon	United States	97239
2	University of Virginia	Charlottesville	Virginia	United States	22908
3	University of British Columbia	Vancouver	British Columbia	Canada	V5Z3N9

Sponsors and Collaborators

• PTC Therapeutics

Investigators

• Study Director: Quintus Ngumah, OD, PhD, PTC Therapeutics

Study Documents (Full-Text)

• Study Protocol - Dec 17, 2019
• Statistical Analysis Plan - Feb 5, 2020

More Information

Publications

None provided.

• Responsible Party: PTC Therapeutics
• ClinicalTrials.gov Identifier: NCT02647359
• Other Study ID Numbers: PTC124-GD-028 ANI
• First Posted: Jan 6, 2016
• Last Update Posted: May 27, 2022
• Last Verified: Apr 1, 2022

• Additional relevant MeSH terms: Aniridia

Study Results

Participant Flow

Arm/Group Title	Ataluren	Placebo
Arm/Group Description	Participants received ataluren orally 3 times a day (TID) at a dose of 10 milligrams (mg)/kilogram (kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Participants received placebo matched to ataluren TID orally in the morning, at midday, and in the evening for 48 weeks in Stage 1 (double-masked period) and ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.
Period Title: Stage 1: Double-Masked Period (48 Weeks)
STARTED	26	13
Received at Least 1 Dose of Study Drug	26	13
COMPLETED	22	12
NOT COMPLETED	4	1
Period Title: Stage 1: Double-Masked Period (48 Weeks)
STARTED	22	11
COMPLETED	12	7
NOT COMPLETED	10	4
Period Title: Stage 1: Double-Masked Period (48 Weeks)
STARTED	10	7
COMPLETED	2	3
NOT COMPLETED	8	4

Baseline Characteristics

Arm/Group Title	Ataluren	Placebo	Total
Arm/Group Description	Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Participants received placebo matched to ataluren TID orally in the morning, at midday, and in the evening for 48 weeks in Stage 1 (double-masked period) and ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Total of all reporting groups
Overall Participants	26	13	39
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	14.1 (10.12)	19.2 (19.43)	15.8 (13.88)
Sex: Female, Male (Count of Participants)
Female	10 38.5%	8 61.5%	18 46.2%
Male	16 61.5%	5 38.5%	21 53.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 7.7%	1 2.6%
Not Hispanic or Latino	26 100%	12 92.3%	38 97.4%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 3.8%	0 0%	1 2.6%
Asian	3 11.5%	2 15.4%	5 12.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	22 84.6%	11 84.6%	33 84.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline in Maximum Reading Speed of Oculus Unitas (OU) (Both Eyes) at Week 48, as Measured Using the Minnesota Low Vision Reading Test (MNREAD) Acuity Charts
Description	MNREAD Acuity Chart can only be used to assess participants ≥8 years old. MNREAD Acuity Chart measures reading speed as a function of print size in participants with normal and low vision. The test consists of short sentences with print size decreasing by 0.1 log unit steps from a maximum of 1.3 logarithm of the minimum angle of resolution (logMAR) (equivalent to 20/400 or 6/120 when viewed at 40 centimeters [cm]) to -0.5 logMAR (equivalent to 20/6 or 6/2). An MNREAD Acuity Chart curve of reading speed vs print size has a typical shape for normally sighted persons and many low-vision individuals. This curve is characterized by 3 summary values. At large print sizes, reading speed remains fairly constant, forming a plateau that represents the maximum reading speed. As the print size decreases, a critical print size (CPS) is reached at which reading speed begins to decline rapidly. Finally, the smallest print size that can be read is defined as the reading acuity (RA).
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population included all randomized participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Ataluren	Placebo
Arm/Group Description	Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Participants received placebo matched to ataluren TID orally in the morning, at midday, and in the evening for 48 weeks in Stage 1 (double-masked period) and ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.
Measure Participants	11	5
Least Squares Mean (Standard Error) [percent change]	9.87 (7.425)	-0.89 (11.809)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ataluren, Placebo
	Comments	Analysis was performed using analysis of covariance (ANCOVA) with age and baseline Maximum Reading Speed (both eyes) as covariates, and treatment as a factor.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4868
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Square (LS) Mean Difference
	Estimated Value	10.76
	Confidence Interval	(2-Sided) 95%; -21.914 to 43.434
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Reading Accessibility Index of Both Eyes at Week 48
Description	Reading Accessibility Index is defined as the mean reading speed in words per minute (wpm) across the 10 largest physical print sizes on the MNREAD Acuity Chart, normalized by the value for a group of normally sighted young adults. For a viewing distance of 40 cm, this range of print sizes corresponds to 0.4 to 1.3 logMAR. This range of print sizes was chosen for 2 reasons. First, it sustains the manifest refraction spherical equivalent (MRS) in normally sighted persons. Second, it covers most contemporary printed text found in everyday life. Because the Reading Accessibility Index is normalized by the value for a group of normally sighted young adults (aged 18 to 39 years), a Reading Accessibility Index of 1.0 represents normal performance for this age group. Values less than 1.0 mean reduced accessibility to printed text within the range of print size encountered in daily life. Missing data was imputed using last observation carried forward (LOCF) method.
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Ataluren	Placebo
Arm/Group Description	Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Participants received placebo matched to ataluren TID orally in the morning, at midday, and in the evening for 48 weeks in Stage 1 (double-masked period) and ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.
Measure Participants	11	6
Mean (Standard Deviation) [units on a scale]	0.10 (0.241)	0.02 (0.267)

3. Secondary Outcome

Title	Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 48
Description	The BCVA was evaluated using the Early Treatment Diabetic Retinopathy Study (ETDRS) Method. Missing data was imputed using LOCF method.
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants evaluable for specified category.

Arm/Group Title	Ataluren	Placebo
Arm/Group Description	Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Participants received placebo matched to ataluren TID orally in the morning, at midday, and in the evening for 48 weeks in Stage 1 (double-masked period) and ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.
Measure Participants	24	13
Left Eye	-0.00 (0.076)	0.01 (0.103)
Right Eye	0.03 (0.125)	-0.04 (0.138)

4. Secondary Outcome

Title	Percent Change From Baseline in Maximum Reading Speed of Oculus Dexter (OD) (Right Eye) and Oculus Sinister (OS) (Left Eye) at Week 48
Description	Maximum Reading Speed was measured using the MNREAD Acuity Chart, which can only be used to assess participants ≥8 years old. The MNREAD Acuity Chart measures reading speed as a function of print size in participants with normal and low vision. The test consists of short sentences with print size decreasing by 0.1 log unit steps from a maximum of 1.3 logMAR (equivalent to 20/400 or 6/120 when viewed at 40 cm) to -0.5 logMAR (equivalent to 20/6 or 6/2). An MNREAD Acuity Chart curve of reading speed vs print size has a typical shape for normally sighted persons and many low-vision individuals. This curve is characterized by 3 summary values. At large print sizes, reading speed remains fairly constant, forming a plateau that represents the maximum reading speed. As the print size decreases, a CPS is reached at which reading speed begins to decline rapidly. Finally, the smallest print size that can be read is defined as the RA.
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants evaluable for specified category.

Arm/Group Title	Ataluren	Placebo
Arm/Group Description	Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Participants received placebo matched to ataluren TID orally in the morning, at midday, and in the evening for 48 weeks in Stage 1 (double-masked period) and ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.
Measure Participants	10	6
Left Eye	8.70 (36.464)	-4.11 (38.380)
Right Eye	19.05 (39.116)	-3.83 (21.091)

5. Secondary Outcome

Title	Change From Baseline in Reading Accessibility Index of Right Eye and Left Eye at Week 48
Description	Reading Accessibility Index is defined as the mean reading speed in wpm across the 10 largest physical print sizes on the MNREAD Acuity Chart, normalized by the value for a group of normally sighted young adults. For a viewing distance of 40 cm, this range of print sizes corresponds to 0.4 to 1.3 logMAR. This range of print sizes was chosen for 2 reasons. First, it sustains the MRS in normally sighted persons. Second, it covers most contemporary printed text found in everyday life. Because the Reading Accessibility Index is normalized by the value for a group of normally sighted young adults (aged 18 to 39 years), a Reading Accessibility Index of 1.0 represents normal performance for this age group. Values less than 1.0 mean reduced accessibility to printed text within the range of print size encountered in daily life. Missing data was imputed using LOCF method.
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants evaluable for specified category.

Arm/Group Title	Ataluren	Placebo
Arm/Group Description	Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Participants received placebo matched to ataluren TID orally in the morning, at midday, and in the evening for 48 weeks in Stage 1 (double-masked period) and ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.
Measure Participants	11	6
Left Eye	-0.70 (2.601)	0.01 (0.224)
Right Eye	0.04 (0.048)	0.05 (0.128)

6. Secondary Outcome

Title	Change From Baseline in Critical Print Size (CPS) of Both Eyes, Right Eye, and Left Eye at Week 48
Description	The MNREAD Acuity Chart measures reading speed as a function of print size in participants with normal and low vision. The test consists of short sentences with print size decreasing by 0.1 log unit steps from a maximum of 1.3 logMAR (equivalent to 20/400 or 6/120 when viewed at 40 cm) to -0.5 logMAR (equivalent to 20/6 or 6/2). An MNREAD Acuity Chart curve of reading speed vs print size has a typical shape for normally sighted persons and many low-vision individuals. This curve is characterized by 3 summary values. At large print sizes, reading speed remains fairly constant, forming a plateau that represents the maximum reading speed. As the print size decreases, a CPS is reached at which reading speed begins to decline rapidly. Finally, the smallest print size that can be read is defined as the RA. Missing data was imputed using LOCF method.
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants evaluable for specified category.

Arm/Group Title	Ataluren	Placebo
Arm/Group Description	Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Participants received placebo matched to ataluren TID orally in the morning, at midday, and in the evening for 48 weeks in Stage 1 (double-masked period) and ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.
Measure Participants	11	6
Both Eyes	-0.19 (0.259)	0.12 (0.433)
Left Eye	-0.05 (0.198)	0.07 (0.271)
Right Eye	0.03 (0.275)	-0.02 (0.452)

7. Secondary Outcome

Title	Change From Baseline in Reading Acuity (RA) of Both Eyes, Right Eye, and Left Eye at Week 48
Description	The MNREAD Acuity Chart measures reading speed as a function of print size in participants with normal and low vision. The test consists of short sentences with print size decreasing by 0.1 log unit steps from a maximum of 1.3 logMAR (equivalent to 20/400 or 6/120 when viewed at 40 cm) to -0.5 logMAR (equivalent to 20/6 or 6/2). An MNREAD Acuity Chart curve of reading speed vs print size has a typical shape for normally sighted persons and many low-vision individuals. This curve is characterized by 3 summary values. At large print sizes, reading speed remains fairly constant, forming a plateau that represents the maximum reading speed. As the print size decreases, a CPS is reached at which reading speed begins to decline rapidly. Finally, the smallest print size that can be read is defined as the RA. Missing data was imputed using LOCF method.
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants evaluable for specified category.

Arm/Group Title	Ataluren	Placebo
Arm/Group Description	Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Participants received placebo matched to ataluren TID orally in the morning, at midday, and in the evening for 48 weeks in Stage 1 (double-masked period) and ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.
Measure Participants	11	6
Both Eyes	-0.06 (0.239)	-0.16 (0.339)
Left Eye	-0.15 (2.723)	-0.16 (0.467)
Right Eye	-0.05 (0.142)	-0.14 (0.236)

8. Secondary Outcome

Title	Number of Participants With Change From Baseline in Severity of Corneal Keratopathy at Week 48
Description	The severity of corneal keratopathy was reported as worsened, not change, or improve. Missing data were imputed using LOCF.
Time Frame	Baseline to Week 48

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants evaluable for specified category.

Arm/Group Title	Ataluren	Placebo
Arm/Group Description	Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Participants received placebo matched to ataluren TID orally in the morning, at midday, and in the evening for 48 weeks in Stage 1 (double-masked period) and ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.
Measure Participants	21	12
Worsened	4 15.4%	2 15.4%
Not change	7 26.9%	2 15.4%
Improved	8 30.8%	3 23.1%
Worsened	4 15.4%	2 15.4%
Not change	7 26.9%	2 15.4%
Improved	10 38.5%	4 30.8%

9. Secondary Outcome

Title	Change From Baseline in Iris Area at Week 48
Description	Missing data were imputed using LOCF.
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants evaluable for specified category.

Arm/Group Title	Ataluren	Placebo
Arm/Group Description	Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Participants received placebo matched to ataluren TID orally in the morning, at midday, and in the evening for 48 weeks in Stage 1 (double-masked period) and ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.
Measure Participants	9	2
Left Eye	-0.15 (0.333)	0.14 (0.129)
Right Eye	-0.06 (0.257)	-0.14

10. Secondary Outcome

Title	Change From Baseline in BCVA at Week 240
Description	The BCVA was evaluated using the ETDRS Method. Missing data were imputed using LOCF method.
Time Frame	Baseline, Week 240

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants evaluable for specified category.

Arm/Group Title	Ataluren	Placebo
Arm/Group Description	Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Participants received placebo matched to ataluren TID orally in the morning, at midday, and in the evening for 48 weeks in Stage 1 (double-masked period) and ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.
Measure Participants	2	0
Left Eye	0.02 (0.141)
Right Eye	0.11 (0.240)

11. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Description	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'. AEs were summarized separately for Stage 1 and for the overall ataluren experience, which included all participants who received ataluren throughput the study (Stage 1, open-label extension period [Stage 2], and sub-study).
Time Frame	Baseline up to Week 244

Outcome Measure Data

Analysis Population Description

The safety population included all randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Stage 1: Ataluren	Stage 1: Placebo	Overall Ataluren Exposure
Arm/Group Description	Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period).	Participants received placebo matched to ataluren TID orally in the morning, at midday, and in the evening for 48 weeks in Stage 1 (double-masked period).	Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.
Measure Participants	26	13	37
Count of Participants [Participants]	22 84.6%	10 76.9%	35 89.7%

Adverse Events

Time Frame	Baseline up to Week 244
Adverse Event Reporting Description	The safety population included all randomized participants who received at least 1 dose of study drug. AEs were summarized separately for Stage 1 and for the overall ataluren experience, which included all participants who received ataluren throughput the study (Stage 1, open-label extension period [Stage 2], and sub-study).
Arm/Group Title	Stage 1: Ataluren		Stage 1: Placebo		Overall Ataluren Exposure
Arm/Group Description	Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period).		Participants received placebo matched to ataluren TID orally in the morning, at midday, and in the evening for 48 weeks in Stage 1 (double-masked period).		Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.
All Cause Mortality
	Stage 1: Ataluren		Stage 1: Placebo		Overall Ataluren Exposure
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		0/13 (0%)		0/37 (0%)
Serious Adverse Events
	Stage 1: Ataluren		Stage 1: Placebo		Overall Ataluren Exposure
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/26 (3.8%)		0/13 (0%)		1/37 (2.7%)
Psychiatric disorders
Mental disorder	1/26 (3.8%)		0/13 (0%)		1/37 (2.7%)
Other (Not Including Serious) Adverse Events
	Stage 1: Ataluren		Stage 1: Placebo		Overall Ataluren Exposure
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/26 (84.6%)		10/13 (76.9%)		35/37 (94.6%)
Congenital, familial and genetic disorders
Phimosis	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Ear and labyrinth disorders
Motion sickness	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Endocrine disorders
Hypothyroidism	1/26 (3.8%)		0/13 (0%)		1/37 (2.7%)
Eye disorders
Dry eye	4/26 (15.4%)		3/13 (23.1%)		9/37 (24.3%)
Lacrimation increased	3/26 (11.5%)		1/13 (7.7%)		10/37 (27%)
Eye pruritus	2/26 (7.7%)		2/13 (15.4%)		13/37 (35.1%)
Corneal opacity	1/26 (3.8%)		0/13 (0%)		1/37 (2.7%)
Eye swelling	1/26 (3.8%)		0/13 (0%)		1/37 (2.7%)
Eyelid ptosis	1/26 (3.8%)		0/13 (0%)		1/37 (2.7%)
Lenticular opacities	1/26 (3.8%)		0/13 (0%)		1/37 (2.7%)
Ocular hyperaemia	1/26 (3.8%)		0/13 (0%)		2/37 (5.4%)
Eye discharge	0/26 (0%)		2/13 (15.4%)		3/37 (8.1%)
Keratopathy	0/26 (0%)		1/13 (7.7%)		1/37 (2.7%)
Vision blurred	0/26 (0%)		1/13 (7.7%)		1/37 (2.7%)
Vitreous detachment	0/26 (0%)		1/13 (7.7%)		0/37 (0%)
Photophobia	0/26 (0%)		0/13 (0%)		17/37 (45.9%)
Eye pain	0/26 (0%)		0/13 (0%)		4/37 (10.8%)
Lens discolouration	0/26 (0%)		0/13 (0%)		2/37 (5.4%)
Blepharospasm	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Cataract	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Eye inflammation	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Eye irritation	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Photokeratitis	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Punctate keratitis	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Visual acuity reduced	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Gastrointestinal disorders
Abdominal pain upper	5/26 (19.2%)		3/13 (23.1%)		9/37 (24.3%)
Vomiting	5/26 (19.2%)		3/13 (23.1%)		8/37 (21.6%)
Nausea	4/26 (15.4%)		2/13 (15.4%)		4/37 (10.8%)
Flatulence	3/26 (11.5%)		1/13 (7.7%)		3/37 (8.1%)
Abdominal distension	2/26 (7.7%)		1/13 (7.7%)		2/37 (5.4%)
Frequent bowel movements	2/26 (7.7%)		0/13 (0%)		2/37 (5.4%)
Abdominal pain	1/26 (3.8%)		0/13 (0%)		2/37 (5.4%)
Dental caries	1/26 (3.8%)		0/13 (0%)		1/37 (2.7%)
Diarrhoea	1/26 (3.8%)		0/13 (0%)		2/37 (5.4%)
Faeces soft	1/26 (3.8%)		0/13 (0%)		1/37 (2.7%)
Tooth impacted	1/26 (3.8%)		0/13 (0%)		1/37 (2.7%)
Abdominal discomfort	0/26 (0%)		2/13 (15.4%)		0/37 (0%)
Constipation	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Gastrointestinal Pain	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
General disorders
Malaise	5/26 (19.2%)		2/13 (15.4%)		9/37 (24.3%)
Fatigue	1/26 (3.8%)		0/13 (0%)		1/37 (2.7%)
Local swelling	1/26 (3.8%)		0/13 (0%)		1/37 (2.7%)
Medical device site reaction	1/26 (3.8%)		0/13 (0%)		1/37 (2.7%)
Pyrexia	1/26 (3.8%)		1/13 (7.7%)		6/37 (16.2%)
Asthenia	0/26 (0%)		1/13 (7.7%)		0/37 (0%)
Sensation of pressure	0/26 (0%)		1/13 (7.7%)		0/37 (0%)
Pain	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Immune system disorders
Seasonal allergy	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Infections and infestations
Gastroenteritis viral	2/26 (7.7%)		0/13 (0%)		7/37 (18.9%)
Conjunctivitis	1/26 (3.8%)		0/13 (0%)		5/37 (13.5%)
Influenza	1/26 (3.8%)		0/13 (0%)		6/37 (16.2%)
Nasopharyngitis	1/26 (3.8%)		1/13 (7.7%)		1/37 (2.7%)
Pharyngitis streptococcal	1/26 (3.8%)		0/13 (0%)		2/37 (5.4%)
Roseola	1/26 (3.8%)		0/13 (0%)		1/37 (2.7%)
Upper respiratory tract infection	1/26 (3.8%)		0/13 (0%)		1/37 (2.7%)
Ear infection	0/26 (0%)		1/13 (7.7%)		0/37 (0%)
Atypical Pneumonia	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Cellulitis of male external genital organ	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Eye infection	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Lyme disease	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Respiratory tract infection	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Injury, poisoning and procedural complications
Fall	1/26 (3.8%)		0/13 (0%)		1/37 (2.7%)
Concussion	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Corneal Abrasion	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Joint dislocation	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Ligament sprain	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Radius fracture	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Sunburn	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Investigations
Urine leukocyte esterase positive	2/26 (7.7%)		0/13 (0%)		0/37 (0%)
Alanine aminotransferase increased	1/26 (3.8%)		0/13 (0%)		2/37 (5.4%)
Upper respiratory tract infection	1/26 (3.8%)		0/13 (0%)		0/37 (0%)
Blood uric acid increased	1/26 (3.8%)		0/13 (0%)		2/37 (5.4%)
Nitrite urine present	1/26 (3.8%)		0/13 (0%)		1/37 (2.7%)
Protein urine present	1/26 (3.8%)		0/13 (0%)		1/37 (2.7%)
Urine ketone body present	1/26 (3.8%)		0/13 (0%)		1/37 (2.7%)
Blood urea increased	0/26 (0%)		0/13 (0%)		2/37 (5.4%)
Intraocular pressure increased	0/26 (0%)		0/13 (0%)		2/37 (5.4%)
Urine Leukocyte esterase positive	0/26 (0%)		0/13 (0%)		2/37 (5.4%)
Aspartate aminotransferase increased	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Bacterial test positive	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Blood bilirubin increased	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Hepatic enzyme increased	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Metabolism and nutrition disorders
Decreased appetite	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Musculoskeletal and connective tissue disorders
Epiphysiolysis	0/26 (0%)		1/13 (7.7%)		0/37 (0%)
Nervous system disorders
Somnolence	1/26 (3.8%)		0/13 (0%)		1/37 (2.7%)
Headache	0/26 (0%)		1/13 (7.7%)		3/37 (8.1%)
Migraine	0/26 (0%)		0/13 (0%)		3/37 (8.1%)
Psychiatric disorders
Insomnia	1/26 (3.8%)		0/13 (0%)		1/37 (2.7%)
Mood altered	1/26 (3.8%)		0/13 (0%)		1/37 (2.7%)
Attention deficit/Hyperactivity disorder	0/26 (0%)		0/13 (0%)		2/37 (5.4%)
Anxiety	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Depression	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Obsessive-compulsive disorder	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Renal and urinary disorders
Haematuria	1/26 (3.8%)		0/13 (0%)		1/37 (2.7%)
Dysuria	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Reproductive system and breast disorders
Menorrhagia	0/26 (0%)		1/13 (7.7%)		0/37 (0%)
Balanoposthitis	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Metrorrhagia	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Respiratory, thoracic and mediastinal disorders
Nasal congestion	0/26 (0%)		1/13 (7.7%)		1/37 (2.7%)
Epistaxis	0/26 (0%)		0/13 (0%)		2/37 (5.4%)
Oropharyngeal pain	0/26 (0%)		0/13 (0%)		2/37 (5.4%)
Rhinorrhoea	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Sneezing	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Throat irritation	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Wheezing	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Skin and subcutaneous tissue disorders
Rash	2/26 (7.7%)		0/13 (0%)		2/37 (5.4%)
Erythema	1/26 (3.8%)		0/13 (0%)		1/37 (2.7%)
Pruritus	1/26 (3.8%)		0/13 (0%)		1/37 (2.7%)
Dermatitis contact	0/26 (0%)		0/13 (0%)		1/37 (2.7%)
Skin discolouration	0/26 (0%)		0/13 (0%)		1/37 (2.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Sponsor can review results and/or communications prior to public release and can embargo communications regarding trial results for a period that is up to 180 days from the time submitted to the sponsor for review. The sponsor may consult with the PI to require changes to the communication or extend the embargo.