Clinical trial NCT03825380
Conditions: Ocular Hypertension Glaucoma
Sponsor: Laboratoires Thea
Start date: 2018-11-23; Completion date: 2021-02-24
Enrollment: 485 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to assess the efficacy and safety of T4032 versus Lumigan.

Detailed description:

Arms: arm 1: None arm 2: None
Interventions: intervention 1: Bimatoprost intervention 2: Lumigan®
Intervention descriptions: intervention 1: Eyedrops intervention 2: Eyedrops

Protocol documents:
Prot_000.pdf: 
Protocol No. LT4032-301 
Laboratoires Théa 
Confidential 
Final Version 3.0 – 05JUL2019 
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PROTOCOL SYNOPSIS 
Title 
Efficacy and safety assessment of T4032 (unpreserved bimatoprost 0.01%) 
versus Lumigan® 0.01% in ocular hypertensive or glaucomatous patients.  
Sponsor 
Laboratoires THÉA 
EudraCT-Number 
2017-000846-23 
Sponsor Study No. 
LT4032-301 
International 
Coordinator 
 
Study Centres 
This international study is planned to be carried out at approximately 130 sites 
spread over 15 to 25 countries. 
Planned Schedule 
Planned initiation: October 2018 
Planned last patient last visit: December 2020 
Study Phase 
Phase III 
Primary Study 
Objective 
To demonstrate the non-inferiority of T4032 unpreserved eye drops compared 
to Lumigan® 0.01% in terms of efficacy. 
Secondary Study 
Objective(s) 
To evaluate the safety and efficacy of T4032 versus Lumigan® 0.01%. 
Sample Size 
360 evaluable patients  
Accounting for a 10% drop-out/non evaluable rate, 400 initially treated 
patients are expected to be randomised. 
Number of screened patients will depend on the screen failure rate and is 
estimated at 668 patients. 
Study Design 
International, multicentre, randomised, 2 parallel groups, investigator-
masked, 3-month treatment. 
4 visits: 
•
Visit #1: Day -49 ± 3 days (Screening Visit)
•
Visit #2: Day 1 (Randomisation Visit)
•
Visit #3: Week 6 (Day 42 ± 3 days)
•
Visit #4: Week 12 (Day 84 ± 7 days) (Final visit)
•
Follow-up phone call: Week 16 (Day 112 ± 7 days)
Run-In/Wash-Out: 
Patient must be willing to discontinue her/his current treatment for 7 weeks 
(49 days ± 3 days) prior to the randomisation visit, in order to determine the 
IOP eligibility. 
Patient must follow a run-in period with only brinzolamide eye drops 
(Azopt®), one drop in each eye twice a day (morning and evening) for 5 weeks. 


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Confidential 
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The Azopt® treatment must be stopped for 2 weeks prior to the randomisation 
visit. 
Study Duration 
23 weeks total of study duration: 
5 weeks of run-in + 2 weeks of wash-out 
12 weeks of treatment duration 
4 weeks of follow-up. 
Investigational 
Product(s) (IP) 
Run-in product: Azopt®
Preserved brinzolamide 10mg/mL eye drops presented in multidose container. 
Route of administration: 
In the conjunctival cul-de-sac of each eye. 
Daily dose regimen: 
1 drop in each eye twice a day, morning and evening during 5 weeks. 
Test product: T4032 
Unpreserved bimatoprost 0.01% eye drops presented in unit dose (UD). 
Comparator product: Lumigan® 0.01% 
Preserved bimatoprost 0.01% eye drops presented in multidose container. 
Route of administration: 
In the conjunctival cul-de-sac of each eye. 
Daily dose regimen: 
1 drop in each eye once daily at 20:00 (± 1 hour) from Day 1 to Week 12. 
Inclusion Criteria 
At Screening Visit (D-49): 
1.1 Informed consent signed and dated. 
1.2 Patient aged ≥18 years old. 
1.3 Both eyes with 500 µm ≤ central corneal thickness ≤ 600 µm. 
1.4 Both eyes with diagnosed open-angle glaucoma or ocular 
hypertension, initially treated and controlled (including IOP ≤ 18 
mmHg) for at least 6 months by any prostaglandin monotherapy. 
1.5 Both eyes with IOP ≤ 18 mmHg. 
At Randomisation Visit (D1) at 8:00: 
1.6  Both eyes with 22 mmHg ≤ IOP < 34 mmHg and with asymmetry 
between eyes ≤ 3 mmHg. 
Exclusion Criteria 
Ophthalmic Exclusion Criteria in AT LEAST ONE EYE [2.1] 
2.1.1 Fundus examination not performed or not available within 12 
months. 
2.1.2 Visual field not performed or not available within 12 months. 
2.1.3 Significant worsening according to the two last visual fields (at least 
6 months between the two visual fields). 
2.1.4 Advance stage of glaucoma, defined by at least one of the following 
criteria: 


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2.1.4.1 
Absolute defect in the ten degrees central point of  the 
visual field. 
2.1.4.2 
Severe visual field loss: MD < -18 dB. 
2.1.4.3  
Risk of visual field worsening as a consequence of 
participation 
in 
the 
study 
according 
to 
the 
investigator’s best judgement. 
Exclusion Criteria 
(continued) 
2.1.5 History of non-responder to bimatoprost therapy. 
2.1.6 Far Best Corrected Visual Acuity ≥ + 0.7 Log Mar (e.g., ≤ 0.2 in 
decimal value or ≤ 20/100 Snellen equivalent or ≤ 50 ETDRS 
letters). 
2.1.7 History of trauma, infection, clinically significant inflammation 
within the 3 previous months. 
2.1.8 Ongoing or known history of ocular allergy and/or uveitis and/or 
viral infection. 
2.1.9 Clinically significant or progressive retinal disease (e.g. retinal 
degeneration, diabetic retinopathy, retinal detachment). 
2.1.10 Presence of at least one severe objective sign among the following: 
2.1.10.1 Conjunctival hyperaemia (Grade 5 / McMonnies scale). 
2.1.10.2 Superficial punctate keratitis (Grade 4/5 / Oxford scale). 
2.1.10.3 Blepharitis (Grade 3 / 0-3 scale). 
2.1.11 Severe dry eye as assessed by the investigator. 
2.1.12 Corneal ulceration. 
2.1.13 Any palpebral abnormality incompatible with a good examination. 
2.1.14 Any other abnormality preventing accurate assessment e.g. reliable 
tonometry measurement, visual field examination, fundus 
examination. 
Systemic/non Ophthalmic Exclusion Criteria [2.2] 
2.2.1 Uncontrolled diabetic patient. 
2.2.2 Known or suspected hypersensitivity to one of the components of 
the investigational products (T4032, Lumigan®, Azopt®) and 
sulphonamides, or auxiliary products (fluorescein, oxybuprocaine 
hydrochloride). 
2.2.3 History of or active relevant systemic condition incompatible with 
the study or likely to interfere with the study results or the patient 
safety according to the investigator’s judgment. 
2.2.4 Severe renal impairment 
2.2.5 
Hyperchloraemic acidosis 


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Specific 
Exclusion 
Criteria 
Regarding 
Childbearing 
Potential 
Women[2.3] 
2.3.1 
Pregnancy or breast feeding. 
2.3.2 
Childbearing potential woman who is not using a reliable method 
of contraception (oral contraceptive, intra-uterine device, 
subcutaneous contraceptive implant, vaginal ring, patch) and is not 
surgically sterilised. 
Exclusion Criteria 
(continued) 
Exclusion Criteria Related to General Conditions [2.4] 
2.4.1. Alcohol addiction and heavy smoker, according to the investigator’s 
judgement. 
2.4.2. Inability of patient to understand the study procedures or to give 
informed consent. 
2.4.3. Non-compliant patient (e.g., not willing to attend a visit; way of life 
interfering with compliance). 
2.4.4. Participation in this study at the same time as another clinical study. 
2.4.5. Participation in this study within the 4 weeks after the end of a 
previous clinical study (or within 5 half-lives of the previously tested 
product if longer than 4 weeks). 
2.4.6. Patient previously randomised in this study. 
2.4.7. Patient being institutionalised because of legal or regulatory order, 
inmate of psychiatric wards, prison or state institutions, or employee 
of the study sites or of the sponsor’s company. 
2.4.8. Patient not covered by the government health care scheme of the 
country in which he/she is living (if applicable). 
Exclusion Criteria Related to Previous and Concomitant Treatments 
(Medications/Non-Medicinal Therapies/Procedures) [2.5] 
2.5.1 Patient with previous, current or anticipated prohibited listed 
treatment (or prohibited modification of treatment regimen). The 
prohibited treatments (or prohibited modifications of treatment 
regimen) and their periods of use prohibition are listed in the 
following Table 1: Prohibited treatments (medications/non-
medicinal therapies/procedures) 


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Table 1: Prohibited treatments (medications/non-medicinal therapies/procedures) 
Ocular surgery or topical treatment concerned both eyes  
Before the Screening Visit 
After the Screening Visit 
At any time 
12 months 
6 months 
1 month 
15 days 
Run-
in/Wash-
out Period 
Treatment 
period 
Filtration surgery for glaucoma……………………………………………………………………… 
Laser procedure for glaucoma and cornea………………………………………… 
Other ocular surgery …………..……..………………………… 
Intra ocular injection ………………..…………….…………… 
Systemic anti-glaucoma treatments………………. 
Any change or predictable change in dose regimen 
for systemic treatments which can have a 
substantial effect on IOP:  
•
Beta-adrenergic blocking agents
•
Beta-adrenergic agonist agents
•
Alpha agonists agents
•
Alpha blocking agents
•
Angiotensin converting enzyme inhibitors
•
Angiotensin II inhibitors
•
Calcium channel blockers
•
Diuretics
•
Corticosteroids
Topical ocular steroids and/ or topical ocular 
nonsteroidal anti-inflammatory drugs (NSAIDs)… 
Systemic immunosuppressive and 
systemic 
nonsteroidal 
anti-
inflammatory drugs……………… 
Any topical ocular treatments* 
(except long-term preservative-free 
lachrymal substitutes)……………. 
Contact lenses wear…… 
* Prostaglandin monotherapy taken for at least 6 months by the patient has to be continued until the
Screening Visit.
Patient Withdrawal 
The investigator must choose to discontinue a patient for the following 
reasons: 
•
Adverse event(s) necessitating discontinuation from the study,
•
Lack of efficacy: if the patient or the investigator does not feel that the
IP (T4032 or Lumigan®) has sufficiently controlled the pathology.
Efficacy Parameters 
•
IOP assessment with Goldmann applanation tonometer in each eye.
Three time points in each eye (8:00; 10:00; 16:00) at Day 1, Week 6
and Week 12.
•
Efficacy assessment by the investigator at week 6 and week 12.


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Safety Parameters 
•
Assessment of the conjunctival hyperaemia on McMonnies
photographic scale in each eye.
•
Score of each ocular symptom throughout the day (irritation/burning,
stinging, itching, tearing, eye dryness feeling, foreign body sensation)
using 0-3 scale.
•
Score of each ocular symptom upon instillation (irritation/burning,
stinging, itching, tearing, eye dryness feeling, foreign body sensation)
using 0-3 scale.
•
Score of each ocular sign (blepharitis, eyelid oedema, iris pigmentation
modification, 
abnormal 
eyelashes 
aspect, 
folliculo-papillary
conjunctivitis) in each eye using 0-3 scale.
•
Corneal fluorescein staining according to Oxford grading scheme in
each eye.
•
Far Best Corrected Visual Acuity in each eye.
•
Ocular tolerance assessed by the investigator.
•
Ocular tolerance assessed by the patient.
•
Ocular AE reporting.
•
Systemic AE reporting.
Primary Efficacy 
Endpoint 
The primary efficacy endpoint is the change from baseline (Day 1) to Week 
12 in IOP at the three time points (8:00; 10:00; 16:00) in the worse eye. 
The worse eye is defined as the eligible eye with the highest IOP at baseline 
at 8:00. In case of no IOP difference between both eyes, the right eye will 
be considered. 
Secondary Efficacy 
Endpoints 
•
Change from baseline to Week 12 in IOP at the three time points (8:00,
10:00 and 16:00) in the contralateral eye.
Others efficacy endpoints will be analysed: 
•
Change from baseline to Week 6 in IOP at the three time points (8:00;
10:00; 16:00) in the worse eye and in the contralateral eye.
•
Efficacy assessed by the investigator.
Safety Endpoints 
•
Conjunctival hyperaemia on McMonnies scale at Week 6 and Week
12.
•
Change from baseline of the conjunctival hyperaemia on McMonnies
scale in 3 classes (improvement, no change, worsening) at Week 6 and
Week 12.
•
Score of each ocular symptom throughout the day and the sum of these
scores.
•
Score of each ocular symptom upon instillation and the sum of these
scores.
•
Score of each ocular sign.
•
Corneal fluorescein staining (Oxford grading scheme).
•
Far Best Corrected Visual Acuity expressed in Log MAR.
•
Ocular tolerance assessed by the investigator.


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•
Ocular tolerance assessed by the patient.
•
Ocular and systemic AE by System Organ Class and Preferred Term.
Statistical Method 
The sample size determination is based on the primary efficacy endpoint, 
i.e. the change in IOP at the three time-points (8:00, 10:00, 16:00) after 12
weeks of treatment, in the worse eye.
Non-inferiority of T4032 versus Lumigan® 0.01% is tested with a non-
inferiority margin of 1.5 mmHg. Non-inferiority will be concluded if it is 
achieved for each of the three time points 8:00, 10:00 and 16:00. 
The evaluation is based upon a two-sided 95% CI on the difference on mean 
change in IOP after 12 weeks of treatment.  
With data available for 180 patients in each arm, there is more than 90 % 
power to show that the T4032 unpreserved eye drops is non-inferior to 
Lumigan® 0.01% preserved eye drops. The hypothesis is based on the 1.5 
mmHg margin, assuming no difference between the 2 groups (average 
difference of 0 mmHg), a standard deviation of 3 mmHg and correlation 
between time-points of 0.7 on the primary efficacy variable.  
Accounting for a 10% drop-out/non evaluable rate, 400 initially treated 
patients are expected to be randomised.  
The sample size of 400 randomised patients is also justify to collect enough 
safety data. Number of screened patients will depend on the screen failure 
rate and is estimated at 668 patients. 
No Interim analysis is planned. 
Schedule of 
Assessments 
Please refer to the Table 2: Schedule of Visits and Procedures. 


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Table 2: Schedule of Visits and Procedures 
Visit# 1 
Screening 
Visit 
Day -49 (± 3 
days) 
 2 weeks 
before visit#2 
Visit# 2 
Randomisation Visit 
Day 1 
Visit# 3 
Day 42 (± 3 days) 
Week 6 
Visit# 4 
Final Visit or 
premature 
discontinuation visit 
Day 84 (± 7 days) 
Week 12 
Follow-up 
Phone call 
Day 112 
(± 7 days) 
Week 16 
First 
ophthalmologist 
investigator 
Wash-out(5) 
First ophthalmologist 
investigator  
Second investigator 
First ophthalmologist investigator 
(the same as Day 1) 
Second investigator 
First ophthalmologist investigator 
(the same as Day 1) 
Second investigator 
Informed consent 
X 
Demography 
X 
History of glaucoma or ocular hypertension 
X 
Ocular medical and surgical history (other than the studied 
disease) 
X 
Systemic medical and surgical history 
X 
Previous and concomitant ocular/non ocular treatments 
X 
X 
X 
X 
X(11) 
Ocular symptoms throughout the day (1) 
X 
X 
X 
X 
Ocular symptoms upon instillation (1) 
X 
X 
Far Best Corrected Visual Acuity (BCVA) 
X 
X 
X 
Intra-Ocular Pressure (IOP) assessment (2) 
X 
X 
X 
X 
Fundus examination 
X(3) 
X(4) 
Central corneal thickness measurement 
X(3) 
Automated visual field 
X(3) 
X(4) 
Slit lamp examination (6) 
X 
X 
X 
X 
Corneal fluorescein staining (Oxford grading scheme) 
X 
X 
X 
X 
Conjunctival hyperaemia (McMonnies scale) 
X 
X 
X 
X 
Pregnancy test (7) 
X 
X 
X 
X 
Adverse event 
X 
X 
X 
X 
X 
X 
X 
Verification of inclusion and exclusion criteria / Patient 
status 
X 
X 
Run-in treatment (Azopt®) dispensation (8) 
X 
Run-in treatment /Wash-out compliance 
X 


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Randomisation (IWRS) 
X 
Investigational Product (IP) dispensation (9) 
X 
X 
IP (T4032 or Lumigan®) compliance 
X 
X 
Efficacy assessment by the investigator (10) 
X 
X 
X 
Ocular tolerance assessment by the investigator (10) 
X 
X 
X 
Ocular tolerance assessment by the patient (10) 
X 
X 
X 
In case of premature discontinuation during the run-in/wash-out period or patient non-eligibility at visit#2, the investigator must perform the evaluations described for the randomization visit (visit 
#2) except to IOP measurements at 10:00 and 16:00, pregnancy test, randomization and IP dispensation. 
All the ocular assessments have to be performed in both eyes. 
(1) Ocular symptoms (irritation/burning, stinging, itching, tearing, eye dryness feeling, foreign body sensation), scored using 0-3 scale, will be collected by the investigator /delegate.
(2) At Screening Visit, one IOP measurement should be performed at 8:00 (± 30 minutes). At Day 1, Day 42/Week 6 and Day 84/Week 12, IOP should be measured at three time points: 8:00, 10:00
and 16:00 (each ± 30 minutes) with a.m. measurements of IOP at least 2 hours apart. IOP measurements should be done at the same hours (± 30 min) than Day 1, by the same investigator and using
the same technique (Goldmann applanation tonometer) for all visits.
(3) To be performed if fundus examination / central corneal thickness measurement / automated visual field not done within the previous 12 months and/or results dating from the last 12 months not
available.
(4) To be performed only if the IOP is not stable at the Week 12 visit or if the ophthalmologist judges that it is necessary.
(5) Azopt® must be stopped for 2 weeks before the Randomisation Visit.
(6) Slit lamp examination: Score of each ocular sign (blepharitis, eyelid oedema, iris pigmentation modification, abnormal eyelashes aspect, folliculo-papillary conjunctivitis or other ocular
abnormality) will be recorded in each eye using 0-3 scale.
(7) Urinary test to be done for childbearing potential women.
(8) Run-in treatment (Azopt®) will be instilled by the patient one drop in each eye twice a day (morning and evening) for 5 weeks.
(9) One drop of IP (T4032 or Lumigan®) will be instilled by the patient in each eye once daily at 20:00 (± 1 hour) for 12 weeks.
(10) Efficacy and ocular tolerance will be assessed by the investigator and the patient as very satisfactory, satisfactory, not very satisfactory, or unsatisfactory.
(11) In case of AE, all treatments of the follow-up period will be collected.

SAP_001.pdf: 
Laboratoires THEA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021 
Page 1/163 
STATISTICAL ANALYSIS PLAN
Protocol: LT4032-301 
European Trial Number: 2017-000846-23 
Efficacy and safety assessment of T4032 (unpreserved bimatoprost 0.01%) versus Lumigan® 0.01% in 
ocular hypertensive or glaucomatous patients 
Phase III, international, multicentre, randomised, 2 parallel groups, investigator-masked, 3-months 
treatment duration 
Final Amendment V01 – 20APR2021 
AUTHOR 
AIXIAL 
3-5 avenue de la Cristallerie
CRISCO 
92310 Sèvres 
FRANCE 
COORDINATOR 
 
SPONSOR 
Laboratoires THEA 
Research and Development Department 12, 
rue Louis Blériot 
63017 Clermont-Ferrand Cedex 2 - FRANCE 
CONFIDENTIAL 


Laboratoires THEA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021 
Page 2/163 
DOCUMENT HISTORY 
Version 
Date 
Description of change 
Performed by 
Draft 1 
11-FEB-2020
First version of the document created. 
Isabelle JOSSE / 
Véronique SOISSON 
Draft 2 
19-JAN-2021
After THEA’s comments (5JAN2021). 
Isabelle JOSSE 
Pre-Final 
25-FEB-2021
After THEA’s comments 
Isabelle JOSSE / 
Véronique SOISSON 
Final 
05-MAR-2021
After THEA’s comments 
Isabelle JOSSE 
Final 2 
16-APR-2021
Add grouping of country (Section 4.3) 
Update of the calculation of the compliance 
for LT4032/Lumigan (Section 4.3.9)  
Update of Section 5.3. The compliance of 
Azopt will be calculated only on mITT set 
Add exploratory analysis on the impact of 
circadian rhythm at Week 6 (Section 6.2.1) 
Minor modification on mock tables 
Isabelle JOSSE 
The SAS code for the exploratory analysis 
was updated (Appendix 1, Section 4.) 
Final 
Amendment 
V01 
20-APR-2021
Minor modification on mock tables and SAP 
content 
Veronique SOISSON 


Laboratoires THEA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021 
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APPROVALS 
Name and Function 
Signature 
Date 
_____________________ 
___ / ___ / ___ 
_____________________ 
___ / ___ / ___ 
_____________________ 
___ / ___ / ___ 
_____________________ 
___ / ___ / ___ 
Clinical Development 
Director Laboratoires THEA 
Medical Development Director 
Laboratoires THEA 
Senior International Clinical 
Project Leader 
Laboratoires THEA 
Biostatistician 
Laboratoires THEA 
Senior Biostatistician 
AIXIAL 
_____________________ 
___ / ___ / ___ 


Laboratoires THEA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021 
Page 4/163 
 
 
 
 
 
TABLE OF CONTENTS 
 
INTRODUCTION 
8 
1 
DESCRIPTION OF THE STUDY 
8 
1.1 STUDY OBJECTIVES 
8 
1.1.1 PRIMARY OBJECTIVE .................................................................................................... 8 
1.1.2 SECONDARY OBJECTIVE(S) ........................................................................................... 8 
1.2 STUDY DESIGN 
8 
1.2.1 DESCRIPTION .............................................................................................................. 8 
1.2.2 SCHEDULE OF ASSESSMENTS AND STUDY PROCEDURES ................................................ 8 
1.3 STUDY ENDPOINTS 
11 
1.3.1 PRIMARY EFFICACY ENDPOINT .................................................................................... 11 
1.3.2 SECONDARY EFFICACY ENDPOINTS ............................................................................. 11 
1.3.3 SAFETY ENDPOINTS ................................................................................................... 11 
1.4 STUDY TREATMENTS 
11 
1.4.1 TREATMENT GROUPS ................................................................................................. 11 
1.4.2 RANDOMISATION ........................................................................................................ 12 
1.4.2.1 Randomisation procedure .........................................................................................12 
1.4.2.2 Masking ....................................................................................................................12 
1.5 SAMPLE SIZE CONSIDERATIONS 
12 
2 
ANALYSIS SETS 
14 
2.1 SAFETY SET AND AZOPT® SAFETY SET 
14 
2.2 INTENT-TO-TREAT SET 
14 
2.3 MODIFIED INTENT-TO-TREAT SET 
14 
2.4 PER-PROTOCOL SET 
14 
3 
GENERAL CONSIDERATIONS FOR DATA ANALYSES 
15 
3.1 DISPLAY OF ANALYSIS RESULTS 
16 
3.2 INTERIM ANALYSES 
16 
3.3 CENTRE EFFECT MANAGEMENT 
16 
3.4 SUBGROUP ANALYSES 
16 
3.5 OTHER STRATA AND COVARIATES 
16 
3.6 MULTIPLE COMPARISONS AND MULTIPLICITY 
16 
4 
DATA HANDLING CONVENTIONS 
17 
4.1 VISIT WINDOWS 
17 
4.2 PREMATURE DISCONTINUATION AND MISSING DATA 
17 
4.3 DERIVED AND TRANSFORMED DATA 
17 
4.3.1 COUNTRY GROUPING ................................................................................................. 17 
4.3.2 BASELINE .................................................................................................................. 17 
4.3.3 POSSIBLE IMPACT OF COVID-19 PANDEMIC ................................................................ 18 
4.3.4 TIME FROM DIAGNOSIS ............................................................................................... 18 


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Statistical Analysis Plan 
Final Amendment V01 
20APR2021 
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4.3.5 WASH-OUT DURATION ................................................................................................ 18 
4.3.6 DURATION OF AZOPT® ................................................................................................ 18 
4.3.7 DURATION OF T4032 OR LUMIGAN® ............................................................................ 18 
4.3.8 COMPLIANCE OF AZOPT® ............................................................................................ 18 
4.3.9 COMPLIANCE OF T4032 OR LUMIGAN® ........................................................................ 19 
4.3.10 CHANGE FROM BASELINE ........................................................................................... 20 
4.3.11 CHANGE FROM BASELINE IN CLASSES .......................................................................... 20 
4.3.12 IOP VALUE ................................................................................................................ 20 
4.3.13 MEAN DIURNAL IOP ................................................................................................... 20 
4.3.14 TOTAL SCORE OF SUBJECTIVE OCULAR SYMPTOMS THROUGHOUT THE DAY ................... 20 
4.3.15 TOTAL SCORE OF SUBJECTIVE OCULAR SYMPTOMS UPON INSTILLATION ......................... 20 
4.3.16 FAR BEST CORRECTED VISUAL ACUITY ........................................................................ 21 
4.3.17 AE TIME TO OCCURENCE ............................................................................................ 21 
4.3.18 AE DURATION ............................................................................................................ 21 
5 
DESCRIPTION OF THE STUDY POPULATION 
22 
5.1 DISPOSITION OF PATIENTS 
22 
5.2 DEMOGRAPHIC AND BASELINE CHARACTERISTICS 
22 
5.3 TREATMENT EXPOSURE AND COMPLIANCE 
24 
6 
EFFICACY ANALYSIS 
25 
6.1 PRIMARY EFFICACY ENDPOINT 
25 
6.1.1 MAIN ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT .................................................. 25 
6.1.2 SENSITIVITY ANALYSES OF THE PRIMARY EFFICACY ENDPOINT ...................................... 25 
6.1.3 SUPPORTING ANALYSES TO CHECK THE VALIDITY OF THE MAIN AND SENSITIVITY ANALYSES
 ..................................................................................................................... 26 
6.1.4 EXPLORATORY ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT ................................... 26 
6.2 SECONDARY EFFICACY ENDPOINTS 
26 
6.2.1 CHANGE FROM BASELINE IN IOP ................................................................................. 26 
6.2.2 OTHER ANALYSES ON IOP .......................................................................................... 27 
6.2.3 GLOBAL ASSESSMENT OF EFFICACY BY THE INVESTIGATOR........................................... 27 
7 
SAFETY ANALYSIS 
28 
7.1 CONJUNCTIVAL HYPERAEMIA – SLIT LAMP EXAMINATION 
28 
7.2 SUBJECTIVE OCULAR SYMPTOMS THROUGHOUT THE DAY 
28 
7.3 SUBJECTIVE OCULAR SYMPTOMS UPON INSTILLATION 
28 
7.4 OCULAR SIGNS – SLIT LAMP EXAMINATION 
29 
7.5 CORNEAL STAINING ACCORDING TO OXFORD GRADING SCHEME 
29 
7.6 FAR BEST CORRECTED VISUAL ACUITY 
29 
7.7 AUTOMATED VISUAL FIELD AND FUNDUSCOPY 
29 
7.8 OCULAR TOLERANCE BY THE INVESTIGATOR 
30 
7.9 OCULAR TOLERANCE BY THE PATIENT 
30 
7.10 OCULAR AND SYSTEMIC ADVERSE EVENTS 
30 
7.10.1 SUMMARY OF TEAES................................................................................................. 30 
7.10.2 DETAILS OF AES ........................................................................................................ 31 
7.10.3 INDIVIDUAL LISTING OF AES ........................................................................................ 31 


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8 
CHANGES FROM PROTOCOL 
33 
9 
VALIDATION OF STATISTICAL PROGRAMMING 
34 
10 REFERENCES 
34 
APPENDIX 1. SAS SYNTAX FOR STATISTICAL MODELS PROGRAMMING 
35 
APPENDIX 2.  TEMPLATES FOR STATISTICAL ANALYSIS AND SUMMARY TABLES 39 
 


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ABBREVIATIONS 
 
AE 
Adverse Event 
ANCOVA 
Analysis of Covariance 
ATC 
Anatomic Therapeutic Chemical 
BCVA 
Best-Corrected Visual Acuity 
CI 
Confidence Interval 
CFS 
Corneal Fluorescein Staining 
CMH 
Cochran-Mantel-Haenszel 
COVID 
Coronavirus Disease 
e-CRF 
Electronic Case Report Form 
ICH 
International Conference on Harmonisation 
IMP  
Investigational Medicinal Product 
IOP 
Intra Ocular Pressure 
ITT 
Intent-To-Treat 
IWRS 
Interactive Web Response System 
LOCF 
Last Observation Carried Forward 
MedDRA 
Medicinal Dictionary for Regulatory Activities 
m-ITT 
modified Intent-To-Treat 
MMRM 
Mixed Model for Repeated Measures 
PP 
Per Protocol 
PT 
Preferred Term 
Q1 
First quartile 
Q3 
Third quartile 
REML 
Restricted Maximum Likelihood 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SOC 
System Organ Class 
TEAE 
Treatment Emergent Adverse Event 
WHO-DD 
World Health Organisation-Drug Dictionary 


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INTRODUCTION 
This Statistical Analysis Plan (SAP) describes the statistical analyses to be performed on study T4032-
301, contains the definition of analysis sets and protocol deviations, defines derived data, and specifies 
the methodology for analysing primary and secondary efficacy endpoints and safety endpoints.  
This SAP is based on: 
1. Study Protocol final version 3.0 dated on 05-JUL-2019 and addendum version 1.0 dated on 05-
JUN-2020 
2. Electronic-Case Report Form (e-CRF) final version 2.0 dated on 31-MAR-2019 
The analyses closely follow the ICH guidelines for industry on topic E3 - Structure and Content of Clinical 
Study Reports and E9 - Statistical Principles for Clinical Trials.  
1 DESCRIPTION OF THE STUDY 
1.1 Study objectives 
1.1.1 
Primary objective  
The primary objective of the study is to demonstrate the non-inferiority of T4032 unpreserved eye drops 
compared to Lumigan® 0.01% in terms of efficacy. 
1.1.2 
Secondary objective(s) 
The secondary objectives of this study are to evaluate the safety and efficacy of T4032 versus Lumigan® 
0.01%. 
1.2 Study design 
1.2.1 
Description 
This is a phase III, international, multicentre, randomised, two parallel groups, investigator-masked,  
3-month treatment duration. It was planned to randomise 400 patients. Considering a screen failure rate 
of about 40%, 668 patients were planned to be selected in order to have 400 randomised patients. 
 
1.2.2 
Schedule of assessments and study procedures 
All patients are expected to attend 4 visits at the investigator centre during the course of the study 
followed by a phone call: 
▪ 
Visit #1: Day -42 or Day -49 ±3 days (Screening Visit) (respectively before or after Clinical Study 
Protocol amendement 1 – 05JUL2019) 
▪ 
Visit #2: Day 1 (Randomisation Visit) 
▪ 
Visit #3: Week 6 (Day 42±3 days) 
▪ 
Visit #4: Week 12 (Day 84±7 days) (Final Visit) 
▪ 
Follow-up phone call: Week 16 (Day 112±7 days) 
 
 


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FLOW CHART: Schedule of visits and procedures 
 
Visit# 1 
Screening 
Visit 
Day -42 or 
Day -49*  
(±3 days) 
14 or7 days 
before 
visit#2* 
Visit# 2 
Randomisation Visit 
Day 1 
Visit# 3 
Day 42 (±3 days) 
Week 6 
Visit# 4 
Final Visit or 
premature 
discontinuation visit 
Day 84 (±7 days) 
Week 12 
Follow-up 
Phone call 
Day 112 
(±7 days) 
Week 16 
 
First 
ophthalmolog
ist 
investigator 
Wash-out(5) 
First ophthalmologist 
investigator 
 
Second investigator 
First ophthalmologist 
investigator (the same as Day 1) 
Second investigator 
First ophthalmologist 
investigator (the same as Day 1) 
Second investigator 
 
Informed consent 
X 
 
Demography 
X 
 
History of glaucoma or ocular hypertension  
X 
 
Ocular medical and surgical history (other than the studied 
disease) 
X 
 
Systemic medical and surgical history 
X 
 
Previous and concomitant ocular/non ocular treatments 
X 
X 
 
 
X 
 
X 
X(11) 
Ocular symptoms throughout the day (1) 
X 
 
X 
 
X 
 
X 
 
Ocular symptoms upon instillation (1) 
 
 
 
 
X 
 
X 
 
Far Best Corrected Visual Acuity (BCVA) 
X 
X 
 
 
 
X 
 
 
Intra-Ocular Pressure (IOP) assessment (2) 
X 
X 
 
X 
 
X 
 
 
Fundus examination 
X(3) 
 
 
 
 
X(4) 
 
 
Central corneal thickness measurement  
X(3) 
 
 
 
 
 
 
 
Automated visual field  
X(3) 
 
 
 
 
X(4) 
 
 
Slit lamp examination (6) 
X 
X 
 
X 
 
X 
 
 
Corneal fluorescein staining (Oxford grading scheme) 
X 
X 
 
X 
 
X 
 
 
Conjunctival hyperaemia (McMonnies scale) 
X 
X 
 
X 
 
X 
 
 
Pregnancy test (7) 
X 
X 
 
 
X 
 
X 
 
Adverse event (AE) 
 
X 
X 
X 
X 
X 
X 
X 
Verification of inclusion and exclusion criteria / Patient 
status 
X 
X 
 
 
 
 
 
 
Run-in treatment (Azopt®) dispensation (8) 
X 
 
 
 
 
 
 
 
Run-in treatment /Wash-out compliance 
 
 
X 
 
 
 
 
 


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Randomisation (IWRS) 
 
 
X 
 
 
 
 
 
Investigational Medical Product (IMP) dispensation (9) 
 
 
X 
 
X 
 
 
 
IMP (T4032 or Lumigan®) compliance 
 
 
 
 
X 
 
X 
 
Efficacy assessment by the investigator (10) 
 
 
X 
 
X 
 
X 
 
 
Ocular tolerance assessment by the investigator (10) 
 
X 
 
X 
 
X 
 
 
Ocular tolerance assessment by the patient (10) 
 
X 
 
 
X 
 
X 
 
 
*Respectively before or after Clinical Study Protocol amendement 1 – 05JUL2019 
In case of premature discontinuation during the run-in/wash-out period or patient non-eligibility at visit#2, the investigator must perform the evaluations described for the randomization 
visit (visit #2) except to IOP measurements at 10:00 and 16:00, pregnancy test, randomization and IMP dispensation. 
All the ocular assessments have to be performed in both eyes.  
(1) Ocular symptoms (irritation/burning, stinging, itching, tearing, eye dryness feeling, foreign body sensation), scored using 0-3 scale, will be collected by the investigator /delegate.  
(2) At Screening Visit, one IOP measurement should be performed at 08:00 (± 30 minutes). At Day 1, Day 42/Week 6 and Day 84/Week 12, IOP should be measured at three time 
points: 08:00, 10:00 and 16:00 (each ± 30 minutes) with a.m. measurements of IOP at least 2 hours apart. IOP measurements should be done at the same hours (± 30 min) than Day 1, by 
the same investigator and using the same technique (Goldmann applanation tonometer) for all visits. 
(3) To be performed if fundus examination / central corneal thickness measurement / automated visual field not done within the previous 12 months and/or results dating from the last 12 
months not available.  
(4) To be performed only if the IOP is not stable at the Week 12 visit or if the ophthalmologist judges that it is necessary.  
(5) Azopt® must be stopped for 2 weeks before the Randomisation Visit.  
(6) Slit lamp examination: Score of each ocular sign (blepharitis, eyelid oedema, iris pigmentation modification, abnormal eyelashes aspect, folliculo-papillary conjunctivitis or other 
ocular abnormality) will be recorded in each eye using 0-3 scale.  
(7) Urinary test to be done for childbearing potential women.  
(8) Run-in treatment (Azopt®) will be instilled by the patient one drop in each eye twice a day (morning and evening) for 5 weeks.  
(9) One drop of IP (T4032 or Lumigan®) will be instilled by the patient in each eye once daily at 20:00 (± 1 hour) for 12 weeks.  
(10) Efficacy and ocular tolerance will be assessed by the investigator and the patient as very satisfactory, satisfactory, not very satisfactory, or unsatisfactory.  
(11) In case of AE, all treatments of the follow-up period will be collected. 
 
 
 


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1.3 Study endpoints 
1.3.1 
Primary efficacy endpoint 
The primary efficacy endpoint is the change in Intra-Ocular Pressure (IOP) from baseline (Day 1) to 
Week 12 at three time points (08:00, 10:00 and 16:00) in the worse eye.  
The worse eye is defined as the eligible eye with the highest IOP at baseline at 08:00. In case of no 
IOP difference between both eyes, the right eye will be considered the worse eye. 
1.3.2 
Secondary efficacy endpoints 
The secondary efficacy endpoints are:  
▪ 
Change in IOP from baseline to Week 12 at three time points (08:00, 10:00 and 16:00) in the 
contralateral eye  
▪ 
Change in IOP from baseline to Week 6 at three time points (08:00, 10:00 and 16:00) in the 
worse eye and in the contralateral eye  
▪ 
Efficacy assessed by the investigator at Week 6 and Week 12 
1.3.3 
Safety endpoints 
Safety and tolerability endpoints are: 
▪ 
Conjunctival hyperaemia on McMonnies scale in each eye at Week 6 and Week 12 
▪ 
Change from baseline of conjunctival hyperaemia on McMonnies scale in three classes 
(improvement, no change, worsening) at Week 6 and Week 12 
▪ 
Score of each ocular symptom throughout the day and the sum of these scores 
▪ 
Score of each ocular symptom upon instillation and the sum of these scores 
▪ 
Score of each ocular sign 
▪ 
Corneal fluorescein staining (CFS) on Oxford scale 
▪ 
Far Best Corrected Visual Acuity expressed in LogMar 
▪ 
Ocular tolerance assessed by the investigator 
▪ 
Ocular tolerance assessed by the patient 
▪ 
Ocular and systemic adverse events (AEs) by System Organ Class (SOC) and Preferred Term 
(PT) 
1.4 Study treatments 
1.4.1 
Treatment groups 
Run-in treatment/wash out 
There is one run-in treatment with the following dose regimen: 
▪ 
Azopt®: a preserved brinzolamide 10mg/ml eye drops suspension in 5 mL multi-dose container. 
It is a white to off-white suspension 
During the run-in period, the patient should instill one drop in each eye twice a day, morning and evening 
for 5 weeks. The Azopt® treatment must be stopped 2 weeks or 1 week before the randomisation visit 
(respectively before or after Clinical Study Protocol amendement 1 – 05JUL2019). 
 
Treatment period 
There are two groups of treatment with the following dose regimen: 
▪ 
T4032: a preservative-free bimatoprost 0.01% eye drops gel in single-dose container. It is a 
sterile, colourless and opalescent gel 


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▪ 
Lumigan® 0.01%: a preserved bimatoprost 0.1 mg/ml eye drops solution in 3 mL multi-dose 
container. It is a colourless solution 
At the randomisation visit, the patient was randomly assigned to receive T4032 or Lumigan® 0,01%. 
The patient should instil one drop once daily at 20:00 (±1 hour) in the conjunctival sac of each eye for 
12 weeks. 
1.4.2 
Randomisation 
1.4.2.1 
Randomisation procedure 
The randomisation code list stratified by site was generated by Aixial. Patients were randomised on a 
1:1 basis to T4032 or Lumigan® 0.01%. The investigational medicinal product (IMP) (T4032 or 
Lumigan®) was allocated to the patients according to randomisation using an interactive web response 
system (IWRS). 
1.4.2.2 
Masking 
This is an investigator-masked clinical study. The first ophthalmologist investigator should therefore 
remain masked to the IMP, and not dispense or receive the returned medication from the patients. 
Masking is achieved by providing the two IMPs (T4032 and Lumigan® 0.01%) in identical cardboard 
containers and by identifying each IMP by an IMP number. 
The code should not be broken except: 
▪ 
in case of medical emergency (where knowledge of the IMP received would affect the treatment 
of the emergency) 
▪ 
or when it is a regulatory requirement 
If an emergency code breaking becomes necessary, the investigator should notify the Sponsor before 
code breaking. The investigator and/or pharmacist are responsible for accessing the IWRS to obtain 
the code of the IMP (T4032 or Lumigan®) allocated to the patient. When a code is broken, the date, 
time and reason must be recorded in the patient’s source documentation as well as in the  
e-CRF, and in any associated Serious AE (SAE) report. The IMP code should not be disclosed in these 
documents.  
During the SAE assessment procedure by the Global Drug Safety & Medical Information Department, 
the code might be broken for reporting purposes. The relevant THEA, Contract Research Organisation, 
and investigator staff remains unaware of the identification of the IMP (T4032 or Lumigan®).  
The overall randomisation list will only be broken for data analysis after database lock 
1.5 Sample size considerations 
The sample size determination was based on the primary efficacy endpoint, i.e., the change in IOP at 
the three time points (08:00, 10:00, 16:00) after 12 weeks of treatment, in the worse eye. 
Non-inferiority of T4032 versus Lumigan® 0.01% will be tested with a non-inferiority margin of 
1.5 mmHg. Non-inferiority will be concluded if it is achieved for each of the three time points 08:00, 
10:00 and 16:00. 
The evaluation will be based upon a two-sided 95% confidence interval (CI) on the difference in mean 
change in IOP after 12 weeks of treatment.  
With data available for 180 patients in each arm, there is more than 90% power to show that the T4032 
unpreserved eye drops is non-inferior to Lumigan® 0.01% preserved eye drops. The hypothesis was 
based on the 1.5 mmHg margin, assuming no difference between the two groups (average difference 
of 0 mmHg), and a standard deviation of 3 mmHg and correlation between time-points of 0.7 on the 
primary efficacy variable.  
Evaluable patients are defined as randomised patients having received at least one dose of IMP (T4032 
or Lumigan®) and with at least one post-randomisation efficacy assessment.  


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Accounting for a 10% dropout/non-evaluable rate, 400 initially treated patients were expected to be 
randomised.  
The sample size of 400 randomised patients is also justified to collect enough safety data. Number of 
screened patients depends on the screen failure rate and was estimated at 668 patients. 
At the end of the recruitment period, 723 patients were screened and 485 patients were randomised. 


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2 ANALYSIS SETS 
The following analysis sets will be considered. 
2.1 Safety set and Azopt® Safety Set 
The Safety set will include all enrolled patients, having received at least one dose of IMP (T4032 or 
Lumigan®) and considered as-treated. Safety endpoints will be analysed on the Safety set. 
The Azopt® Safety set will include all enrolled patients, having received at least one dose of Azopt®. 
Note: Enrolled patients will be patients who have signed the informed consent and for whom the 
screening visit has been recorded in the e-CRF. 
2.2 Intent-to-treat set 
The Intent-to-Treat (ITT) set will include all randomised patients and considered as-randomised (i.e., 
according to the randomisation at Day 1). The ITT set will be considered as a secondary population and 
will be used for sensitivity analyses for the primary efficacy endpoint. 
2.3 Modified intent-to-treat set 
The modified ITT (m-ITT) set will include all randomised patients having received at least one dose of 
IMP (T4032 or Lumigan®), with at least one baseline and one post randomisation efficacy assessment 
and considered as-randomised (i.e., according to the randomisation at Day 1). The m-ITT set will be 
the primary population for efficacy analysis. 
2.4 Per-protocol set 
The Per-protocol (PP) set will include all m-ITT patients without any major protocol violation. Deviations 
from the protocol, including violations of inclusion/exclusion criteria will be detailed in a separate 
document and assessed as “minor” or “major” in cooperation with the Sponsor during a blind review 
meeting prior to the database lock. The PP set will be considered as a secondary population. 
 


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3 GENERAL CONSIDERATIONS FOR DATA ANALYSES 
Statistical analyses will be performed by the Biostatistics unit of AIXIAL. Analyses will be conducted 
with SAS® software, version 9.4 (SAS Institute, North Caroline, USA). 
Continuous data will be described in summary tables presenting, for each treatment group (and for the 
overall population for baseline descriptions), the number of non-missing observations (n), mean, 
standard deviation (SD), median, lower quartile (Q1), upper quartile (Q3), minimum and maximum, and 
95% CI of the mean/median.  
Categorical data will be described in summary tables presenting, for each treatment group (and for the 
overall population for baseline descriptions), the number of non-missing observations (n), count and 
percentage of each modality, and 95% CI. 
95% CI of a proportion will be calculated using the scoring method of Wilson without continuity 
correction: 
Lower Limit = 
(
)
2
2
2
2
4
2
z
n
npq
z
z
z
np
+
+
−
+
 
Upper Limit = 
(
)
2
2
2
2
4
2
z
n
npq
z
z
z
np
+
+
+
+
 
with 
n = number of non-missing observations 
 
p = percentage 
 
q = 1 – p 
 
z = 1.96 for two-sided 95%CI 
 
Except for minimum and maximum, descriptive statistics will be presented with one more decimal than 
the recorded value. 
For all variables, the number of missing values will also be reported in the tables, but they will not be 
counted for the percentage calculation (categorical data). 
Variables recorded for each eye will be described separately for the worse eye and for the other eye (if 
applicable).  
An eye is eligible if inclusion and exclusion (ophthalmological criteria) are respected at screening visit 
and baseline. 
The worse eye is defined as the eligible eye with the highest IOP at baseline at 08:00. In case of no 
IOP difference between both eyes, the right eye will be considered the worse eye. 
Quantitative parameters will be compared between groups using Mixed Model for Repeated Measures 
(MMRM) or Analysis of Covariance (ANCOVA) model. Assumptions underlying the MMRM 
(respectively ANCOVA for the sensitivity analyses) will be checked: 
▪ 
A histogram of residuals will be plotted to check the assumption of normality 
▪ 
The underlying assumptions of normality of residuals for mixed model will also be checked by 
using Skewness and Kurtosis statistics 
▪ 
Normal probability plot and QQ-plot will be performed to check the assumption of normality 
▪ 
Residuals will be plotted against predicted values to check the assumption of heteroscedasticity 
▪ 
Plots of residuals and studentised residuals will be performed to detect outliers. Cook’s distance 
will also be computed. If any outliers are detected, then main model will be performed with and 
then without them 
▪ 
For ANCOVA models, Levene's test will also be performed to check the homogeneity of 
variances 
For each model (MMRM or ANCOVA), if there is a strong violation of normality assumption (or violation 
of homogeneity of variances for ANCOVA), in addition to the initial model, a rank transformation will be 
done, and the model will be applied to ranks. 
The acceptable risk of error for the statistical tests will be set at 5%, except for treatment by covariates 
interactions. For those interactions, the level of significance will be set at 7%.  


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For ordered qualitative variables, treatment groups will be compared using Cochran-Mantel-Haenszel 
(CMH) test stratified by country, with modified ridit scores and “row mean score differ” option. 
Tables and Listings will be provided in separated documents except the listing of Deaths, Other Serious 
adverse events, discontinuations due to adverse events and other adverse events of special interest 
(see Section 7.10.3). 
All individual data will be described in the listings 16.2, by treatment and by patient as follows: 
discontinued patients, protocol deviations, patients excluded from the efficacy analysis, demographic 
data, compliance, individual efficacy response data, adverse event listings, listing of individual 
laboratory measurements. 
All individual data of eCRF will be described in the listing 16.4, by patient. 
3.1 Display of analysis results 
The following labelling for treatment groups will be used in statistical tables: “T4032” and “Lumigan”. 
3.2 Interim analyses 
No interim analysis will be performed. 
3.3 Centre effect management 
For efficacy analysis, centre effect will not be tested, but country effect will be tested (Section 6.1.3). 
3.4 Subgroup analyses 
No subgroup analysis is planned except in case of statistically significant and qualitative treatment by 
covariate interaction. 
3.5 Other strata and covariates 
Country, wash-out duration factor and possible impact of COVID-19 pandemic will be included in 
all models as covariate, and CMH test used for ordered qualitative variables will be stratified by country. 
Baseline value will be included in all MMRM and ANCOVA as covariate:  
▪ 
For analyses on the change from baseline in IOP, baseline IOP will be included as covariate in 
MMRM and ANCOVA 
▪ 
For analysis on the change from baseline in total symptoms score throughout the day, 
corresponding baseline value will be included as covariate in MMRM 
3.6 Multiple comparisons and multiplicity 
There is a single primary efficacy endpoint in the study (change from baseline in IOP at Week 12 in the 
worse eye) and non-inferiority will be achieved if the non-inferiority margin of 1.5 mmHg is met at each 
of the time point assessments: 08:00, 10:00 and 16:00. Other efficacy measures are defined as of 
secondary importance. Consequently, comparisons between T4032 and Lumigan® 0.01% will be 
performed at a two-sided significance level of 5% and no adjustment of the type I error rate will be 
made. 
 


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4 DATA HANDLING CONVENTIONS 
4.1 Visit windows 
All data will be organised and analysed according to the actual observed visits. 
Moreover, for IOP, the recorded value should be allocated to the most appropriate time point. 
Time point 
Interval of time point 
08:00 
Until 09:00 
10:00 
From 9:01 to 13:00 
16:00 
From 13:01 
If more than one record occurs within the same timepoint then the following rule should be applied: the 
closest non-missing result to the scheduled timepoint should be used. To be noted as the record not 
used will be reclassified in another timepoint if it occurs within 30min of interval of timepoint. 
4.2 Premature discontinuation and missing data 
A patient who prematurely discontinues from the study should have, if possible, a premature 
discontinuation visit with the assessment planned on the final visit. This visit should take place as soon 
as possible after the patient stops taking the IMP. 
For patients who prematurely discontinue from the study during the COVID-19 outbreak, the premature 
discontinuation visit was requested by visit on site if possible, else by phone. 
For these patients who prematurely discontinue from the study, evaluations performed during the 
premature withdrawal visit will be considered as the first unobserved scheduled visit whatever their 
actual dates. If the premature withdrawal visit occurs after the discontinuation of the treatment, 
evaluations will be reviewed during the blind review meeting prior to the database lock to confirm their 
use thereof. 
Otherwise, missing data will not be replaced, except for sensitivity analysis of the primary endpoint (see 
Section 6.1.2). Based on the Last Observation Carried Forward (LOCF) method, missing values at 
Week 12 will be replaced by the post-randomisation last available value. For the primary efficacy 
endpoint, a sensitivity analysis considering the post-randomisation last available value will be performed 
for the contralateral eye (see Section 6.2.1). 
4.3 Derived and transformed data 
Following derived data used for analyses will be calculated. 
4.3.1 
Country Grouping 
The patients from the following country will be pooled into one group: Canada, Hungary, Mauritius, and 
UK, as outsiders Countries.  
After this grouping, if the model fails to converge due to low numbers of patients per treatment arm by 
grouping countries, other grouping should be reconsidered and explained in the footnote. 
4.3.2 
Baseline 
Baseline will be defined for each assessment as an evaluation before the first instillation of the IMP: 
▪ 
For IOP, the value recorded at 08:00 at Day 1, respectively at 10:00 and at 16:00, will be the 
baseline for analysis of IOP at 08:00, respectively at 10:00 and at 16:00 
▪ 
For visual field, fundoscopy and corneal thickness, the value recorded at screening visit will be 
the baseline 
▪ 
For others parameters, the value recorded at Day 1, will be the baseline for analysis 


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4.3.3 
Possible impact of COVID-19 pandemic 
To investigate the biais of recruitment before and after the recruitment interruption, patients will be 
classified with or without possible impact of COVID-19 pandemic based on their screening visit date 
respectively up to and including 18-MARS-2020, or after the 18-MAR-2020. 
4.3.4 
Time from diagnosis 
Time from diagnosis (months) will be calculated as:  
(Date of randomisation visit (Day 1) – Date of diagnosis) / 365.25 x 12.  
If the day is missing and month is present the 15th day of the month will be used. If year is present and 
day and month are missing, the time to diagnosis will be calculated as (Year of randomisation visit (Day 
1) – Year of diagnosis) x 12. 
4.3.5 
Wash-out duration 
Wash-out duration (days) will be calculated as (Date of randomisation visit – Date of last Azopt® 
instillation). 
4.3.6 
Duration of Azopt® 
Duration of Azopt® (days) will be calculated as (Date of last instillation – Date of first instillation) + 1. If 
the day or the month is missing for one of the dates, the duration of Azopt® will be missing. 
4.3.7 
Duration of T4032 or Lumigan® 
Duration of T4032/Lumigan® (days) will be calculated as (Date of last instillation at Week 12 or 
premature discontinuation visit – Date of first instillation at Day 1) + 1. If the day or the month is missing 
for one of the dates, the duration of T4032/Lumigan® will be missing. 
Note: This duration is also called time of exposure. 
4.3.8 
Compliance of Azopt® 
Compliance of Azopt® will be calculated for the worse eye and the contralateral eye separately. 
Compliance of Azopt® (%) 
Compliance of Azopt® will be calculated for each eye as follows:  
(Actual number of instillations of Azopt®) / (Theoretical number of instillations of Azopt®) x 100 with: 
▪ 
Theoretical number of instillations of Azopt® = (Date of randomisation visit – 8 or – 15 
(respectively before or after Clinical Study Protocol amendement 1 – 05JUL2019 based on the 
recorded information on the e-CRF) – Date of screening visit + 1) *2, (*2: as patients should 
instil one drop twice a day in each eye) 
▪ 
Maximum number of instillations of Azopt® = (Date of last instillation – Date of first 
instillation + 1) *2, as patients should instil one drop twice a day in each eye 
▪ 
Actual number of instillations: 
- 
If no change in Azopt® instillation is recorded in the e-CRF, the actual number of 
instillations will be considered as equal to the maximum number of instillations 
- 
If changes in Azopt® instillation are recorded in the e-CRF, the actual number of 
instillations will be equal to:  
(Date of last instillation – Date of first instillation + 1) *2 
 – [ 
(∑ Number of days with number of instillations per day in the corresponding 
eye=0 x 2)  
+ ∑ Number of days with number of instillations per day in the corresponding 
eye=1)] 
+ ∑ Number of days x (Number of instillations per day in the corresponding eye when 
number of instillations is >2 -2) 


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4.3.9 
Compliance of T4032 or Lumigan® 
Compliance will be calculated for the worse eye and the contralateral eye separately. For the 
calculation, the premature discontinuation is taken into account (reclassification of visits). 
Compliance (%) from Day 1 to Week 6 
Compliance from Day 1 to Week 6 will be calculated for each eye as follows:  
(Actual number of instillations from Day 1 to Week 6) / (Theoretical number of instillations from Day 1 
to Week 6) x 100 with: 
▪ 
Theoretical number of instillations = (Date of Visit V3 – Date of randomisation visit), as patients 
should instil one drop of IMP once daily in each eye 
▪ 
Maximum number of instillations = (Date of last instillation* – Date of first instillation + 1), as 
patients should instil one drop of IMP once daily in each eye 
▪ 
Actual number of instillations: 
- 
If no change in the IMP instillation is recorded from Day 1 to Week 6 in the e-CRF, the 
actual number of instillations will be considered as equal to the maximum number of 
instillations 
- 
If changes in the IMP instillation are recorded from Day 1 to Week 6 in the e-CRF, the 
actual number of instillations will be equal to: Date of last instillation* – Date of first 
instillation + 1 – ∑ Number of days with number of instillations per day in the 
corresponding eye=0 + ∑ Number of days x (-1 + Number of instillations per day in the 
corresponding eye when number of instillations is >1) 
Compliance (%) from Week 6 to Week 12 
Compliance from Week 6 to Week 12 will be calculated for each eye, for patients not withdrawn before 
Week 6 as follows:  
((Actual number of instillations from Week 6 to Week 12) / (Theoretical number of instillations from 
Week 6 to Week 12)) x 100 with: 
▪ 
Theoretical number of instillations = (Date of Visit V4 – Date of V3), as patients should instil 
one drop of IMP once daily in each eye 
▪ 
Maximum number of instillations = (Date of last instillation* – Date of first instillation + 1), as 
patients should instil one drop of IMP once daily in each eye  
▪ 
Actual number of instillations: 
- 
If no change in the IMP instillation is recorded from Week 6 to Week 12 in the e-CRF, 
the actual number of instillations will be considered as equal to the maximum number 
of instillations 
- 
If changes in the IMP instillation are recorded from Week 6 to Week 12 in the e-CRF, 
the actual number of instillations will be equal to: Date of last instillation* – Date of first 
instillation + 1 – ∑ Number of days with number of instillations per day in the 
corresponding eye=0 + ∑ Number of days x (-1 + Number of instillations per day in the 
corresponding eye when number of instillations is >1) 
Compliance (%) from Day 1 to Week 12 
Compliance from Day 1 to Week 12 will be calculated for each eye as follows:  
((Actual number of instillations from Day 1 to Week 6 + Actual number of instillations from Week 6 to 
Week 12) / (Theoretical number of instillations from Day 1 to Week 6 + Theoretical number of 
instillations from Week 6 to Week 12)) x 100. 
For patients withdrawn before Week 6, actual and theoretical numbers of instillations from Week 6 to 
Week 12 will not be considered for the calculation. 
Individual data regarding changes in the study product instillation will be examined during a blind review 
meeting before database lock. In case of missing data (missing date(s), missing number of days or 
missing number of instillations per day), rules for calculation will be decided on a case by case basis. 
 
* If the date of the last instillation is on/after the date of the Visit, the last date of instillation will be 
replaced by the day before the date of the Visit. In this case, the date of the Visit will be assumed as 


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the date of the first instillation for the subsequent treatment period, if applicable (I.e., for Compliance 
from Week 6 to Week 12). 
4.3.10 Change from baseline 
Change from baseline will be calculated as the difference:  
Assessment at the visit – Assessment at baseline. 
4.3.11 Change from baseline in classes 
Change from baseline in classes will be defined as detailed below:  
In four classes: 
▪ 
Improvement (Decrease of score from baseline): Change from baseline <0 
▪ 
Absence stable: Change from baseline = 0 and absence of symptoms 
▪ 
Presence stable: Change from baseline = 0 and presence of symptoms 
▪ 
Worsening (Increase of score from baseline): Change from baseline >0 
In three classes compared to 0: 
▪ 
Improvement (Decrease of score from baseline): Change from baseline <0 
▪ 
No change: Change from baseline = 0 
▪ 
Worsening (Increase of score from baseline): Change from baseline >0 
In three classes compared to -1/1: 
▪ 
Improvement of more than 1 point: Change from baseline <-1 
▪ 
No significant change: Change from baseline ≥-1 and ≤1 
▪ 
Worsening of more than 1 point: Change from baseline >1 
4.3.12 IOP value 
The IOP value will be calculated for each eye as follows: 
▪ 
If the first 2 readings differ by 2 mmHg or less, the mean IOP will be the average of the first 2 
readings, regardless of the third reading 
▪ 
If the first 2 readings differ by more than 2 mmHg and the third reading is recorded, the mean 
IOP will be the average of the 3 readings 
▪ 
If the first 2 readings differ by more than 2 mmHg and the third reading is not recorded, the 
mean IOP will be the average of the first 2 readings 
▪ 
If only one reading is recorded, this single reading will be used for assessment of the mean IOP 
4.3.13 Mean diurnal IOP 
Mean diurnal IOP will be calculated as the mean of the IOP value at 08:00, 10:00 and 16:00. If any 
individual IOP is missing, the mean diurnal IOP will also be missing. 
Change from baseline of mean diurnal IOP will be calculated as defined in Section 4.3.10. 
4.3.14 Total score of subjective ocular symptoms throughout the day 
The total score of subjective ocular symptoms throughout the day (ranging from 0 to 18) will be 
calculated by adding the individual scores of the 6 following symptoms: irritation/burning, stinging, 
itching, tearing, eye dryness feeling, foreign body sensation. If any individual score is missing, the total 
score will also be missing. 
4.3.15 Total score of subjective ocular symptoms upon instillation 
The total score of subjective ocular symptoms upon instillation (ranging from 0 to 18) will be calculated 
by adding the individual scores of the 6 following symptoms: irritation/burning, stinging, itching, tearing, 
eye dryness feeling, foreign body sensation. If any individual score is missing, the total score will also 
be missing. 
 


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4.3.16 Far best corrected visual acuity 
Far best corrected visual acuity will be calculated in Log Mar as: Log10 (10/ Visual acuity) with Visual 
acuity expressed in /10 unit. 
4.3.17 AE time to occurence 
Time to occurence (days) of an AE will be calculated as follows: Date of onset – Date of IMP first 
instillation. 
4.3.18 AE duration 
Duration (days) of an AE will be calculated as follows: (Date of recovery – Date of onset) + 1. 


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5 DESCRIPTION OF THE STUDY POPULATION 
5.1 Disposition of patients 
The number of enrolled patients will be presented overall. The number (%) of patients included in Azopt® 
Safety set will be presented overall. The number (%) of patients included in each other analysis set 
(Safety, ITT, m-ITT and PP) will be presented by treatment group and overall. It will also be presented 
by possible impact of COVID-19 pandemic classes. 
The number (%) of patients by country will be presented by treatment group and overall, for each 
analysis set. The number (%) of patients by country will be also presented for patients who prematurely 
discontinued the study for COVID-19 crisis and by possible impact of COVID-19 pandemic classes for 
the Safety set. 
The number (%) of patients per visit as considered in the analysis will be described by treatment group 
and overall for the Safety set, for the ITT set (if it differs from the Safety set) for the m-ITT set and for 
PP. It will also be described by possible impact of COVID-19 pandemic classes for each population.  
A listing of patients with populations, treatment group (planned group and actual group), worse eye of 
the enrolled patients and possible impact of COVID-19 pandemic classes and a listing of visits and 
visits as considered in the analysis (see Sections 4.1 and 4.2) will be produced for the Safety set. 
The number (%) of patients who prematurely discontinued the study and the primary reason for 
discontinuation will be presented by treatment group and overall for the Safety set, ITT set (if it differs 
from the Safety set) and m-ITT set. A listing will be produced presenting the patients who prematurely 
discontinued the study with the detailed reason for discontinuation. The number (%) of patients by 
country will be also presented for patients who prematurely discontinued the study and for those who 
prematurely discontinued for COVID-19 crisis. 
The number (%) of patients with at least one major deviation, the number (%) of patients with only minor 
deviations (without major deviations) and the number (%) of patients with minor deviations (including 
those with major deviations) will be presented by treatment group and overall for the m-ITT set. The 
reasons for deviation will also be described for the m-ITT set and an individual patient data listing with 
all minor/major deviations will be provided. This description will also be performed possible impact of 
COVID-19 pandemic classes. 
A listing of patients excluded from the Azopt® Safety, Safety, ITT, m-ITT and PP sets, presenting the 
reason for exclusion, will be produced on the enrolled patients’ population. 
5.2 Demographic and baseline characteristics 
The demographic and baseline characteristics of the patients will be described overall and by treatment 
group for the m-ITT set, Safety set, ITT set (if it differs from the Safety set) and PP set. 
The following characteristics will be summarised: 
▪ 
Demographic characteristics: 
- 
Age (years) as continuous and in classes (<65, ≥65 years old) 
- 
Gender 
- 
Gender by age class (<65, ≥65 years old) 
▪ 
Medical history (*) 
- 
Ocular medical history other than the studied disease 
- 
Systemic medical history 
▪ 
Surgical history (*) 
- 
Ocular surgical history related to another disease than the studied one  
- 
Systemic surgical history 


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(*) Diagnoses (for medical history) and surgical procedures (for surgical history) will be coded using 
the Medicinal Dictionary for Regulatory Activities (MedDRA) version the most recent possible at the 
database lock. Number (%) of patients will be presented by SOC and PT by treatment group and 
overall. 
▪ 
Ocular treatments (**) 
- 
Previous ocular treatments 
- 
Concomitant ocular treatments 
▪ 
Non-ocular treatments (**) 
- 
Previous non-ocular treatments 
- 
Concomitant non-ocular treatments 
(**) All previous and concomitant ocular and non-ocular treatments will be coded using the World 
Health Organisation-Drug Dictionary (WHO-DD version Q1 2018). Treatments will be summarised 
according to the Anatomical therapeutic chemical (ATC) class (level 2 and level 4) of the WHO-DD 
dictionary by treatment group and overall. A previous treatment will be defined as a treatment 
stopped prior to (or the same day as) the first instillation of T4032 or Lumigan®. A concomitant 
treatment will be defined as a treatment i) started after (or the same day as) the first instillation of 
the T4032/ Lumigan®, ii) started prior to and continued after the first instillation of the T4032/ 
Lumigan®. If the classification is not possible due to partial start/end date(s) of treatment, the 
treatment will be considered as concomitant. 
▪ 
History of glaucoma or ocular hypertension: 
- 
Diagnosis in the worse and contralateral eye (Ocular hypertension / Primary Open 
Angle Glaucoma / Secondary Open Angle Glaucoma: Exfoliation Glaucoma / 
Secondary Open Angle Glaucoma: Pigmentary Glaucoma) 
- 
Time from diagnosis in the worse and contralateral eye (months) 
- 
Previous treatment (Bimatoprost/Latanoprost/Tafluprost/Travoprost/Other) 
- 
Surgical history related to the glaucoma or ocular hypertension in the worse and 
contralateral eye (by SOC and PT) 
▪ 
Results of the automated visual field (Normal/Abnormal; If abnormal, clinically significant 
[Yes/No]) for the worse and the contralateral eyes 
▪ 
Central corneal thickness measurement (µm) for the worse and contralateral eye as continuous 
and in classes (<555, ≥555 µm) 
▪ 
Fundus examination (listing) 
▪ 
IOP data during run-in period: Descriptive statistics will be performed on IOP at 08:00, for the 
worse and contralateral eye, at each assessment time (i.e., screened visit and randomisation 
visit). Change from screening to randomisation will be described. The descriptions will also be 
performed depending on the wash-out duration (≤8 days, >8 days).  
Data regarding contraception status and pregnancy test results (for women) will be presented in an 
individual data listing (Section 16.2). 
In addition, the following data will be described for the Safety set: 
▪ 
Number of patients and cumulative time of exposure (in days) 
▪ 
Number of patients and cumulative time of exposure (in days) by age group (<65 years old, ≥65 
and <75 years old, ≥75 and <85 years old, ≥85 years old) and gender 
▪ 
Number of patients and cumumative time of exposure (in days) by IMP exposure in classes (<1 
month, ≥1 and <3 months, ≥3 months) 


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Demographics characteristics, history of glaucoma or ocular hypertension, automated visual field, 
central corneal thickness measurement, IOP data during run-in period, baseline values of IOP will be 
also presented for patients who prematurely discontinued the study for COVID-19 crisis for the Safety 
set, by possible impact of COVID-19 pandemic classes for m-ITT, Safety and PP sets and according to 
the following groups: Patients from ITT set included in m-ITT set versus Patients from ITT set not 
included in m-ITT set. 
Baseline values of the efficacy and safety endpoints will be provided in statistical tables with 
assessments at Week 6 (if applicable) and Week 12 (see Sections 6 and 7). 
5.3 Treatment exposure and compliance 
The following data on the use of Azopt® will be summarised overall for the Azopt® Safety set and by 
treatment group for the m-ITT set: 
▪ 
Duration of Azopt® (days) 
▪ 
Frequency distribution of patients with any absence or modification of Azopt® instillation 
(Yes/No) from the first to the last instillation 
The following data on the use of Azopt® will be summarised by treatment group for the m-ITT set: 
▪ 
Compliance (%) for each eye from the first to the last instillation, as continuous variable and in 
categories (<80%, ≥80% and ≤120%, >120%) 
Details of data relative to Azopt® instillation and modification of Azopt® instillation will be provided in 
individual data listing. 
The following data on the use of the IMP T4032 or Lumigan® will be summarised overall and by 
treatment group for the Safety and m-ITT sets and it will also be summarised by possible impact of 
COVID-19 pandemic classes: 
▪ 
Duration of treatment (days) 
▪ 
Frequency distribution of patients with any absence or modification of instillation (Yes/No) from 
the first to the last instillation, between Day 1 and Week 6, Week 6 and Week 12, Day 1 and 
Week 12 
▪ 
Frequency distribution of patients with any instillation time modifications (Yes/No) from the first 
to the last instillation, Day 1 and Week 6, Week 6 and Week 12, Day 1 and Week 12 
▪ 
Compliance (%) for the worse and contralateral eye from the first to the last instillation, from 
Day 1 and Week 6, Week 6 and Week 12, Day 1 and Week 12, as continuous variable and in 
categories (<80%, ≥80% and ≤120%, >120%) 
Details of data relative to IMP instillation, absence of instillations and instillation time modifications will 
be provided in individual data listings. 


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6 EFFICACY ANALYSIS 
The primary efficacy endpoint will be primarily analysed on the m-ITT set. Sensitivity analyses will be 
performed on the ITT and PP sets. Secondary efficacy endpoints will be analysed on the m-ITT set and 
on PP set. 
For efficacy variables, descriptions will be given by treatment group at each assessment time. Change 
from baseline will also be presented. 
Of note, for analyses on change from baseline in IOP at 10:00 (respectively at 16:00) in the worse eye 
and in the contralateral eye, the baseline IOP is the IOP recorded at 10:00 (respectively at 16:00) at 
Day 1, before the first instillation. 
6.1 Primary efficacy endpoint 
The primary efficacy endpoint is the change from baseline in IOP (average of the 2 or 3 recorded values 
- see the calculation in Section 4.3.12) at Week 12 at the three time points (08:00, 10:00 and 16:00) in 
the worse eye (see the definition for the worse eye in Section 3).  
Inferential analyses of the primary endpoint will aim to assess the non-inferiority of T4032 to Lumigan® 
0.01%. The non-inferiority testing will be performed on the basis of a 95% CI for the difference between 
the two treatment groups in the change from baseline in IOP. 
Descriptive statistics will be performed on IOP at 08:00, 10:00 and 16:00 for the worse eye at each 
assessment time (i.e., baseline, Week 6 and Week 12). Change from baseline to Week 6 and change 
from baseline to Week 12 will be described as well. These descriptions will also be performed by country 
and by possible impact of COVID-19 pandemic classes. 
6.1.1 
Main analysis of the primary efficacy endpoint 
The non-inferiority of T4032 to Lumigan® 0.01% on the change from baseline in IOP will be primarily 
tested using a MMRM approach. Three independent models will be performed, one for each time point 
(i.e., at 08:00, 10:00 and 16:00). Each model will include as fixed factors, treatment, scheduled visit 
time point (Week 6 and Week 12), baseline IOP, wash-out duration, country as covariates, treatment 
by visit interaction, baseline IOP by visit interaction, and patient as random factor. The Restricted 
Maximum Likelihood (REML) estimation approach will be used, and the default covariance structure 
will be unstructured. Consistent with MMRM model fitting, no explicit imputation of missing assessments 
for a given visit time point will be performed. The 95% CI for treatment effect (difference T4032 - 
Lumigan® 0.01%) will be estimated at Week 12 in this model. Non-inferiority will be achieved if the upper 
bound of the 95% CI for the difference between treatment groups (T4032 - Lumigan® 0.01%) is lower 
than the margin of +1.5 mmHg for each of the three time points 08:00, 10:00 and 16:00.  
The syntax with SAS using the MIXED procedure is detailed in Appendix 1. 
6.1.2 
Sensitivity analyses of the primary efficacy endpoint 
Whilst patients who have missing data at Week 12 but who have an earlier recorded value (i.e., Week 6) 
will be included in the MMRM primary analysis, the interpretability of the results from the primary model 
will depend on the missing data satisfying the Missing at Random. To support the validity of the 
conclusions drawn from this analysis, sensitivity analyses will be performed to explore the dropout 
pattern and its possible impact on treatment comparisons. 
1) Missing values at Week 12 at 08:00, respectively at 10:00 and at 16:00, will be replaced by the post-
randomisation last available value (i.e., the Week 6-based IOP, if available) at 08:00, respectively at 
10:00 and at 16:00, i.e., based on LOCF method. The change from baseline in IOP at Week 12 will be 
analysed using an ANCOVA including treatment, baseline IOP, wash-out duration and country. Three 
independent ANCOVA will be performed, one for each time point (i.e., at 08:00, 10:00 and 16:00). The 
adjusted mean treatment differences (T4032 - Lumigan® 0.01%) and their corresponding 95% CI will 
be estimated in these models to test the non-inferiority hypothesis.  


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2) The same analyses as the ones planned on the post-randomisation last available value will be 
performed on the observed value at Week 12 (i.e., missing values at Week 12 will not be replaced). 
The change from baseline in IOP recorded at Week 12 will be analysed using an ANCOVA including 
treatment (T4032/Lumigan®), baseline IOP, wash-out duration and country. Three independent 
ANCOVA will be performed, one for each time point (i.e., at 08:00, 10:00 and 16:00). The adjusted 
mean treatment differences (T4032 - Lumigan® 0.01%) and their corresponding 95% CI will be 
estimated in these models to test the non-inferiority hypothesis.  
The syntax with SAS using the MIXED procedure is detailed in Appendix 1. 
The primary analysis (i.e., based on the MMRM approach) and the same sensitivity analyses presented 
here above will be performed in the ITT and PP sets. 
6.1.3 
Supporting analyses to check the validity of the main and sensitivity 
analyses 
Possible treatment by covariate (baseline IOP, wash-out duration and country) interaction will be 
investigated in the separated MMRM models (resp. in the ANCOVA models for the sensitivity analysis) 
including the additional interaction term of interest for the m-ITT set. 
The tests for interactions will be interpreted at the 7% level of significance. 
The adjusted mean difference between treatment groups will be computed. If the p-value is lower than 
7% and the interaction is qualitative, then the main model will be performed by covariate in classes. 
The syntax with SAS using the MIXED procedure is detailed in Appendix 1. 
6.1.4 
Exploratory analysis of the primary efficacy endpoint  
Possible covariate effect (Possible impact of COVID-19 pandemic) will be investigated in the MMRM 
model (resp. in the ANCOVA model for the sensitivity analysis). Covariate of interest and covariate by 
treatment interaction will be added to the main model on the m-ITT set. 
The tests for interactions will be interpreted at the 7% level of significance. 
The adjusted mean difference between treatment groups will be computed. If the p-value is lower than 
7% and the interaction is qualitative, then the main model will be performed by inclusion period. 
The impact of circadian rhythm will also be assessed by using time factor within the model, as patient 
nested in time, i.e. the model will include as fixed factors, treatment, scheduled visit time point (Week 6 
and Week 12), time (8:00, 10:00 and 16:00), wash-out duration, country as covariates, treatment by 
visit interaction, treatment by time interaction, and patient nested in time. The adjusted mean treatment 
differences (T4032 - Lumigan® 0.01%) and their corresponding 95% CI will be estimated at each time 
at Week 12. 
The syntax with SAS using the MIXED procedure is detailed in Appendix 1.  
6.2 Secondary efficacy endpoints 
Secondary efficacy endpoints will be analysed on the m-ITT set and on PP set. 
6.2.1 
Change from baseline in IOP 
Descriptive statistics will be performed on IOP at 08:00,10:00 and 16:00 for the contralateral eye at 
each assessment time (i.e., baseline, Week 6 and Week 12). Change from baseline to Week 6 and 
change from baseline to Week 12 will be described as well. These descriptions will also be performed 
by country and by possible impact of COVID-19 pandemic classes. 
 


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Using the same MMRM as for the main analysis of the primary efficacy endpoint, 95% CI of the adjusted 
mean difference between treatment groups will be estimated for:  
▪ 
Change from baseline in IOP at Week 12 at 08:00, 10:00 and 16:00 in the contralateral eye  
▪ 
Change from baseline in IOP at Week 6 at 08:00, 10:00 and 16:00 in the worse eye and in the 
contralateral eye  
As for the primary endpoint, sensitivity analyses based on ANCOVA: using i) the LOCF method and ii) 
observed value at Week 12 will be performed for the contralateral eye. The 95% CI of the adjusted 
mean difference between treatment groups in the change from baseline to Week 12 in IOP will be 
provided. 
ANCOVA on the change from baseline in IOP at Week 6 will also be performed for the worse eye and 
for the contralateral eye. The 95% CI of the adjusted mean difference between treatment groups will be 
provided. 
The exploratory analysis on the impact of circadian rhythm will also be assessed at Week 6 by using 
the same model described in Section 6.1.4 for this parameter. 
6.2.2 
Other analyses on IOP 
Frequency distribution of patients with IOP <18 mmHg and IOP ≥18 mmHg will be described by 
treatment group at each assessment time (Baseline [Day 1] at 08:00, 10:00 and 16:00, Week 6 at 08:00, 
10:00 and 16:00 and Week 12 at 08:00, 10:00 and 16:00), separately for the worse eye and the 
contralateral eye. 
Descriptive statistics will be performed on IOP at 08:00, 10:00 and 16:00 and on changes from baseline 
for the worse eye and for the contralateral eye at each assessment time (i.e., baseline, Week 6 and 
Week 12), depending on the History of glaucoma or ocular hypertension. 
Descriptive statistics will be performed on the mean diurnal IOP at baseline, Week 6 and Week 12. 
Change from baseline to Week 6 and change from baseline to Week 12 will be described. 
6.2.3 
Global assessment of efficacy by the investigator 
Global judgment of efficacy by investigator will be assessed on a 4-point ordinal scale (Very satisfactory, 
Satisfactory, Not very satisfactory, Unsatisfactory). 
Assessment of Azopt® efficacy will be presented by frequency distribution for each modality and 
frequency distribution after regrouping ‘very satisfactory’ with ‘satisfactory’, and ‘not very satisfactory’ 
with ‘unsatisfactory’. 
Assessment of LT4032 or Lumigan® efficacy will be presented by frequency distribution for each 
modality and frequency distribution after regrouping ‘very satisfactory’ with ‘satisfactory’, and ‘not very 
satisfactory’ with ‘unsatisfactory’, at Week 6 and Week 12. After regrouping in 2 classes, comparison 
of treatment groups at Week 6 and Week 12 will be performed using a CMH test stratified by country. 


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7 SAFETY ANALYSIS 
Safety endpoints will be analysed on the Safety set, by treatment group except when specify on the 
Azopt® Safety set overall. 
7.1 Conjunctival hyperaemia – Slit lamp examination 
Conjunctival hyperaemia assessed for each eye using the McMonnies photographic 6-point ordinal 
scale from 0 to 5 will be presented by frequency distribution at each assessment time (screening, 
baseline [Day 1], Week 6 and Week 12), for the worse eye and contralateral eye. Comparison between 
treatment groups will be performed at Week 6 and at Week 12, using a CMH test with modified ridit 
scores stratified by country, separately for the worse eye and for the contralateral eye. 
In addition, frequency distribution of change from baseline will be presented for conjunctival hyperaemia 
at Week 6 and Week 12 for the worse eye and contralateral eye. The following categories will be defined 
and presented: i) improvement (i.e., decrease of symptom score from baseline), absence stable, 
presence stable, worsening (i.e., increase of symptom score from baseline), ii) improvement, no 
change, worsening, iii) improvement of more than 1 point (i.e., change from baseline <-1, no significant 
change (i.e., change from baseline ≥-1 and ≤1), worsening of more than 1 point (i.e., change from 
baseline >1). Comparison of changes from baseline in 3 classes (improvement, no change, worsening) 
for conjunctival hyperaemia between treatment groups will be performed at Week 6 and Week 12, using 
a CMH test with modified ridit scores stratified by country, separately for the worse eye and for the 
contralateral eye. 
7.2 Subjective ocular symptoms throughout the day 
Subjective ocular symptoms throughout the day (irritation/burning, stinging, itching, tearing, eye dryness 
feeling, foreign body sensation) will be assessed using a 4-point ordinal scale from 0 to 3, 0 indicating 
no symptom and 3 indicating very disturbing symptom. 
Frequency distribution of each symptom will be presented at screening, baseline (Day 1), Week 6 and 
Week 12. Comparison between treatment groups will be performed for each symptom at Week 6 and 
at Week 12 using a CMH test with modified ridit scores stratified by country. 
The total score of the 6 symptoms, ranging from 0 to 18, will be calculated and presented for screening, 
baseline (Day 1), Week 6 and Week 12. Change in total score from baseline will also be described at 
Week 6 and Week 12. Comparison of the change from baseline in total score between treatment groups 
will be performed at Week 6 and Week 12 using an MMRM model. The model will include as fixed 
factors, treatment, scheduled visit time point (Week 6 and Week 12), baseline, wash-out duration and 
country, treatment by visit interaction and patient as random factor. 
Data relative to other symptoms will be provided in individual data listing. Other symptoms will be coded 
using MedDRA dictionary version the most recent possible at the database lock. 
Note: If the patient did not feel any ocular symptom throughout the day, each symptom will be scored 
0. 
7.3 Subjective ocular symptoms upon instillation 
Subjective ocular symptoms upon instillation (irritation/burning, stinging, itching, tearing, eye dryness 
feeling, foreign body sensation) will be assessed using a 4-point ordinal scale from 0 to 3, 0 indicating 
no symptom and 3 indicating very disturbing symptom. 
Frequency distribution of each symptom will be presented at Week 6 and Week 12. Comparison of each 
symptom between treatment groups, separately for Week 6 and Week 12 will be performed using a 
CMH test with modified ridit scores stratified by country. 
The total score of the 6 symptoms, ranging from 0 to 18, will be calculated and presented for Week 6 
and Week 12. 
Comparison of the total score between treatment will be performed at Week 6 and Week 12 using an 
MMRM model. The model will include as fixed factors, treatment, scheduled visit time point (Week 6 
and Week 12), country, wash-out duration treatment by visit interaction and patient as random factor. 


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Data relative to other symptoms will be provided in individual data listing. Other symptoms will be coded 
using MedDRA dictionary version the most recent possible at the database lock. 
Note: If the patient did not feel any ocular symptom upon instillation, each symptom will be scored 0. 
7.4 Ocular signs – Slit lamp examination 
Each ocular sign (blepharitis, eyelid oedema, iris hyperpigmentation, abnormal eyelashes aspect, 
folliculo-papillary conjunctivitis) assessed for each eye on a 4-point ordinal scale from 0 to 3, 0 indicating 
absence and 3 indicating severe sign. 
Frequency distribution of each ocular sign will be presented at screening, baseline (Day 1), Week 6 and 
Week 12, on the worse eye and the contralateral eye. Comparison between treatment groups will be 
performed for each ocular sign, at Week 6 and at Week 12, using a CMH test with modified ridit scores 
stratified by country, separately for the worse eye and for the contralateral eye. 
Data relative to other ocular abnormalities will be provided in individual data listing. Other ocular 
abnormalities will be coded using MedDRA dictionary version the most recent possible at the database 
lock. 
7.5 Corneal staining according to Oxford grading scheme 
The Oxford 0-5 grading scheme assesses the staining of the corneal area. 
The CFS score (ranging from 0 to 5) will be calculated and frequency distribution will be presented at 
screening, baseline (Day 1), Week 6 and Week 12, for the worse eye and for the contralateral eye. 
Comparison of the CFS score between treatment groups will be performed at Week 6 and at Week 12 
using a CMH test with modified ridit scores stratified by country, separately for the worse eye and for 
the contralateral eye. 
7.6 Far best corrected visual acuity 
Far best corrected visual acuity in LogMar will be summarised at screening, baseline (Day 1) and Week 
12 using usual descriptive statistics for continuous variable, for the worse eye and for the contralateral 
eye. 
Frequency distribution in classes (i.e., values from 1/10 to 10/10, including NA category, with non-
integer numbers rounded to the nearest integer) will also be presented. 
7.7 Automated visual field and Funduscopy 
Visual field and the funduscopy at Week 12 will be listed also including screening results and IOP values 
at each visit (Section 16.2). 


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7.8 Ocular tolerance by the investigator 
Ocular tolerance by the investigator will be assessed on a 4-point ordinal scale (Very 
satisfactory/Satisfactory/Not very satisfactory/Unsatisfactory). 
Assessment of Azopt® ocular tolerance by the investigator at Visit 2 will be presented by frequency 
distribution for each modality and frequency distribution after regrouping ‘very satisfactory’ with 
‘satisfactory’, and ‘not very satisfactory’ with ‘unsatisfactory’, on Azopt® Safety set, overall. 
Assessment of LT4032 or Lumigan® ocular tolerance by the investigator will be presented by frequency 
distribution for each modality and frequency distribution after regrouping ‘very satisfactory’ with 
‘satisfactory’, and ‘not very satisfactory’ with ‘unsatisfactory’. After regrouping in 2 classes, comparison 
of treatment groups at Week 6 and Week 12 will be performed using a CMH stratified by country. 
7.9 Ocular tolerance by the patient 
Ocular tolerance by the patient will be assessed on a 4-point ordinal scale (Very 
satisfactory/Satisfactory/Not very satisfactory/Unsatisfactory). 
Assessment of Azopt® ocular tolerance at Visit 2 by the patient will be presented by frequency 
distribution for each modality and frequency distribution after regrouping ‘very satisfactory’ with 
‘satisfactory’, and ‘not very satisfactory’ with ‘unsatisfactory’, on Azopt® Safety set, overall. 
Assessment of LT4032 or Lumigan® ocular tolerance by the patient will be presented by frequency 
distribution for each modality and frequency distribution after regrouping ‘very satisfactory’ with 
‘satisfactory’, and ‘not very satisfactory’ with ‘unsatisfactory’. After regrouping in 2 classes, comparison 
of treatment groups at Week 6 and Week 12 will be performed using a CMH stratified. 
7.10 Ocular and systemic adverse events 
All AEs reported during the study will be coded with MedDRA version the most recent possible at the 
database lock. 
Ocular and systemic AEs will be analysed separately on the basis of the localisation as recorded by the 
investigator in the CRF. 
Summary tables will be produced for treatment-emergent AEs (TEAEs).  
TEAEs for Azopt® are AEs that occurred the same day or after the first Azopt® instillation and until the 
day of the first IMP (LT4032 or Lumigan®). 
TEAEs for LT4032 or Lumigan® are AEs that occurred the same day or after the first IMP (LT4032 or 
Lumigan®) instillation and before or the day of the maximal date between last IMP instillation and Visit 
4 (Week 12).  
AEs that occurred the day of the first Azopt® instillation will be reviewed during a blind review meeting 
to decide if they have to be considered as a TEAE for Azopt® or not. AEs that occurred the day of the 
first IMP instillation will be reviewed during a blind review meeting to decide if they have to be considered 
as a TEAE for LT4032 or Lumigan® or a TEAE for Azopt®. 
7.10.1 Summary of TEAEs 
Separate summaries of treatment-emergent ocular and systemic AEs will be produced by treatment 
group presenting the number and percentages of patients experiencing at least one: 
▪ 
AE, 
▪ 
SAE, 
▪ 
IMP-related AE (i.e., related or missing relationship with the IMP), 
▪ 
AE leading to premature study IMP withdrawal. 
This table will be presented overall on the Azopt® safety set for TEAE for Azopt® and by treatment group 
on the Safety set for TEAE for LT4032 or Lumigan® 


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7.10.2 Details of AEs 
Separate descriptions of treatment-emergent ocular and systemic AEs for Azopt® will be produced 
overall on Azopt® Safety set: 
▪ 
Number and percentage of patients experiencing at least one TEAE, as well as the number of 
TEAEs, by SOC and PT. The same summary table will be produced for SAEs (if any), and AEs 
related to Azopt® and AEs leading to premature IMP drug withdrawal 
 
Separate descriptions of treatment-emergent ocular and systemic AEs for LT4032 or Lumigan® will be 
produced by treatment group on the Safety set. 
▪ 
Number and percentage of patients experiencing at least one TEAEs as well as the number of 
TEAEs by SOC and PT. The same summary table will be produced for SAEs, IMP-related AEs, 
IMP-related SAEs and AEs leading to premature IMP drug withdrawal 
▪ 
Number and percentage of patients experiencing at least one TEAEs as well as the number of 
TEAEs by SOC, PT and severity 
▪ 
Number and percentage of patients experiencing at least one TEAEs as well as the number of 
TEAEs by SOC, PT and relationship with IMP 
▪ 
Number and percentage of patients with TEAEs by SOC, PT and maximal severity  
▪ 
Number of patients with TEAEs by SOC, PT and strongest relationship 
 
Summary of treatment-emergent non serious AEs (ocular or systemic) will be produced by treatment 
group, for LT4032 or Lumigan® presenting the number and percentages of patients experiencing: 
▪ 
at least one non serious AE 
▪ 
at least one non serious AE when percentages by PT is >=5% for one group, 
as well as the number of these TEAEs by SOC and PT 
7.10.3 Individual listing of AEs 
Patient data listings of AEs (ocular and systemic together) will be produced: 
▪ 
for non emergent AEs on enrolled patients 
▪ 
for TEAE, serious TEAE, drug related TEAE and TEAE leading to premature IMP drug 
withdrawal, separetly TEAE for Azopt and TEAE for T4032 or Lumigan® 
▪ 
for Post-treatment AE, ie. after the day of the maximal date between last IMP instillation and 
Visit 4 (Week 12) 
Patient data listings of COVID-19 AEs (PT: COVID-19, Coronavirus infection) will also be produced. 
 
The following variables will be presented:  
▪ 
Treatment group 
▪ 
Patient’s identifier 
▪ 
Worse eye (Right Eye/Left eye) 
▪ 
Gender 
▪ 
Age at baseline (Day 1) 
▪ 
Diagnosis (Verbatim) 
▪ 
SOC 
▪ 
PT 
▪ 
Localisation 
▪ 
Date / time of occurence 
▪ 
Time to occurence (days) from the date of the first IMP instillation 
▪ 
Date / time of recovery/date of death, if any 
▪ 
Duration (days) 
▪ 
Outcome 


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▪ 
Frequency and details 
▪ 
Severity 
▪ 
Action taken regarding the IMP 
▪ 
Requirement for therapy adjustment/modification 
▪ 
Requirement for surgical/medical procedure, 
▪ 
Seriousness, 
▪ 
Relationship with T4032/Lumigan® in the investigator’s opinion, 
▪ 
Relationship with Azopt® in the investigator’s opinion, 
▪ 
Relationship with protocol procedure. 
Listings will be sorted by treatment group, patient’s identifier and date of onset. 
Listing of Deaths, Other Serious adverse events, discontinuations due to adverse events and other 
adverse events of special interest will be also provided for narratives. 
Discontinuations due to adverse events include drug related AE leading to premature IMP drug OR 
study withdrawal (ie drug related AE with action taken = drug withdrawn OR End of study with premature 
discontinuation due to this AE). 
 


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8 CHANGES FROM PROTOCOL 
Changes from protocol are the following: 
▪ 
Regarding Safety set (Section 2.1), due to Azopt® is an IMP, Azopt® Safety Set has been added. 
▪ 
Baseline definition has been completed (Section 4.3.2). 
▪ 
Regarding IOPs: 
- 
Descriptions during the run-in period have been added (Section 5.2) 
- 
Descriptions during the treatment period depending on the History of glaucoma or 
ocular hypertension (Section 6.2.2) have been added 
- 
Descriptions of the mean diurnal IOP have been added (Section 6.2.2) 
- 
Exploratory analysis of impact of circadian rhythm on IOP have been added (Sections 
6.1.4 and 6.2.1) 
▪ 
Regarding COVID-19 crisis, some analyses have been added to explore the consequence on 
this trial: 
- 
Descriptions of disposition of patients (Section 5.1) and demographic and baseline 
characteristics (Section 5.2) for patients who prematurely discontinued the study for 
COVID-19 crisis and by possible impact of COVID-19 pandemic classes have been 
added 
- 
Descriptions of demographic and baseline characteristics (Section 5.2) according to 
the following groups have been added: Patients from ITT set included in m-ITT set 
versus Patients from ITT set not included in m-ITT set 
- 
Descriptive statistics of IOP (Section 6.1) and exploratory analysis (Section 6.1.4) on 
possible impact of COVID-19 pandemic classes have been added 
- 
Listing of patients with COVID-19 AE (Section 7.10.3) 
▪ 
Regarding secondary efficacy endpoints (Section 6.2), they will be performed on PP 
▪ 
Regarding subjective ocular symptoms throughout the day (Section 7.2) and subjective ocular 
symptoms upon instillation (Section 7.3), due to data are repeated at Week 6 and Week 12, 
ANCOVA models at Week 6 and Week 12 have been replaced by MMRM models 
▪ 
Regarding adverse events (Section 7.10): 
- 
Due to a follow-up visit is performed and Azopt® is an IMP, the period of emergence 
for each product has been reviewed 
- 
Description of treatment emergent non serious AEs for LT4032 or Lumigan® have been 
added 
- 
Necessary listings of AEs have been modified 


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9 VALIDATION OF STATISTICAL PROGRAMMING 
Validation of statistical programming will be performed in agreement with Aixial SOP. 
Logs of all programs used for analysis and data preparation will be checked for errors and unexpected 
warnings. 
Double programming of ITT population, worse/contralateral eye, derivation and analyses regarding 
primary endpoint (i.e., IOP) will be performed by the lead statistician. Double programming of all derived 
will be also performed by a third party. A third party will review all statistical outputs (tables, figures) and 
results from statistical tests/models, as well as SAS code of all statistical programs. This includes 
macros programs developed for the study. 
Any undocumented updating of study data in statistical programs instead of change in clinical database 
(or source data) is not allowed. Specifically, this refers to the cases where patients or the data are 
added/changed using a statistical program rather than updating the database. This kind of hard coding 
is usually proposed to correct deficiencies (missing values, wrong values, and wrong measurement 
units) in the database when these errors are detected after database lock.  
No hard coding is done in any programs used for the creation of analysis data sets, tables, listings, or 
analyses that are intended for external reporting after database lock (i.e., clinical study reports, 
publications, abstracts, etc.).   
This policy ensures integrity of clinical data, since no changes are made to the study data without 
appropriate documentation from the investigator sites and appropriate audit trails within the clinical trial 
database. 
10 REFERENCES 
[1] ICH guidelines - E9: Statistical Principles for Clinical Trials, Adopted in EU by CPMP, March 
1998, issued as CPMP/ICH/363/96  
[2] ICH guidelines - E3: Structure and Content of Clinical Study Reports, Adopted in EU by CPMP, 
December 95, issued as CPMP/ICH/137/95  


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APPENDIX 1. SAS SYNTAX FOR STATISTICAL MODELS 
PROGRAMMING 
 
1. Main analysis of the primary efficacy endpoint (Section 6.1.1) 
Mixed Model for Repeated Measures (MMRM) 
The syntax with SAS using the MIXED procedure will be: 
 
Proc mixed data = … method = REML; 
 
Class patient treatment visit country; 
Model changeIOP = treatment visit baselineIOP washoutdur country 
treatment*visit baselineIOP*visit / ddfm = satterth solution alpha=0.05; 
Repeated visit / type = UN subject = patient; 
 
Lsmeans treatment*visit / pdiff cl; 
 
Estimate "Week 12 – Diff T4032 – Lumigan" treatment 1 -1  
treatment*visit 0 1 0 -1 / cl; 
 
Estimate "Week 6 – Diff T4032 – Lumigan" treatment 1 -1  
treatment*visit 1 0 -1 0 / cl; 
Run; 
 
2. Sensitivity analyses of the primary efficacy endpoint (Section 6.1.2) 
ANCOVA considering the post-randomisation last available value (LOCF) 
The syntax with SAS using the MIXED procedure will be: 
 
Proc mixed data = … ; 
 
Class treatment country; 
Model last_changeIOP = treatment baselineIOP washoutdur country / solution 
ddfm=satterth; 
LSmeans treatment / pdiff cl; 
 
Estimate "Week 12 – Diff T4032 – Lumigan " treatment 1 -1 / cl; 
Run; 
 
ANCOVA considering the observed value 
The syntax with SAS using the MIXED procedure will be: 
 
Proc mixed data = … ; 
 
Class treatment country; 
Model changeIOP_W12 = treatment baselineIOP washoutdur country/ solution 
ddfm=satterth; 
LSmeans treatment / pdiff cl; 
 
Estimate "Week 12 – Diff T4032 – Lumigan" treatment 1 -1 / cl; 
Run; 
 
3. Supporting analyses to check the validity of the main analysis (Section 6.1.3) 
3.1. Investigation of treatment by baseline IOP interaction 
The syntax with SAS using the MIXED procedure will be: 
Proc mixed data = … method = REML; 
 
Class patient treatment visit country; 
Model changeIOP = treatment visit baselineIOP washoutdur country 
treatment*visit baselineIOP*visit treatment*baselineIOP / ddfm = satterth 
solution alpha=0.07; 
 
Repeated visit / type = UN subject = patient; 
 
LSmeans treatment*visit / pdiff cl; 
Run; 
 


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3.2. Investigation of treatment by wash-out duration interaction 
The syntax with SAS using the MIXED procedure will be: 
Proc mixed data = … method = REML; 
 
Class patient treatment visit country; 
Model changeIOP = treatment visit baselineIOP washoutdur country 
treatment*visit baselineIOP*visit treatment*washoutdur / ddfm = satterth 
solution alpha=0.07; 
 
Repeated visit / type = UN subject = patient; 
 
LSmeans treatment*visit / pdiff cl; 
Run; 
 
3.3. Investigation of treatment by country interaction 
The syntax with SAS using the MIXED procedure will be: 
Proc mixed data = … method = REML; 
 
Class patient treatment visit country; 
Model changeIOP = treatment visit baselineIOP washoutdur country 
treatment*visit baselineIOP*visit treatment*country / ddfm = satterth 
solution alpha=0.07; 
 
Repeated visit / type = UN subject = patient; 
 
LSmeans treatment*visit / pdiff cl slice = ; 
Run; 
 
3.4. Supporting analyses to check the validity of the ANCOVA 
For the treatment by baseline IOP interaction, the syntax with SAS using the MIXED procedure will be: 
Proc mixed data = … ; 
 
Class treatment country; 
Model last_changeIOP = treatment baselineIOP washoutdur country 
treatment*baselineIOP / solution ddfm=satterth alpha=0.07; 
 
LSmeans treatment*visit / pdiff cl; 
Run; 
 
For the treatment by washout duration interaction, the syntax with SAS using the MIXED procedure will 
be: 
Proc mixed data = … ; 
 
Class treatment country; 
Model last_changeIOP = treatment baselineIOP washoutdur country 
treatment*washoutdur / solution ddfm=satterth alpha=0.07; 
 
LSmeans treatment*visit / pdiff cl; 
Run; 
 
For the treatment by country interaction, the syntax with SAS using the MIXED procedure will be: 
Proc mixed data = … ; 
 
Class treatment country; 
Model last_changeIOP = treatment baselineIOP washoutdur country 
treatment*country / solution ddfm=satterth alpha=0.07; 
 
LSmeans treatment*visit / pdiff cl; 
Run; 


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4. Exploratory analyses of the primary efficacy endpoint analysis (Section 
6.1.4) 
For treatment by possible impact of COVID-19 pandemic interaction for MMRM, the syntax with SAS 
using the MIXED procedure will be: 
 
Proc mixed data = … method = REML; 
 
Class patient treatment visit country impactcovid; 
Model changeIOP = treatment visit baselineIOP washoutdur country impactcovid 
treatment*visit baselineIOP*visit treatment*impactcovid / ddfm = satterth 
solution alpha=0.07; 
 
Repeated visit / type = UN subject = patient; 
 
LSmeans treatment*visit / pdiff cl; 
Run; 
 
For treatment by possible impact of COVID-19 pandemic interaction for ANCOVA, the syntax with SAS 
using the MIXED procedure will be: 
 
Proc mixed data = … ; 
 
Class treatment country impactcovid; 
Model last_changeIOP = treatment baselineIOP washoutdur country impactcovid 
treatment*impactcovid / solution ddfm=satterth alpha=0.07; 
 
LSmeans treatment*visit / pdiff cl; 
Run; 
 
For the impact of circadian rhythm, the syntax with SAS using the MIXED procedure will be: 
Proc mixed data= … covtest method=REML; 
Class patient treatment time visit country; 
Model changeIOP = treatment time visit country washoutdur treatment*time 
treatment*visit / solution;  
Repeated visit / subject= patient(time) type=unstructured; 
 
Estimate 'Week 12 8am – Diff T4032 – Lumigan' treatment 1 -1  
treatment*time 0 0 1 0 0 -1 treatment*visit 0 1 0 -1 / cl; 
Estimate 'Week 12 10am – Diff T4032 – Lumigan' treatment 1 -1  
treatment*time 1 0 0 -1 0 0 treatment*visit 0 1 0 -1 / cl; 
Estimate 'Week 12 4pm – Diff T4032 – Lumigan' treatment 1 -1  
treatment*time 0 1 0 0 -1 0 treatment*visit 0 1 0 -1 / cl; 
Estimate 'Week 6 8am – Diff T4032 – Lumigan' treatment 1 -1  
treatment*time 0 0 1 0 0 -1 treatment*visit 1 0 -1 0 / cl; 
Estimate 'Week 6 10am – Diff T4032 – Lumigan' treatment 1 -1  
treatment*time 1 0 0 -1 0 0 treatment*visit 1 0 -1 0 / cl; 
Estimate 'Week 6 4pm – Diff T4032 – Lumigan' treatment 1 -1  
treatment*time 0 1 0 0 -1 0 treatment*visit 1 0 -1 0 / cl; 
 
Estimate 'Week 12 8am - T4032' intercept 1 treatment 1 0  
time 0 0 1 visit 0 1 treatment*time 0 0 1 0 0 0 
treatment*visit 0 1 0 0 washoutdur xxx*/ cl; 
Estimate 'Week 12 10am – T4032' intercept 1 treatment 1 0  
time 1 0 0 visit 0 1 treatment*time 1 0 0 0 0 0 
treatment*visit 0 1 0 0 washoutdur xxx*/ cl; 
Estimate 'Week 12 4pm – T4032' intercept 1 treatment 1 0  
time 0 1 0 visit 0 1 treatment*time 0 1 0 0 0 0 
treatment*visit 0 1 0 0 washoutdur xxx*/ cl; 
Estimate 'Week 12 8am - Lumigan' intercept 1 treatment 0 1  
time 0 0 1 visit 0 1 treatment*time 0 0 0 0 0 1 
treatment*visit 0 0 0 1 washoutdur xxx*/ cl; 
Estimate 'Week 12 10am – Lumigan' intercept 1 treatment 0 1  
time 1 0 0 visit 0 1 treatment*time 0 0 0 1 0 0 
treatment*visit 0 0 0 1 washoutdur xxx*/ cl; 
Estimate 'Week 12 4pm – Lumigan' intercept 1 treatment 0 1  
time 0 1 0 visit 0 1 treatment*time 0 0 0 0 1 0 
treatment*visit 0 0 0 1 washoutdur xxx*/ cl; 


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Estimate 'Week 6 8am - T4032' intercept 1 treatment 1 0  
time 0 0 1 visit 1 0 treatment*time 0 0 1 0 0 0 
treatment*visit 1 0 0 0 washoutdur xxx*/ cl; 
Estimate 'Week 6 10am – T4032' intercept 1 treatment 1 0  
time 1 0 0 visit 1 0 treatment*time 1 0 0 0 0 0 
treatment*visit 1 0 0 0 washoutdur xxx*/ cl; 
Estimate 'Week 6 4pm – T4032' intercept 1 treatment 1 0  
time 0 1 0 visit 1 0 treatment*time 0 1 0 0 0 0 
treatment*visit 1 0 0 0 washoutdur xxx*/ cl; 
Estimate 'Week 6 8am - Lumigan' intercept 1 treatment 0 1  
time 0 0 1 visit 1 0 treatment*time 0 0 0 0 0 1 
treatment*visit 0 0 1 0 washoutdur xxx*/ cl; 
Estimate 'Week 6 10am – Lumigan' intercept 1 treatment 0 1  
time 1 0 0 visit 1 0 treatment*time 0 0 0 1 0 0 
treatment*visit 0 0 1 0 washoutdur xxx*/ cl; 
Estimate 'Week 6 4pm – Lumigan' intercept 1 treatment 0 1  
time 0 1 0 visit 1 0 treatment*time 0 0 0 0 1 0 
treatment*visit 0 0 1 0 washoutdur xxx*/ cl; 
 
run; 
* xxx= Mean of washout duration values in the population 
 


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APPENDIX 2.  TEMPLATES FOR STATISTICAL ANALYSIS AND 
SUMMARY TABLES 
 
Table of contents 
 
1 Disposition of patients 
TABLE 1.1 – NUMBER OF PATIENTS IN EACH ANALYSIS SET – ENROLLED PATIENTS .............................................. 57 
TABLE 1.2 – NUMBER OF PATIENTS IN EACH ANALYSIS SET – WITH POSSIBLE IMPACT OF COVID-19 PANDEMIC – 
ENROLLED PATIENTS ................................................................................................................. 57 
TABLE 1.3 – NUMBER OF PATIENTS IN EACH ANALYSIS SET – WITHOUT POSSIBLE IMPACT OF COVID-19 
PANDEMIC – ENROLLED PATIENTS ............................................................................................. 57 
LISTING 1.1 – DISPOSITION OF PATIENTS – ENROLLED PATIENTS .......................................................................... 58 
TABLE 1.4 – NUMBER OF ENROLLED PATIENTS BY COUNTRY – ENROLLED PATIENTS ............................................ 59 
TABLE 1.5 – NUMBER OF PATIENTS BY COUNTRY – AZOPT SAFETY SET ............................................................... 59 
TABLE 1.6 – NUMBER OF PATIENTS BY COUNTRY – SAFETY SET ........................................................................... 60 
TABLE 1.7 – NUMBER OF PATIENTS BY COUNTRY – FOR PATIENTS WHO PREMATURELY DISCONTINUED THE STUDY 
FOR COVID-19 CRISIS – SAFETY SET ........................................................................................ 60 
TABLE 1.8 – NUMBER OF PATIENTS BY COUNTRY – WITH POSSIBLE IMPACT OF COVID-19 PANDEMIC – SAFETY 
SET ............................................................................................................................................ 61 
TABLE 1.9 – NUMBER OF PATIENTS BY COUNTRY – WITHOUT POSSIBLE IMPACT OF COVID-19 PANDEMIC – 
SAFETY SET ............................................................................................................................... 61 
TABLE 1.10 – NUMBER OF PATIENTS BY COUNTRY – ITT SET ................................................................................ 61 
TABLE 1.11 – NUMBER OF PATIENTS BY COUNTRY – M-ITT SET ........................................................................... 61 
TABLE 1.12 – NUMBER OF PATIENTS BY COUNTRY – PP SET ................................................................................. 61 
TABLE 1.13 – NUMBER OF PATIENTS AT EACH VISIT AS CONSIDERED IN THE ANALYSIS – SAFETY SET .................. 62 
TABLE 1.14 – NUMBER OF PATIENTS AT EACH VISIT AS CONSIDERED IN THE ANALYSIS – WITH POSSIBLE IMPACT 
OF COVID-19 PANDEMIC – SAFETY SET ................................................................................... 62 
TABLE 1.15 – NUMBER OF PATIENTS AT EACH VISIT AS CONSIDERED IN THE ANALYSIS – WITHOUT POSSIBLE 
IMPACT OF COVID-19 PANDEMIC – SAFETY SET....................................................................... 62 
TABLE 1.16 – NUMBER OF PATIENTS AT EACH VISIT AS CONSIDERED IN THE ANALYSIS – ITT SET ........................ 63 
TABLE 1.17 – NUMBER OF PATIENTS AT EACH VISIT AS CONSIDERED IN THE ANALYSIS – WITH POSSIBLE IMPACT 
OF COVID-19 PANDEMIC – ITT SET .......................................................................................... 63 
TABLE 1.18 – NUMBER OF PATIENTS AT EACH VISIT AS CONSIDERED IN THE ANALYSIS – WITHOUT POSSIBLE 
IMPACT OF COVID-19 PANDEMIC – ITT SET ............................................................................. 63 
TABLE 1.19 – NUMBER OF PATIENTS AT EACH VISIT AS CONSIDERED IN THE ANALYSIS – M-ITT SET .................... 63 
TABLE 1.20 – NUMBER OF PATIENTS AT EACH VISIT AS CONSIDERED IN THE ANALYSIS – WITH POSSIBLE IMPACT 
OF COVID-19 PANDEMIC – M-ITT SET ..................................................................................... 63 
TABLE 1.21 – NUMBER OF PATIENTS AT EACH VISIT AS CONSIDERED IN THE ANALYSIS – WITHOUT POSSIBLE 
IMPACT OF COVID-19 PANDEMIC – M-ITT SET ......................................................................... 64 
TABLE 1.22 – NUMBER OF PATIENTS AT EACH VISIT AS CONSIDERED IN THE ANALYSIS – PP SET .......................... 64 
TABLE 1.23 – NUMBER OF PATIENTS AT EACH VISIT AS CONSIDERED IN THE ANALYSIS – WITH POSSIBLE IMPACT 
OF COVID-19 PANDEMIC – PP SET ........................................................................................... 64 
TABLE 1.24 – NUMBER OF PATIENTS AT EACH VISIT AS CONSIDERED IN THE ANALYSIS – WITHOUT POSSIBLE 
IMPACT OF COVID-19 PANDEMIC – PP SET............................................................................... 64 
LISTING 1.2 – VISIT AS CONSIDERED IN THE ANALYSIS – SAFETY SET ................................................................... 65 
TABLE 1.25 – PREMATURE STUDY DISCONTINUATION – SAFETY SET .................................................................... 66 
TABLE 1.26 – PREMATURE STUDY DISCONTINUATION – ITT SET ........................................................................... 67 
TABLE 1.27 – PREMATURE STUDY DISCONTINUATION – M-ITT SET....................................................................... 67 
LISTING 1.3 – LISTING OF PREMATURE STUDY DISCONTINUATIONS – SAFETY SET ................................................ 68 
TABLE 1.28 – PROTOCOL DEVIATIONS – M-ITT SET .............................................................................................. 69 
TABLE 1.29 – PROTOCOL DEVIATIONS – WITH POSSIBLE IMPACT OF COVID-19 PANDEMIC – M-ITT SET ............. 69 
TABLE 1.30 – PROTOCOL DEVIATIONS – WITHOUT POSSIBLE IMPACT OF COVID-19 PANDEMIC – M-ITT SET ...... 69 
LISTING 1.4 – LISTING OF PROTOCOL DEVIATIONS – M-ITT SET ............................................................................ 70 
LISTING 1.5 – LISTING OF PATIENTS EXCLUDED FROM AZOPT SAFETY, SAFETY, ITT, M-ITT, AND PP SETS – 
ENROLLED PATIENTS ................................................................................................................. 71 
 


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2 Demographics and Baseline characteristics 
TABLE 2.1 – DEMOGRAPHIC CHARACTERISTICS – M-ITT SET ................................................................................ 72 
TABLE 2.2 – OCULAR MEDICAL HISTORY OTHER THAN THE STUDIED DISEASE BY SOC AND PT – M-ITT SET ....... 74 
TABLE 2.3 – OCULAR SURGICAL HISTORY RELATED TO ANOTHER DISEASE THAN THE STUDIED ONE BY SOC AND 
PT – M-ITT SET ......................................................................................................................... 75 
TABLE 2.4 – SYSTEMIC MEDICAL HISTORY BY SOC AND PT – M-ITT SET ............................................................. 75 
TABLE 2.5 – SYSTEMIC SURGICAL HISTORY BY SOC AND PT – M-ITT SET ........................................................... 75 
TABLE 2.6 – PREVIOUS OCULAR TREATMENTS BY WHO-DRUG ATC2 AND ATC4 – M-ITT SET ........................... 76 
TABLE 2.7 – CONCOMITANT OCULAR TREATMENTS BY WHO-DRUG ATC2 AND ATC4 – M-ITT SET................... 76 
TABLE 2.8 – PREVIOUS NON-OCULAR TREATMENTS BY WHO-DRUG ATC2 AND ATC4 – M-ITT SET .................. 76 
TABLE 2.9 – CONCOMITANT NON-OCULAR TREATMENTS BY WHO-DRUG ATC2 AND ATC4 – M-ITT SET .......... 76 
TABLE 2.10 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – DIAGNOSIS – WORSE EYE – M-ITT SET ...... 77 
TABLE 2.11 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – DIAGNOSIS – CONTRALATERAL EYE – M-ITT 
SET ............................................................................................................................................ 77 
TABLE 2.12 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – PREVIOUS TREATMENT – M-ITT SET .......... 78 
TABLE 2.13 – SURGICAL HISTORY OF GLAUCOMA AND OCULAR HYPERTENSION BY SYSTEM ORGAN CLASS AND 
PREFERRED TERM – WORSE EYE - M-ITT SET ............................................................................ 79 
TABLE 2.14  – SURGICAL HISTORY OF GLAUCOMA AND OCULAR HYPERTENSION BY SYSTEM ORGAN CLASS AND 
PREFERRED TERM – CONTRALATERAL EYE - M-ITT SET ............................................................ 79 
TABLE 2.15 – AUTOMATED VISUAL FIELD AT SCREENING VISIT – WORSE EYE – M-ITT SET .................................. 80 
TABLE 2.16 – AUTOMATED VISUAL FIELD AT SCREENING VISIT – CONTRALATERAL EYE – M-ITT SET .................. 80 
TABLE 2.17 – CENTRAL CORNEAL THICKNESS MEASUREMENT (µM) AT SCREENING VISIT – WORSE EYE – M-ITT 
SET ............................................................................................................................................ 81 
TABLE 2.18 – CENTRAL CORNEAL THICKNESS MEASUREMENT (µM) AT SCREENING VISIT – CONTRALATERAL EYE –  
M-ITT SET ................................................................................................................................. 81 
TABLE 2.19 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 – WORSE EYE –  M-ITT 
SET ............................................................................................................................................ 82 
TABLE 2.20 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 –  WASH-OUT 
DURATION <= 8 DAYS – WORSE EYE – M-ITT SET ..................................................................... 82 
TABLE 2.21 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 –  WASH-OUT 
DURATION > 8 DAYS – WORSE EYE – M-ITT SET ....................................................................... 83 
TABLE 2.22 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 – CONTRALATERAL 
EYE –  M-ITT SET....................................................................................................................... 83 
TABLE 2.23 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 –  WASH-OUT 
DURATION <= 8 DAYS – CONTRALATERAL EYE – M-ITT SET ..................................................... 83 
TABLE 2.24 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 –  WASH-OUT 
DURATION > 8 DAYS – CONTRALATERAL EYE – M-ITT SET ....................................................... 83 
TABLE 2.25 – DEMOGRAPHIC CHARACTERISTICS –WITH POSSIBLE IMPACT OF COVID-19 PANDEMIC – M-ITT SET
 .................................................................................................................................................. 84 
TABLE 2.26 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – DIAGNOSIS – WORSE EYE – WITH POSSIBLE 
IMPACT OF COVID-19 PANDEMIC – M-ITT SET ......................................................................... 84 
TABLE 2.27 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – DIAGNOSIS – CONTRALATERAL EYE – WITH 
POSSIBLE IMPACT OF COVID-19 PANDEMIC – M-ITT SET ......................................................... 84 
TABLE 2.28 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – PREVIOUS TREATMENT – WITH POSSIBLE 
IMPACT OF COVID-19 PANDEMIC – M-ITT SET ......................................................................... 84 
TABLE 2.29 – SURGICAL HISTORY OF GLAUCOMA AND OCULAR HYPERTENSION BY SYSTEM ORGAN CLASS AND 
PREFERRED TERM – WORSE EYE – WITH POSSIBLE IMPACT OF COVID-19 PANDEMIC – M-ITT 
SET ............................................................................................................................................ 84 
TABLE 2.30 – SURGICAL HISTORY OF GLAUCOMA AND OCULAR HYPERTENSION BY SYSTEM ORGAN CLASS AND 
PREFERRED TERM – CONTRALATERAL EYE – WITH POSSIBLE IMPACT OF COVID-19 PANDEMIC 
– M-ITT SET .............................................................................................................................. 84 
TABLE 2.31 – AUTOMATED VISUAL FIELD AT SCREENING VISIT – WORSE EYE – WITH POSSIBLE IMPACT OF 
COVID-19 PANDEMIC – M-ITT SET .......................................................................................... 84 
TABLE 2.32 – AUTOMATED VISUAL FIELD AT SCREENING VISIT – CONTRALATERAL EYE – WITH POSSIBLE IMPACT 
OF COVID-19 PANDEMIC – M-ITT SET ..................................................................................... 84 
TABLE 2.33 – CENTRAL CORNEAL THICKNESS MEASUREMENT (µM) AT SCREENING VISIT – WORSE EYE – WITH 
POSSIBLE IMPACT OF COVID-19 PANDEMIC – M-ITT SET ......................................................... 84 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Admendment V01 
20APR2021 
Page 41/163 
 
 
 
 
 
TABLE 2.34 – CENTRAL CORNEAL THICKNESS MEASUREMENT (µM) AT SCREENING VISIT – CONTRALATERAL EYE – 
WITH POSSIBLE IMPACT OF COVID-19 PANDEMIC – M-ITT SET ............................................... 84 
TABLE 2.35 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 – WORSE EYE – WITH 
POSSIBLE IMPACT OF COVID-19 PANDEMIC – M-ITT SET ......................................................... 84 
TABLE 2.36 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 – CONTRALATERAL 
EYE – WITH POSSIBLE IMPACT OF COVID-19 PANDEMIC – M-ITT SET ...................................... 84 
TABLE 2.37 – DEMOGRAPHIC CHARACTERISTICS –WITHOUT POSSIBLE IMPACT OF COVID-19 PANDEMIC – M-ITT 
SET ............................................................................................................................................ 84 
TABLE 2.38 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – DIAGNOSIS – WORSE EYE – WITHOUT 
POSSIBLE IMPACT OF COVID-19 PANDEMIC – M-ITT SET ......................................................... 84 
TABLE 2.39 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – DIAGNOSIS – CONTRALATERAL EYE – 
WITHOUT POSSIBLE IMPACT OF COVID-19 PANDEMIC – M-ITT SET ......................................... 84 
TABLE 2.40 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – PREVIOUS TREATMENT – WITHOUT POSSIBLE 
IMPACT OF COVID-19 PANDEMIC – M-ITT SET ......................................................................... 84 
TABLE 2.41 – SURGICAL HISTORY OF GLAUCOMA AND OCULAR HYPERTENSION BY SYSTEM ORGAN CLASS AND 
PREFERRED TERM – WORSE EYE – WITHOUT POSSIBLE IMPACT OF COVID-19 PANDEMIC – M-
ITT SET ..................................................................................................................................... 84 
TABLE 2.42 – SURGICAL HISTORY OF GLAUCOMA AND OCULAR HYPERTENSION BY SYSTEM ORGAN CLASS AND 
PREFERRED TERM – CONTRALATERAL EYE – WITHOUT POSSIBLE IMPACT OF COVID-19 
PANDEMIC – M-ITT SET ............................................................................................................. 84 
TABLE 2.43 – AUTOMATED VISUAL FIELD AT SCREENING VISIT – WORSE EYE – WITHOUT POSSIBLE IMPACT OF 
COVID-19 PANDEMIC – M-ITT SET .......................................................................................... 84 
TABLE 2.44 – AUTOMATED VISUAL FIELD AT SCREENING VISIT – CONTRALATERAL EYE – WITHOUT POSSIBLE 
IMPACT OF COVID-19 PANDEMIC – M-ITT SET ......................................................................... 84 
TABLE 2.45 – CENTRAL CORNEAL THICKNESS MEASUREMENT (µM) AT SCREENING VISIT – WORSE EYE – WITHOUT 
POSSIBLE IMPACT OF COVID-19 PANDEMIC – M-ITT SET ......................................................... 84 
TABLE 2.46 – CENTRAL CORNEAL THICKNESS MEASUREMENT (µM) AT SCREENING VISIT – CONTRALATERAL EYE – 
WITHOUT POSSIBLE IMPACT OF COVID-19 PANDEMIC – M-ITT SET ......................................... 84 
TABLE 2.47 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 – WORSE EYE – 
WITHOUT POSSIBLE IMPACT OF COVID-19 PANDEMIC – M-ITT SET ......................................... 84 
TABLE 2.48 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 – CONTRALATERAL 
EYE – WITHOUT POSSIBLE IMPACT OF COVID-19 PANDEMIC – M-ITT SET ............................... 84 
TABLE 2.49 – DEMOGRAPHIC CHARACTERISTICS – SAFETY SET ........................................................................... 85 
TABLE 2.50 – OCULAR MEDICAL HISTORY OTHER THAN THE STUDIED DISEASE BY SYSTEM ORGAN CLASS AND 
PREFERRED TERM– SAFETY SET................................................................................................. 85 
TABLE 2.51 – OCULAR SURGICAL HISTORY RELATED TO ANOTHER DISEASE THAN THE STUDIED ONE BY SYSTEM 
ORGAN CLASS AND PREFERRED TERM – SAFETY SET ................................................................. 85 
TABLE 2.52 – SYSTEMIC MEDICAL HISTORY BY SYSTEM ORGAN CLASS AND PREFERRED TERM – SAFETY SET ...... 85 
TABLE 2.53 – SYSTEMIC SURGICAL HISTORY BY SYSTEM ORGAN CLASS AND PREFERRED TERM – SAFETY SET ..... 85 
TABLE 2.54 – PREVIOUS OCULAR TREATMENTS BY WHO-DRUG ATC2 AND ATC4 – SAFETY SET ...................... 85 
TABLE 2.55 – CONCOMITANT OCULAR TREATMENTS BY WHO-DRUG ATC2 AND ATC4 – SAFETY SET .............. 85 
TABLE 2.56 – PREVIOUS NON-OCULAR TREATMENTS BY WHO-DRUG ATC2 AND ATC4 – SAFETY SET .............. 85 
TABLE 2.57 – CONCOMITANT NON-OCULAR TREATMENTS BY WHO-DRUG ATC2 AND ATC4 – SAFETY SET ...... 85 
TABLE 2.58 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – DIAGNOSIS – WORSE EYE – SAFETY SET .... 85 
TABLE 2.59 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – DIAGNOSIS – CONTRALATERAL EYE - 
SAFETY SET ............................................................................................................................... 85 
TABLE 2.60 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – PREVIOUS TREATMENT – SAFETY SET ........ 85 
TABLE 2.61 – SURGICAL HISTORY OF GLAUCOMA AND OCULAR HYPERTENSION BY SYSTEM ORGAN CLASS AND 
PREFERRED TERM – WORSE EYE – SAFETY SET ......................................................................... 85 
TABLE 2.62 – SURGICAL HISTORY OF GLAUCOMA AND OCULAR HYPERTENSION BY SYSTEM ORGAN CLASS AND 
PREFERRED TERM – CONTRALATERAL EYE – SAFETY SET ......................................................... 85 
TABLE 2.63 – AUTOMATED VISUAL FIELD AT SCREENING VISIT – WORSE EYE – SAFETY SET ................................ 85 
TABLE 2.64 – AUTOMATED VISUAL FIELD AT SCREENING VISIT – CONTRALATERAL EYE – SAFETY SET ............... 85 
TABLE 2.65 – CENTRAL CORNEAL THICKNESS MEASUREMENT (µM) AT SCREENING VISIT – WORSE EYE – SAFETY 
SET ............................................................................................................................................ 85 
TABLE 2.66 – CENTRAL CORNEAL THICKNESS MEASUREMENT (µM) AT SCREENING VISIT – CONTRALATERAL EYE –  
SAFETY SET ............................................................................................................................... 85 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Admendment V01 
20APR2021 
Page 42/163 
 
 
 
 
 
TABLE 2.67 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 – WORSE EYE –  
SAFETY SET ............................................................................................................................... 85 
TABLE 2.68 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 –  WASH-OUT 
DURATION <= 8 DAYS – WORSE EYE – SAFETY SET ................................................................... 85 
TABLE 2.69 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 –  WASH-OUT 
DURATION > 8 DAYS – WORSE EYE – SAFETY SET ..................................................................... 85 
TABLE 2.70 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 – CONTRALATERAL 
EYE – SAFETY SET ..................................................................................................................... 85 
TABLE 2.71 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 –  WASH-OUT 
DURATION <= 8 DAYS – CONTRALATERAL EYE – SAFETY SET ................................................... 85 
TABLE 2.72 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 –  WASH-OUT 
DURATION > 8 DAYS – CONTRALATERAL EYE – SAFETY SET ..................................................... 85 
LISTING 2.1 – FUNDUS EXAMINATION AT SCREENING VISIT – SAFETY SET ............................................................ 86 
TABLE 2.73 – NUMBER OF PATIENTS AND CUMULATIVE TIME OF EXPOSURE (IN DAYS) – SAFETY SET .................. 87 
TABLE 2.74 – NUMBER OF PATIENTS AND CUMULATIVE TIME OF EXPOSURE (IN DAYS) BY AGE GROUP AND GENDER 
–  SAFETY SET ........................................................................................................................... 87 
TABLE 2.75 – NUMBER OF PATIENTS AND CUMULATIVE TIME OF EXPOSURE (IN DAYS) BY EXPOSURE IN CLASSES  – 
SAFETY SET ............................................................................................................................... 87 
TABLE 2.76 – DEMOGRAPHIC CHARACTERISTICS –FOR PATIENTS WHO PREMATURELY DISCONTINUED THE STUDY 
FOR COVID-19 CRISIS – SAFETY SET ........................................................................................ 88 
TABLE 2.77 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – DIAGNOSIS – WORSE EYE – FOR PATIENTS 
WHO PREMATURELY DISCONTINUED THE STUDY FOR COVID-19 CRISIS – SAFETY SET ............ 88 
TABLE 2.78 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – DIAGNOSIS – CONTRALATERAL EYE – FOR 
PATIENTS WHO PREMATURELY DISCONTINUED THE STUDY FOR COVID-19 CRISIS – SAFETY SET
 .................................................................................................................................................. 88 
TABLE 2.79 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – PREVIOUS TREATMENT – FOR PATIENTS WHO 
PREMATURELY DISCONTINUED THE STUDY FOR COVID-19 CRISIS – SAFETY SET ..................... 88 
TABLE 2.80 – SURGICAL HISTORY OF GLAUCOMA AND OCULAR HYPERTENSION BY SYSTEM ORGAN CLASS AND 
PREFERRED TERM – WORSE EYE – FOR PATIENTS WHO PREMATURELY DISCONTINUED THE 
STUDY FOR COVID-19 CRISIS – SAFETY SET ............................................................................ 88 
TABLE 2.81 – SURGICAL HISTORY OF GLAUCOMA AND OCULAR HYPERTENSION BY SYSTEM ORGAN CLASS AND 
PREFERRED TERM – CONTRALATERAL EYE – FOR PATIENTS WHO PREMATURELY DISCONTINUED 
THE STUDY FOR COVID-19 CRISIS – SAFETY SET...................................................................... 88 
TABLE 2.82 – AUTOMATED VISUAL FIELD AT SCREENING VISIT – WORSE EYE – FOR PATIENTS WHO PREMATURELY 
DISCONTINUED THE STUDY FOR COVID-19 CRISIS – SAFETY SET ............................................. 88 
TABLE 2.83 – AUTOMATED VISUAL FIELD AT SCREENING VISIT – CONTRALATERAL EYE – FOR PATIENTS WHO 
PREMATURELY DISCONTINUED THE STUDY FOR COVID-19 CRISIS – SAFETY SET ..................... 88 
TABLE 2.84 – CENTRAL CORNEAL THICKNESS MEASUREMENT (µM) AT SCREENING VISIT – WORSE EYE – FOR 
PATIENTS WHO PREMATURELY DISCONTINUED THE STUDY FOR COVID-19 CRISIS – SAFETY SET
 .................................................................................................................................................. 88 
TABLE 2.85 – CENTRAL CORNEAL THICKNESS MEASUREMENT (µM) AT SCREENING VISIT – CONTRALATERAL EYE – 
FOR PATIENTS WHO PREMATURELY DISCONTINUED THE STUDY FOR COVID-19 CRISIS – SAFETY 
SET ............................................................................................................................................ 88 
TABLE 2.86 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 – WORSE EYE – FOR 
PATIENTS WHO PREMATURELY DISCONTINUED THE STUDY FOR COVID-19 CRISIS – SAFETY SET
 .................................................................................................................................................. 88 
TABLE 2.87 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 – CONTRALATERAL 
EYE – FOR PATIENTS WHO PREMATURELY DISCONTINUED THE STUDY FOR COVID-19 CRISIS – 
SAFETY SET ............................................................................................................................... 88 
TABLE 2.88 – SUMMARY OF BASELINE IOP (MMHG) – WORSE EYE – FOR PATIENTS WHO PREMATURELY 
DISCONTINUED THE STUDY FOR COVID-19 CRISIS – SAFETY SET ............................................. 89 
TABLE 2.89 – SUMMARY OF BASELINE IOP (MMHG) – CONTRALATERAL EYE – FOR PATIENTS WHO PREMATURELY 
DISCONTINUED THE STUDY FOR COVID-19 CRISIS – SAFETY SET ............................................. 89 
TABLE 2.90 – DEMOGRAPHIC CHARACTERISTICS –WITH POSSIBLE IMPACT OF COVID-19 PANDEMIC – SAFETY SET
 .................................................................................................................................................. 91 
TABLE 2.91 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – DIAGNOSIS – WORSE EYE – WITH POSSIBLE 
IMPACT OF COVID-19 PANDEMIC – SAFETY SET....................................................................... 91 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Admendment V01 
20APR2021 
Page 43/163 
 
 
 
 
 
TABLE 2.92 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – DIAGNOSIS – CONTRALATERAL EYE – WITH 
POSSIBLE IMPACT OF COVID-19 PANDEMIC – SAFETY SET ....................................................... 91 
TABLE 2.93 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – PREVIOUS TREATMENT – WITH POSSIBLE 
IMPACT OF COVID-19 PANDEMIC – SAFETY SET....................................................................... 91 
TABLE 2.94 – SURGICAL HISTORY OF GLAUCOMA AND OCULAR HYPERTENSION BY SYSTEM ORGAN CLASS AND 
PREFERRED TERM – WORSE EYE – WITH POSSIBLE IMPACT OF COVID-19 PANDEMIC – SAFETY 
SET ............................................................................................................................................ 91 
TABLE 2.95 – SURGICAL HISTORY OF GLAUCOMA AND OCULAR HYPERTENSION BY SYSTEM ORGAN CLASS AND 
PREFERRED TERM – CONTRALATERAL EYE – WITH POSSIBLE IMPACT OF COVID-19 PANDEMIC 
– SAFETY SET ............................................................................................................................ 91 
TABLE 2.96 – AUTOMATED VISUAL FIELD AT SCREENING VISIT – WORSE EYE – WITH POSSIBLE IMPACT OF 
COVID-19 PANDEMIC – SAFETY SET ........................................................................................ 91 
TABLE 2.97 – AUTOMATED VISUAL FIELD AT SCREENING VISIT – CONTRALATERAL EYE – WITH POSSIBLE IMPACT 
OF COVID-19 PANDEMIC – SAFETY SET ................................................................................... 91 
TABLE 2.98 – CENTRAL CORNEAL THICKNESS MEASUREMENT (µM) AT SCREENING VISIT – WORSE EYE – WITH 
POSSIBLE IMPACT OF COVID-19 PANDEMIC – SAFETY SET ....................................................... 91 
TABLE 2.99 – CENTRAL CORNEAL THICKNESS MEASUREMENT (µM) AT SCREENING VISIT – CONTRALATERAL EYE – 
WITH POSSIBLE IMPACT OF COVID-19 PANDEMIC – SAFETY SET ............................................. 91 
TABLE 2.100 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 – WORSE EYE – WITH 
POSSIBLE IMPACT OF COVID-19 PANDEMIC – SAFETY SET ....................................................... 91 
TABLE 2.101 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 – CONTRALATERAL 
EYE – WITH POSSIBLE IMPACT OF COVID-19 PANDEMIC – SAFETY SET ................................... 91 
TABLE 2.102 – SUMMARY OF BASELINE IOP (MMHG) – WORSE EYE – WITH POSSIBLE IMPACT OF COVID-19 
PANDEMIC – SAFETY SET ........................................................................................................... 91 
TABLE 2.103 – SUMMARY OF BASELINE IOP (MMHG) – CONTRALATERAL EYE – WITH POSSIBLE IMPACT OF 
COVID-19 PANDEMIC – SAFETY SET ........................................................................................ 91 
TABLE 2.104 – DEMOGRAPHIC CHARACTERISTICS –WITHOUT POSSIBLE IMPACT OF COVID-19 PANDEMIC – 
SAFETY SET ............................................................................................................................... 92 
TABLE 2.105 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – DIAGNOSIS – WORSE EYE – WITHOUT 
POSSIBLE IMPACT OF COVID-19 PANDEMIC – SAFETY SET ....................................................... 92 
TABLE 2.106 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – DIAGNOSIS – CONTRALATERAL EYE – 
WITHOUT POSSIBLE IMPACT OF COVID-19 PANDEMIC – SAFETY SET ....................................... 92 
TABLE 2.107 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – PREVIOUS TREATMENT – WITHOUT 
POSSIBLE IMPACT OF COVID-19 PANDEMIC – SAFETY SET ....................................................... 92 
TABLE 2.108 – SURGICAL HISTORY OF GLAUCOMA AND OCULAR HYPERTENSION BY SYSTEM ORGAN CLASS AND 
PREFERRED TERM – WORSE EYE – WITHOUT POSSIBLE IMPACT OF COVID-19 PANDEMIC – 
SAFETY SET ............................................................................................................................... 92 
TABLE 2.109 – SURGICAL HISTORY OF GLAUCOMA AND OCULAR HYPERTENSION BY SYSTEM ORGAN CLASS AND 
PREFERRED TERM – CONTRALATERAL EYE – WITHOUT POSSIBLE IMPACT OF COVID-19 
PANDEMIC – SAFETY SET ........................................................................................................... 92 
TABLE 2.110 – AUTOMATED VISUAL FIELD AT SCREENING VISIT – WORSE EYE – WITHOUT POSSIBLE IMPACT OF 
COVID-19 PANDEMIC – SAFETY SET ........................................................................................ 92 
TABLE 2.111 – AUTOMATED VISUAL FIELD AT SCREENING VISIT – CONTRALATERAL EYE – WITHOUT POSSIBLE 
IMPACT OF COVID-19 PANDEMIC – SAFETY SET....................................................................... 92 
TABLE 2.112 – CENTRAL CORNEAL THICKNESS MEASUREMENT (µM) AT SCREENING VISIT – WORSE EYE – 
WITHOUT POSSIBLE IMPACT OF COVID-19 PANDEMIC – SAFETY SET ....................................... 92 
TABLE 2.113 – CENTRAL CORNEAL THICKNESS MEASUREMENT (µM) AT SCREENING VISIT – CONTRALATERAL EYE 
– WITHOUT POSSIBLE IMPACT OF COVID-19 PANDEMIC – SAFETY SET .................................... 92 
TABLE 2.114 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 – WORSE EYE – 
WITHOUT POSSIBLE IMPACT OF COVID-19 PANDEMIC – SAFETY SET ....................................... 92 
TABLE 2.115 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 – CONTRALATERAL 
EYE – WITHOUT POSSIBLE IMPACT OF COVID-19 PANDEMIC – SAFETY SET ............................. 92 
TABLE 2.116 – SUMMARY OF BASELINE IOP (MMHG) – WORSE EYE – WITHOUT POSSIBLE IMPACT OF COVID-19 
PANDEMIC – SAFETY SET ........................................................................................................... 92 
TABLE 2.117 – SUMMARY OF BASELINE IOP (MMHG) – CONTRALATERAL EYE – WITHOUT POSSIBLE IMPACT OF 
COVID-19 PANDEMIC – SAFETY SET ........................................................................................ 92 
TABLE 2.118 – DEMOGRAPHIC CHARACTERISTICS – ITT SET ................................................................................ 93 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Admendment V01 
20APR2021 
Page 44/163 
 
 
 
 
 
TABLE 2.119 – OCULAR MEDICAL HISTORY OTHER THAN THE STUDIED DISEASE BY SYSTEM ORGAN CLASS AND 
PREFERRED TERM– ITT SET ....................................................................................................... 93 
TABLE 2.120 – OCULAR SURGICAL HISTORY RELATED TO ANOTHER DISEASE THAN THE STUDIED ONE BY SYSTEM 
ORGAN CLASS AND PREFERRED TERM – ITT SET ........................................................................ 93 
TABLE 2.121 – SYSTEMIC MEDICAL HISTORY BY SYSTEM ORGAN CLASS AND PREFERRED TERM – ITT SET .......... 93 
TABLE 2.122 – SYSTEMIC SURGICAL HISTORY BY SYSTEM ORGAN CLASS AND PREFERRED TERM – ITT SET ......... 93 
TABLE 2.123 – PREVIOUS OCULAR TREATMENTS BY WHO-DRUG ATC2 AND ATC4 – ITT SET ........................... 93 
TABLE 2.124 – CONCOMITANT OCULAR TREATMENTS BY WHO-DRUG ATC2 AND ATC4 – ITT SET ................... 93 
TABLE 2.125 – PREVIOUS NON-OCULAR TREATMENTS BY WHO-DRUG ATC2 AND ATC4 – ITT SET .................. 93 
TABLE 2.126 – CONCOMITANT NON-OCULAR TREATMENTS BY WHO-DRUG ATC2 AND ATC4 – ITT SET .......... 93 
TABLE 2.127 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – DIAGNOSIS – WORSE EYE – ITT SET ........ 93 
TABLE 2.128 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – DIAGNOSIS – CONTRALATERAL EYE - ITT 
SET ............................................................................................................................................ 93 
TABLE 2.129 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – PREVIOUS TREATMENT - ITT SET ............. 93 
TABLE 2.130 – SURGICAL HISTORY OF GLAUCOMA AND OCULAR HYPERTENSION BY SYSTEM ORGAN CLASS AND 
PREFERRED TERM – WORSE EYE – ITT SET ............................................................................... 93 
TABLE 2.131 – SURGICAL HISTORY OF GLAUCOMA AND OCULAR HYPERTENSION BY SYSTEM ORGAN CLASS AND 
PREFERRED TERM – CONTRALATERAL EYE – ITT SET ............................................................... 93 
TABLE 2.132 – AUTOMATED VISUAL FIELD AT SCREENING VISIT – WORSE EYE – ITT SET .................................... 93 
TABLE 2.133 – AUTOMATED VISUAL FIELD AT SCREENING VISIT – CONTRALATERAL EYE – ITT SET .................... 93 
TABLE 2.134 – CENTRAL CORNEAL THICKNESS MEASUREMENT (µM) AT SCREENING VISIT – WORSE EYE – ITT SET
 .................................................................................................................................................. 93 
TABLE 2.135 – CENTRAL CORNEAL THICKNESS MEASUREMENT (µM) AT SCREENING VISIT – CONTRALATERAL EYE 
– ITT SET .................................................................................................................................. 93 
TABLE 2.136– SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 – WORSE EYE – ITT 
SET ............................................................................................................................................ 93 
TABLE 2.137 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 –  WASH-OUT 
DURATION <= 8 DAYS – WORSE EYE – ITT SET ......................................................................... 93 
TABLE 2.138 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 –  WASH-OUT 
DURATION > 8 DAYS – WORSE EYE – ITT SET ........................................................................... 93 
TABLE 2.139 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 – CONTRALATERAL 
EYE – ITT SET ........................................................................................................................... 93 
TABLE 2.140 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 –  WASH-OUT 
DURATION <= 8 DAYS – CONTRALATERAL EYE – ITT SET ......................................................... 93 
TABLE 2.141 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 –  WASH-OUT 
DURATION > 8 DAYS – CONTRALATERAL EYE – ITT SET ........................................................... 93 
TABLE 2.142 – DEMOGRAPHIC CHARACTERISTICS –PATIENTS INCLUDED IN M-ITT SET – ITT SET ....................... 94 
TABLE 2.143 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – DIAGNOSIS – WORSE EYE – PATIENTS 
INCLUDED IN M-ITT SET – ITT SET ............................................................................................ 94 
TABLE 2.144 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – DIAGNOSIS – CONTRALATERAL EYE – 
PATIENTS INCLUDED IN M-ITT SET – ITT SET............................................................................ 94 
TABLE 2.145 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – PREVIOUS TREATMENT – PATIENTS 
INCLUDED IN M-ITT SET – ITT SET ............................................................................................ 94 
TABLE 2.146 – SURGICAL HISTORY OF GLAUCOMA AND OCULAR HYPERTENSION BY SYSTEM ORGAN CLASS AND 
PREFERRED TERM – WORSE EYE – PATIENTS INCLUDED IN M-ITT SET – ITT SET ..................... 94 
TABLE 2.147 – SURGICAL HISTORY OF GLAUCOMA AND OCULAR HYPERTENSION BY SYSTEM ORGAN CLASS AND 
PREFERRED TERM – CONTRALATERAL EYE – PATIENTS INCLUDED IN M-ITT SET – ITT SET ..... 94 
TABLE 2.148 – AUTOMATED VISUAL FIELD AT SCREENING VISIT – WORSE EYE – PATIENTS INCLUDED IN M-ITT 
SET – ITT SET ............................................................................................................................ 94 
TABLE 2.149 – AUTOMATED VISUAL FIELD AT SCREENING VISIT – CONTRALATERAL EYE – PATIENTS INCLUDED IN 
M-ITT SET – ITT SET ................................................................................................................. 94 
TABLE 2.150 – CENTRAL CORNEAL THICKNESS MEASUREMENT (µM) AT SCREENING VISIT – WORSE EYE – 
PATIENTS INCLUDED IN M-ITT SET – ITT SET............................................................................ 94 
TABLE 2.151 – CENTRAL CORNEAL THICKNESS MEASUREMENT (µM) AT SCREENING VISIT – CONTRALATERAL EYE 
– PATIENTS INCLUDED IN M-ITT SET – ITT SET ......................................................................... 94 
TABLE 2.152 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 – WORSE EYE – 
PATIENTS INCLUDED IN M-ITT SET – ITT SET............................................................................ 94 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Admendment V01 
20APR2021 
Page 45/163 
 
 
 
 
 
TABLE 2.153 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 – CONTRALATERAL 
EYE – PATIENTS INCLUDED IN M-ITT SET – ITT SET .................................................................. 94 
TABLE 2.154 – SUMMARY OF BASELINE IOP (MMHG) – WORSE EYE – PATIENTS INCLUDED IN M-ITT SET – ITT 
SET ............................................................................................................................................ 94 
TABLE 2.155 – SUMMARY OF BASELINE IOP (MMHG) – CONTRALATERAL EYE – PATIENTS INCLUDED IN M-ITT 
SET – ITT SET ............................................................................................................................ 94 
TABLE 2.156 – DEMOGRAPHIC CHARACTERISTICS –PATIENTS NOT INCLUDED IN M-ITT SET – ITT SET ................ 94 
TABLE 2.157 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – DIAGNOSIS – WORSE EYE – PATIENTS NOT 
INCLUDED IN M-ITT SET – ITT SET ............................................................................................ 94 
TABLE 2.158 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – DIAGNOSIS – CONTRALATERAL EYE – 
PATIENTS NOT INCLUDED IN M-ITT SET – ITT SET .................................................................... 94 
TABLE 2.159 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – PREVIOUS TREATMENT – PATIENTS NOT 
INCLUDED IN M-ITT SET – ITT SET ............................................................................................ 94 
TABLE 2.160 – SURGICAL HISTORY OF GLAUCOMA AND OCULAR HYPERTENSION BY SYSTEM ORGAN CLASS AND 
PREFERRED TERM – WORSE EYE – PATIENTS NOT INCLUDED IN M-ITT SET – ITT SET .............. 94 
TABLE 2.161 – SURGICAL HISTORY OF GLAUCOMA AND OCULAR HYPERTENSION BY SYSTEM ORGAN CLASS AND 
PREFERRED TERM – CONTRALATERAL EYE – PATIENTS NOT INCLUDED IN M-ITT SET – ITT SET
 .................................................................................................................................................. 94 
TABLE 2.162 – AUTOMATED VISUAL FIELD AT SCREENING VISIT – WORSE EYE – PATIENTS NOT INCLUDED IN M-
ITT SET – ITT SET ..................................................................................................................... 94 
TABLE 2.163 – AUTOMATED VISUAL FIELD AT SCREENING VISIT – CONTRALATERAL EYE – PATIENTS NOT 
INCLUDED IN  M-ITT SET – ITT SET ........................................................................................... 94 
TABLE 2.164 – CENTRAL CORNEAL THICKNESS MEASUREMENT (µM) AT SCREENING VISIT – WORSE EYE – 
PATIENTS NOT INCLUDED IN M-ITT SET – ITT SET .................................................................... 94 
TABLE 2.165 – CENTRAL CORNEAL THICKNESS MEASUREMENT (µM) AT SCREENING VISIT – CONTRALATERAL EYE 
– PATIENTS NOT INCLUDED IN M-ITT SET – ITT SET ................................................................. 94 
TABLE 2.166 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 – WORSE EYE – 
PATIENTS NOT INCLUDED IN M-ITT SET – ITT SET .................................................................... 94 
TABLE 2.167 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 – CONTRALATERAL 
EYE – PATIENTS NOT INCLUDED IN M-ITT SET – ITT SET .......................................................... 94 
TABLE 2.168 – SUMMARY OF BASELINE IOP (MMHG) – WORSE EYE – PATIENTS NOT INCLUDED IN M-ITT SET – 
ITT SET ..................................................................................................................................... 94 
TABLE 2.169 – SUMMARY OF BASELINE IOP (MMHG) – CONTRALATERAL EYE – PATIENTS NOT INCLUDED IN M-
ITT SET – ITT SET ..................................................................................................................... 94 
TABLE 2.170 – DEMOGRAPHIC CHARACTERISTICS – PP SET ................................................................................. 96 
TABLE 2.171 – OCULAR MEDICAL HISTORY OTHER THAN THE STUDIED DISEASE BY SYSTEM ORGAN CLASS AND 
PREFERRED TERM– PP SET ......................................................................................................... 96 
TABLE 2.172 – OCULAR SURGICAL HISTORY RELATED TO ANOTHER DISEASE THAN THE STUDIED ONE BY SYSTEM 
ORGAN CLASS AND PREFERRED TERM – PP SET ......................................................................... 96 
TABLE 2.173 – SYSTEMIC MEDICAL HISTORY BY SYSTEM ORGAN CLASS AND PREFERRED TERM – PP SET ............ 96 
TABLE 2.174 – SYSTEMIC SURGICAL HISTORY BY SYSTEM ORGAN CLASS AND PREFERRED TERM – PP SET ........... 96 
TABLE 2.175 – PREVIOUS OCULAR TREATMENTS BY WHO-DRUG ATC2 AND ATC4 – PP SET ............................ 96 
TABLE 2.176 – CONCOMITANT OCULAR TREATMENTS BY WHO-DRUG ATC2 AND ATC4 – PP SET .................... 96 
TABLE 2.177 – PREVIOUS NON-OCULAR TREATMENTS BY WHO-DRUG ATC2 AND ATC4 – PP SET .................... 96 
TABLE 2.178 – CONCOMITANT NON-OCULAR TREATMENTS BY WHO-DRUG ATC2 AND ATC4 – PP SET ............ 96 
TABLE 2.179 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – DIAGNOSIS – WORSE EYE – PP SET .......... 96 
TABLE 2.180 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – DIAGNOSIS – CONTRALATERAL EYE - PP 
SET ............................................................................................................................................ 96 
TABLE 2.181 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – PREVIOUS TREATMENT –- PP SET ............ 96 
TABLE 2.182 – SURGICAL HISTORY OF GLAUCOMA AND OCULAR HYPERTENSION BY SYSTEM ORGAN CLASS AND 
PREFERRED TERM – WORSE EYE – PP SET ................................................................................. 96 
TABLE 2.183 – SURGICAL HISTORY OF GLAUCOMA AND OCULAR HYPERTENSION BY SYSTEM ORGAN CLASS AND 
PREFERRED TERM – CONTRALATERAL EYE – PP SET ................................................................. 96 
TABLE 2.184 – AUTOMATED VISUAL FIELD AT SCREENING VISIT – WORSE EYE – PP SET ...................................... 96 
TABLE 2.185 – AUTOMATED VISUAL FIELD AT SCREENING VISIT – CONTRALATERAL EYE – PP SET...................... 96 
TABLE 2.186 – CENTRAL CORNEAL THICKNESS MEASUREMENT (µM) AT SCREENING VISIT – WORSE EYE – PP SET
 .................................................................................................................................................. 96 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Admendment V01 
20APR2021 
Page 46/163 
 
 
 
 
 
TABLE 2.187 – CENTRAL CORNEAL THICKNESS MEASUREMENT (µM) AT SCREENING VISIT – CONTRALATERAL EYE 
– PP SET .................................................................................................................................... 96 
TABLE 2.188– SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 – WORSE EYE – PP 
SET ............................................................................................................................................ 96 
TABLE 2.189 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 –  WASH-OUT 
DURATION <= 8 DAYS – WORSE EYE – PP SET ........................................................................... 96 
TABLE 2.190 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 –  WASH-OUT 
DURATION > 8 DAYS – WORSE EYE – PP SET ............................................................................. 96 
TABLE 2.191 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 – CONTRALATERAL 
EYE – PP SET ............................................................................................................................. 96 
TABLE 2.192 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 –  WASH-OUT 
DURATION <= 8 DAYS – CONTRALATERAL EYE – PP SET ........................................................... 96 
TABLE 2.193 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 –  WASH-OUT 
DURATION > 8 DAYS – CONTRALATERAL EYE – PP SET ............................................................. 96 
TABLE 2.194 – DEMOGRAPHIC CHARACTERISTICS –WITH POSSIBLE IMPACT OF COVID-19 PANDEMIC – PP SET . 97 
TABLE 2.195 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – DIAGNOSIS – WORSE EYE – WITH POSSIBLE 
IMPACT OF COVID-19 PANDEMIC – PP SET............................................................................... 97 
TABLE 2.196 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – DIAGNOSIS – CONTRALATERAL EYE – WITH 
POSSIBLE IMPACT OF COVID-19 PANDEMIC – PP SET ............................................................... 97 
TABLE 2.197 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – PREVIOUS TREATMENT – WITH POSSIBLE 
IMPACT OF COVID-19 PANDEMIC – PP SET............................................................................... 97 
TABLE 2.198 – SURGICAL HISTORY OF GLAUCOMA AND OCULAR HYPERTENSION BY SYSTEM ORGAN CLASS AND 
PREFERRED TERM – WORSE EYE – WITH POSSIBLE IMPACT OF COVID-19 PANDEMIC – PP SET 97 
TABLE 2.199 – SURGICAL HISTORY OF GLAUCOMA AND OCULAR HYPERTENSION BY SYSTEM ORGAN CLASS AND 
PREFERRED TERM – CONTRALATERAL EYE – WITH POSSIBLE IMPACT OF COVID-19 PANDEMIC 
– PP SET .................................................................................................................................... 97 
TABLE 2.200 – AUTOMATED VISUAL FIELD AT SCREENING VISIT – WORSE EYE – WITH POSSIBLE IMPACT OF 
COVID-19 PANDEMIC – PP SET ................................................................................................ 97 
TABLE 2.201 – AUTOMATED VISUAL FIELD AT SCREENING VISIT – CONTRALATERAL EYE – WITH POSSIBLE IMPACT 
OF COVID-19 PANDEMIC – PP SET ........................................................................................... 97 
TABLE 2.202 – CENTRAL CORNEAL THICKNESS MEASUREMENT (µM) AT SCREENING VISIT – WORSE EYE – WITH 
POSSIBLE IMPACT OF COVID-19 PANDEMIC – PP SET ............................................................... 97 
TABLE 2.203 – CENTRAL CORNEAL THICKNESS MEASUREMENT (µM) AT SCREENING VISIT – CONTRALATERAL EYE 
– WITH POSSIBLE IMPACT OF COVID-19 PANDEMIC – PP SET .................................................. 97 
TABLE 2.204 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 – WORSE EYE – WITH 
POSSIBLE IMPACT OF COVID-19 PANDEMIC – PP SET ............................................................... 97 
TABLE 2.205 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 – CONTRALATERAL 
EYE – WITH POSSIBLE IMPACT OF COVID-19 PANDEMIC – PP SET............................................ 97 
TABLE 2.206 – DEMOGRAPHIC CHARACTERISTICS –WITHOUT POSSIBLE IMPACT OF COVID-19 PANDEMIC – PP 
SET ............................................................................................................................................ 97 
TABLE 2.207 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – DIAGNOSIS – WORSE EYE – WITHOUT 
POSSIBLE IMPACT OF COVID-19 PANDEMIC – PP SET ............................................................... 97 
TABLE 2.208 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – DIAGNOSIS – CONTRALATERAL EYE – 
WITHOUT POSSIBLE IMPACT OF COVID-19 PANDEMIC – PP SET ............................................... 97 
TABLE 2.209 – HISTORY OF GLAUCOMA OR OCULAR HYPERTENSION – PREVIOUS TREATMENT – WITHOUT 
POSSIBLE IMPACT OF COVID-19 PANDEMIC – PP SET ............................................................... 97 
TABLE 2.210 – SURGICAL HISTORY OF GLAUCOMA AND OCULAR HYPERTENSION BY SYSTEM ORGAN CLASS AND 
PREFERRED TERM – WORSE EYE – WITHOUT POSSIBLE IMPACT OF COVID-19 PANDEMIC – PP 
SET ............................................................................................................................................ 97 
TABLE 2.211 – SURGICAL HISTORY OF GLAUCOMA AND OCULAR HYPERTENSION BY SYSTEM ORGAN CLASS AND 
PREFERRED TERM – CONTRALATERAL EYE – WITHOUT POSSIBLE IMPACT OF COVID-19 
PANDEMIC – PP SET ................................................................................................................... 97 
TABLE 2.212 – AUTOMATED VISUAL FIELD AT SCREENING VISIT – WORSE EYE – WITHOUT POSSIBLE IMPACT OF 
COVID-19 PANDEMIC – PP SET ................................................................................................ 97 
TABLE 2.213 – AUTOMATED VISUAL FIELD AT SCREENING VISIT – CONTRALATERAL EYE – WITHOUT POSSIBLE 
IMPACT OF COVID-19 PANDEMIC – PP SET............................................................................... 97 
TABLE 2.214 – CENTRAL CORNEAL THICKNESS MEASUREMENT (µM) AT SCREENING VISIT – WORSE EYE – 
WITHOUT POSSIBLE IMPACT OF COVID-19 PANDEMIC – PP SET ............................................... 97 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Admendment V01 
20APR2021 
Page 47/163 
 
 
 
 
 
TABLE 2.215 – CENTRAL CORNEAL THICKNESS MEASUREMENT (µM) AT SCREENING VISIT – CONTRALATERAL EYE 
– WITHOUT POSSIBLE IMPACT OF COVID-19 PANDEMIC – PP SET ............................................ 97 
TABLE 2.216 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 – WORSE EYE – 
WITHOUT POSSIBLE IMPACT OF COVID-19 PANDEMIC – PP SET ............................................... 97 
TABLE 2.217 – SUMMARY OF IOP (MMHG) AND CHANGE FROM SCREENING IN IOP AT 08:00 – CONTRALATERAL 
EYE – WITHOUT POSSIBLE IMPACT OF COVID-19 PANDEMIC – PP SET ..................................... 97 
 
3 Treatment exposure and compliance 
TABLE 3.1 – AZOPT EXPOSURE – AZOPT SAFETY SET ............................................................................................ 98 
TABLE 3.2 – CHANGES IN THE AZOPT INSTILLATIONS – AZOPT SAFETY SET ......................................................... 99 
LISTING 3.1 – LISTING OF DATA RELATIVE TO AZOPT INSTILLATIONS MODIFICATIONS – AZOPT SAFETY SET ...... 100 
TABLE 3.3 – AZOPT EXPOSURE – M-ITT SET ........................................................................................................ 100 
TABLE 3.4 – CHANGES IN THE AZOPT INSTILLATIONS – M-ITT SET ..................................................................... 100 
TABLE 3.5 – COMPLIANCE OF AZOPT (%) – WORSE EYE – M-ITT SET ................................................................. 101 
TABLE 3.6 – COMPLIANCE OF AZOPT (%) – CONTRALATERAL EYE– M-ITT SET ................................................. 101 
TABLE 3.7 – TREATMENT EXPOSURE – SAFETY SET ............................................................................................. 102 
TABLE 3.8 – CHANGES IN THE IMP INSTILLATION (BETWEEN THE FIRST AND THE LAST INSTILLATION) – FROM 
DAY 1 TO WEEK 6 – SAFETY SET ............................................................................................. 103 
TABLE 3.9 – CHANGES IN THE IMP INSTILLATIONS (BETWEEN THE FIRST AND THE LAST INSTILLATION) – FROM 
WEEK 6 TO WEEK 12 – SAFETY SET ........................................................................................ 103 
TABLE 3.10 – CHANGES IN THE IMP INSTILLATIONS (BETWEEN THE FIRST AND THE LAST INSTILLATION) – FROM 
DAY 1 TO WEEK 12 - SAFETY SET ........................................................................................... 103 
TABLE 3.11 – COMPLIANCE (%) – WORSE EYE – FROM DAY 1 TO WEEK 6 – SAFETY SET ................................... 104 
TABLE 3.12 – COMPLIANCE (%) – WORSE EYE – FROM WEEK 6 TO WEEK 12 – SAFETY SET .............................. 104 
TABLE 3.13 – COMPLIANCE (%) – WORSE EYE – FROM DAY 1 TO WEEK 12 – SAFETY SET ................................. 104 
TABLE 3.14 – COMPLIANCE (%) – CONTRALATERAL EYE – FROM DAY 1 TOWEEK 6 - SAFETY SET .................... 105 
TABLE 3.15 – COMPLIANCE (%) – CONTRALATERAL EYE – FROM WEEK 6 TO WEEK 12 – SAFETY SET .............. 105 
TABLE 3.16 – COMPLIANCE (%) – CONTRALATERAL EYE – FROM DAY 1 TO WEEK 12 – SAFETY SET ................ 105 
LISTING 3.2 – LISTING OF DATA RELATIVE TO IMP INSTILLATIONS MODIFICATIONS – SAFETY SET ..................... 106 
LISTING 3.3 – LISTING OF DATA RELATIVE TO IMP INSTILLATION TIME MODIFICATIONS – SAFETY SET .............. 106 
TABLE 3.17 – TREATMENT EXPOSURE – WITH POSSIBLE IMPACT OF COVID-19 PANDEMIC – SAFETY SET ......... 107 
TABLE 3.18 – CHANGES IN THE IMP INSTILLATIONS (BETWEEN THE FIRST AND THE LAST INSTILLATION) – FROM 
DAY 1 TO WEEK 6 – WITH POSSIBLE IMPACT OF COVID-19 PANDEMIC – SAFETY SET ........... 107 
TABLE 3.19 – CHANGES IN THE IMP INSTILLATIONS (BETWEEN THE FIRST AND THE LAST INSTILLATION) – FROM 
WEEK 6 TO WEEK 12 – WITH POSSIBLE IMPACT OF COVID-19 PANDEMIC – SAFETY SET ...... 107 
TABLE 3.20 – CHANGES IN THE IMP INSTILLATIONS (BETWEEN THE FIRST AND THE LAST INSTILLATION) – FROM 
DAY 1 TO WEEK 12 – WITH POSSIBLE IMPACT OF COVID-19 PANDEMIC – SAFETY SET ......... 107 
TABLE 3.21 – COMPLIANCE (%) – WORSE EYE – FROM DAY 1 TO WEEK 6 – WITH POSSIBLE IMPACT OF COVID-
19 PANDEMIC – SAFETY SET .................................................................................................... 107 
TABLE 3.22 – COMPLIANCE (%) – WORSE EYE – FROM WEEK 6 TO WEEK 12 – WITH POSSIBLE IMPACT OF 
COVID-19 PANDEMIC – SAFETY SET ...................................................................................... 107 
TABLE 3.23 – COMPLIANCE (%) – WORSE EYE – FROM DAY 1 TO WEEK 12 – WITH POSSIBLE IMPACT OF COVID-
19 PANDEMIC – SAFETY SET .................................................................................................... 107 
TABLE 3.24 – COMPLIANCE (%) – CONTRALATERAL EYE – FROM DAY 1 TOWEEK 6 – WITH POSSIBLE IMPACT OF 
COVID-19 PANDEMIC – SAFETY SET ...................................................................................... 107 
TABLE 3.25 – COMPLIANCE (%) – CONTRALATERAL EYE – FROM WEEK 6 TO WEEK 12 – WITH POSSIBLE IMPACT 
OF COVID-19 PANDEMIC – SAFETY SET ................................................................................. 107 
TABLE 3.26 – COMPLIANCE (%) – CONTRALATERAL EYE – FROM DAY 1 TO WEEK 12 – WITH POSSIBLE IMPACT OF 
COVID-19 PANDEMIC – SAFETY SET ...................................................................................... 107 
TABLE 3.27 – TREATMENT EXPOSURE – WITHOUT POSSIBLE IMPACT OF COVID-19 PANDEMIC – SAFETY SET .. 107 
TABLE 3.28 – CHANGES IN THE IMP INSTILLATIONS (BETWEEN THE FIRST AND THE LAST INSTILLATION) – FROM 
DAY 1 TO WEEK 6 – WITHOUT POSSIBLE IMPACT OF COVID-19 PANDEMIC – SAFETY SET .... 107 
TABLE 3.29 – CHANGES IN THE IMP INSTILLATIONS (BETWEEN THE FIRST AND THE LAST INSTILLATION) – FROM 
WEEK 6 TO WEEK 12 – WITHOUT POSSIBLE IMPACT OF COVID-19 PANDEMIC – SAFETY SET 107 
TABLE 3.30 – CHANGES IN THE IMP INSTILLATIONS (BETWEEN THE FIRST AND THE LAST INSTILLATION) – FROM 
DAY 1 TO WEEK 12 – WITHOUT POSSIBLE IMPACT OF COVID-19 PANDEMIC – SAFETY SET .. 107 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Admendment V01 
20APR2021 
Page 48/163 
 
 
 
 
 
TABLE 3.31 – COMPLIANCE (%) – WORSE EYE – FROM DAY 1 TO WEEK 6 – WITHOUT POSSIBLE IMPACT OF 
COVID-19 PANDEMIC – SAFETY SET ...................................................................................... 107 
TABLE 3.32 – COMPLIANCE (%) – WORSE EYE – FROM WEEK 6 TO WEEK 12 – WITHOUT POSSIBLE IMPACT OF 
COVID-19 PANDEMIC – SAFETY SET ...................................................................................... 107 
TABLE 3.33 – COMPLIANCE (%) – WORSE EYE – FROM DAY 1 TO WEEK 12 – WITHOUT POSSIBLE IMPACT OF 
COVID-19 PANDEMIC – SAFETY SET ...................................................................................... 107 
TABLE 3.34 – COMPLIANCE (%) – CONTRALATERAL EYE – FROM DAY 1 TOWEEK 6 – WITHOUT POSSIBLE IMPACT 
OF COVID-19 PANDEMIC – SAFETY SET ................................................................................. 107 
TABLE 3.35 – COMPLIANCE (%) – CONTRALATERAL EYE – FROM WEEK 6 TO WEEK 12 – WITHOUT POSSIBLE 
IMPACT OF COVID-19 PANDEMIC – SAFETY SET..................................................................... 107 
TABLE 3.36 – COMPLIANCE (%) – CONTRALATERAL EYE – FROM DAY 1 TO WEEK 12 – WITHOUT POSSIBLE 
IMPACT OF COVID-19 PANDEMIC – SAFETY SET..................................................................... 107 
TABLE 3.37 – TREATMENT EXPOSURE – M-ITT SET ............................................................................................. 108 
TABLE 3.38 – CHANGES IN THE IMP INSTILLATIONS (BETWEEN THE FIRST AND THE LAST INSTILLATION) – FROM 
DAY 1 TO WEEK 6 – M-ITT SET ............................................................................................... 108 
TABLE 3.39 – CHANGES IN THE IMP INSTILLATIONS (BETWEEN THE FIRST AND THE LAST INSTILLATION) – FROM 
WEEK 6 TO WEEK 12 – M-ITT SET .......................................................................................... 108 
TABLE 3.40 – CHANGES IN THE IMP INSTILLATIONS (BETWEEN THE FIRST AND THE LAST INSTILLATION) – FROM 
DAY 1 TO WEEK 12 – M-ITT SET ............................................................................................. 108 
TABLE 3.41 – COMPLIANCE (%) – WORSE EYE – FROM DAY 1 TO WEEK 6 – M-ITT SET ..................................... 108 
TABLE 3.42 – COMPLIANCE (%) – WORSE EYE – FROM WEEK 6 TO WEEK 12 – M-ITT SET ................................ 108 
TABLE 3.43 – COMPLIANCE (%) – WORSE EYE – FROM DAY 1 TO WEEK 12 – M-ITT SET ................................... 108 
TABLE 3.44 – COMPLIANCE (%) – CONTRALATERAL EYE – FROM DAY 1 TOWEEK 6 – M-ITT SET ..................... 108 
TABLE 3.45 – COMPLIANCE (%) – CONTRALATERAL EYE – FROM WEEK 6 TO WEEK 12 – M-ITT SET ................ 108 
TABLE 3.46 – COMPLIANCE (%) – CONTRALATERAL EYE – FROM DAY 1 TO WEEK 12 – M-ITT SET ................... 108 
TABLE 3.47 – TREATMENT EXPOSURE – WITH POSSIBLE IMPACT OF COVID-19 PANDEMIC – M-ITT SET ........... 109 
TABLE 3.48 – CHANGES IN THE IMP INSTILLATIONS (BETWEEN THE FIRST AND THE LAST INSTILLATION) – FROM 
DAY 1 TO WEEK 6 – WITH POSSIBLE IMPACT OF COVID-19 PANDEMIC – M-ITT SET ............. 109 
TABLE 3.49 – CHANGES IN THE IMP INSTILLATIONS (BETWEEN THE FIRST AND THE LAST INSTILLATION) – FROM 
WEEK 6 TO WEEK 12 – WITH POSSIBLE IMPACT OF COVID-19 PANDEMIC – M-ITT SET ......... 109 
TABLE 3.50 – CHANGES IN THE IMP INSTILLATIONS (BETWEEN THE FIRST AND THE LAST INSTILLATION) – FROM 
DAY 1 TO WEEK 12 – WITH POSSIBLE IMPACT OF COVID-19 PANDEMIC – M-ITT SET ........... 109 
TABLE 3.51 – COMPLIANCE (%) – WORSE EYE – FROM DAY 1 TO WEEK 6 – WITH POSSIBLE IMPACT OF COVID-
19 PANDEMIC – M-ITT SET ...................................................................................................... 109 
TABLE 3.52 – COMPLIANCE (%) – WORSE EYE – FROM WEEK 6 TO WEEK 12 – WITH POSSIBLE IMPACT OF 
COVID-19 PANDEMIC – M-ITT SET ........................................................................................ 109 
TABLE 3.53 – COMPLIANCE (%) – WORSE EYE – FROM DAY 1 TO WEEK 12 – WITH POSSIBLE IMPACT OF COVID-
19 PANDEMIC – M-ITT SET ...................................................................................................... 109 
TABLE 3.54 – COMPLIANCE (%) – CONTRALATERAL EYE – FROM DAY 1 TOWEEK 6 – WITH POSSIBLE IMPACT OF 
COVID-19 PANDEMIC – M-ITT SET ........................................................................................ 109 
TABLE 3.55 – COMPLIANCE (%) – CONTRALATERAL EYE – FROM WEEK 6 TO WEEK 12 – WITH POSSIBLE IMPACT 
OF COVID-19 PANDEMIC – M-ITT SET ................................................................................... 109 
TABLE 3.56 – COMPLIANCE (%) – CONTRALATERAL EYE – FROM DAY 1 TO WEEK 12 – WITH POSSIBLE IMPACT OF 
COVID-19 PANDEMIC – M-ITT SET ........................................................................................ 109 
TABLE 3.57 – TREATMENT EXPOSURE – WITHOUT POSSIBLE IMPACT OF COVID-19 PANDEMIC – M-ITT SET..... 109 
TABLE 3.58 – CHANGES IN THE IMP INSTILLATIONS (BETWEEN THE FIRST AND THE LAST INSTILLATION) – FROM 
DAY 1 TO WEEK 6 – WITHOUT POSSIBLE IMPACT OF COVID-19 PANDEMIC – M-ITT SET....... 109 
TABLE 3.59 – CHANGES IN THE IMP INSTILLATIONS (BETWEEN THE FIRST AND THE LAST INSTILLATION) – FROM 
WEEK 6 TO WEEK 12 – WITHOUT POSSIBLE IMPACT OF COVID-19 PANDEMIC – M-ITT SET .. 109 
TABLE 3.60 – CHANGES IN THE IMP INSTILLATIONS (BETWEEN THE FIRST AND THE LAST INSTILLATION) – FROM 
DAY 1 TO WEEK 12 – WITHOUT POSSIBLE IMPACT OF COVID-19 PANDEMIC – M-ITT SET..... 109 
TABLE 3.61 – COMPLIANCE (%) – WORSE EYE – FROM DAY 1 TO WEEK 6 – WITHOUT POSSIBLE IMPACT OF 
COVID-19 PANDEMIC – M-ITT SET ........................................................................................ 109 
TABLE 3.62 – COMPLIANCE (%) – WORSE EYE – FROM WEEK 6 TO WEEK 12 – WITHOUT POSSIBLE IMPACT OF 
COVID-19 PANDEMIC – M-ITT SET ........................................................................................ 109 
TABLE 3.63 – COMPLIANCE (%) – WORSE EYE – FROM DAY 1 TO WEEK 12 – WITHOUT POSSIBLE IMPACT OF 
COVID-19 PANDEMIC – M-ITT SET ........................................................................................ 109 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Admendment V01 
20APR2021 
Page 49/163 
 
 
 
 
 
TABLE 3.64 – COMPLIANCE (%) – CONTRALATERAL EYE – FROM DAY 1 TOWEEK 6 – WITHOUT POSSIBLE IMPACT 
OF COVID-19 PANDEMIC – M-ITT SET ................................................................................... 109 
TABLE 3.65 – COMPLIANCE (%) – CONTRALATERAL EYE – FROM WEEK 6 TO WEEK 12 – WITHOUT POSSIBLE 
IMPACT OF COVID-19 PANDEMIC – M-ITT SET ....................................................................... 109 
TABLE 3.66 – COMPLIANCE (%) – CONTRALATERAL EYE – FROM DAY 1 TO WEEK 12 – WITHOUT POSSIBLE 
IMPACT OF COVID-19 PANDEMIC – M-ITT SET ....................................................................... 109 
 
4. Efficacy analyses 
TABLE 4.1 – SUMMARY OF IOP (MMHG) AND CHANGE FROM BASELINE IN IOP – WORSE EYE – M-ITT SET ....... 110 
TABLE 4.2 – SUMMARY OF IOP (MMHG) AND CHANGE FROM BASELINE IN IOP – WORSE EYE – ITT SET ........... 110 
TABLE 4.3 – SUMMARY OF IOP (MMHG) AND CHANGE FROM BASELINE IN IOP – WORSE EYE – PP SET ............ 110 
TABLE 4.4 – SUMMARY OF IOP (MMHG) AND CHANGE FROM BASELINE IN IOP – WORSE EYE – (*) – M-ITT SET
 ................................................................................................................................................ 110 
TABLE 4.5 – SUMMARY OF IOP (MMHG) AND CHANGE FROM BASELINE IN IOP – WORSE EYE – (*) – ITT SET... 110 
TABLE 4.6 – SUMMARY OF IOP (MMHG) AND CHANGE FROM BASELINE IN IOP – WORSE EYE – (*) – PP SET .... 110 
TABLE 4.7 – PRIMARY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 12 – 
MMRM ANALYSIS – WORSE EYE – M-ITT SET ....................................................................... 111 
TABLE 4.8 – PRIMARY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 12 – 
MMRM ANALYSIS – WORSE EYE – M-ITT SET ....................................................................... 111 
TABLE 4.9 – PRIMARY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 12 – 
MMRM ANALYSIS – WORSE EYE – M-ITT SET ....................................................................... 111 
TABLE 4.10 –ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 12 – MMRM 
ANALYSIS – WORSE EYE – ITT SET.......................................................................................... 111 
TABLE 4.11 –ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 12 – MMRM 
ANALYSIS – WORSE EYE – ITT SET.......................................................................................... 111 
TABLE 4.12 –ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 12 – MMRM 
ANALYSIS – WORSE EYE – ITT SET.......................................................................................... 111 
TABLE 4.13 –ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 12 – MMRM 
ANALYSIS – WORSE EYE – PP SET ........................................................................................... 111 
TABLE 4.14 –ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 12 – MMRM 
ANALYSIS – WORSE EYE – PP SET ........................................................................................... 111 
TABLE 4.15 –ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 12 – MMRM 
ANALYSIS – WORSE EYE – PP SET ........................................................................................... 111 
TABLE 4.16 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 12 
(LOCF) – ANCOVA – WORSE EYE – M-ITT SET .................................................................... 112 
TABLE 4.17 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 12 
(LOCF) – ANCOVA – WORSE EYE – M-ITT SET .................................................................... 112 
TABLE 4.18 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 12 
(LOCF) – ANCOVA – WORSE EYE – M-ITT SET .................................................................... 112 
TABLE 4.19 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 12 
(LOCF) – ANCOVA – WORSE EYE – ITT SET ........................................................................ 112 
TABLE 4.20 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 12 
(LOCF) – ANCOVA – WORSE EYE – ITT SET ........................................................................ 112 
TABLE 4.21 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 12 
(LOCF) – ANCOVA – WORSE EYE – ITT SET ........................................................................ 112 
TABLE 4.22 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 12 
(LOCF) – ANCOVA – WORSE EYE – PP SET .......................................................................... 112 
TABLE 4.23 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 12 
(LOCF) – ANCOVA – WORSE EYE – PP SET .......................................................................... 112 
TABLE 4.24 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 12 
(LOCF) – ANCOVA – WORSE EYE – PP SET .......................................................................... 112 
TABLE 4.25 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 12 
(OBSERVED) – ANCOVA – WORSE EYE – M-ITT SET ............................................................. 113 
TABLE 4.26 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 12 
(OBSERVED) – ANCOVA – WORSE EYE – M-ITT SET ............................................................. 113 
TABLE 4.27 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 12 
(OBSERVED) – ANCOVA – WORSE EYE – M-ITT SET ............................................................. 113 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Admendment V01 
20APR2021 
Page 50/163 
 
 
 
 
 
TABLE 4.28 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 12 
(OBSERVED) – ANCOVA – WORSE EYE – ITT SET ................................................................. 113 
TABLE 4.29 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 12 
(OBSERVED) – ANCOVA – WORSE EYE – ITT SET ................................................................. 113 
TABLE 4.30 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 12 
(OBSERVED) – ANCOVA – WORSE EYE – ITT SET ................................................................. 113 
TABLE 4.31 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 12 
(OBSERVED) – ANCOVA – WORSE EYE – PP SET .................................................................. 113 
TABLE 4.32 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 12 
(OBSERVED) – ANCOVA – WORSE EYE – PP SET .................................................................. 113 
TABLE 4.33 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 12 
(OBSERVED) – ANCOVA – WORSE EYE – PP SET .................................................................. 113 
TABLE 4.34 – SUPPORTING ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 12 – 
MMRM ANALYSIS – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY BASELINE IOP’ 
INTERACTION – M-ITT SET ...................................................................................................... 114 
TABLE 4.35 – SUPPORTING ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 12 – 
MMRM ANALYSIS – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY BASELINE IOP’ 
INTERACTION – M-ITT SET ...................................................................................................... 114 
TABLE 4.36 – SUPPORTING ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 12 – 
MMRM ANALYSIS – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY BASELINE IOP’ 
INTERACTION – M-ITT SET ...................................................................................................... 114 
TABLE 4.37 – SUPPORTING ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 12 – 
MMRM ANALYSIS – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY WASH-OUT DURATION’ 
INTERACTION – M-ITT SET ...................................................................................................... 115 
TABLE 4.38 – SUPPORTING ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 12 – 
MMRM ANALYSIS – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY WASH-OUT DURATION’ 
INTERACTION – M-ITT SET ...................................................................................................... 115 
TABLE 4.39 – SUPPORTING ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 12 – 
MMRM ANALYSIS – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY WASH-OUT DURATION’ 
INTERACTION – M-ITT SET ...................................................................................................... 115 
TABLE 4.40 – SUPPORTING ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 12 – 
MMRM ANALYSIS – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY COUNTRY’ 
INTERACTION – M-ITT SET ...................................................................................................... 116 
TABLE 4.41 – SUPPORTING ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 12 – 
MMRM ANALYSIS – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY COUNTRY’ 
INTERACTION – M-ITT SET ...................................................................................................... 116 
TABLE 4.42 – SUPPORTING ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 12 – 
MMRM ANALYSIS – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY COUNTRY’ 
INTERACTION – M-ITT SET ...................................................................................................... 116 
TABLE 4.43 – SUPPORTING ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 12 
(LOCF) – ANCOVA – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY BASELINE IOP’ 
INTERACTION – M-ITT SET ...................................................................................................... 117 
TABLE 4.44 – SUPPORTING ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 12 
(LOCF) – ANCOVA – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY BASELINE IOP’ 
INTERACTION – M-ITT SET ...................................................................................................... 117 
TABLE 4.45 – SUPPORTING ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 12 
(LOCF) – ANCOVA – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY BASELINE IOP’ 
INTERACTION – M-ITT SET ...................................................................................................... 117 
TABLE 4.46 – SUPPORTING ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 12 
(LOCF) – ANCOVA – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY WASH-OUT 
DURATION’ INTERACTION –  M-ITT SET ................................................................................... 118 
TABLE 4.47 – SUPPORTING ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 12 
(LOCF) – ANCOVA – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY WASH-OUT 
DURATION’ INTERACTION –  M-ITT SET ................................................................................... 118 
TABLE 4.48 – SUPPORTING ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 12 
(LOCF) – ANCOVA – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY WASH-OUT 
DURATION’ INTERACTION –  M-ITT SET ................................................................................... 118 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Admendment V01 
20APR2021 
Page 51/163 
 
 
 
 
 
TABLE 4.49 – SUPPORTING ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 12 
(LOCF) – ANCOVA – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY COUNTRY’ 
INTERACTION –  M-ITT SET ..................................................................................................... 119 
TABLE 4.50 – SUPPORTING ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 12 
(LOCF) – ANCOVA – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY COUNTRY’ 
INTERACTION – M-ITT SET ...................................................................................................... 119 
TABLE 4.51 – SUPPORTING ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 12 
(LOCF) – ANCOVA – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY COUNTRY’ 
INTERACTION – M-ITT SET ...................................................................................................... 119 
TABLE 4.52 – SUPPORTING ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 12 
(OBSERVED) – ANCOVA – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY BASELINE IOP’ 
INTERACTION – M-ITT SET ...................................................................................................... 120 
TABLE 4.53 – SUPPORTING ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 12 
(OBSERVED) – ANCOVA – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY BASELINE IOP’ 
INTERACTION – M-ITT SET ...................................................................................................... 120 
TABLE 4.54 – SUPPORTING ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 12 
(OBSERVED) – ANCOVA – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY BASELINE IOP’ 
INTERACTION – M-ITT SET ...................................................................................................... 120 
TABLE 4.55 – SUPPORTING ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 12 
(OBSERVED) – ANCOVA – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY WASH-OUT 
DURATION’ INTERACTION –  M-ITT SET ................................................................................... 121 
TABLE 4.56 – SUPPORTING ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 12 
(OBSERVED) – ANCOVA – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY WASH-OUT 
DURATION’ INTERACTION – M-ITT SET ................................................................................... 121 
TABLE 4.57 – SUPPORTING ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 12 
(OBSERVED) – ANCOVA – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY WASH-OUT 
DURATION’ INTERACTION – M-ITT SET ................................................................................... 121 
TABLE 4.58 – SUPPORTING ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 12 
(OBSERVED) – ANCOVA – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY COUNTRY’ 
INTERACTION –  M-ITT SET ..................................................................................................... 122 
TABLE 4.59 – SUPPORTING ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 12 
(OBSERVED) – ANCOVA – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY COUNTRY’ 
INTERACTION – M-ITT SET ...................................................................................................... 122 
TABLE 4.60 – SUPPORTING ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 12 
(OBSERVED) – ANCOVA – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY COUNTRY’ 
INTERACTION – M-ITT SET ...................................................................................................... 122 
TABLE 4.61 – EXPLORATORY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 12 – 
MMRM ANALYSIS – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY POSSIBLE IMPACT OF 
COVID-19 PANDEMIC’ INTERACTION – M-ITT SET ................................................................. 123 
TABLE 4.62 – EXPLORATORY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 12 – 
MMRM ANALYSIS – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY POSSIBLE IMPACT OF 
COVID-19 PANDEMIC’ INTERACTION – M-ITT SET ................................................................. 123 
TABLE 4.63 – EXPLORATORY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 12 – 
MMRM ANALYSIS – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY POSSIBLE IMPACT OF 
COVID-19 PANDEMIC’ INTERACTION – M-ITT SET ................................................................. 123 
TABLE 4.64 – EXPLORATORY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 12 
(LOCF) – ANCOVA – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY POSSIBLE IMPACT OF 
COVID-19 PANDEMIC’ INTERACTION – M-ITT SET ................................................................. 124 
TABLE 4.65 – EXPLORATORY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 12 
(LOCF) – ANCOVA – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY POSSIBLE IMPACT OF 
COVID-19 PANDEMIC’ INTERACTION – M-ITT SET ................................................................. 124 
TABLE 4.66 – SUPPORTING ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 12 
(LOCF) – ANCOVA – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY POSSIBLE IMPACT OF 
COVID-19 PANDEMIC’ INTERACTION – M-ITT SET ................................................................. 124 
TABLE 4.67 – EXPLORATORY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 12 
(OBSERVED) – ANCOVA – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY POSSIBLE 
IMPACT OF COVID-19 PANDEMIC’ INTERACTION –  M-ITT SET .............................................. 125 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Admendment V01 
20APR2021 
Page 52/163 
 
 
 
 
 
TABLE 4.68 – EXPLORATORY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 12 
(OBSERVED) – ANCOVA – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY POSSIBLE 
IMPACT OF COVID-19 PANDEMIC’ INTERACTION – M-ITT SET ............................................... 125 
TABLE 4.69 – EXPLORATORY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 12 
(OBSERVED) – ANCOVA – WORSE EYE – INVESTIGATION OF ‘TREATMENT BY POSSIBLE 
IMPACT OF COVID-19 PANDEMIC’ INTERACTION – M-ITT SET ............................................... 125 
TABLE 4.70 – EXPLORATORY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT WEEK 12 – WORSE 
EYE – IMPACT OF CIRCADIAN RHYTHM – M-ITT SET ................................................................ 126 
TABLE 4.71 – SUMMARY OF IOP (MMHG) AND CHANGE FROM BASELINE IN IOP – CONTRALATERAL EYE – M-ITT 
SET .......................................................................................................................................... 127 
TABLE 4.72 – SUMMARY OF IOP (MMHG) AND CHANGE FROM BASELINE IN IOP – CONTRALATERAL EYE – PP SET
 ................................................................................................................................................ 127 
TABLE 4.73 – SUMMARY OF IOP (MMHG) AND CHANGE FROM BASELINE IN IOP – CONTRALATERAL EYE – (*) –  
M-ITT SET ............................................................................................................................... 127 
TABLE 4.74 – SUMMARY OF IOP (MMHG) AND CHANGE FROM BASELINE IN IOP – CONTRALATERAL EYE – (*) –  
PP SET ..................................................................................................................................... 127 
TABLE 4.75 –ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 12 – MMRM 
ANALYSIS – CONTRALATERAL EYE – M-ITT SET ..................................................................... 127 
TABLE 4.76 –ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 12 – MMRM 
ANALYSIS – CONTRALATERAL EYE – M-ITT SET ..................................................................... 127 
TABLE 4.77 –ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 12 – MMRM 
ANALYSIS – CONTRALATERAL EYE – M-ITT SET ..................................................................... 127 
TABLE 4.78 –ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 12 – MMRM 
ANALYSIS – CONTRALATERAL EYE – PP SET ........................................................................... 127 
TABLE 4.79 –ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 12 – MMRM 
ANALYSIS – CONTRALATERAL EYE – PP SET ........................................................................... 127 
TABLE 4.80 –ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 12 – MMRM 
ANALYSIS – CONTRALATERAL EYE – PP SET ........................................................................... 127 
TABLE 4.81 –SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 12 
(LOCF) – ANCOVA – CONTRALATERAL EYE – M-ITT SET .................................................... 127 
TABLE 4.82 –SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 12 
(LOCF) – ANCOVA – CONTRALATERAL EYE – M-ITT SET .................................................... 127 
TABLE 4.83 –SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 12 
(LOCF) – ANCOVA – CONTRALATERAL EYE – M-ITT SET .................................................... 127 
TABLE 4.84 –SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 12 
(LOCF) – ANCOVA – CONTRALATERAL EYE – PP SET ......................................................... 127 
TABLE 4.85 –SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 12 
(LOCF) – ANCOVA – CONTRALATERAL EYE – PP SET ......................................................... 127 
TABLE 4.86 –SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 12 
(LOCF) – ANCOVA – CONTRALATERAL EYE – PP SET ......................................................... 127 
TABLE 4.87 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 12 
(OBSERVED) – ANCOVA – CONTRALATERAL EYE – M-ITT SET ............................................ 128 
TABLE 4.88 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 12 
(OBSERVED) – ANCOVA – CONTRALATERAL EYE – M-ITT SET ............................................ 128 
TABLE 4.89 –SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 12 
(OBSERVED) – ANCOVA – CONTRALATERAL EYE – M-ITT SET ............................................ 128 
TABLE 4.90 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 12 
(OBSERVED) – ANCOVA – CONTRALATERAL EYE – PP SET .................................................. 128 
TABLE 4.91 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 12 
(OBSERVED) – ANCOVA – CONTRALATERAL EYE – PP SET .................................................. 128 
TABLE 4.92 –SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 12 
(OBSERVED) – ANCOVA – CONTRALATERAL EYE – PP SET .................................................. 128 
TABLE 4.93 – ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 6 – MMRM 
ANALYSIS – WORSE EYE – M-ITT SET ..................................................................................... 129 
TABLE 4.94 –ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 6 – MMRM 
ANALYSIS – WORSE EYE – M-ITT SET ..................................................................................... 129 
TABLE 4.95 –ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 6 – MMRM 
ANALYSIS – WORSE EYE – M-ITT SET ..................................................................................... 129 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Admendment V01 
20APR2021 
Page 53/163 
 
 
 
 
 
TABLE 4.96 –ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 6 – MMRM 
ANALYSIS – WORSE EYE – PP SET ........................................................................................... 129 
TABLE 4.97 –ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 6 – MMRM 
ANALYSIS – WORSE EYE – PP SET ........................................................................................... 129 
TABLE 4.98 –ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 6 – MMRM 
ANALYSIS – WORSE EYE – PP SET ........................................................................................... 129 
TABLE 4.99 –ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 6 – MMRM 
ANALYSIS – CONTRALATERAL EYE – M-ITT SET ..................................................................... 129 
TABLE 4.100 –ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 6 – MMRM 
ANALYSIS – CONTRALATERAL EYE – M-ITT SET ..................................................................... 129 
TABLE 4.101 –ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 6 – MMRM 
ANALYSIS – CONTRALATERAL EYE – M-ITT SET ..................................................................... 129 
TABLE 4.102 –ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 6 – MMRM 
ANALYSIS – CONTRALATERAL EYE – PP SET ........................................................................... 130 
TABLE 4.103 –ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 6 – MMRM 
ANALYSIS – CONTRALATERAL EYE – PP SET ........................................................................... 130 
TABLE 4.104 –ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 6 – MMRM 
ANALYSIS – CONTRALATERAL EYE – PP SET ........................................................................... 130 
TABLE 4.105 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 6 
(OBSERVED) – ANCOVA – WORSE EYE – M-ITT SET ............................................................. 131 
TABLE 4.106 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 6 
(OBSERVED) – ANCOVA – WORSE EYE – M-ITT SET ............................................................. 131 
TABLE 4.107 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 6 
(OBSERVED) – ANCOVA – WORSE EYE – M-ITT SET ............................................................. 131 
TABLE 4.108 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 6 
(OBSERVED) – ANCOVA – WORSE EYE – PP SET ................................................................... 131 
TABLE 4.109 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 6 
(OBSERVED) – ANCOVA – WORSE EYE – PP SET ................................................................... 131 
TABLE 4.110 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 6 
(OBSERVED) – ANCOVA – WORSE EYE – PP SET ................................................................... 131 
TABLE 4.111 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 6 
(OBSERVED) – ANCOVA – CONTRALATERAL EYE – M-ITT SET ............................................. 131 
TABLE 4.112 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 6 
(OBSERVED) – ANCOVA – CONTRALATERAL EYE – M-ITT SET ............................................. 131 
TABLE 4.113 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 6 
(OBSERVED) – ANCOVA – CONTRALATERAL EYE – M-ITT SET ............................................. 131 
TABLE 4.114 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 08:00 AT WEEK 6 
(OBSERVED) – ANCOVA – CONTRALATERAL EYE – PP SET ................................................... 131 
TABLE 4.115 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 10:00 AT WEEK 6 
(OBSERVED) – ANCOVA – CONTRALATERAL EYE – PP SET ................................................... 131 
TABLE 4.116 – SENSITIVITY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT 16:00 AT WEEK 6 
(OBSERVED) – ANCOVA – CONTRALATERAL EYE – PP SET ................................................... 131 
TABLE 4.117 – EXPLORATORY ANALYSIS OF THE CHANGE FROM BASELINE IN IOP (MMHG) AT WEEK 6 – WORSE 
EYE – IMPACT OF CIRCADIAN RHYTHM – M-ITT SET ................................................................ 132 
TABLE 4.118 – SUMMARY OF IOP (IN CLASSES) – WORSE EYE – M-ITT SET ....................................................... 133 
TABLE 4.119 – SUMMARY OF IOP (IN CLASSES) – WORSE EYE – PP SET ............................................................. 133 
TABLE 4.120 – SUMMARY OF IOP (IN CLASSES) – CONTRALATERAL EYE – M-ITT SET ....................................... 133 
TABLE 4.121 – SUMMARY OF IOP (IN CLASSES) – CONTRALATERAL EYE – PP SET ............................................. 133 
TABLE 4.122 – SUMMARY OF IOP (MMHG) AND CHANGE FROM BASELINE IN IOP – WORSE EYE – PATIENTS WITH 
HISTORY OF GLAUCOMA – M-ITT SET ...................................................................................... 133 
TABLE 4.123 – SUMMARY OF IOP (MMHG) AND CHANGE FROM BASELINE IN IOP – WORSE EYE – PATIENTS WITH 
HISTORY OF OCULAR HYPERTENSION – M-ITT SET .................................................................. 133 
TABLE 4.124 – SUMMARY OF IOP (MMHG) AND CHANGE FROM BASELINE IN IOP – WORSE EYE – PATIENTS WITH 
HISTORY OF GLAUCOMA – PP SET ............................................................................................ 133 
TABLE 4.125 – SUMMARY OF IOP (MMHG) AND CHANGE FROM BASELINE IN IOP – WORSE EYE – PATIENTS WITH 
HISTORY OF OCULAR HYPERTENSION – PP SET ........................................................................ 133 
TABLE 4.126 – SUMMARY OF IOP (MMHG) AND CHANGE FROM BASELINE IN IOP – CONTRALATERAL EYE – 
PATIENTS WITH HISTORY OF GLAUCOMA – M-ITT SET ............................................................ 133 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Admendment V01 
20APR2021 
Page 54/163 
 
 
 
 
 
TABLE 4.127 – SUMMARY OF IOP (MMHG) AND CHANGE FROM BASELINE IN IOP – CONTRALATERAL EYE – 
PATIENTS WITH HISTORY OF OCULAR HYPERTENSION – M-ITT SET ......................................... 133 
TABLE 4.128 – SUMMARY OF IOP (MMHG) AND CHANGE FROM BASELINE IN IOP – CONTRALATERAL EYE – 
PATIENTS WITH HISTORY OF GLAUCOMA – PP SET .................................................................. 133 
TABLE 4.129 – SUMMARY OF IOP (MMHG) AND CHANGE FROM BASELINE IN IOP – CONTRALATERAL EYE – 
PATIENTS WITH HISTORY OF OCULAR HYPERTENSION – PP SET ............................................... 133 
TABLE 4.130 – SUMMARY OF IOP (MMHG) AND CHANGE FROM BASELINE IN IOP – MEAN DIURNAL IOP – WORSE 
EYE – M-ITT SET ..................................................................................................................... 134 
TABLE 4.131 – SUMMARY OF IOP (MMHG) AND CHANGE FROM BASELINE IN IOP – MEAN DIURNAL IOP – WORSE 
EYE – PP SET ........................................................................................................................... 134 
TABLE 4.132 – SUMMARY OF IOP (MMHG) AND CHANGE FROM BASELINE IN IOP – MEAN DIURNAL IOP – 
CONTRALATERAL EYE – M-ITT SET ........................................................................................ 134 
TABLE 4.133 – SUMMARY OF IOP (MMHG) AND CHANGE FROM BASELINE IN IOP – MEAN DIURNAL IOP – 
CONTRALATERAL EYE – PP SET .............................................................................................. 134 
TABLE 4.134 – GLOBAL ASSESSMENT OF AZOPT EFFICACY BY THE INVESTIGATOR – M-ITT SET ........................ 135 
TABLE 4.135 – GLOBAL ASSESSMENT OF AZOPT EFFICACY BY THE INVESTIGATOR – PP SET .............................. 135 
TABLE 4.136 – GLOBAL ASSESSMENT OF EFFICACY BY THE INVESTIGATOR – M-ITT SET .................................... 136 
TABLE 4.137 – GLOBAL ASSESSMENT OF EFFICACY BY THE INVESTIGATOR – PP SET .......................................... 136 
 
5 Safety analyses 
TABLE 5.1 – CONJUNCTIVAL HYPERAEMIA USING SLIT LAMP EXAMINATION – WORSE EYE – SAFETY SET .......... 137 
TABLE 5.2 – CONJUNCTIVAL HYPERAEMIA USING SLIT LAMP EXAMINATION – CHANGE FROM BASELINE (IN 
CLASSES) – WORSE EYE – SAFETY SET .................................................................................... 138 
TABLE 5.3 – CONJUNCTIVAL HYPERAEMIA USING SLIT LAMP EXAMINATION – CONTRALATERAL EYE – SAFETY SET
 ................................................................................................................................................ 139 
TABLE 5.4 – CONJUNCTIVAL HYPERAEMIA USING SLIT LAMP EXAMINATION – CHANGE FROM BASELINE (IN 
CLASSES) – CONTRALATERAL EYE – SAFETY SET .................................................................... 139 
TABLE 5.5 – SUBJECTIVE OCULAR SYMPTOMS THROUGHOUT THE DAY – SYMPTOM (*) – SAFETY SET ................. 140 
TABLE 5.6 – TOTAL SCORE OF SUBJECTIVE OCULAR SYMPTOMS THROUGHOUT THE DAY – SAFETY SET .............. 141 
TABLE 5.7 – ANALYSIS OF THE CHANGE FROM BASELINE IN TOTAL SCORE OF SUBJECTIVE OCULAR SYMPTOMS 
THROUGHOUT THE DAY – MMRM ANALYSIS– SAFETY SET .................................................... 142 
LISTING 5.1 – LISTING OF DATA RELATIVE TO OTHER OCULAR SYMPTOMS THROUGHOUT THE DAY – SAFETY SET
 ................................................................................................................................................ 143 
TABLE 5.8 – SUBJECTIVE OCULAR SYMPTOMS UPON INSTILLATION – SYMPTOM (*) – SAFETY SET ...................... 144 
TABLE 5.9 – TOTAL SCORE OF SUBJECTIVE OCULAR SYMPTOMS UPON INSTILLATION – SAFETY SET ................... 145 
TABLE 5.10 – ANALYSIS OF TOTAL SCORE OF SUBJECTIVE OCULAR SYMPTOMS UPON INSTILLATION AT WEEK 6 - 
MMRM ANALYSIS – SAFETY SET ............................................................................................ 146 
LISTING 5.2 – LISTING OF DATA RELATIVE TO OTHER OCULAR SYMPTOMS UPON INSTILLATION – SAFETY SET ... 147 
TABLE 5.11 – OCULAR SIGNS USING SLIT LAMP EXAMINATION - SIGN (*) – WORSE EYE – SAFETY SET ............... 148 
TABLE 5.12 – OCULAR SIGNS USING SLIT LAMP EXAMINATION - SIGN (*) – CONTRALATERAL EYE – SAFETY SET
 ................................................................................................................................................ 148 
LISTING 5.3 – LISTING OF DATA RELATIVE TO OTHER OCULAR ABNORMALITIES – SAFETY SET ........................... 149 
TABLE 5.13 – CORNEAL STAINING ACCORDING TO OXFORD GRADING SCHEME – WORSE EYE – SAFETY SET ...... 150 
TABLE 5.14 – CORNEAL STAINING ACCORDING TO OXFORD GRADING SCHEME – CONTRALATERAL EYE – SAFETY 
SET .......................................................................................................................................... 150 
TABLE 5.15 – FAR BEST CORRECTED VISUAL ACUITY – WORSE EYE – SAFETY SET ............................................. 151 
TABLE 5.16 – FAR BEST CORRECTED VISUAL ACUITY – CONTRALATERAL EYE – SAFETY SET ............................. 151 
TABLE 5.17 – AZOPT OCULAR TOLERANCE BY THE INVESTIGATOR – AZOPT SAFETY SET ................................... 152 
TABLE 5.18 – AZOPT OCULAR TOLERANCE BY THE PATIENT – AZOPT SAFETY SET ............................................. 152 
TABLE 5.19 – T4032 OR LUMIGAN OCULAR TOLERANCE BY THE INVESTIGATOR – SAFETY SET ......................... 153 
TABLE 5.20 – T4032 OR LUMIGAN OCULAR TOLERANCE BY THE PATIENT – SAFETY SET ................................... 153 
TABLE 5.21 – OVERVIEW OF OCULAR TREATMENT-EMERGENT ADVERSE EVENTS FOR AZOPT – AZOPT SAFETY SET
 ................................................................................................................................................ 154 
TABLE 5.22 – OVERVIEW OF OCULAR TREATMENT-EMERGENT ADVERSE EVENTS FOR T4032 OR LUMIGAN – 
SAFETY SET ............................................................................................................................. 154 
TABLE 5.23 – SUMMARY OF TREATMENT-EMERGENT OCULAR AES FOR AZOPT PER SOC AND PT – AZOPT SAFETY 
SET .......................................................................................................................................... 155 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Admendment V01 
20APR2021 
Page 55/163 
 
 
 
 
 
TABLE 5.24 – SUMMARY OF TREATMENT-EMERGENT OCULAR SAES FOR AZOPT PER SOC AND PT – AZOPT 
SAFETY SET ............................................................................................................................. 155 
TABLE 5.25 – SUMMARY OF TREATMENT-EMERGENT OCULAR IMP-RELATED AES FOR AZOPT PER SOC AND PT – 
AZOPT SAFETY SET ................................................................................................................. 155 
TABLE 5.26 – SUMMARY OF TREATMENT-EMERGENT OCULAR AES FOR AZOPT LEADING TO PREMATURE IMP 
DRUG WITHDRAWAL PER SOC AND PT – AZOPT SAFETY SET.................................................. 155 
TABLE 5.27 – SUMMARY OF TREATMENT-EMERGENT OCULAR AES FOR LT4032 OR LUMIGAN PER SOC AND PT – 
SAFETY SET ............................................................................................................................. 156 
TABLE 5.28 – SUMMARY OF TREATMENT-EMERGENT OCULAR SAES FOR LT4032 OR LUMIGAN PER SOC AND PT 
– SAFETY SET .......................................................................................................................... 156 
TABLE 5.29 – SUMMARY OF TREATMENT-EMERGENT OCULAR IMP-RELATED AES FOR LT4032 OR LUMIGAN PER 
SOC AND PT – SAFETY SET..................................................................................................... 156 
TABLE 5.30 – SUMMARY OF TREATMENT-EMERGENT OCULAR IMP-RELATED SAES FOR LT4032 OR LUMIGAN PER 
SOC AND PT – SAFETY SET..................................................................................................... 156 
TABLE 5.31 – SUMMARY OF TREATMENT-EMERGENT OCULAR AES FOR LT4032 OR LUMIGAN LEADING TO 
PREMATURE IMP DRUG WITHDRAWAL PER SOC AND PT – SAFETY SET ................................. 156 
TABLE 5.32 – SUMMARY OF TREATMENT-EMERGENT OCULAR AES FOR LT4032 OR LUMIGAN PER SOC, PT AND 
SEVERITY – SAFETY SET .......................................................................................................... 157 
TABLE 5.33 – SUMMARY OF TREATMENT-EMERGENT OCULAR AES FOR LT4032 OR LUMIGAN PER SOC, PT AND 
RELATIONSHIP WITH THE IMP – SAFETY SET ........................................................................... 158 
TABLE 5.34 – SUMMARY OF TREATMENT-EMERGENT OCULAR AES FOR T4032 GROUPBY SOC, PT AND MAXIMAL 
SEVERITY  – SAFETY SET ......................................................................................................... 159 
TABLE 5.36 – SUMMARY OF TREATMENT-EMERGENT OCULAR AES FOR T4032 PER SOC, PT AND STRONGEST 
RELATIONSHIP –SAFETY SET ................................................................................................... 160 
TABLE 5.37 – SUMMARY OF TREATMENT-EMERGENT OCULAR AES FOR LUMIGAN PER SOC, PT AND STRONGEST 
RELATIONSHIP –SAFETY SET ................................................................................................... 160 
TABLE 5.38 – OVERVIEW OF SYSTEMIC TREATMENT-EMERGENT ADVERSE EVENTS FOR AZOPT – AZOPT SAFETY 
SET .......................................................................................................................................... 161 
TABLE 5.39 – OVERVIEW OF SYSTEMIC TREATMENT-EMERGENT ADVERSE EVENTS FOR LT4032 OR LUMIGAN –  
SAFETY SET ............................................................................................................................. 161 
TABLE 5.40 – SUMMARY OF TREATMENT-EMERGENT SYSTEMIC AES FOR AZOPT PER SOC AND PT – AZOPT 
SAFETY SET ............................................................................................................................. 161 
TABLE 5.41 – SUMMARY OF TREATMENT-EMERGENT SYSTEMIC SAES FOR AZOPT PER SOC AND PT –  AZOPT 
SAFETY SET ............................................................................................................................. 161 
TABLE 5.42 – SUMMARY OF TREATMENT-EMERGENT SYSTEMIC IMP-RELATED AES FOR AZOPT PER SOC AND PT 
– AZOPT SAFETY SET ............................................................................................................... 161 
TABLE 5.43 – SUMMARY OF TREATMENT-EMERGENT SYSTEMIC AES FOR AZOPT LEADING TO PREMATURE IMP 
DRUG WITHDRAWAL PER SOC AND PT – AZOPT SAFETY SET.................................................. 161 
TABLE 5.44 – SUMMARY OF TREATMENT-EMERGENT SYSTEMIC AES FOR LT4032 OR LUMIGAN PER SOC AND PT 
– SAFETY SET .......................................................................................................................... 161 
TABLE 5.45 – SUMMARY OF TREATMENT-EMERGENT SYSTEMIC SAES FOR LT4032 OR LUMIGAN PER SOC AND 
PT – SAFETY SET ..................................................................................................................... 161 
TABLE 5.46 – SUMMARY OF TREATMENT-EMERGENT SYSTEMIC IMP-RELATED AES FOR LT4032 OR LUMIGAN PER 
SOC AND PT – SAFETY SET..................................................................................................... 161 
TABLE 5.47 – SUMMARY OF TREATMENT-EMERGENT SYSTEMIC IMP-RELATED SAES FOR LT4032 OR LUMIGAN 
PER SOC AND PT – SAFETY SET .............................................................................................. 161 
TABLE 5. 48 – SUMMARY OF TREATMENT-EMERGENT SYSTEMIC AES FOR LT4032 OR LUMIGAN LEADING TO 
PREMATURE STUDY DRUG WITHDRAWAL PER SOC AND PT – SAFETY SET .............................. 161 
TABLE 5.49 – SUMMARY OF TREATMENT-EMERGENT SYSTEMIC AES FOR LT4032 OR LUMIGAN PER SOC, PT AND 
SEVERITY – SAFETY SET .......................................................................................................... 161 
TABLE 5.50 – SUMMARY OF TREATMENT-EMERGENT SYSTEMIC AES FOR LT4032 OR LUMIGAN PER SOC, PT AND 
RELATIONSHIP WITH THE IMP – SAFETY SET ........................................................................... 161 
TABLE 5.51 – SUMMARY OF TREATMENT-EMERGENT SYSTEMIC AES FOR T4032 PER SOC, PT AND MAXIMAL 
SEVERITY –SAFETY SET ........................................................................................................... 161 
TABLE 5.52 – SUMMARY OF TREATMENT-EMERGENT SYSTEMIC AES FOR LUMIGAN PER SOC, PT AND MAXIMAL 
SEVERITY –SAFETY SET ........................................................................................................... 161 
TABLE 5.53 – SUMMARY OF TREATMENT-EMERGENT SYSTEMIC AES FOR T4032 PER SOC, PT AND STRONGEST 
RELATIONSHIP –SAFETY SET ................................................................................................... 161 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Admendment V01 
20APR2021 
Page 56/163 
 
 
 
 
 
TABLE 5.54 – SUMMARY OF TREATMENT-EMERGENT SYSTEMIC AES FOR LUMIGAN PER SOC, PT AND STRONGEST 
RELATIONSHIP –SAFETY SET ................................................................................................... 161 
TABLE 5.55 – SUMMARY OF TREATMENT-EMERGENT NON-SERIOUS AES FOR LT4032 OR LUMIGAN PER SOC AND 
PT – SAFETY SET ..................................................................................................................... 161 
TABLE 5.56 – SUMMARY OF TREATMENT-EMERGENT NON-SERIOUS AES FOR LT4032 OR LUMIGAN PER SOC AND 
PT WITH PT IS ≥5% FOR ONE GROUP – SAFETY SET................................................................. 161 
LISTING 5.6 – LISTING OF NON EMERGENT AES – ENROLLED PATIENTS ............................................................. 162 
LISTING 5.7 – LISTING OF TREATMENT-EMERGENT AES FOR AZOPT – AZOPT SAFETY SET ................................. 162 
LISTING 5.8 – LISTING OF TREATMENT-EMERGENT SAES FOR AZOPT – AZOPT SAFETY SET .............................. 162 
LISTING 5.9 – LISTING OF TREATMENT-EMERGENT IMP-RELATED AES FOR AZOPT – AZOPT SAFETY SET ......... 162 
LISTING 5.10 – LISTING OF TREATMENT-EMERGENT SYSTEMIC AES FOR AZOPT LEADING TO PREMATURE IMP 
DRUG WITHDRAWAL – AZOPT SAFETY SET ............................................................................. 162 
LISTING 5.11 – LISTING OF TREATMENT-EMERGENT AES FOR T4032 OR LUMIGAN – SAFETY SET ..................... 162 
LISTING 5.12 – LISTING OF TREATMENT-EMERGENT SAES FOR T4032 OR LUMIGAN – SAFETY SET ................... 162 
LISTING 5.13 – LISTING OF TREATMENT-EMERGENT IMP-RELATED AES FOR T4032 OR LUMIGAN – SAFETY SET
 ................................................................................................................................................ 162 
LISTING 5.14 – LISTING OF TREATMENT-EMERGENT SYSTEMIC AES FOR T4032 OR LUMIGAN LEADING TO 
PREMATURE IMP DRUG WITHDRAWAL – SAFETY SET ............................................................. 162 
LISTING 5.15 – LISTING OF AES FOR T4032 OR LUMIGAN OCCUR AFTER THE DAY OF THE MAXIMAL DATE 
BETWEEN LAST IMP INSTILLATION AND VISIT 4 (WEEK 12) –SAFETY SET ............................. 162 
LISTING 5.16 – LISTINGS OF COVID-19 AES – ENROLLED PATIENTS ................................................................. 163 
LISTING 5.17 – LISTINGS OF DEATHS, OTHER SERIOUS ADVERSE EVENTS, DISCONTINUATIONS DUE TO ADVERSE 
EVENTS AND OTHER ADVERSE EVENTS OF SPECIAL INTEREST (FOR NARRATIVES)– ENROLLED 
PATIENTS ................................................................................................................................. 163 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 57/163 
 
 
 
 
 
 
 
 
 
1. Disposition of patients 
 
Study: LT4032-301  
Page X / N 
Population: Enrolled patients 
 
Table 1.1 – Number of patients in each analysis set – Enrolled patients 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Total 
(N=XX) 
Enrolled patients 
 
 
xx 
 
 
 
 
Azopt Safety set 
 
 
xx (xx.x%) 
Safety set 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
Intent-To-Treat set (ITT set) 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
m-ITT set 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
Per-protocol set (PP set) 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: Enrolled patients 
 
Table 1.2 – Number of patients in each analysis set – With possible impact of COVID-19 pandemic – 
Enrolled patients 
Same as Table 1.1 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: Enrolled patients 
 
Table 1.3 – Number of patients in each analysis set – Without possible impact of COVID-19 pandemic – 
Enrolled patients 
Same as Table 1.1 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 58/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Enrolled patients 
 
Listing 1.1 – Disposition of patients – Enrolled patients 
 
Planned 
group 
Actual 
group 
Patient 
number 
Worse 
Eye 
Possible impact 
of COVID-19 
pandemic 
 
Azopt 
Safety set 
Safety 
set 
ITT Set m-ITT Set PP Set 
 
 
 
 
 
 
 
 
 
 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 


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Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 59/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301 
Page X / N 
Population: Enrolled patients 
 
Table 1.4 – Number of enrolled patients by country – Enrolled patients 
 
 
Total 
(N=XX) 
Belgium 
xx (xx.x%) 
Canada 
xx (xx.x%) 
Czech Republic 
xx (xx.x%) 
Estonia 
xx (xx.x%) 
France 
xx (xx.x%) 
Germany 
xx (xx.x%) 
Greece 
xx (xx.x%) 
Italy 
xx (xx.x%) 
Latvia 
xx (xx.x%) 
Lithuania 
xx (xx.x%) 
Mauritius 
xx (xx.x%) 
Poland 
xx (xx.x%) 
Russian  
xx (xx.x%) 
Slovakia 
xx (xx.x%) 
Spain 
xx (xx.x%) 
Ukraine 
xx (xx.x%) 
United Kingdom 
xx (xx.x%) 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: Azopt Safety Set 
 
Table 1.5 – Number of patients by country – Azopt Safety Set 
Same as Table 1.4 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 60/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 1.6 – Number of patients by country – Safety set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Total 
(N=XX) 
Belgium 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
Canada 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
Czech Republic 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
Estonia 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
France 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
Germany 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
Greece 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
Italy 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
Latvia 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
Lithuania 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
Mauritius 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
Poland 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
Russian  
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
Slovakia 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
Spain 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
Ukraine 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
United Kingdom 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 1.7 – Number of patients by country – For patients who prematurely discontinued the study for 
COVID-19 crisis – Safety set 
Same as Table 1.6 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 61/163 
 
 
 
 
 
 
 
 
 
  
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 1.8 – Number of patients by country – With possible impact of COVID-19 pandemic – Safety set 
Same as Table 1.6 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 1.9 – Number of patients by country – Without possible impact of COVID-19 pandemic – Safety set 
Same as Table 1.6 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: ITT set 
 
Table 1.10 – Number of patients by country – ITT set 
Same as Table 1.6 (if the ITT set differs from the Safety set) 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 1.11 – Number of patients by country – m-ITT set 
Same as Table 1.6 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: PP set 
 
Table 1.12 – Number of patients by country – PP set 
Same as Table 1.6 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 62/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 1.13 – Number of patients at each visit as considered in the analysis – Safety set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Total 
(N=XX) 
Visit 1 - Screening visit – Day -42 or Day-49* 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
Visit 2 - Randomisation visit – Day 1 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
Visit 3 - Day 42 - Week 6 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
Visit 4 - Day 84 - Week 12 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
Follow-up phone call - Day 112 - Week 16 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
*Respectively before or after Clinical Study Protocol amendment 1 - 05JUL2019 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 1.14 – Number of patients at each visit as considered in the analysis – With possible impact of 
COVID-19 pandemic – Safety set 
Same as Table 1.13 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 1.15 – Number of patients at each visit as considered in the analysis – Without possible impact of 
COVID-19 pandemic – Safety set 
Same as Table 1.13 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 63/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: ITT set 
 
Table 1.16 – Number of patients at each visit as considered in the analysis – ITT set 
Same as Table 1.13 (if the ITT set differs from the Safety set) 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: ITT set 
 
Table 1.17 – Number of patients at each visit as considered in the analysis – With possible impact of 
COVID-19 pandemic – ITT set 
Same as Table 1.13 (if the ITT set differs from the Safety set) 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: ITT set 
 
Table 1.18 – Number of patients at each visit as considered in the analysis – Without possible impact of 
COVID-19 pandemic – ITT set 
Same as Table 1.13 (if the ITT set differs from the Safety set) 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 1.19 – Number of patients at each visit as considered in the analysis – m-ITT set 
Same as Table 1.13 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 1.20 – Number of patients at each visit as considered in the analysis – With possible impact of 
COVID-19 pandemic – m-ITT set 
Same as Table 1.13 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 64/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 1.21 – Number of patients at each visit as considered in the analysis – Without possible impact of 
COVID-19 pandemic – m-ITT set 
Same as Table 1.13 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 1.22 – Number of patients at each visit as considered in the analysis – PP set 
Same as Table 1.13 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 1.23 – Number of patients at each visit as considered in the analysis – With possible impact of 
COVID-19 pandemic – PP set 
Same as Table 1.13 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 1.24 – Number of patients at each visit as considered in the analysis – Without possible impact of 
COVID-19 pandemic – PP set 
Same as Table 1.13 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 65/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety Set 
 
Listing 1.2 – Visit as considered in the analysis – Safety set 
 
Planned 
group 
Actual 
group 
Patient 
number 
Possible impact 
of COVID-19 
pandemic 
Visit 
 
Date of 
Visit 
Time interval 
between Visit 
and Day 1 
(days)* 
Last 
instillation 
date 
Analysis Visit 
 
 
 
 
 
 
 
 
 
Visit xx 
*Time interval = Date of Visit – Date of randomization visit 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 66/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 1.25 – Premature study discontinuation – Safety set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Total 
(N=XX) 
Has the patient completed the study? 
 
 
 
   n 
xx 
xx 
xx 
  Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   95% CI (Yes) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   95% CI (No) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   Missing data 
xx 
xx 
xx 
 
 
 
 
If yes, country 
 
 
 
   n 
xx 
xx 
xx 
   Belgium 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Canada 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   … 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Missing data 
xx 
xx 
xx 
 
 
 
 
Reason for discontinuation 
 
 
 
   n 
xx 
xx 
xx 
 Screen failure 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 Adverse event 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 Lack of efficacy 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 Patient’s request 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 Lost to follow-up 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 COVID-19 crisis 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Missing data 
xx 
xx 
xx 
 
 
 
 
If COVID-19 crisis, country 
 
 
 
   n 
xx 
xx 
xx 
   Belgium 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Canada 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   … 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Missing data 
xx 
xx 
xx 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 67/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: ITT set 
 
Table 1.26 – Premature study discontinuation – ITT set 
Same as Table 1.25 (if the ITT set differs from the Safety set) 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 1.27 – Premature study discontinuation – m-ITT set 
Same as Table 1.25 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 


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Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 68/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Listing 1.3 – Listing of premature study discontinuations – Safety set 
 
Planned 
group 
Actual 
group 
Patient 
number 
Possible impact of 
COVID-19 
pandemic  
Safety set ITT Set mITT Set 
Date of 
discontinuation 
Primary reason 
for 
discontinuation 
Detail regarding 
reason for 
discontinuation 
 
 
 
 
 
 
 
 
 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 69/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 1.28 – Protocol deviations – m-ITT set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
 
Total 
(N=XX) 
At least one major deviation 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
 Deviation 1 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
 Deviation 2 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
 … 
 
 
 
 
 
 
 
 
 
At least one minor deviation* 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
 Deviation 1 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
 Deviation 2 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
 … 
 
 
 
 
 
 
 
 
 
Only minor deviation 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
 Deviation 1 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
 Deviation 2 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
 … 
 
 
 
 
* includes major deviations 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 1.29 – Protocol deviations – With possible impact of COVID-19 pandemic – m-ITT set 
Same as Table 1.28 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 1.30 – Protocol deviations – Without possible impact of COVID-19 pandemic – m-ITT set 
Same as Table 1.28 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 


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Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 70/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Listing 1.4 – Listing of protocol deviations – m-ITT set 
 
Planned 
group 
Actual 
group 
Patient 
number 
Possible impact 
of COVID-19 
pandemic 
Deviation 
number 
Class of 
deviation 
Deviation term 
Description 
 
 
 
 
 
 
 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 71/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Enrolled patients 
 
Listing 1.5 – Listing of patients excluded from Azopt Safety, Safety, ITT, m-ITT, and PP sets – Enrolled 
patients 
 
Planned 
group 
Actual 
group 
Patient 
number 
Azopt Safety set 
Safety set 
ITT set m-ITT 
set 
PP Set 
Reason for exclusion 
for ITT, m-ITT and/or 
PP sets 
Patient in 
Azopt 
Safety set 
Reason 
for 
exclusion 
Patient in 
Safety set 
Reason for 
exclusion 
 
 
 
 
 
 
 
Yes / No 
 
Yes / No 
 
Yes/No Yes/No Yes/No 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 72/163 
 
 
 
 
 
 
 
 
 
2. Demographics and baseline characteristics 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 2.1 – Demographic characteristics – m-ITT set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Total 
(N=XX) 
Age (years) 
 
 
 
   n 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
   95% CI (mean) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   Median 
xx.x 
xx.x 
xx.x 
   Q1 ; Q3 
xx.x 
xx.x 
xx.x 
   Min. ; Max. 
xx ; xx 
xx ; xx 
xx ; xx 
   Missing data 
xx 
xx 
xx 
 
 
 
 
Age (years) in classes 
 
 
 
   n 
xx 
xx 
xx 
   < 65 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   95% CI (< 65) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   >= 65 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   95% CI (>= 65) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   Missing data 
xx 
xx 
xx 
 
 
 
 
Gender 
 
 
 
   n 
xx 
xx 
xx 
   Female 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   95% CI (Female) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   Male 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   95% CI (Male) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   Missing data 
xx 
xx 
xx 
 
 
 
 
Gender of patients <65 years old 
 
 
 
   n 
xx 
xx 
xx 
   Female 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   95% CI (Female) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   Male 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   95% CI (Male) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   Missing data 
xx 
xx 
xx 
 
 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 73/163 
 
 
 
 
 
 
 
 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Total 
(N=XX) 
Gender of patients >=65 years old 
 
 
 
   n 
xx 
xx 
xx 
   Female 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   95% CI (Female) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   Male 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   95% CI (Male) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   Missing data 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 74/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 2.2 – Ocular medical history other than the studied disease by SOC and PT – m-ITT set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Total 
(N=XX) 
Patients having at least one ocular medical history other than the 
studied disease 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
SOC 1 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
     PT 1_1 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
     PT 1_2 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
      … 
 
 
 
SOC 2 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
     PT 2_1 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
      … 
 
 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 75/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 2.3 – Ocular surgical history related to another disease than the studied one by SOC and PT – m-
ITT set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Total 
(N=XX) 
Patients having at least one ocular surgical history related to 
another disease than the studied one 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
SOC 1 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
     PT 1_1 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
     PT 1_2 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
      … 
 
 
 
SOC 2 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
     PT 2_1 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
      … 
 
 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 2.4 – Systemic medical history by SOC and PT – m-ITT set 
Same as Table 2.2 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 2.5 – Systemic surgical history by SOC and PT – m-ITT set 
Same as Table 2.3 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 76/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 2.6 – Previous ocular treatments by WHO-Drug ATC2 and ATC4 – m-ITT set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Total 
(N=XX) 
Any previous ocular treatment 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
ATC class 2_1 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
   ATC class 4_1_1 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
   ATC class 4_1_2 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
   … 
 
 
 
ATC class 2_2 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
   ATC class 4_2_1 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
   ATC class 4_2_2 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
   … 
 
 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 2.7 – Concomitant ocular treatments by WHO-Drug ATC2 and ATC4 – m-ITT set 
Same as Table 2.6 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 2.8 – Previous non-ocular treatments by WHO-Drug ATC2 and ATC4 – m-ITT set 
Same as Table 2.6 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 2.9 – Concomitant non-ocular treatments by WHO-Drug ATC2 and ATC4 – m-ITT set 
Same as Table 2.6 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 77/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 2.10 – History of glaucoma or ocular hypertension – Diagnosis – Worse eye – m-ITT set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Total 
(N=XX) 
Diagnosis 
 
 
 
   n 
xx 
xx 
xx 
   Ocular hypertension 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   95% CI (Ocular hypertension) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   Primary open angle glaucoma 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   95% CI (Primary open angle glaucoma) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   Secondary 
open 
angle 
glaucoma: 
Exfoliation 
Glaucoma 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   95% CI (Secondary open angle glaucoma: Exfoliation 
Glaucoma) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   Secondary 
open angle glaucoma: Pigmentary 
Glaucoma 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   95% 
CI 
(Secondary 
open 
angle 
glaucoma: 
Pigmentary Glaucoma) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   Missing data 
xx 
xx 
xx 
 
 
 
 
Time between diagnosis (months) and randomisation 
visit 
 
 
 
      n 
xx 
xx 
xx 
      Mean (SD) 
xx.x (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
      95% CI (mean) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
      Median 
xx.x 
xx.x 
xx.x 
      Q1 ; Q3 
xx.x 
xx.x 
xx.x 
      Min. ; Max. 
xx ; xx 
xx ; xx 
xx ; xx 
      Missing data 
xx 
xx 
xx 
 
 
 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 2.11 – History of glaucoma or ocular hypertension – Diagnosis – Contralateral eye – m-ITT set 
Same as Table 2.10 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 78/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 2.12 – History of glaucoma or ocular hypertension – Previous treatment – m-ITT set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Total 
(N=XX) 
Previous treatment 
 
 
 
   n 
xx 
xx 
xx 
   Bimatoprost 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   95% CI (Bimatoprost) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   Latanoprost 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   95% CI (Latanoprost) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   Tafluprost 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   95% CI (Tafluprost) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   Travoprost 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   95% CI (Travoprost) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   95% CI (Other) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   Missing data 
xx 
xx 
xx 
 
 
 
 
 Treated for at least 6 months 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 79/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 2.13 – Surgical history of glaucoma and ocular hypertension by system organ class and preferred 
term – Worse eye - m-ITT set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Total 
(N=XX) 
Patients having at least one surgical history related to the studied 
disease 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
SOC 1 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
     PT 1_1 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
     PT 1_2 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
      … 
 
 
 
SOC 2 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
     PT 2_1 
xx (xx.x%) xx (xx.x%) xx (xx.x%) 
      … 
 
 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 2.14  – Surgical history of glaucoma and ocular hypertension by system organ class and preferred 
term – Contralateral eye - m-ITT set 
Same as Table 2.13 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 80/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 2.15 – Automated visual field at screening visit – Worse eye – m-ITT set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Total 
(N=XX) 
Result 
 
 
 
      n 
xx 
xx 
xx 
      Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      95% CI (Normal) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
      Abnormal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      95% CI (Abnormal) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
      Missing data 
xx 
xx 
xx 
 
 
 
 
If abnormal, clinically significant 
 
 
 
      n 
xx 
xx 
xx 
      Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      95% CI (Yes) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
      No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      95% CI (No) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
      Missing data 
xx 
xx 
xx 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 2.16 – Automated visual field at screening visit – Contralateral eye – m-ITT set 
Same as Table 2.15 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 81/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 2.17 – Central corneal thickness measurement (µm) at screening visit – Worse eye – m-ITT set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Total 
(N=XX) 
Corneal thickness 
measurement (µm) 
 
 
 
   n 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
   95% CI (mean) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   Median 
xx.x 
xx.x 
xx.x 
   Q1 ; Q3 
xx.x 
xx.x 
xx.x 
   Min. ; Max. 
xx ; xx 
xx ; xx 
xx ; xx 
   Missing data 
xx 
xx 
xx 
 
 
 
 
Corneal thickness 
measurement (µm) in classes 
 
 
 
   n 
xx 
xx 
xx 
   < 555 µm 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   95% CI (< 555 µm) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   >= 555 µm 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   95% CI (>= 555 µm) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   Missing data 
xx 
xx 
xx 
 
 
 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 2.18 – Central corneal thickness measurement (µm) at screening visit – Contralateral eye –  
m-ITT set 
Same as Table 2.17 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 82/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 2.19 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 – Worse eye –  
m-ITT set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Total 
(N=XX) 
Screening 
 
 
 
   n 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
   95% CI (mean) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   Median 
xx.x 
xx.x 
xx.x 
   Q1 ; Q3 
xx.x 
xx.x 
xx.x 
   Median 
xx.x 
xx.x 
xx.x 
   Min. ; Max. 
xx ; xx 
xx ; xx 
xx ; xx 
   Missing data 
xx 
xx 
xx 
 
 
 
 
Randomisation – Day 1 
 
 
 
   n 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
   95% CI (mean) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   Median 
xx.x 
xx.x 
xx.x 
   Q1 ; Q3 
xx.x 
xx.x 
xx.x 
   Median 
xx.x 
xx.x 
xx.x 
   Min. ; Max. 
xx ; xx 
xx ; xx 
xx ; xx 
   Missing data 
xx 
xx 
xx 
 
 
 
 
Change from screening to randomisation – Day 1 
 
 
 
   n 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
   95% CI (mean) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   Median 
xx.x 
xx.x 
xx.x 
   Q1 ; Q3 
xx.x 
xx.x 
xx.x 
   Median 
xx.x 
xx.x 
xx.x 
   Min. ; Max. 
xx ; xx 
xx ; xx 
xx ; xx 
   Missing data 
xx 
xx 
xx 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 2.20 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 –  
Wash-out duration <= 8 days – Worse eye – m-ITT set 
Same as Table 2.19 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 83/163 
 
 
 
 
 
 
 
 
 
Date and time program was run: JJMMMYYYY HH:MM 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 2.21 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 –  
Wash-out duration > 8 days – Worse eye – m-ITT set 
Same as Table 2.19 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 2.22 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 – Contralateral eye –  
m-ITT set 
Same as Table 2.19 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 2.23 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 –  
Wash-out duration <= 8 days – Contralateral eye – m-ITT set 
Same as Table 2.19 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 2.24 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 –  
Wash-out duration > 8 days – Contralateral eye – m-ITT set 
Same as Table 2.19 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 84/163 
 
 
 
 
 
 
 
 
 
Following Tables related to Demographics and Baseline Characteristics will be repeated on the m-ITT set 
according to the possible impact of COVID-19 pandemic classes: 
 
Table 2.25 – Demographic characteristics –With possible impact of COVID-19 pandemic – m-ITT set 
Table 2.26 – History of glaucoma or ocular hypertension – Diagnosis – Worse eye – With possible impact 
of COVID-19 pandemic – m-ITT set 
Table 2.27 – History of glaucoma or ocular hypertension – Diagnosis – Contralateral eye – With possible 
impact of COVID-19 pandemic – m-ITT set 
Table 2.28 – History of glaucoma or ocular hypertension – Previous treatment – With possible impact of 
COVID-19 pandemic – m-ITT set 
Table 2.29 – Surgical history of glaucoma and ocular hypertension by system organ class and preferred 
term – Worse Eye – With possible impact of COVID-19 pandemic – m-ITT set 
Table 2.30 – Surgical history of glaucoma and ocular hypertension by system organ class and preferred 
term – Contralateral Eye – With possible impact of COVID-19 pandemic – m-ITT set 
Table 2.31 – Automated visual field at screening visit – Worse eye – With possible impact of COVID-19 
pandemic – m-ITT set 
Table 2.32 – Automated visual field at screening visit – Contralateral eye – With possible impact of 
COVID-19 pandemic – m-ITT set 
Table 2.33 – Central corneal thickness measurement (µm) at screening visit – Worse eye – With possible 
impact of COVID-19 pandemic – m-ITT set 
Table 2.34 – Central corneal thickness measurement (µm) at screening visit – Contralateral eye – With 
possible impact of COVID-19 pandemic – m-ITT set 
Table 2.35 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 – Worse eye – With 
possible impact of COVID-19 pandemic – m-ITT set 
Table 2.36 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 – Contralateral eye – 
With possible impact of COVID-19 pandemic – m-ITT set 
 
Table 2.37 – Demographic characteristics –Without possible impact of COVID-19 pandemic – m-ITT set 
Table 2.38 – History of glaucoma or ocular hypertension – Diagnosis – Worse eye – Without possible 
impact of COVID-19 pandemic – m-ITT set 
Table 2.39 – History of glaucoma or ocular hypertension – Diagnosis – Contralateral eye – Without 
possible impact of COVID-19 pandemic – m-ITT set 
Table 2.40 – History of glaucoma or ocular hypertension – Previous treatment – Without possible impact 
of COVID-19 pandemic – m-ITT set 
Table 2.41 – Surgical history of glaucoma and ocular hypertension by system organ class and preferred 
term – Worse Eye – Without possible impact of COVID-19 pandemic – m-ITT set 
Table 2.42 – Surgical history of glaucoma and ocular hypertension by system organ class and preferred 
term – Contralateral Eye – Without possible impact of COVID-19 pandemic – m-ITT set 
Table 2.43 – Automated visual field at screening visit – Worse eye – Without possible impact of COVID-
19 pandemic – m-ITT set 
Table 2.44 – Automated visual field at screening visit – Contralateral eye – Without possible impact of 
COVID-19 pandemic – m-ITT set 
Table 2.45 – Central corneal thickness measurement (µm) at screening visit – Worse eye – Without 
possible impact of COVID-19 pandemic – m-ITT set 
Table 2.46 – Central corneal thickness measurement (µm) at screening visit – Contralateral eye – Without 
possible impact of COVID-19 pandemic – m-ITT set 
Table 2.47 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 – Worse eye – 
Without possible impact of COVID-19 pandemic – m-ITT set 
Table 2.48 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 – Contralateral eye – 
Without possible impact of COVID-19 pandemic – m-ITT set 
 
Same as Table 2.1 to 2.24 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 85/163 
 
 
 
 
 
 
 
 
 
All Tables related to Demographics and Baseline Characteristics will be repeated on the Safety set: 
 
Table 2.49 – Demographic characteristics – Safety Set 
Table 2.50 – Ocular medical history other than the studied disease by system organ class and preferred 
term– Safety set 
Table 2.51 – Ocular surgical history related to another disease than the studied one by system organ class 
and preferred term – Safety set 
Table 2.52 – Systemic medical history by system organ class and preferred term – Safety set 
Table 2.53 – Systemic surgical history by system organ class and preferred term – Safety set 
Table 2.54 – Previous ocular treatments by WHO-Drug ATC2 and ATC4 – Safety set 
Table 2.55 – Concomitant ocular treatments by WHO-Drug ATC2 and ATC4 – Safety set 
Table 2.56 – Previous non-ocular treatments by WHO-Drug ATC2 and ATC4 – Safety set 
Table 2.57 – Concomitant non-ocular treatments by WHO-Drug ATC2 and ATC4 – Safety set 
Table 2.58 – History of glaucoma or ocular hypertension – Diagnosis – Worse eye – Safety set 
Table 2.59 – History of glaucoma or ocular hypertension – Diagnosis – Contralateral eye - Safety set 
Table 2.60 – History of glaucoma or ocular hypertension – Previous treatment – Safety set 
Table 2.61 – Surgical history of glaucoma and ocular hypertension by system organ class and preferred 
term – Worse Eye – Safety set 
Table 2.62 – Surgical history of glaucoma and ocular hypertension by system organ class and preferred 
term – Contralateral Eye – Safety set 
Table 2.63 – Automated visual field at screening visit – Worse eye – Safety set 
Table 2.64 – Automated visual field at screening visit – Contralateral eye – Safety set 
Table 2.65 – Central corneal thickness measurement (µm) at screening visit – Worse eye – Safety set 
Table 2.66 – Central corneal thickness measurement (µm) at screening visit – Contralateral eye –  
Safety set 
Table 2.67 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 – Worse eye –  
Safety set 
Table 2.68 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 –  
Wash-out duration <= 8 days – Worse eye – Safety set 
Table 2.69 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 –  
Wash-out duration > 8 days – Worse eye – Safety set 
Table 2.70 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 – Contralateral eye – 
Safety set 
Table 2.71 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 –  
Wash-out duration <= 8 days – Contralateral eye – Safety set 
Table 2.72 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 –  
Wash-out duration > 8 days – Contralateral eye – Safety set 
 
Same as Table 2.1 to 2.24 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 86/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Listing 2.1 – Fundus examination at screening visit – Safety set 
 
Planned 
group 
Actual 
group 
Patient 
number 
Possible impact 
of COVID-19 
pandemic 
ITT Set m-ITT Set 
PP Set 
Date of fundus 
examination Abnormality 
Eye 
 
 
 
 
 
 
 
 
 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 87/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 2.73 – Number of Patients and cumulative time of exposure (in days) – Safety set 
T4032 
Lumigan 
 
Patients 
Person time 
Patients 
Person time 
Total person time 
xx 
xx 
xx 
xx 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 2.74 – Number of Patients and cumulative time of exposure (in days) by age group and gender –  
Safety set 
 
Patient 
Person time 
 
T4032 
Lumigan 
T4032 
Lumigan 
Age group 
Male 
Female 
Male 
Female 
Male 
Female 
Male 
Female 
< 65 years 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
>= 65 years and < 75 years 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
>= 75 years and < 85 years 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
Total 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 2.75 – Number of Patients and cumulative time of exposure (in days) by exposure in classes 
 – Safety set 
T4032 
Lumigan 
Duration of exposure 
Patients 
Person time 
Patients 
Person time 
< 1 months 
xx 
xx 
xx 
xx 
>= 1 months and < 3 months 
xx 
xx 
xx 
xx 
>= 3 months 
xx 
xx 
xx 
xx 
Total 
xx 
xx 
xx 
xx 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 88/163 
 
 
 
 
 
 
 
 
 
Following Tables related to Demographics and Baseline Characteristics will be repeated on the Safety set 
for patients who prematurely discontinued the study for COVID-19 crisis: 
 
Table 2.76 – Demographic characteristics –For patients who prematurely discontinued the study for 
COVID-19 crisis – Safety set 
Table 2.77 – History of glaucoma or ocular hypertension – Diagnosis – Worse eye – For patients who 
prematurely discontinued the study for COVID-19 crisis – Safety set 
Table 2.78 – History of glaucoma or ocular hypertension – Diagnosis – Contralateral eye – For patients 
who prematurely discontinued the study for COVID-19 crisis – Safety set 
Table 2.79 – History of glaucoma or ocular hypertension – Previous treatment – For patients who 
prematurely discontinued the study for COVID-19 crisis – Safety set 
Table 2.80 – Surgical history of glaucoma and ocular hypertension by system organ class and preferred 
term – Worse Eye – For patients who prematurely discontinued the study for COVID-19 crisis – Safety 
set 
Table 2.81 – Surgical history of glaucoma and ocular hypertension by system organ class and preferred 
term – Contralateral Eye – For patients who prematurely discontinued the study for COVID-19 crisis – 
Safety set 
Table 2.82 – Automated visual field at screening visit – Worse eye – For patients who prematurely 
discontinued the study for COVID-19 crisis – Safety set 
Table 2.83 – Automated visual field at screening visit – Contralateral eye – For patients who prematurely 
discontinued the study for COVID-19 crisis – Safety set 
Table 2.84 – Central corneal thickness measurement (µm) at screening visit – Worse eye – For patients 
who prematurely discontinued the study for Covid-19 crisis – Safety set 
Table 2.85 – Central corneal thickness measurement (µm) at screening visit – Contralateral eye – For 
patients who prematurely discontinued the study for Covid-19 crisis – Safety set 
Table 2.86 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 – Worse eye – For 
patients who prematurely discontinued the study for COVID-19 crisis – Safety set 
Table 2.87 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 – Contralateral eye – 
For patients who prematurely discontinued the study for COVID-19 crisis – Safety set 
 
Same as Table 2.1 to 2.24 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 89/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 2.88 – Summary of baseline IOP (mmHg) – Worse eye – For patients who prematurely 
discontinued the study for COVID-19 crisis – Safety set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Total 
(N=XX) 
08:00  
 
 
 
   n 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
   95% CI (mean) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   Median 
xx.x 
xx.x 
xx.x 
   Q1 ; Q3 
xx.x 
xx.x 
xx.x 
   Median 
xx.x 
xx.x 
xx.x 
   Min. ; Max. 
xx ; xx 
xx ; xx 
xx ; xx 
   Missing data 
xx 
xx 
xx 
 
 
 
 
10:00 
 
 
 
   n 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
   95% CI (mean) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   Median 
xx.x 
xx.x 
xx.x 
   Q1 ; Q3 
xx.x 
xx.x 
xx.x 
   Median 
xx.x 
xx.x 
xx.x 
   Min. ; Max. 
xx ; xx 
xx ; xx 
xx ; xx 
   Missing data 
xx 
xx 
xx 
 
 
 
 
16:00 
 
 
 
   n 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
   95% CI (mean) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   Median 
xx.x 
xx.x 
xx.x 
   Q1 ; Q3 
xx.x 
xx.x 
xx.x 
   Median 
xx.x 
xx.x 
xx.x 
   Min. ; Max. 
xx ; xx 
xx ; xx 
xx ; xx 
   Missing data 
xx 
xx 
xx 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 2.89 – Summary of baseline IOP (mmHg) – Contralateral eye – For patients who prematurely 
discontinued the study for COVID-19 crisis – Safety set 
Same as Table 2.88 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 90/163 
 
 
 
 
 
 
 
 
 
Date and time program was run: JJMMMYYYY HH:MM 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 91/163 
 
 
 
 
 
 
 
 
 
Following Tables related to Demographics and Baseline Characteristics will be repeated on the Safety set 
according to the possible impact of COVID-19 pandemic classes: 
 
Table 2.90 – Demographic characteristics –With possible impact of COVID-19 pandemic – Safety set 
Table 2.91 – History of glaucoma or ocular hypertension – Diagnosis – Worse eye – With possible impact 
of COVID-19 pandemic – Safety set 
Table 2.92 – History of glaucoma or ocular hypertension – Diagnosis – Contralateral eye – With possible 
impact of COVID-19 pandemic – Safety set 
Table 2.93 – History of glaucoma or ocular hypertension – Previous treatment – With possible impact of 
COVID-19 pandemic – Safety set 
Table 2.94 – Surgical history of glaucoma and ocular hypertension by system organ class and preferred 
term – Worse Eye – With possible impact of COVID-19 pandemic – Safety set 
Table 2.95 – Surgical history of glaucoma and ocular hypertension by system organ class and preferred 
term – Contralateral Eye – With possible impact of COVID-19 pandemic – Safety set 
Table 2.96 – Automated visual field at screening visit – Worse eye – With possible impact of COVID-19 
pandemic – Safety set 
Table 2.97 – Automated visual field at screening visit – Contralateral eye – With possible impact of 
COVID-19 pandemic – Safety set 
Table 2.98 – Central corneal thickness measurement (µm) at screening visit – Worse eye – With possible 
impact of COVID-19 pandemic – Safety set 
Table 2.99 – Central corneal thickness measurement (µm) at screening visit – Contralateral eye – With 
possible impact of COVID-19 pandemic – Safety set 
Table 2.100 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 – Worse eye – With 
possible impact of COVID-19 pandemic – Safety set 
Table 2.101 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 – Contralateral eye 
– With possible impact of COVID-19 pandemic – Safety set 
Table 2.102 – Summary of baseline IOP (mmHg) – Worse eye – With possible impact of COVID-19 
pandemic – Safety set 
Table 2.103 – Summary of baseline IOP (mmHg) – Contralateral eye – With possible impact of COVID-
19 pandemic – Safety set 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 92/163 
 
 
 
 
 
 
 
 
 
Table 2.104 – Demographic characteristics –Without possible impact of COVID-19 pandemic – Safety set 
Table 2.105 – History of glaucoma or ocular hypertension – Diagnosis – Worse eye – Without possible 
impact of COVID-19 pandemic – Safety set 
Table 2.106 – History of glaucoma or ocular hypertension – Diagnosis – Contralateral eye – Without 
possible impact of COVID-19 pandemic – Safety set 
Table 2.107 – History of glaucoma or ocular hypertension – Previous treatment – Without possible 
impact of COVID-19 pandemic – Safety set 
Table 2.108 – Surgical history of glaucoma and ocular hypertension by system organ class and preferred 
term – Worse Eye – Without possible impact of COVID-19 pandemic – Safety set 
Table 2.109 – Surgical history of glaucoma and ocular hypertension by system organ class and preferred 
term – Contralateral Eye – Without possible impact of COVID-19 pandemic – Safety set 
Table 2.110 – Automated visual field at screening visit – Worse eye – Without possible impact of COVID-
19 pandemic – Safety set 
Table 2.111 – Automated visual field at screening visit – Contralateral eye – Without possible impact of 
COVID-19 pandemic – Safety set 
Table 2.112 – Central corneal thickness measurement (µm) at screening visit – Worse eye – Without 
possible impact of COVID-19 pandemic – Safety set 
Table 2.113 – Central corneal thickness measurement (µm) at screening visit – Contralateral eye – 
Without possible impact of COVID-19 pandemic – Safety set 
Table 2.114 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 – Worse eye – 
Without possible impact of COVID-19 pandemic – Safety set 
Table 2.115 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 – Contralateral eye 
– Without possible impact of COVID-19 pandemic – Safety set 
Table 2.116 – Summary of baseline IOP (mmHg) – Worse eye – Without possible impact of COVID-19 
pandemic – Safety set 
Table 2.117 – Summary of baseline IOP (mmHg) – Contralateral eye – Without possible impact of 
COVID-19 pandemic – Safety set 
 
Same as Table 2.76 to 2.89 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 93/163 
 
 
 
 
 
 
 
 
 
All Tables related to Demographics and Baseline Characteristics will be repeated on the ITT set if it differs 
from the Safety set: 
 
Table 2.118 – Demographic characteristics – ITT Set 
Table 2.119 – Ocular medical history other than the studied disease by system organ class and preferred 
term– ITT set 
Table 2.120 – Ocular surgical history related to another disease than the studied one by system organ 
class and preferred term – ITT set 
Table 2.121 – Systemic medical history by system organ class and preferred term – ITT set 
Table 2.122 – Systemic surgical history by system organ class and preferred term – ITT set 
Table 2.123 – Previous ocular treatments by WHO-Drug ATC2 and ATC4 – ITT set 
Table 2.124 – Concomitant ocular treatments by WHO-Drug ATC2 and ATC4 – ITT set 
Table 2.125 – Previous non-ocular treatments by WHO-Drug ATC2 and ATC4 – ITT set 
Table 2.126 – Concomitant non-ocular treatments by WHO-Drug ATC2 and ATC4 – ITT set 
Table 2.127 – History of glaucoma or ocular hypertension – Diagnosis – Worse eye – ITT set 
Table 2.128 – History of glaucoma or ocular hypertension – Diagnosis – Contralateral eye - ITT set 
Table 2.129 – History of glaucoma or ocular hypertension – Previous treatment - ITT set 
Table 2.130 – Surgical history of glaucoma and ocular hypertension by system organ class and preferred 
term – Worse Eye – ITT set 
Table 2.131 – Surgical history of glaucoma and ocular hypertension by system organ class and preferred 
term – Contralateral Eye – ITT set 
Table 2.132 – Automated visual field at screening visit – Worse eye – ITT set 
Table 2.133 – Automated visual field at screening visit – Contralateral eye – ITT set 
Table 2.134 – Central corneal thickness measurement (µm) at screening visit – Worse eye – ITT set 
Table 2.135 – Central corneal thickness measurement (µm) at screening visit – Contralateral eye – ITT 
set 
Table 2.136– Summary of IOP (mmHg) and Change from screening in IOP at 08:00 – Worse eye – ITT 
set 
Table 2.137 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 –  
Wash-out duration <= 8 days – Worse eye – ITT set 
Table 2.138 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 –  
Wash-out duration > 8 days – Worse eye – ITT set 
Table 2.139 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 – Contralateral eye 
– ITT set 
Table 2.140 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 –  
Wash-out duration <= 8 days – Contralateral eye – ITT set 
Table 2.141 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 –  
Wash-out duration > 8 days – Contralateral eye – ITT set 
 
Same as Table 2.1 to 2.24 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 94/163 
 
 
 
 
 
 
 
 
 
Following Tables related to Demographics and Baseline Characteristics will be repeated on the ITT set for 
patients included in m-ITT set and for patients not included in m-ITT set: 
 
Table 2.142 – Demographic characteristics –Patients included in m-ITT set – ITT set 
Table 2.143 – History of glaucoma or ocular hypertension – Diagnosis – Worse eye – Patients included in 
m-ITT set – ITT set 
Table 2.144 – History of glaucoma or ocular hypertension – Diagnosis – Contralateral eye – Patients 
included in m-ITT set – ITT set 
Table 2.145 – History of glaucoma or ocular hypertension – Previous treatment – Patients included in m-
ITT set – ITT set 
Table 2.146 – Surgical history of glaucoma and ocular hypertension by system organ class and preferred 
term – Worse Eye – Patients included in m-ITT set – ITT set 
Table 2.147 – Surgical history of glaucoma and ocular hypertension by system organ class and preferred 
term – Contralateral Eye – Patients included in m-ITT set – ITT set 
Table 2.148 – Automated visual field at screening visit – Worse eye – Patients included in m-ITT set – 
ITT set 
Table 2.149 – Automated visual field at screening visit – Contralateral eye – Patients included in m-ITT 
set – ITT set 
Table 2.150 – Central corneal thickness measurement (µm) at screening visit – Worse eye – Patients 
included in m-ITT set – ITT set 
Table 2.151 – Central corneal thickness measurement (µm) at screening visit – Contralateral eye – 
Patients included in m-ITT set – ITT set 
Table 2.152 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 – Worse eye – 
Patients included in m-ITT set – ITT set 
Table 2.153 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 – Contralateral eye 
– Patients included in m-ITT set – ITT set 
Table 2.154 – Summary of baseline IOP (mmHg) – Worse eye – Patients included in m-ITT set – ITT set 
Table 2.155 – Summary of baseline IOP (mmHg) – Contralateral eye – Patients included in m-ITT set – 
ITT set 
 
Table 2.156 – Demographic characteristics –Patients not included in m-ITT set – ITT set 
Table 2.157 – History of glaucoma or ocular hypertension – Diagnosis – Worse eye – Patients not included 
in m-ITT set – ITT set 
Table 2.158 – History of glaucoma or ocular hypertension – Diagnosis – Contralateral eye – Patients not 
included in m-ITT set – ITT set 
Table 2.159 – History of glaucoma or ocular hypertension – Previous treatment – Patients not included in 
m-ITT set – ITT set 
Table 2.160 – Surgical history of glaucoma and ocular hypertension by system organ class and preferred 
term – Worse Eye – Patients not included in m-ITT set – ITT set 
Table 2.161 – Surgical history of glaucoma and ocular hypertension by system organ class and preferred 
term – Contralateral Eye – Patients not included in m-ITT set – ITT set 
Table 2.162 – Automated visual field at screening visit – Worse eye – Patients not included in m-ITT set – 
ITT set 
Table 2.163 – Automated visual field at screening visit – Contralateral eye – Patients not included in  
m-ITT set – ITT set 
Table 2.164 – Central corneal thickness measurement (µm) at screening visit – Worse eye – Patients not 
included in m-ITT set – ITT set 
Table 2.165 – Central corneal thickness measurement (µm) at screening visit – Contralateral eye – 
Patients not included in m-ITT set – ITT set 
Table 2.166 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 – Worse eye – 
Patients not included in m-ITT set – ITT set 
Table 2.167 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 – Contralateral eye 
– Patients not included in m-ITT set – ITT set 
Table 2.168 – Summary of baseline IOP (mmHg) – Worse eye – Patients not included in m-ITT set – ITT set 
Table 2.169 – Summary of baseline IOP (mmHg) – Contralateral eye – Patients not included in m-ITT set 
– ITT set 
 


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Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 95/163 
 
 
 
 
 
 
 
 
 
Same as Table 2.76 to 2.89 


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Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 96/163 
 
 
 
 
 
 
 
 
 
All Tables related to Demographics and Baseline Characteristics will be repeated on the PP set. 
 
Table 2.170 – Demographic characteristics – PP Set 
Table 2.171 – Ocular medical history other than the studied disease by system organ class and preferred 
term– PP set 
Table 2.172 – Ocular surgical history related to another disease than the studied one by system organ 
class and preferred term – PP set 
Table 2.173 – Systemic medical history by system organ class and preferred term – PP set 
Table 2.174 – Systemic surgical history by system organ class and preferred term – PP set 
Table 2.175 – Previous ocular treatments by WHO-Drug ATC2 and ATC4 – PP set 
Table 2.176 – Concomitant ocular treatments by WHO-Drug ATC2 and ATC4 – PP set 
Table 2.177 – Previous non-ocular treatments by WHO-Drug ATC2 and ATC4 – PP set 
Table 2.178 – Concomitant non-ocular treatments by WHO-Drug ATC2 and ATC4 – PP set 
Table 2.179 – History of glaucoma or ocular hypertension – Diagnosis – Worse eye – PP set 
Table 2.180 – History of glaucoma or ocular hypertension – Diagnosis – Contralateral eye - PP set 
Table 2.181 – History of glaucoma or ocular hypertension – Previous treatment –- PP set 
Table 2.182 – Surgical history of glaucoma and ocular hypertension by system organ class and preferred 
term – Worse Eye – PP set 
Table 2.183 – Surgical history of glaucoma and ocular hypertension by system organ class and preferred 
term – Contralateral Eye – PP set 
Table 2.184 – Automated visual field at screening visit – Worse eye – PP set 
Table 2.185 – Automated visual field at screening visit – Contralateral eye – PP set 
Table 2.186 – Central corneal thickness measurement (µm) at screening visit – Worse eye – PP set 
Table 2.187 – Central corneal thickness measurement (µm) at screening visit – Contralateral eye – PP set 
Table 2.188– Summary of IOP (mmHg) and Change from screening in IOP at 08:00 – Worse eye – PP set 
Table 2.189 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 –  
Wash-out duration <= 8 days – Worse eye – PP set 
Table 2.190 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 –  
Wash-out duration > 8 days – Worse eye – PP set 
Table 2.191 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 – Contralateral eye 
– PP set 
Table 2.192 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 –  
Wash-out duration <= 8 days – Contralateral eye – PP set 
Table 2.193 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 –  
Wash-out duration > 8 days – Contralateral eye – PP set 
 
Same as Table 2.1 to 2.24 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 97/163 
 
 
 
 
 
 
 
 
 
Following Tables related to Demographics and Baseline Characteristics will be repeated on the PP set 
according to the possible impact of COVID-19 pandemic classes: 
 
Table 2.194 – Demographic characteristics –With possible impact of COVID-19 pandemic – PP set 
Table 2.195 – History of glaucoma or ocular hypertension – Diagnosis – Worse eye – With possible impact 
of COVID-19 pandemic – PP set 
Table 2.196 – History of glaucoma or ocular hypertension – Diagnosis – Contralateral eye – With possible 
impact of COVID-19 pandemic – PP set 
Table 2.197 – History of glaucoma or ocular hypertension – Previous treatment – With possible impact of 
COVID-19 pandemic – PP set 
Table 2.198 – Surgical history of glaucoma and ocular hypertension by system organ class and preferred 
term – Worse Eye – With possible impact of COVID-19 pandemic – PP set 
Table 2.199 – Surgical history of glaucoma and ocular hypertension by system organ class and preferred 
term – Contralateral Eye – With possible impact of COVID-19 pandemic – PP set 
Table 2.200 – Automated visual field at screening visit – Worse eye – With possible impact of COVID-19 
pandemic – PP set 
Table 2.201 – Automated visual field at screening visit – Contralateral eye – With possible impact of 
COVID-19 pandemic – PP set 
Table 2.202 – Central corneal thickness measurement (µm) at screening visit – Worse eye – With possible 
impact of COVID-19 pandemic – PP set 
Table 2.203 – Central corneal thickness measurement (µm) at screening visit – Contralateral eye – With 
possible impact of COVID-19 pandemic – PP set 
Table 2.204 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 – Worse eye – With 
possible impact of COVID-19 pandemic – PP set 
Table 2.205 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 – Contralateral eye 
– With possible impact of COVID-19 pandemic – PP set 
 
Table 2.206 – Demographic characteristics –Without possible impact of COVID-19 pandemic – PP set 
Table 2.207 – History of glaucoma or ocular hypertension – Diagnosis – Worse eye – Without possible 
impact of COVID-19 pandemic – PP set 
Table 2.208 – History of glaucoma or ocular hypertension – Diagnosis – Contralateral eye – Without 
possible impact of COVID-19 pandemic – PP set 
Table 2.209 – History of glaucoma or ocular hypertension – Previous treatment – Without possible 
impact of COVID-19 pandemic – PP set 
Table 2.210 – Surgical history of glaucoma and ocular hypertension by system organ class and preferred 
term – Worse Eye – Without possible impact of COVID-19 pandemic – PP set 
Table 2.211 – Surgical history of glaucoma and ocular hypertension by system organ class and preferred 
term – Contralateral Eye – Without possible impact of COVID-19 pandemic – PP set 
Table 2.212 – Automated visual field at screening visit – Worse eye – Without possible impact of COVID-
19 pandemic – PP set 
Table 2.213 – Automated visual field at screening visit – Contralateral eye – Without possible impact of 
COVID-19 pandemic – PP set 
Table 2.214 – Central corneal thickness measurement (µm) at screening visit – Worse eye – Without 
possible impact of COVID-19 pandemic – PP set 
Table 2.215 – Central corneal thickness measurement (µm) at screening visit – Contralateral eye – 
Without possible impact of COVID-19 pandemic – PP set 
Table 2.216 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 – Worse eye – 
Without possible impact of COVID-19 pandemic – PP set 
Table 2.217 – Summary of IOP (mmHg) and Change from screening in IOP at 08:00 – Contralateral eye 
– Without possible impact of COVID-19 pandemic – PP set 
 
Same as Table 2.1 to 2.24 
 
 


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Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 98/163 
 
 
 
 
 
 
 
 
 
3. Treatment exposure and compliance 
 
Study: LT4032-301  
Page X / N 
Population: Azopt Safety set 
 
Table 3.1 – Azopt exposure – Azopt Safety set 
 
 
Total 
(N=XX) 
Duration of Azopt (days) 
 
   n 
xx 
   Mean (SD) 
xx.x (xx.x) 
   95% CI (mean) 
[xx.x%;xx.x%] 
   Median 
xx.x 
   Q1 ; Q3 
xx.x 
   Median 
xx.x 
   Min. ; Max. 
xx ; xx 
   Missing data 
xx 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 99/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Azopt Safety set 
 
Table 3.2 – Changes in the Azopt instillations – Azopt Safety set 
 
 
Total 
(N=XX) 
Absence or Modification of instillations 
 
      n 
xx 
      Yes 
xx.x (xx.x) 
      95% CI (Yes) 
[xx.x%;xx.x%] 
      No 
xx.x (xx.x) 
      95% CI (No) 
[xx.x%;xx.x%] 
      Missing data 
xx 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 100/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Azopt Safety set 
 
Listing 3.1 – Listing of data relative to Azopt instillations modifications – Azopt Safety set 
 
Actual 
group 
Planned 
group 
Patient 
number 
Azopt 
Safety 
set 
m-ITT 
set 
Date of 
first / last 
instillation 
Absence or 
Modification 
of 
instillations 
Start date / 
end date 
Number 
of days 
Number of 
instillation / day 
Worse 
eye 
Contralateral 
eye 
 
 
 
 
 
 
Yes 
 
 
 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
All Tables related to Azopt Exposure will be repeated by treatment group on the m-ITT set: 
 
Table 3.3 – Azopt exposure – m-ITT set 
Table 3.4 – Changes in the Azopt instillations – m-ITT set 
Same as Table 3.1 to 3.2 
 
 


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Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 101/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 3.5 – Compliance of Azopt (%) – Worse eye – m-ITT set 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Total 
(N=XX) 
Compliance (%) 
 
 
 
   n 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
   95% CI (mean) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   Median 
xx.x 
xx.x 
xx.x 
   Q1 ; Q3 
xx.x 
xx.x 
xx.x 
   Min. ; Max. 
xx ; xx 
xx ; xx 
xx ; xx 
   Missing data 
xx 
xx 
xx 
 
 
 
 
Compliance (%) in classes 
 
 
 
   n 
xx.x (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
   < 80% 
xx.x (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
   95% CI (< 80%) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   ≥ 80% - ≤ 120% 
xx.x (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
   95% CI (≥ 80% - ≤ 120%) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   > 120% 
xx.x (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
   95% CI (> 120%) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
 
 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 3.6 – Compliance of Azopt (%) – Contralateral eye– m-ITT set 
Same as Table 3.5 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 


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Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 102/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 3.7 – Treatment exposure – Safety set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Total 
(N=XX) 
Duration of treatment (days) 
 
 
 
   n 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
   95% CI (mean) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   Median 
xx.x 
xx.x 
xx.x 
   Q1 ; Q3 
xx.x 
xx.x 
xx.x 
   Median 
xx.x 
xx.x 
xx.x 
   Min. ; Max. 
xx ; xx 
xx ; xx 
xx ; xx 
   Missing data 
xx 
xx 
xx 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 103/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 3.8 – Changes in the IMP instillation (between the first and the last instillation) – From Day 1 to 
Week 6 – Safety set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Total 
(N=XX) 
Absence of instillation 
 
 
 
      n 
xx 
xx 
xx 
      Yes 
xx.x (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
      95% CI (Yes) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
      No 
xx.x (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
      95% CI (No) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
      Missing data 
xx 
xx 
xx 
 
 
 
 
Instillation time modification 
 
 
 
      n 
xx 
xx 
xx 
      Yes 
xx.x (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
      95% CI (Yes) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
      No 
xx.x (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
      95% CI (No) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
      Missing data 
xx 
xx 
xx 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 3.9 – Changes in the IMP instillations (between the first and the last instillation) – From Week 6 to 
Week 12 – Safety set 
Same as Table 3.8 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 3.10 – Changes in the IMP instillations (between the first and the last instillation) – From Day 1 to 
Week 12 - Safety set 
Same as Table 3.8 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 


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Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 104/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 3.11 – Compliance (%) – Worse eye – From Day 1 to Week 6 – Safety set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Total 
(N=XX) 
Compliance (%) 
 
 
 
   n 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
   95% CI (mean) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   Median 
xx.x 
xx.x 
xx.x 
   Q1 ; Q3 
xx.x 
xx.x 
xx.x 
   Min. ; Max. 
xx ; xx 
xx ; xx 
xx ; xx 
   Missing data 
xx 
xx 
xx 
 
 
 
 
Compliance (%) in classes 
 
 
 
   n 
xx.x (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
   < 80% 
xx.x (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
   95% CI (< 80%) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   ≥ 80% - ≤ 120% 
xx.x (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
   95% CI (≥ 80% - ≤ 120%) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   > 120% 
xx.x (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
   95% CI (> 120%) 
[xx.x%;xx.x%] [xx.x%;xx.x%] [xx.x%;xx.x%] 
   Missing data 
xx 
xx 
xx 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 3.12 – Compliance (%) – Worse eye – From Week 6 to Week 12 – Safety set 
Same as Table 3.11 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 3.13 – Compliance (%) – Worse eye – From Day 1 to Week 12 – Safety set 
Same as Table 3.11 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 105/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 3.14 – Compliance (%) – Contralateral eye – From Day 1 toWeek 6 - Safety set 
Same as Table 3.11 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 3.15 – Compliance (%) – Contralateral eye – From Week 6 to Week 12 – Safety set 
Same as Table 3.11 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 3.16 – Compliance (%) – Contralateral eye – From Day 1 to Week 12 – Safety set 
Same as Table 3.11 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 106/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Listing 3.2 – Listing of data relative to IMP instillations modifications – Safety set 
 
Actual 
group 
Planned 
group 
Patient 
number 
Possible 
impact of 
COVID-19 
pandemic 
m-ITT 
set 
Visit 
Date of first / 
last instillation 
Absence of 
instillations 
Modification 
start date / 
end date 
Number 
of days 
Number of instillations 
/ day 
Worse 
eye 
Contralateral 
eye 
 
 
 
 
 
Week 6 / 
Week 12 
 
Yes 
 
 
 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Listing 3.3 – Listing of data relative to IMP instillation time modifications – Safety set 
 
Actual 
group 
Planned 
group 
Patient 
number 
Possible 
impact of 
COVID-19 
pandemic 
m-ITT 
set 
Visit 
Date of first / 
last 
instillation 
Time 
modifications 
Modification 
start date / 
end date 
Number 
of days 
Time of instillation 
Worse 
eye 
Contralateral 
eye 
 
 
 
 
 
Week 6 / 
Week 12 
 
Yes 
 
 
 
 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
 
 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 107/163 
 
 
 
 
 
 
 
 
 
Following Tables related to Demographics and Baseline Characteristics will be repeated on the Safety set 
according to the possible impact of COVID-19 pandemic classes: 
 
Table 3.17 – Treatment exposure – With possible impact of COVID-19 pandemic – Safety set 
Table 3.18 – Changes in the IMP instillations (between the first and the last instillation) – From Day 1 to 
Week 6 – With possible impact of COVID-19 pandemic – Safety set 
Table 3.19 – Changes in the IMP instillations (between the first and the last instillation) – From Week 6 to 
Week 12 – With possible impact of COVID-19 pandemic – Safety set 
Table 3.20 – Changes in the IMP instillations (between the first and the last instillation) – From Day 1 to 
Week 12 – With possible impact of COVID-19 pandemic – Safety set 
Table 3.21 – Compliance (%) – Worse eye – From Day 1 to Week 6 – With possible impact of COVID-19 
pandemic – Safety set 
Table 3.22 – Compliance (%) – Worse eye – From Week 6 to Week 12 – With possible impact of COVID-
19 pandemic – Safety set 
Table 3.23 – Compliance (%) – Worse eye – From Day 1 to Week 12 – With possible impact of COVID-19 
pandemic – Safety set 
Table 3.24 – Compliance (%) – Contralateral eye – From Day 1 toWeek 6 – With possible impact of 
COVID-19 pandemic – Safety set 
Table 3.25 – Compliance (%) – Contralateral eye – From Week 6 to Week 12 – With possible impact of 
COVID-19 pandemic – Safety set 
Table 3.26 – Compliance (%) – Contralateral eye – From Day 1 to Week 12 – With possible impact of 
COVID-19 pandemic – Safety set 
 
Table 3.27 – Treatment exposure – Without possible impact of COVID-19 pandemic – Safety set 
Table 3.28 – Changes in the IMP instillations (between the first and the last instillation) – From Day 1 to 
Week 6 – Without possible impact of COVID-19 pandemic – Safety set 
Table 3.29 – Changes in the IMP instillations (between the first and the last instillation) – From Week 6 to 
Week 12 – Without possible impact of COVID-19 pandemic – Safety set 
Table 3.30 – Changes in the IMP instillations (between the first and the last instillation) – From Day 1 to 
Week 12 – Without possible impact of COVID-19 pandemic – Safety set 
Table 3.31 – Compliance (%) – Worse eye – From Day 1 to Week 6 – Without possible impact of COVID-
19 pandemic – Safety set 
Table 3.32 – Compliance (%) – Worse eye – From Week 6 to Week 12 – Without possible impact of 
COVID-19 pandemic – Safety set 
Table 3.33 – Compliance (%) – Worse eye – From Day 1 to Week 12 – Without possible impact of 
COVID-19 pandemic – Safety set 
Table 3.34 – Compliance (%) – Contralateral eye – From Day 1 toWeek 6 – Without possible impact of 
COVID-19 pandemic – Safety set 
Table 3.35 – Compliance (%) – Contralateral eye – From Week 6 to Week 12 – Without possible impact 
of COVID-19 pandemic – Safety set 
Table 3.36 – Compliance (%) – Contralateral eye – From Day 1 to Week 12 – Without possible impact of 
COVID-19 pandemic – Safety set 
 
Same as Table 3.7 to 3.16 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 108/163 
 
 
 
 
 
 
 
 
 
All Tables related to Treatment Exposure and Compliance will be repeated on the m-ITT set: 
 
Table 3.37 – Treatment exposure – m-ITT set 
Table 3.38 – Changes in the IMP instillations (between the first and the last instillation) – From Day 1 to 
Week 6 – m-ITT set 
Table 3.39 – Changes in the IMP instillations (between the first and the last instillation) – From Week 6 to 
Week 12 – m-ITT set 
Table 3.40 – Changes in the IMP instillations (between the first and the last instillation) – From Day 1 to 
Week 12 – m-ITT set 
Table 3.41 – Compliance (%) – Worse eye – From Day 1 to Week 6 – m-ITT set 
Table 3.42 – Compliance (%) – Worse eye – From Week 6 to Week 12 – m-ITT set 
Table 3.43 – Compliance (%) – Worse eye – From Day 1 to Week 12 – m-ITT set 
Table 3.44 – Compliance (%) – Contralateral eye – From Day 1 toWeek 6 – m-ITT set 
Table 3.45 – Compliance (%) – Contralateral eye – From Week 6 to Week 12 – m-ITT set 
Table 3.46 – Compliance (%) – Contralateral eye – From Day 1 to Week 12 – m-ITT set 
 
Same as Table 3.7 to 3.16 
 
 


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Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
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Following Tables related to Demographics and Baseline Characteristics will be repeated on the m-ITT set 
according to the possible impact of COVID-19 pandemic classes: 
 
Table 3.47 – Treatment exposure – With possible impact of COVID-19 pandemic – m-ITT set 
Table 3.48 – Changes in the IMP instillations (between the first and the last instillation) – From Day 1 to 
Week 6 – With possible impact of COVID-19 pandemic – m-ITT set 
Table 3.49 – Changes in the IMP instillations (between the first and the last instillation) – From Week 6 to 
Week 12 – With possible impact of COVID-19 pandemic – m-ITT set 
Table 3.50 – Changes in the IMP instillations (between the first and the last instillation) – From Day 1 to 
Week 12 – With possible impact of COVID-19 pandemic – m-ITT set 
Table 3.51 – Compliance (%) – Worse eye – From Day 1 to Week 6 – With possible impact of COVID-19 
pandemic – m-ITT set 
Table 3.52 – Compliance (%) – Worse eye – From Week 6 to Week 12 – With possible impact of COVID-
19 pandemic – m-ITT set 
Table 3.53 – Compliance (%) – Worse eye – From Day 1 to Week 12 – With possible impact of COVID-19 
pandemic – m-ITT set 
Table 3.54 – Compliance (%) – Contralateral eye – From Day 1 toWeek 6 – With possible impact of 
COVID-19 pandemic – m-ITT set 
Table 3.55 – Compliance (%) – Contralateral eye – From Week 6 to Week 12 – With possible impact of 
COVID-19 pandemic – m-ITT set 
Table 3.56 – Compliance (%) – Contralateral eye – From Day 1 to Week 12 – With possible impact of 
COVID-19 pandemic – m-ITT set 
 
Table 3.57 – Treatment exposure – Without possible impact of COVID-19 pandemic – m-ITT set 
Table 3.58 – Changes in the IMP instillations (between the first and the last instillation) – From Day 1 to 
Week 6 – Without possible impact of COVID-19 pandemic – m-ITT set 
Table 3.59 – Changes in the IMP instillations (between the first and the last instillation) – From Week 6 to 
Week 12 – Without possible impact of COVID-19 pandemic – m-ITT set 
Table 3.60 – Changes in the IMP instillations (between the first and the last instillation) – From Day 1 to 
Week 12 – Without possible impact of COVID-19 pandemic – m-ITT set 
Table 3.61 – Compliance (%) – Worse eye – From Day 1 to Week 6 – Without possible impact of COVID-
19 pandemic – m-ITT set 
Table 3.62 – Compliance (%) – Worse eye – From Week 6 to Week 12 – Without possible impact of 
COVID-19 pandemic – m-ITT set 
Table 3.63 – Compliance (%) – Worse eye – From Day 1 to Week 12 – Without possible impact of 
COVID-19 pandemic – m-ITT set 
Table 3.64 – Compliance (%) – Contralateral eye – From Day 1 toWeek 6 – Without possible impact of 
COVID-19 pandemic – m-ITT set 
Table 3.65 – Compliance (%) – Contralateral eye – From Week 6 to Week 12 – Without possible impact 
of COVID-19 pandemic – m-ITT set 
Table 3.66 – Compliance (%) – Contralateral eye – From Day 1 to Week 12 – Without possible impact of 
COVID-19 pandemic – m-ITT set 
 
Same as Table 3.7 to 3.16 
 


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Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
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4. Efficacy analysis 
 
Primary efficacy endpoint 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 4.1 – Summary of IOP (mmHg) and Change from baseline in IOP – Worse eye – m-ITT set 
 
 
Parameter at each visit 
Change from Baseline 
Variable 
Treatment group 
N 
Visit 
n 
Mean (SD) 
Median Min ; Max 95% CI (Mean) 
n 
Mean (SD) 
Median Min ; Max 95% CI (Mean) 
IOP 
(mmHg) 
at (*) 
T4032 
XX Baseline XX XX.X (X.X) 
XX.X 
XX ; XX 
[XX.X;XX.X] 
 
 
 
 
 
 
 
 
Week 6 XX XX.X (X.X) 
XX.X 
XX ; XX 
[XX.X;XX.X] 
XX XX.X (X.X) 
XX.X 
XX ; XX 
[XX.X;XX.X] 
 
 
 
Week 12 XX XX.X (X.X) 
XX.X 
XX ; XX 
[XX.X;XX.X] 
XX XX.X (X.X) 
XX.X 
XX ; XX 
[XX.X;XX.X] 
 
 
 
Week 12 
(LOCF) 
XX XX.X (X.X) 
XX.X 
XX ; XX 
[XX.X;XX.X] 
XX XX.X (X.X) 
XX.X 
XX ; XX 
[XX.X;XX.X] 
 
Lumigan 
XX Baseline XX XX.X (X.X) 
XX.X 
XX ; XX 
[XX.X;XX.X] 
 
 
 
 
 
 
 
 
Week 6 XX XX.X (X.X) 
XX.X 
XX ; XX 
[XX.X;XX.X] 
XX XX.X (X.X) 
XX.X 
XX ; XX 
[XX.X;XX.X] 
 
 
 
Week 12 XX XX.X (X.X) 
XX.X 
XX ; XX 
[XX.X;XX.X] 
XX XX.X (X.X) 
XX.X 
XX ; XX 
[XX.X;XX.X] 
 
 
 
Week 12 
(LOCF) 
XX XX.X (X.X) 
XX.X 
XX ; XX 
[XX.X;XX.X] 
XX XX.X (X.X) 
XX.X 
XX ; XX 
[XX.X;XX.X] 
(LOCF) Last observation carried forward 
(*) at 08:00, 10:00 and 16:00 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Table 4.2 – Summary of IOP (mmHg) and Change from baseline in IOP – Worse eye – ITT set 
Table 4.3 – Summary of IOP (mmHg) and Change from baseline in IOP – Worse eye – PP set 
 
Table 4.4 – Summary of IOP (mmHg) and Change from baseline in IOP – Worse eye – (*) – m-ITT set 
Table 4.5 – Summary of IOP (mmHg) and Change from baseline in IOP – Worse eye – (*) – ITT set 
Table 4.6 – Summary of IOP (mmHg) and Change from baseline in IOP – Worse eye – (*) – PP set 
(*) Country: Belgium, Canada, Czech Republic, Estonia, France, Germany, Greece, Italy, Latvia, Lithuania, 
Mauritius, Poland, Russian, Slovakia, Spain, Ukraine, United Kingdom   
Possible impact of COVID-19 pandemic: With impact of of COVID-19 pandemic, Without of COVID-19 pandemic 
 
Same as Table 4.1 


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Statistical Analysis Plan 
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20APR2021  
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Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 4.7 – Primary analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 12 – MMRM 
analysis – Worse eye – m-ITT set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Number of patients in the model 
xx 
xx 
 
 
 
Change from baseline at 08:00 at Week 12 
 
 
   Adjusted mean (SE) 
xx.x (xx.x) 
xx.x (xx.x) 
   Adjusted mean difference (T4032 vs Lumigan) (SE) 
xx.x (xx.x) 
 
   95% CI of adjusted mean difference 
[xx.x ; xx.x] 
 
   p-value 
0.xxx 
 
 
 
 
Type III test of fixed effects (p-value) 
 
 
   Treatment 
0.xxx 
 
   Visit 
0.xxx 
 
   Baseline IOP 
0.xxx 
 
   Wash-out duration 
0.xxx 
 
   Country 
0.xxx 
 
   Treatment x Visit Interaction 
0.xxx 
  
   Baseline IOP x Visit Interaction 
0.xxx 
 
Non-inferiority will be achieved if the upper bound of the 95% CI for the difference 
between treatment groups (T4032 – Lumigan 0.01%) is lower than the margin of +1.5 
mmHg for each of the three time points 08:00, 10:00 and 16:00. 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Table 4.8 – Primary analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 12 – MMRM 
analysis – Worse eye – m-ITT set 
Table 4.9 – Primary analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 12 – MMRM 
analysis – Worse eye – m-ITT set 
 
Table 4.10 –Analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 12 – MMRM analysis 
– Worse eye – ITT set 
Table 4.11 –Analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 12 – MMRM analysis 
– Worse eye – ITT set 
Table 4.12 –Analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 12 – MMRM analysis 
– Worse eye – ITT set 
 
Table 4.13 –Analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 12 – MMRM analysis 
– Worse eye – PP set 
Table 4.14 –Analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 12 – MMRM analysis 
– Worse eye – PP set 
Table 4.15 –Analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 12 – MMRM analysis 
– Worse eye – PP set 
 
Same as Table 4.7 
 
 


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Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
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Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 4.16 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 12 (LOCF) 
– ANCOVA – Worse eye – m-ITT set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Number of patients in the model 
xx 
xx 
 
 
 
Change from baseline at 08:00 at Week 12 (LOCF) 
 
 
   Adjusted mean (SE) 
xx.x (xx.x) xx.x (xx.x) 
   Adjusted mean difference (T4032 vs Lumigan) (SE) 
xx.x (xx.x) 
 
   95%CI of adjusted mean difference 
[xx.x ; xx.x] 
 
   p-value 
0.xxx 
 
 
 
 
Type III test of fixed effects (p-value) 
 
 
   Treatment 
0.xxx 
 
   Baseline IOP 
0.xxx 
 
   Wash-out duration 
0.xxx 
 
   Country 
0.xxx 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Table 4.17 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 12 (LOCF) 
– ANCOVA – Worse eye – m-ITT set 
Table 4.18 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 12 (LOCF) 
– ANCOVA – Worse eye – m-ITT set 
 
Table 4.19 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 12 (LOCF) 
– ANCOVA – Worse eye – ITT set 
Table 4.20 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 12 (LOCF) 
– ANCOVA – Worse eye – ITT set 
Table 4.21 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 12 (LOCF) 
– ANCOVA – Worse eye – ITT set 
 
Table 4.22 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 12 (LOCF) 
– ANCOVA – Worse eye – PP set 
Table 4.23 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 12 (LOCF) 
– ANCOVA – Worse eye – PP set 
Table 4.24 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 12 (LOCF) 
– ANCOVA – Worse eye – PP set 
 
Same as Table 4.16 
 


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Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
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Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 4.25 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 12 
(Observed) – ANCOVA – Worse eye – m-ITT set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Number of patients in the model 
xx 
xx 
 
 
 
Change from baseline at 08:00 at Week 12 (Observed) 
 
 
   Adjusted mean (SE) 
xx.x (xx.x) xx.x (xx.x) 
   Adjusted mean difference (T4032 vs Lumigan) (SE) 
xx.x (xx.x) 
 
   95%CI of adjusted mean difference 
[xx.x ; xx.x] 
 
   p-value 
0.xxx 
 
 
 
 
Type III test of fixed effects (p-value) 
 
 
   Treatment 
0.xxx 
 
   Baseline IOP 
0.xxx 
 
   Wash-out duration 
0.xxx 
 
   Country 
0.xxx 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Table 4.26 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 12 
(Observed) – ANCOVA – Worse eye – m-ITT set 
Table 4.27 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 12 
(Observed) – ANCOVA – Worse eye – m-ITT set 
 
Table 4.28 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 12 
(Observed) – ANCOVA – Worse eye – ITT set 
Table 4.29 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 12 
(Observed) – ANCOVA – Worse eye – ITT set 
Table 4.30 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 12 
(Observed) – ANCOVA – Worse eye – ITT set 
 
Table 4.31 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 12 
(Observed) – ANCOVA – Worse eye – PP set 
Table 4.32 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 12 
(Observed) – ANCOVA – Worse eye – PP set 
Table 4.33 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 12 
(Observed) – ANCOVA – Worse eye – PP set 
 
Same as Table 4.25 
 


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Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
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Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 4.34 – Supporting analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 12 – 
MMRM analysis – Worse eye – Investigation of ‘Treatment by Baseline IOP’ interaction – m-ITT set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Number of patients in the model 
xx 
xx 
 
 
 
Change from baseline at 08:00 at Week 12 
 
 
   Adjusted mean (SE) 
xx.x (xx.x) 
xx.x (xx.x) 
   Adjusted mean difference (T4032 vs Lumigan) (SE) 
xx.x (xx.x) 
 
   95% CI of adjusted mean difference 
[xx.x ; xx.x] 
 
   p-value 
0.xxx 
 
 
 
 
Type III test of fixed effects (p-value) 
 
 
   Treatment 
0.xxx 
 
   Visit 
0.xxx 
 
   Baseline IOP 
0.xxx 
 
   Wash-out duration 
0.xxx 
 
   Country 
 
 
   Treatment x Visit Interaction 
0.xxx 
 
   Baseline IOP x Visit Interaction 
0.xxx 
 
   Treatment x Baseline IOP Interaction 
0.xxx 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
Table 4.35 – Supporting analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 12 – 
MMRM analysis – Worse eye – Investigation of ‘Treatment by Baseline IOP’ interaction – m-ITT set 
Table 4.36 – Supporting analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 12 – 
MMRM analysis – Worse eye – Investigation of ‘Treatment by Baseline IOP’ interaction – m-ITT set 
 
Same as Table 4.34 


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Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
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Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 4.37 – Supporting analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 12 – 
MMRM analysis – Worse eye – Investigation of ‘Treatment by Wash-out duration’ interaction – m-ITT 
set 
 
 
T4032 
(N=XX) 
T4030b 
(N=XX) 
Number of patients in the model 
xx 
xx 
 
 
 
Change from baseline at 08:00 at Week 12 
 
 
   Adjusted mean (SE) 
xx.x (xx.x) 
xx.x (xx.x) 
   Adjusted mean difference (T4032 vs Lumigan) (SE) 
xx.x (xx.x) 
 
   95% CI of adjusted mean difference 
[xx.x ; xx.x] 
 
   p-value 
0.xxx 
 
 
 
 
Type III test of fixed effects (p-value) 
 
 
   Treatment 
0.xxx 
 
   Visit 
0.xxx 
 
   Baseline IOP 
0.xxx 
 
   Wash-out Duration 
0.xxx 
 
   Country 
0.xxx 
 
   Treatment x Visit Interaction 
0.xxx 
 
   Baseline IOP x Visit Interaction 
0.xxx 
 
   Treatment x Wash-out duration 
0.xxx 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Table 4.38 – Supporting analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 12 – 
MMRM analysis – Worse eye – Investigation of ‘Treatment by Wash-out duration’ interaction – m-ITT 
set 
Table 4.39 – Supporting analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 12 – 
MMRM analysis – Worse eye – Investigation of ‘Treatment by Wash-out duration’ interaction – m-ITT 
set 
 
Same as Table 4.37 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
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Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 4.40 – Supporting analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 12 – 
MMRM analysis – Worse eye – Investigation of ‘Treatment by Country’ interaction – m-ITT set 
 
 
T4032 
(N=XX) 
T4030b 
(N=XX) 
Number of patients in the model 
xx 
xx 
 
 
 
Change from baseline at 08:00 at Week 12 
 
 
   Adjusted mean (SE) 
xx.x (xx.x) 
xx.x (xx.x) 
   Adjusted mean difference (T4032 vs Lumigan) (SE) 
xx.x (xx.x) 
 
   95% CI of adjusted mean difference 
[xx.x ; xx.x] 
 
   p-value 
0.xxx 
 
 
 
 
Type III test of fixed effects (p-value) 
 
 
   Treatment 
0.xxx 
 
   Visit 
0.xxx 
 
   Baseline IOP 
0.xxx 
 
   Wash-out Duration 
0.xxx 
 
   Country 
0.xxx 
 
   Treatment x Visit Interaction 
0.xxx 
 
   Baseline IOP x Visit Interaction 
0.xxx 
 
   Treatment x Country 
0.xxx 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
Note for programming: 
If the p value of the interaction term is lower than 7%, qualitative interaction will be graphically investigated. 
If the interaction is qualitative, then the primary model will be performed by modality of the covariate. 
 
 
Table 4.41 – Supporting analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 12 – 
MMRM analysis – Worse eye – Investigation of ‘Treatment by Country’ interaction – m-ITT set 
Table 4.42 – Supporting analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 12 – 
MMRM analysis – Worse eye – Investigation of ‘Treatment by Country’ interaction – m-ITT set 
 
Same as Table 4.40 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
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Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 4.43 – Supporting analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 12 
(LOCF) – ANCOVA – Worse eye – Investigation of ‘Treatment by Baseline IOP’ interaction – m-ITT set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Number of patients in the model 
xx 
xx 
 
 
 
Change from baseline at 08:00 at Week 12 (LOCF) 
 
 
   Adjusted mean (SE) 
xx.x (xx.x) xx.x (xx.x) 
   Adjusted mean difference (T4032 vs Lumigan) (SE) 
xx.x (xx.x) 
 
   95%CI of adjusted mean difference 
[xx.x ; xx.x] 
 
   p-value 
0.xxx 
 
 
 
 
Type III test of fixed effects (p-value) 
 
 
   Treatment 
0.xxx 
 
   Baseline IOP 
0.xxx 
 
   Wash-out duration 
0.xxx 
 
   Country 
0.xxx 
 
   Treatment x Baseline IOP Interaction 
0.xxx 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Table 4.44 – Supporting analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 12 
(LOCF) – ANCOVA – Worse eye – Investigation of ‘Treatment by Baseline IOP’ interaction – m-ITT set 
Table 4.45 – Supporting analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 12 
(LOCF) – ANCOVA – Worse eye – Investigation of ‘Treatment by Baseline IOP’ interaction – m-ITT set 
 
Same as Table 4.43 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 118/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 4.46 – Supporting analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 12 
(LOCF) – ANCOVA – Worse eye – Investigation of ‘Treatment by Wash-out duration’ interaction –  
m-ITT set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Number of patients in the model 
xx 
xx 
 
 
 
Change from baseline at 08:00 at Week 12 (LOCF) 
 
 
   Adjusted mean (SE) 
xx.x (xx.x) xx.x (xx.x) 
   Adjusted mean difference (T4032 vs Lumigan) (SE) 
xx.x (xx.x) 
 
   95%CI of adjusted mean difference 
[xx.x ; xx.x] 
 
   p-value 
0.xxx 
 
 
 
 
Type III test of fixed effects (p-value) 
 
 
   Treatment 
0.xxx 
 
   Baseline IOP 
0.xxx 
 
   Wash-out duration 
0.xxx 
 
   Country 
0.xxx 
 
   Treatment x Wash-out duration 
0.xxx 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Table 4.47 – Supporting analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 12 
(LOCF) – ANCOVA – Worse eye – Investigation of ‘Treatment by Wash-out duration’ interaction –  
m-ITT set 
Table 4.48 – Supporting analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 12 
(LOCF) – ANCOVA – Worse eye – Investigation of ‘Treatment by Wash-out duration’ interaction –  
m-ITT set 
 
Same as Table 4.46 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 119/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 4.49 – Supporting analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 12 
(LOCF) – ANCOVA – Worse eye – Investigation of ‘Treatment by Country’ interaction –  
m-ITT set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Number of patients in the model 
xx 
xx 
 
 
 
Change from baseline at 08:00 at Week 12 (LOCF) 
 
 
   Adjusted mean (SE) 
xx.x (xx.x) xx.x (xx.x) 
   Adjusted mean difference (T4032 vs Lumigan) (SE) 
xx.x (xx.x) 
 
   95%CI of adjusted mean difference 
[xx.x ; xx.x] 
 
   p-value 
0.xxx 
 
 
 
 
Type III test of fixed effects (p-value) 
 
 
   Treatment 
0.xxx 
 
   Baseline IOP 
0.xxx 
 
   Wash-out duration 
0.xxx 
 
   Country 
0.xxx 
 
   Treatment x Country 
0.xxx 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
Note for programming: 
If the p value of the interaction term is lower than 7%, qualitative interaction will be graphically investigated. 
If the interaction is qualitative, then the primary model will be performed by modality of the covariate. 
 
 
Table 4.50 – Supporting analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 12 
(LOCF) – ANCOVA – Worse eye – Investigation of ‘Treatment by Country’ interaction – m-ITT set 
Table 4.51 – Supporting analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 12 
(LOCF) – ANCOVA – Worse eye – Investigation of ‘Treatment by Country’ interaction – m-ITT set 
 
Same as Table 4.49 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 120/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 4.52 – Supporting analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 12 
(observed) – ANCOVA – Worse eye – Investigation of ‘Treatment by Baseline IOP’ interaction – m-ITT 
set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Number of patients in the model 
xx 
xx 
 
 
 
Change from baseline at 08:00 at Week 12 (Observed) 
 
 
   Adjusted mean (SE) 
xx.x (xx.x) xx.x (xx.x) 
   Adjusted mean difference (T4032 vs Lumigan) (SE) 
xx.x (xx.x) 
 
   95%CI of adjusted mean difference 
[xx.x ; xx.x] 
 
   p-value 
0.xxx 
 
 
 
 
Type III test of fixed effects (p-value) 
 
 
   Treatment 
0.xxx 
 
   Baseline IOP 
0.xxx 
 
   Wash-out duration 
0.xxx 
 
   Country 
0.xxx 
 
   Treatment x Baseline IOP Interaction 
0.xxx 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Table 4.53 – Supporting analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 12 
(observed) – ANCOVA – Worse eye – Investigation of ‘Treatment by Baseline IOP’ interaction – m-ITT 
set 
Table 4.54 – Supporting analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 12 
(observed) – ANCOVA – Worse eye – Investigation of ‘Treatment by Baseline IOP’ interaction – m-ITT 
set 
 
Same as Table 4.52 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 121/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 4.55 – Supporting analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 12 
(observed) – ANCOVA – Worse eye – Investigation of ‘Treatment by Wash-out duration’ interaction –  
m-ITT set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Number of patients in the model 
xx 
xx 
 
 
 
Change from baseline at 08:00 at Week 12 (Observed) 
 
 
   Adjusted mean (SE) 
xx.x (xx.x) xx.x (xx.x) 
   Adjusted mean difference (T4032 vs Lumigan) (SE) 
xx.x (xx.x) 
 
   95%CI of adjusted mean difference 
[xx.x ; xx.x] 
 
   p-value 
0.xxx 
 
 
 
 
Type III test of fixed effects (p-value) 
 
 
   Treatment 
0.xxx 
 
   Baseline IOP 
0.xxx 
 
   Wash-out duration 
0.xxx 
 
   Country 
0.xxx 
 
   Treatment x Wash-out duration Interaction 
0.xxx 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Table 4.56 – Supporting analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 12 
(observed) – ANCOVA – Worse eye – Investigation of ‘Treatment by Wash-out duration’ interaction – 
m-ITT set 
Table 4.57 – Supporting analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 12 
(observed) – ANCOVA – Worse eye – Investigation of ‘Treatment by Wash-out duration’ interaction – 
m-ITT set 
 
Same as Table 4.55 
 


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Page X / N 
Population: m-ITT set 
 
Table 4.58 – Supporting analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 12 
(observed) – ANCOVA – Worse eye – Investigation of ‘Treatment by Country’ interaction –  
m-ITT set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Number of patients in the model 
xx 
xx 
 
 
 
Change from baseline at 08:00 at Week 12 (Observed) 
 
 
   Adjusted mean (SE) 
xx.x (xx.x) xx.x (xx.x) 
   Adjusted mean difference (T4032 vs Lumigan) (SE) 
xx.x (xx.x) 
 
   95%CI of adjusted mean difference 
[xx.x ; xx.x] 
 
   p-value 
0.xxx 
 
 
 
 
Type III test of fixed effects (p-value) 
 
 
   Treatment 
0.xxx 
 
   Baseline IOP 
0.xxx 
 
   Wash-out duration 
0.xxx 
 
   Country 
0.xxx 
 
   Treatment x Country Interaction 
0.xxx 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Table 4.59 – Supporting analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 12 
(observed) – ANCOVA – Worse eye – Investigation of ‘Treatment by Country’ interaction – m-ITT set 
Table 4.60 – Supporting analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 12 
(observed) – ANCOVA – Worse eye – Investigation of ‘Treatment by Country’ interaction – m-ITT set 
 
Same as Table 4.58 
 
 


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Statistical Analysis Plan 
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Page X / N 
Population: m-ITT set 
 
Table 4.61 – Exploratory analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 12 – 
MMRM analysis – Worse eye – Investigation of ‘Treatment by Possible impact of COVID-19 pandemic’ 
interaction – m-ITT set 
 
 
T4032 
(N=XX) 
T4030b 
(N=XX) 
Number of patients in the model 
xx 
xx 
 
 
 
Change from baseline at 08:00 at Week 12 
 
 
   Adjusted mean (SE) 
xx.x (xx.x) 
xx.x (xx.x) 
   Adjusted mean difference (T4032 vs Lumigan) (SE) 
xx.x (xx.x) 
 
   95% CI of adjusted mean difference 
[xx.x ; xx.x] 
 
   p-value 
0.xxx 
 
 
 
 
Type III test of fixed effects (p-value) 
 
 
   Treatment 
0.xxx 
 
   Visit 
0.xxx 
 
   Baseline IOP 
0.xxx 
 
   Wash-out Duration 
0.xxx 
 
   Country 
0.xxx 
 
   Possible impact of COVID-19 pandemic 
0.xxx 
 
   Treatment x Visit Interaction 
0.xxx 
 
   Baseline IOP x Visit Interaction 
0.xxx 
 
   Treatment x Possible impact of COVID-19 pandemic 
0.xxx 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
Note for programming: 
If the p value of the interaction term is lower than 7%, qualitative interaction will be graphically investigated. 
If the interaction is qualitative, then the primary model will be performed by modality of the covariate. 
 
 
Table 4.62 – Exploratory analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 12 – 
MMRM analysis – Worse eye – Investigation of ‘Treatment by Possible impact of COVID-19 pandemic’ 
interaction – m-ITT set 
Table 4.63 – Exploratory analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 12 – 
MMRM analysis – Worse eye – Investigation of ‘Treatment by Possible impact of COVID-19 pandemic’ 
interaction – m-ITT set 
 
Same as Table 4.61 


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Statistical Analysis Plan 
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Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 4.64 – Exploratory analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 12 
(LOCF) – ANCOVA – Worse eye – Investigation of ‘Treatment by possible impact of COVID-19 
pandemic’ interaction – m-ITT set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Number of patients in the model 
xx 
xx 
 
 
 
Change from baseline at 08:00 at Week 12 (LOCF) 
 
 
   Adjusted mean (SE) 
xx.x (xx.x) xx.x (xx.x) 
   Adjusted mean difference (T4032 vs Lumigan) (SE) 
xx.x (xx.x) 
 
   95%CI of adjusted mean difference 
[xx.x ; xx.x] 
 
   p-value 
0.xxx 
 
 
 
 
Type III test of fixed effects (p-value) 
 
 
   Treatment 
0.xxx 
 
   Baseline IOP 
0.xxx 
 
   Wash-out duration 
0.xxx 
 
   Country 
0.xxx 
 
   Possible impact of COVID-19 pandemic 
0.xxx 
 
   Treatment x Possible impact of COVID-19 pandemic 
0.xxx 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
Note for programming: 
If the p value of the interaction term is lower than 7%, qualitative interaction will be graphically investigated. 
If the interaction is qualitative, then the primary model will be performed by modality of the covariate. 
 
 
Table 4.65 – Exploratory analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 12 
(LOCF) – ANCOVA – Worse eye – Investigation of ‘Treatment by Possible impact of COVID-19 
pandemic’ interaction – m-ITT set 
Table 4.66 – Supporting analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 12 
(LOCF) – ANCOVA – Worse eye – Investigation of ‘Treatment by Possible impact of COVID-19 
pandemic’ interaction – m-ITT set 
 
Same as Table 4.64 


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Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
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Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 4.67 – Exploratory analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 12 
(observed) – ANCOVA – Worse eye – Investigation of ‘Treatment by Possible impact of COVID-19 
pandemic’ interaction –  
m-ITT set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Number of patients in the model 
xx 
xx 
 
 
 
Change from baseline at 08:00 at Week 12 (Observed) 
 
 
   Adjusted mean (SE) 
xx.x (xx.x) xx.x (xx.x) 
   Adjusted mean difference (T4032 vs Lumigan) (SE) 
xx.x (xx.x) 
 
   95%CI of adjusted mean difference 
[xx.x ; xx.x] 
 
   p-value 
0.xxx 
 
 
 
 
Type III test of fixed effects (p-value) 
 
 
   Treatment 
0.xxx 
 
   Baseline IOP 
0.xxx 
 
   Wash-out duration 
0.xxx 
 
   Country 
0.xxx 
 
   Possible impact of COVID-19 pandemic 
0.xxx 
 
   Treatment x Possible impact of COVID-19 pandemic 
0.xxx 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
Note for programming: 
If the p value of the interaction term is lower than 7%, qualitative interaction will be graphically investigated. 
If the interaction is qualitative, then the primary model will be performed by modality of the covariate. 
 
 
Table 4.68 – Exploratory analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 12 
(observed) – ANCOVA – Worse eye – Investigation of ‘Treatment by Possible impact of COVID-19 
pandemic’ interaction – m-ITT set 
Table 4.69 – Exploratory analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 12 
(observed) – ANCOVA – Worse eye – Investigation of ‘Treatment by Possible impact of COVID-19 
pandemic’ interaction – m-ITT set 
 
Same as Table 4.67 


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Statistical Analysis Plan 
Final Amendment V01 
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Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 4.70 – Exploratory analysis of the change from baseline in IOP (mmHg) at Week 12 – Worse eye – 
Impact of circadian rhythm – m-ITT set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Number of patients in the model 
xx 
xx 
 
 
 
Change from baseline at 08:00 at Week 12 
 
 
   Adjusted mean (SE) 
xx.x (xx.x) 
xx.x (xx.x) 
   Adjusted mean difference (T4032 vs Lumigan) 
xx.x (xx.x) 
 
   95% CI of adjusted mean difference 
[xx.x ; xx.x] 
 
   p-value 
0.xxx 
 
 
 
 
Change from baseline at 10:00 at Week 12 
 
 
   Adjusted mean (SE) 
xx.x (xx.x) 
xx.x (xx.x) 
   Adjusted mean difference (T4032 vs Lumigan) 
xx.x (xx.x) 
 
   95% CI of adjusted mean difference 
[xx.x ; xx.x] 
 
   p-value 
0.xxx 
 
 
 
 
Change from baseline at 16:00 at Week 12 
 
 
   Adjusted mean (SE) 
xx.x (xx.x) 
xx.x (xx.x) 
   Adjusted mean difference (T4032 vs Lumigan) 
xx.x (xx.x) 
 
   95% CI of adjusted mean difference 
[xx.x ; xx.x] 
 
   p-value 
0.xxx 
 
 
 
 
 
 
 
Type III test of fixed effects (p-value) 
 
 
   Treatment 
0.xxx 
 
   Visit 
0.xxx 
 
   Time 
0.xxx 
 
   Wash-out duration 
0.xxx 
 
   Country 
0.xxx 
 
   Treatment x Visit Interaction 
0.xxx 
  
   Teatment x Time Interaction 
0.xxx 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 


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Secondary efficacy endpoints 
 
Table 4.71 – Summary of IOP (mmHg) and Change from baseline in IOP – Contralateral eye – m-ITT set 
Table 4.72 – Summary of IOP (mmHg) and Change from baseline in IOP – Contralateral eye – PP set 
Table 4.73 – Summary of IOP (mmHg) and Change from baseline in IOP – Contralateral eye – (*) –  
m-ITT set 
Table 4.74 – Summary of IOP (mmHg) and Change from baseline in IOP – Contralateral eye – (*) –  
PP set 
(*) Country: Belgium, Canada, Czech Republic, Estonia, France, Germany, Greece, Italy, Latvia, Lithuania, 
Mauritius, Poland, Russian, Slovakia, Spain, Ukraine, United Kingdom   
Possible impact of COVID-19 pandemic: With impact of of COVID-19 pandemic, Without of COVID-19 pandemic 
 
Same as Table 4.1 
 
 
Table 4.75 –Analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 12 – MMRM analysis 
– Contralateral eye – m-ITT set 
Table 4.76 –Analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 12 – MMRM analysis 
– Contralateral eye – m-ITT set 
Table 4.77 –Analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 12 – MMRM analysis 
– Contralateral eye – m-ITT set 
 
Table 4.78 –Analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 12 – MMRM analysis 
– Contralateral eye – PP set 
Table 4.79 –Analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 12 – MMRM analysis 
– Contralateral eye – PP set 
Table 4.80 –Analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 12 – MMRM analysis 
– Contralateral eye – PP set 
 
Same as Table 4.7 
 
 
Table 4.81 –Sensitivity analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 12 (LOCF) 
– ANCOVA – Contralateral eye – m-ITT set 
Table 4.82 –Sensitivity analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 12 (LOCF) 
– ANCOVA – Contralateral eye – m-ITT set 
Table 4.83 –Sensitivity analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 12 (LOCF) 
– ANCOVA – Contralateral eye – m-ITT set 
 
Table 4.84 –Sensitivity analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 12 (LOCF) 
– ANCOVA – Contralateral eye – PP set 
Table 4.85 –Sensitivity analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 12 (LOCF) 
– ANCOVA – Contralateral eye – PP set 
Table 4.86 –Sensitivity analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 12 (LOCF) 
– ANCOVA – Contralateral eye – PP set 
 
Same table 4.16 
 
 


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20APR2021  
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Table 4.87 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 12 
(Observed) – ANCOVA – Contralateral eye – m-ITT set 
Table 4.88 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 12 
(Observed) – ANCOVA – Contralateral eye – m-ITT set 
Table 4.89 –Sensitivity analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 12 
(Observed) – ANCOVA – Contralateral eye – m-ITT set 
 
Table 4.90 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 12 
(Observed) – ANCOVA – Contralateral eye – PP set 
Table 4.91 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 12 
(Observed) – ANCOVA – Contralateral eye – PP set 
Table 4.92 –Sensitivity analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 12 
(Observed) – ANCOVA – Contralateral eye – PP set 
 
Same as Table 4.25 


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Statistical Analysis Plan 
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Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 4.93 – Analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 6 – MMRM analysis 
– Worse eye – m-ITT set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Number of patients in the model 
xx 
xx 
 
 
 
Change from baseline at 08:00 at Week 6 
 
 
   Adjusted mean (SE) 
xx.x (xx.x) xx.x (xx.x) 
   Adjusted mean difference (T4032 vs Lumigan) 
xx.x (xx.x) 
 
   95% CI of adjusted mean difference 
[xx.x ; xx.x] 
 
   p-value 
0.xxx 
 
 
 
 
Type III test of fixed effects (p-value) 
 
 
   Treatment 
0.xxx 
 
   Visit 
0.xxx 
 
   Baseline IOP 
0.xxx 
 
   Wash-out duration 
0.xxx 
 
   Country 
0.xxx 
 
   Treatment x Visit Interaction 
0.xxx 
  
   Baseline IOP x Visit Interaction 
0.xxx 
 
Using the MMRM model presented in Table 4.7 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
Table 4.94 –Analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 6 – MMRM analysis – 
Worse eye – m-ITT set 
Table 4.95 –Analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 6 – MMRM analysis – 
Worse eye – m-ITT set 
 
Table 4.96 –Analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 6 – MMRM analysis – 
Worse eye – PP set 
Table 4.97 –Analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 6 – MMRM analysis – 
Worse eye – PP set 
Table 4.98 –Analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 6 – MMRM analysis – 
Worse eye – PP set 
 
Table 4.99 –Analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 6 – MMRM analysis – 
Contralateral eye – m-ITT set 
Table 4.100 –Analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 6 – MMRM analysis 
– Contralateral eye – m-ITT set 
Table 4.101 –Analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 6 – MMRM analysis 
– Contralateral eye – m-ITT set 
 
 
 
 
 
 
 


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20APR2021  
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Table 4.102 –Analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 6 – MMRM analysis 
– Contralateral eye – PP set 
Table 4.103 –Analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 6 – MMRM analysis 
– Contralateral eye – PP set 
Table 4.104 –Analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 6 – MMRM analysis 
– Contralateral eye – PP set 
 
Same as Table 4.93 


Laboratoires THÉA  
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Statistical Analysis Plan 
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Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 4.105 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 6 
(observed) – ANCOVA – Worse eye – m-ITT set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Number of patients in the model 
xx 
xx 
 
 
 
Change from baseline at 08:00 at Week 6 (observed) 
 
 
   Adjusted mean (SE) 
xx.x (xx.x) xx.x (xx.x) 
   Adjusted mean difference (T4032 vs Lumigan) (SE) 
xx.x (xx.x) 
 
   95%CI of adjusted mean difference 
[xx.x ; xx.x] 
 
   p-value 
0.xxx 
 
 
 
 
Type III test of fixed effects (p-value) 
 
 
   Treatment 
0.xxx 
 
   Baseline IOP 
0.xxx 
 
   Wash-out duration 
0.xxx 
 
   Country 
0.xxx 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Table 4.106 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 6 
(observed) – ANCOVA – Worse eye – m-ITT set 
Table 4.107 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 6 
(observed) – ANCOVA – Worse eye – m-ITT set 
 
Table 4.108 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 6 
(observed) – ANCOVA – Worse eye – PP set 
Table 4.109 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 6 
(observed) – ANCOVA – Worse eye – PP set 
Table 4.110 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 6 
(observed) – ANCOVA – Worse eye – PP set 
 
Table 4.111 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 6 
(observed) – ANCOVA – Contralateral eye – m-ITT set 
Table 4.112 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 6 
(observed) – ANCOVA – Contralateral eye – m-ITT set 
Table 4.113 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 6 
(observed) – ANCOVA – Contralateral eye – m-ITT set 
 
Table 4.114 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 08:00 at Week 6 
(observed) – ANCOVA – Contralateral eye – PP set 
Table 4.115 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 10:00 at Week 6 
(observed) – ANCOVA – Contralateral eye – PP set 
Table 4.116 – Sensitivity analysis of the change from baseline in IOP (mmHg) at 16:00 at Week 6 
(observed) – ANCOVA – Contralateral eye – PP set 
 
Same as Table 4.103 
 


Laboratoires THÉA  
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Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
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Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 4.117 – Exploratory analysis of the change from baseline in IOP (mmHg) at Week 6 – Worse eye – 
Impact of circadian rhythm – m-ITT set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Number of patients in the model 
xx 
xx 
 
 
 
Change from baseline at 08:00 at Week 6 
 
 
   Adjusted mean (SE) 
xx.x (xx.x) 
xx.x (xx.x) 
   Adjusted mean difference (T4032 vs Lumigan) 
xx.x (xx.x) 
 
   95% CI of adjusted mean difference 
[xx.x ; xx.x] 
 
   p-value 
0.xxx 
 
 
 
 
Change from baseline at 10:00 at Week 6 
 
 
   Adjusted mean (SE) 
xx.x (xx.x) 
xx.x (xx.x) 
   Adjusted mean difference (T4032 vs Lumigan) 
xx.x (xx.x) 
 
   95% CI of adjusted mean difference 
[xx.x ; xx.x] 
 
   p-value 
0.xxx 
 
 
 
 
Change from baseline at 16:00 at Week 6 
 
 
   Adjusted mean (SE) 
xx.x (xx.x) 
xx.x (xx.x) 
   Adjusted mean difference (T4032 vs Lumigan) 
xx.x (xx.x) 
 
   95% CI of adjusted mean difference 
[xx.x ; xx.x] 
 
   p-value 
0.xxx 
 
 
 
 
 
 
 
Type III test of fixed effects (p-value) 
 
 
   Treatment 
0.xxx 
 
   Visit 
0.xxx 
 
   Time 
0.xxx 
 
   Wash-out duration 
0.xxx 
 
   Country 
0.xxx 
 
   Treatment x Visit Interaction 
0.xxx 
  
   Teatment x Time Interaction 
0.xxx 
 
Using the same model presented in Table 4.70 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
 


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Statistical Analysis Plan 
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Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 4.118 – Summary of IOP (in classes) – Worse eye – m-ITT set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
IOP at (*) 
 
 
   n 
xx 
xx 
   < 18 mmHg 
xx.x (xx.x) 
xx.x (xx.x) 
   95% CI (< 18 mmHg) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
   >= 18 mmHg 
xx.x (xx.x) 
xx.x (xx.x) 
   95% CI (>= 18 mmHg) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
   Missing data 
xx 
xx 
 (*) Baseline [Day 1], Week 6 and Week 12 at 08:00, 10:00 and 16:00 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Table 4.119 – Summary of IOP (in classes) – Worse eye – PP set 
 
Table 4.120 – Summary of IOP (in classes) – Contralateral eye – m-ITT set 
Table 4.121 – Summary of IOP (in classes) – Contralateral eye – PP set 
 
Same as Table 4.118 
 
 
Table 4.122 – Summary of IOP (mmHg) and Change from baseline in IOP – Worse eye – Patients with 
history of glaucoma – m-ITT set 
Table 4.123 – Summary of IOP (mmHg) and Change from baseline in IOP – Worse eye – Patients with 
history of ocular hypertension – m-ITT set 
 
Table 4.124 – Summary of IOP (mmHg) and Change from baseline in IOP – Worse eye – Patients with 
history of glaucoma – PP set 
Table 4.125 – Summary of IOP (mmHg) and Change from baseline in IOP – Worse eye – Patients with 
history of ocular hypertension – PP set 
 
Table 4.126 – Summary of IOP (mmHg) and Change from baseline in IOP – Contralateral eye – Patients 
with history of glaucoma – m-ITT set 
Table 4.127 – Summary of IOP (mmHg) and Change from baseline in IOP – Contralateral eye – Patients 
with history of ocular hypertension – m-ITT set 
 
Table 4.128 – Summary of IOP (mmHg) and Change from baseline in IOP – Contralateral eye – Patients 
with history of glaucoma – PP set 
Table 4.129 – Summary of IOP (mmHg) and Change from baseline in IOP – Contralateral eye – Patients 
with history of ocular hypertension – PP set 
 
Same as Table 4.1 
 


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Statistical Analysis Plan 
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20APR2021  
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Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 4.130 – Summary of IOP (mmHg) and Change from baseline in IOP – Mean diurnal IOP – Worse 
Eye – m-ITT set 
 
 
Parameter at each visit 
Change from Baseline 
Variable 
Treatment group 
N 
Visit 
n 
Mean (SD) 
Median Min ; Max 95% CI (Mean) 
n 
Mean (SD) 
Median Min ; Max 95% CI (Mean) 
IOP 
(mmHg)  
T4032 
XX Baseline XX XX.X (X.X) 
XX.X 
XX ; XX 
[XX.X;XX.X] 
 
 
 
 
 
 
 
 
Week 6 XX XX.X (X.X) 
XX.X 
XX ; XX 
[XX.X;XX.X] 
XX XX.X (X.X) 
XX.X 
XX ; XX 
[XX.X;XX.X] 
 
 
 
Week 12 XX XX.X (X.X) 
XX.X 
XX ; XX 
[XX.X;XX.X] 
XX XX.X (X.X) 
XX.X 
XX ; XX 
[XX.X;XX.X] 
 
Lumigan 
XX Baseline XX XX.X (X.X) 
XX.X 
XX ; XX 
[XX.X;XX.X] 
 
 
 
 
 
 
 
 
Week 6 XX XX.X (X.X) 
XX.X 
XX ; XX 
[XX.X;XX.X] 
XX XX.X (X.X) 
XX.X 
XX ; XX 
[XX.X;XX.X] 
 
 
 
Week 12 XX XX.X (X.X) 
XX.X 
XX ; XX 
[XX.X;XX.X] 
XX XX.X (X.X) 
XX.X 
XX ; XX 
[XX.X;XX.X] 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Table 4.131 – Summary of IOP (mmHg) and Change from baseline in IOP – Mean diurnal IOP – Worse 
Eye – PP set 
 
Table 4.132 – Summary of IOP (mmHg) and Change from baseline in IOP – Mean diurnal IOP – 
Contralateral Eye – m-ITT set 
Table 4.133 – Summary of IOP (mmHg) and Change from baseline in IOP – Mean diurnal IOP – 
Contralateral Eye – PP set 
 
Same as Table 130 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 135/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT Set 
 
Table 4.134 – Global assessment of Azopt efficacy by the investigator – m-ITT Set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Global judgment of Azopt efficacy 
 
 
      n 
xx 
xx 
      Very satisfactory 
xx (xx.x%) 
xx (xx.x%) 
      95% CI (Very satisfactory) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
      Satisfactory 
xx (xx.x%) 
xx (xx.x%) 
      95% CI (Satisfactory) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
      Not very satisfactory 
xx (xx.x%) 
xx (xx.x%) 
      95% CI (Not very satisfactory) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
      Unsatisfactory 
xx (xx.x%) 
xx (xx.x%) 
      95% CI (Unsatisfactory) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
      Missing data 
xx 
xx 
 
 
 
Global judgment of Azopt efficacy (grouping) 
 
 
      n 
xx 
xx 
      Very satisfactory + Satisfactory 
xx (xx.x%) 
xx (xx.x%) 
      95% CI (Very satisfactory + Satisfactory) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
      Not very satisfactory + Unsatisfactory 
xx (xx.x%) 
xx (xx.x%) 
      95% CI (Not very satisfactory + Unsatisfactory) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
      Missing data 
xx 
xx 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: PP set 
 
Table 4.135 – Global assessment of Azopt efficacy by the investigator – PP set 
Same as Table 134 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 136/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: m-ITT set 
 
Table 4.136 – Global assessment of efficacy by the investigator – m-ITT set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
p-value 
Time (*) 
 
 
 
   Global judgment of the efficacy 
 
 
 
      n 
xx 
xx 
 
      Very satisfactory 
xx (xx.x%) 
xx (xx.x%) 
 
      95% CI (Very satisfactory) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
      Satisfactory 
xx (xx.x%) 
xx (xx.x%) 
 
      95% CI (Satisfactory) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
      Not very satisfactory 
xx (xx.x%) 
xx (xx.x%) 
 
      95% CI (Not very satisfactory) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
      Unsatisfactory 
xx (xx.x%) 
xx (xx.x%) 
 
      95% CI (Unsatisfactory) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
      Missing data 
xx 
xx 
 
 
 
 
 
   Global judgment of the efficacy (grouping) 
 
 
0.xxx (CMH) 
      n 
xx 
xx 
 
      Very satisfactory + Satisfactory 
xx (xx.x%) 
xx (xx.x%) 
 
      95% CI (Very satisfactory + Satisfactory) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
      Not very satisfactory + Unsatisfactory 
xx (xx.x%) 
xx (xx.x%) 
 
      95% CI (Not very satisfactory + Unsatisfactory) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
      Missing data 
xx 
xx 
 
 
 
 
 
CMH : Cochran-Mantel-Haenszel stratified by country 
       (*) Week 6 / Week 12 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: PP set 
 
Table 4.137 – Global assessment of efficacy by the investigator – PP set 
Same as Table 136 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 137/163 
 
 
 
 
 
 
 
 
 
5. Safety analysis 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 5.1 – Conjunctival hyperaemia using slit lamp examination – Worse eye – Safety set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
p-value (**) 
(*) 
 
 
0.xxx (CMH) 
  n 
xx 
xx 
 
  0 
xx (xx.x%) 
xx (xx.x%) 
 
  95% CI (0) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
  1 
xx (xx.x%) 
xx (xx.x%) 
 
  95% CI (1) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
  2 
xx (xx.x%) 
xx (xx.x%) 
 
  95% CI (2) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
  3 
xx (xx.x%) 
xx (xx.x%) 
 
  95% CI (3) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
  4 
xx (xx.x%) 
xx (xx.x%) 
 
  95% CI (4) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
  5 
xx (xx.x%) 
xx (xx.x%) 
 
  95% CI (5) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
  Missing data 
xx (xx.x%) 
xx (xx.x%) 
 
(CMH) Cochran Mantel Haenszel test with modified ridit scores  
(*) Screening / Baseline – Day 1/Week 6 / Week 12 
(**) p-value for Week 6 and Week 12 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 138/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 5.2 – Conjunctival hyperaemia using slit lamp examination – Change from baseline (in classes) – 
Worse eye – Safety set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
p-value 
(*) 
 
 
 
   Change from baseline 
 
 
 
       n 
xx 
xx 
 
       … 
xx (xx.x%) 
xx (xx.x%) 
 
       -1 
xx (xx.x%) 
xx (xx.x%) 
 
       0 
xx (xx.x%) 
xx (xx.x%) 
 
       1 
xx (xx.x%) 
xx (xx.x%) 
 
       … 
xx (xx.x%) 
xx (xx.x%) 
 
       Missing data 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
   Change from baseline 
 
 
 
       n 
xx 
xx 
 
       Improvement 
xx (xx.x%) 
xx (xx.x%) 
 
       95% CI (Improvement) 
[xx.x%;xx.x%] 
[xx.x%;xx.x%] 
 
       Absence stable 
xx (xx.x%) 
xx (xx.x%) 
 
       95% CI (Absence stable) 
[xx.x%;xx.x%] 
[xx.x%;xx.x%] 
 
       Presence stable 
xx (xx.x%) 
xx (xx.x%) 
 
       95% CI (Presence stable) 
[xx.x%;xx.x%] 
[xx.x%;xx.x%] 
 
       Worsening 
xx (xx.x%) 
xx (xx.x%) 
 
       95% CI (Worsening) 
[xx.x%;xx.x%] 
[xx.x%;xx.x%] 
 
       Missing data 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
   Change from baseline 
 
 
0.xxx (CMH) 
       n 
xx 
xx 
 
       Improvement 
xx (xx.x%) 
xx (xx.x%) 
 
       95% CI (Improvement) 
[xx.x%;xx.x%] 
[xx.x%;xx.x%] 
 
       No change 
xx (xx.x%) 
xx (xx.x%) 
 
       95% CI (No change) 
[xx.x%;xx.x%] 
[xx.x%;xx.x%] 
 
       Worsening 
xx (xx.x%) 
xx (xx.x%) 
 
       95% CI (Worsening) 
[xx.x%;xx.x%] 
[xx.x%;xx.x%] 
 
       Missing data 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
   Change from baseline 
 
 
 
       n 
xx 
xx 
 
       Improvement of more than 1 point 
xx (xx.x%) 
xx (xx.x%) 
 
       95% CI (Improvement of more than 1 point) 
[xx.x%;xx.x%] 
[xx.x%;xx.x%] 
 
       No significant change (change between -1 and 1). 
xx (xx.x%) 
xx (xx.x%) 
 
       95% CI (No significant change (change between -1 and 1)) 
[xx.x%;xx.x%] 
[xx.x%;xx.x%] 
 
       Worsening of more than 1 point 
xx (xx.x%) 
xx (xx.x%) 
 
       95% CI (Worsening of more than 1 point) 
[xx.x%;xx.x%] 
[xx.x%;xx.x%] 
 
       Missing data 
xx (xx.x%) 
xx (xx.x%) 
 
(CMH) Cochran Mantel Haenszel test with modified ridit scores  
(*) Week 6 / Week 12 
 
Name of SAS program: P:\ THEA\LT2347\Analyse\Pgm\nom_du_programme.sas 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 139/163 
 
 
 
 
 
 
 
 
 
Date and time program was run: JJMMMYYYY HH:MM 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 5.3 – Conjunctival hyperaemia using slit lamp examination – Contralateral eye – Safety set 
Same as Table 5.1 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 5.4 – Conjunctival hyperaemia using slit lamp examination – Change from baseline (in classes) – 
Contralateral eye – Safety set 
Same as Table 5.2 
 
Name of SAS program: P:\ THEA\LT2347\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 140/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 5.5 – Subjective ocular symptoms throughout the day – Symptom (*) – Safety set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
p-value (***) 
(**) 
 
 
0.xxx (CMH) 
  n 
xx 
xx 
 
  0: Absent 
xx (xx.x%) 
xx (xx.x%) 
 
  95% CI (0) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
  1: Present but not disturbing 
xx (xx.x%) 
xx (xx.x%) 
 
  95% CI (1) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
  2: Disturbing 
xx (xx.x%) 
xx (xx.x%) 
 
  95% CI (2) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
  3: Very distressing 
xx (xx.x%) 
xx (xx.x%) 
 
  95% CI (3) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
  Missing data 
xx (xx.x%) 
xx (xx.x%) 
 
(CMH) Cochran Mantel Haenszel test with modified ridit scores  
(*) Irritation-burning / Stinging / Itching / Tearing / Eye dryness feeling / Foreign body sensation 
(**) Screening / Baseline – Day 1 / Week 6 / Week 12 
(***) p-alue for Week 6 and Week 12 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 141/163 
 
 
 
 
 
 
 
 
 
 Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 5.6 – Total score of subjective ocular symptoms throughout the day – Safety set 
 
 
 
 
 
Parameter at each visit 
Change from Baseline 
Variable 
Treatment group 
N 
Visit 
n 
Mean (SD) Median Min ; Max 95% CI (Mean) 
n 
Mean (SD) Median Min ; Max 95% CI (Mean) 
Total score 
T4032 
XX Screening XX 
XX.X (X.X) XX.X 
XX ; XX 
[XX.X;XX.X] 
 
 
 
 
 
 
 
 
Baseline 
XX 
XX.X (X.X) XX.X 
XX ; XX 
[XX.X;XX.X] 
 
 
 
 
 
 
 
 
Week 6 
XX 
XX.X (X.X) XX.X 
XX ; XX 
[XX.X;XX.X] XX XX.X (X.X) XX.X 
XX ; XX 
[XX.X;XX.X] 
 
 
 
Week 12 
XX 
XX.X (X.X) XX.X 
XX ; XX 
[XX.X;XX.X] XX XX.X (X.X) XX.X 
XX ; XX 
[XX.X;XX.X] 
 
Lumigan 
XX Screening XX 
XX.X (X.X) XX.X 
XX ; XX 
[XX.X;XX.X] 
 
 
 
 
 
 
 
 
Baseline 
XX 
XX.X (X.X) XX.X 
XX ; XX 
[XX.X;XX.X] 
 
 
 
 
 
 
 
 
Week 6 
XX 
XX.X (X.X) XX.X 
XX ; XX 
[XX.X;XX.X] XX XX.X (X.X) XX.X 
XX ; XX 
[XX.X;XX.X] 
 
 
 
Week 12 
XX 
XX.X (X.X) XX.X 
XX ; XX 
[XX.X;XX.X] XX XX.X (X.X) XX.X 
XX ; XX 
[XX.X;XX.X] 
Total score ranges from 0 (no symptom) to 18 (very disturbing symptoms) 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 142/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 5.7 – Analysis of the change from baseline in total score of subjective ocular symptoms throughout 
the day – MMRM analysis– Safety set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Number of patients in the model 
xx 
xx 
 
 
 
Change from baseline in total score at Week 6 
 
 
   Adjusted mean (SE) 
xx.x (xx.x) xx.x (xx.x) 
   Adjusted mean difference (T4032 vs Lumigan) (SE) 
xx.x (xx.x) 
 
   95% CI of adjusted mean difference 
[xx.x ; xx.x] 
 
   p-value 
0.xxx 
 
 
 
 
Change from baseline in total score at Week 12 
 
 
   Adjusted mean (SE) 
xx.x (xx.x) xx.x (xx.x) 
   Adjusted mean difference (T4032 vs Lumigan) (SE) 
xx.x (xx.x) 
 
   95% CI of adjusted mean difference 
[xx.x ; xx.x] 
 
   p-value 
0.xxx 
 
 
 
 
Type III test of fixed effects (p-value) 
 
 
   Treatment 
0.xxx 
 
   Visit 
0.xxx 
 
   Baseline value 
0.xxx 
 
   Wash-out duration 
0.xxx 
 
   Country 
0.xxx 
 
   Treatment x Visit Interaction 
0.xxx 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 143/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Listing 5.1 – Listing of data relative to other ocular symptoms throughout the day – Safety set 
 
Actual group Patient 
number 
Assessment time 
Other symptoms 
(SOC / PT) 
Severity 
 
 
Screening 
Baseline – Day 1 
Week 6 
Week 12 
 
 
0 = Absent, 1 = Present but not disturbing, 2 = Disturbing, 3 = Very distressing 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 144/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 5.8 – Subjective ocular symptoms upon instillation – Symptom (*) – Safety set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
p-value 
(**) 
 
 
0.xxx (CMH) 
  n 
xx 
xx 
 
  0: Absent 
xx (xx.x%) 
xx (xx.x%) 
 
  95% CI (0) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
  1: Present but not disturbing 
xx (xx.x%) 
xx (xx.x%) 
 
  95% CI (1) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
  2: Disturbing  
xx (xx.x%) 
xx (xx.x%) 
 
  95% CI (2) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
  3: Very distressing 
xx (xx.x%) 
xx (xx.x%) 
 
  95% CI (3) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
  Missing data 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
(CMH) Cochran Mantel Haenszel test with modified ridit scores  
(*) Irritation-burning / Stinging / Itching / Tearing / Eye dryness feeling / Foreign body sensation 
(**) Week 6 / Week 12 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 145/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 5.9 – Total score of subjective ocular symptoms upon instillation – Safety set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Week 6 
 
 
   n 
xx 
xx 
   Mean (SD) 
xx.x (xx.x) 
xx.x (xx.x) 
   95% CI (mean) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
   Median 
xx.x 
xx.x 
   Q1 ; Q3 
xx.x 
xx.x 
   Min. ; Max. 
xx ; xx 
xx ; xx 
   Missing data 
xx 
xx 
 
 
 
Week 12 
 
 
   n 
xx 
xx 
   Mean (SD) 
xx.x (xx.x) 
xx.x (xx.x) 
   95% CI (mean) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
   Median 
xx.x 
xx.x 
   Q1 ; Q3 
xx.x 
xx.x 
   Min. ; Max. 
xx ; xx 
xx ; xx 
   Missing data 
xx 
xx 
Total score ranges from 0 (no symptom) to 18 (very disturbing symptoms) 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 146/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 5.10 – Analysis of total score of subjective ocular symptoms upon instillation at week 6 - MMRM 
analysis – Safety set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Number of patients in the model 
xx 
xx 
 
 
 
Total Score at Week 6 
 
 
   Adjusted mean (SE) 
xx.x (xx.x) xx.x (xx.x) 
   Adjusted mean difference (T4032 vs Lumigan) (SE) 
xx.x (xx.x) 
 
   95% CI of adjusted mean difference 
[xx.x ; xx.x] 
 
   p-value 
0.xxx 
 
 
 
 
Total Score at Week 12 
 
 
   Adjusted mean (SE) 
xx.x (xx.x) xx.x (xx.x) 
   Adjusted mean difference (T4032 vs Lumigan) (SE) 
xx.x (xx.x) 
 
   95% CI of adjusted mean difference 
[xx.x ; xx.x] 
 
   p-value 
0.xxx 
 
 
 
 
Type III test of fixed effects (p-value) 
 
 
   Treatment 
0.xxx 
 
   Visit 
0.xxx 
 
   Wash-out duration 
0.xxx 
 
   Country 
0.xxx 
 
   Treatment x Visit Interaction 
0.xxx 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 147/163 
 
 
 
 
 
 
 
 
 
 Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Listing 5.2 – Listing of data relative to other ocular symptoms upon instillation – Safety set 
 
Actual group Patient 
number Assessment time 
Other symptoms 
(SOC / PT) 
Severity 
 
 
Week 6 
Week 12 
 
 
0 = Absent, 1 = Present but not disturbing, 2 = Disturbing, 3 = Very distressing 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 148/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 5.11 – Ocular signs using slit lamp examination - Sign (*) – Worse eye – Safety set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
p-value (***) 
(**) 
 
 
0.xxx (CMH) 
  n 
xx 
xx 
 
  0: None 
xx (xx.x%) 
xx (xx.x%) 
 
  95% CI (0) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
  1: Mild 
xx (xx.x%) 
xx (xx.x%) 
 
  95% CI (1) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
  2: Moderate 
xx (xx.x%) 
xx (xx.x%) 
 
  95% CI (2) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
  3: Severe 
xx (xx.x%) 
xx (xx.x%) 
 
  95% CI (3) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
  0: None 
xx (xx.x%) 
xx (xx.x%) 
 
  Missing data 
xx (xx.x%) 
xx (xx.x%) 
 
(CMH) Cochran Mantel Haenszel test with modified ridit scores  
(*) Blepharitis / Eyelid oedema / Abnormal eyelashes aspect / Folliculo-papillary conjunctivitis / Iris pigmentation 
(**) Screening / Baseline – Day 1 / Week 6 / Week 12 
(***) p-value for Week 6 and Week 12 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 5.12 – Ocular signs using slit lamp examination - Sign (*) – Contralateral eye – Safety set 
Same as Table 5.11 
 
(*) Blepharitis / Eyelid oedema / Abnormal eyelashes aspect / Folliculo-papillary conjunctivitis / Iris pigmentation 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 149/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Listing 5.3 – Listing of data relative to other ocular abnormalities – Safety set 
 
Actual group Patient 
number 
Worse Eye 
Assessment time 
Other symptoms 
(SOC / PT) 
Severity 
Worse eye 
Contralateral eye 
 
 
 
Screening 
Baseline 
Week 6 
Week 12 
 
 
 
0 = Absent, 1 = Present but not disturbing, 2 = Disturbing, 3 = Very distressing 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 150/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 5.13 – Corneal staining according to Oxford grading scheme – Worse eye – Safety set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
p-value(**) 
(*) 
 
 
0.xxx (CMH) 
  n 
xx 
xx 
 
  Grade 0 
xx (xx.x%) 
xx (xx.x%) 
 
  95% CI (Grade 0) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
  Grade 1 
xx (xx.x%) 
xx (xx.x%) 
 
  95% CI (Grade 1) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
  Grade 2 
xx (xx.x%) 
xx (xx.x%) 
 
  95% CI (Grade 2) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
  Grade 3 
xx (xx.x%) 
xx (xx.x%) 
 
  95% CI (Grade 3) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
  Grade 4 
xx (xx.x%) 
xx (xx.x%) 
 
  95% CI (Grade 4) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
  Grade 5 
xx (xx.x%) 
xx (xx.x%) 
 
  95% CI (Grade 5) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
  Missing data 
xx (xx.x%) 
xx (xx.x%) 
 
(CMH) Cochran Mantel Haenszel test with modified ridit scores  
(*) Screening / Baseline – Day 1 / Week 6 / Week 12 
(**) p-value for Week 6 and Week 12 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 5.14 – Corneal staining according to Oxford grading scheme – Contralateral eye – Safety set 
Same as Table 5.13 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 


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Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 151/163 
 
 
 
 
 
 
 
 
 
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Page X / N 
Population: Safety set 
 
Table 5.15 – Far best corrected visual acuity – Worse eye – Safety set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
(*) (LogMar) 
 
 
   n 
xx 
xx 
   Mean (SD) 
xx.x (xx.x) 
xx.x (xx.x) 
   95% CI (mean) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
   Median 
xx.x 
xx.x 
   Q1 ; Q3 
xx.x 
xx.x 
   Min. ; Max. 
xx ; xx 
xx ; xx 
   Missing data 
xx 
xx 
(*) (in classes) 
 
 
   n 
xx 
xx 
   1/10 
xx (xx.x%) 
xx (xx.x%) 
   95% CI (1/10) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
   … 
xx (xx.x%) 
xx (xx.x%) 
   10/10 
xx (xx.x%) 
xx (xx.x%) 
   95% CI (10/10) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
   NA 
xx (xx.x%) 
xx (xx.x%) 
   95% CI (NA) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
   Missing data 
xx 
xx 
 
 
 
(*) Screening / Baseline – Day 1 / Week 12 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 5.16 – Far best corrected visual acuity – Contralateral eye – Safety set 
Same as Table 5.15 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 


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Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 152/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Azopt Safety Set 
 
Table 5.17 – Azopt Ocular tolerance by the investigator – Azopt Safety Set 
 
 
Total 
(N=XX) 
Global judgment of the Azopt ocular tolerance 
 
      n 
xx 
      Very satisfactory 
xx (xx.x%) 
      95% CI (Very satisfactory) 
[xx.x%;xx.x%] 
      Satisfactory 
xx (xx.x%) 
      95% CI (Satisfactory) 
[xx.x%;xx.x%] 
      Not very satisfactory 
xx (xx.x%) 
      95% CI (Not very satisfactory) 
[xx.x%;xx.x%] 
      Unsatisfactory 
xx (xx.x%) 
      95% CI (Unsatisfactory) 
[xx.x%;xx.x%] 
      Missing data 
xx 
 
 
Global judgment of the Azopt ocular tolerance 
(grouping) 
 
      n 
xx 
      Very satisfactory + Satisfactory 
xx (xx.x%) 
      95% CI (Very satisfactory + Satisfactory) 
[xx.x%;xx.x%] 
      Not very satisfactory + Unsatisfactory 
xx (xx.x%) 
      95% CI (Not very satisfactory + Unsatisfactory) 
[xx.x%;xx.x%] 
      Missing data 
xx 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Azopt Safety Set 
 
Table 5.18 – Azopt Ocular tolerance by the patient – Azopt Safety Set 
Same as Table 5.17 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 


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Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 153/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 5.19 – T4032 or Lumigan Ocular tolerance by the investigator – Safety set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
p-value 
Time (*) 
 
 
 
   Global judgment of the safety 
 
 
 
      n 
xx 
xx 
 
      Very satisfactory 
xx (xx.x%) 
xx (xx.x%) 
 
      95% CI (Very satisfactory) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
      Satisfactory 
xx (xx.x%) 
xx (xx.x%) 
 
      95% CI (Satisfactory) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
      Not very satisfactory 
xx (xx.x%) 
xx (xx.x%) 
 
      95% CI (Not very satisfactory) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
      Unsatisfactory 
xx (xx.x%) 
xx (xx.x%) 
 
      95% CI (Unsatisfactory) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
      Missing data 
xx 
xx 
 
 
 
 
 
   Global judgment of the safety (grouping) 
 
 
0.xxx (CMH) 
      n 
xx 
xx 
 
      Very satisfactory + Satisfactory 
xx (xx.x%) 
xx (xx.x%) 
 
      95% CI (Very satisfactory + Satisfactory) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
      Not very satisfactory + Unsatisfactory 
xx (xx.x%) 
xx (xx.x%) 
 
      95% CI (Not very satisfactory + Unsatisfactory) 
[xx.x%;xx.x%] [xx.x%;xx.x%] 
 
      Missing data 
xx 
xx 
 
 
 
 
 
(CMH) Cochran Mantel Haenszel test  
       (*) Week 6 / Week 12 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 5.20 – T4032 or Lumigan Ocular tolerance by the patient – Safety set 
Same as Table 5.19 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 154/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Azopt Safety set 
 
Table 5.21 – Overview of ocular treatment-emergent adverse events for Azopt – Azopt Safety set 
 
 
Total 
(N=XX) 
Any TEAE 
xx (xx.x%) 
Any serious TEAE 
xx (xx.x%) 
Any IMP-related TEAE 
xx (xx.x%) 
Any TEAE leading to premature IMP withdrawal 
xx (xx.x%) 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 5.22 – Overview of ocular treatment-emergent adverse events for T4032 or Lumigan – Safety set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
Any TEAE 
xx (xx.x%) 
xx (xx.x%) 
Any serious TEAE 
xx (xx.x%) 
xx (xx.x%) 
Any IMP-related TEAE 
xx (xx.x%) 
xx (xx.x%) 
Any TEAE leading to premature IMP withdrawal 
xx (xx.x%) 
xx (xx.x%) 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 


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Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 155/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Azopt Safety set 
 
Table 5.23 – Summary of treatment-emergent ocular AEs for Azopt per SOC and PT – Azopt Safety set 
 
 
Total 
(N=XX) 
 
Nb of AEs 
Nb (%) of 
patients 
At least one (*) 
xx 
x (xx.x%) 
 
 
 
Body system 1 
xx 
xx (xx.x%) 
Preferred term 1 
xx 
xx (xx.x%) 
Preferred term 2 
xx 
xx (xx.x%) 
       … 
 
 
Preferred term n 
xx 
xx (xx.x%) 
Body system 2 
xx 
xx (xx.x%) 
Preferred term 1 
xx 
xx (xx.x%) 
Preferred term 2 
xx 
xx (xx.x%) 
       … 
 
 
Preferred term n 
xx 
xx (xx.x%) 
…. 
 
 
Body system n 
xx 
xx (xx.x%) 
Preferred term 1 
xx 
xx (xx.x%) 
Preferred term 2 
xx 
xx (xx.x%) 
       … 
 
 
Preferred term n 
xx 
xx (xx.x%) 
 
 
 
 (*) TEAE / Serious TEAE / IMP-related TEAE / TEAE leading to premature study drug withdrawal 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Table 5.24 – Summary of treatment-emergent ocular SAEs for Azopt per SOC and PT – Azopt Safety set 
Table 5.25 – Summary of treatment-emergent ocular IMP-related AEs for Azopt per SOC and PT – 
Azopt Safety set 
Table 5.26 – Summary of treatment-emergent ocular AEs for Azopt leading to premature IMP drug 
withdrawal per SOC and PT – Azopt Safety set 
Same as Table 5.23 
 


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Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 156/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 5.27 – Summary of treatment-emergent ocular AEs for LT4032 or Lumigan per SOC and PT – 
Safety set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
 
Nb of AEs 
Nb (%) of 
patients 
Nb of AEs 
Nb (%) of 
patients 
At least one (*) 
xx 
x (xx.x%) 
xx 
x (xx.x%) 
 
 
 
 
 
Body system 1 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
Preferred term 1 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
Preferred term 2 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
       … 
 
 
 
 
Preferred term n 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
Body system 2 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
Preferred term 1 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
Preferred term 2 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
       … 
 
 
 
 
Preferred term n 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
…. 
 
 
 
 
Body system n 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
Preferred term 1 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
Preferred term 2 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
       … 
 
 
 
 
Preferred term n 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
 
 
 
 
 
Nb of AEs: Number of adverse events – Each AE is counted once per System Organ Class 
/ Preferred Term 
Nb (%) of patients: Number (%) of patients with at least one AE - Each patient is counted 
once per Preferred Term then per System Organ Class 
 (*) TEAE / Serious TEAE / IMP-related TEAE / IMP-related Serious TEAE / TEAE leading to premature study 
drug withdrawal 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Table 5.28 – Summary of treatment-emergent ocular SAEs for LT4032 or Lumigan per SOC and PT – 
Safety set 
Table 5.29 – Summary of treatment-emergent ocular IMP-related AEs for LT4032 or Lumigan per SOC 
and PT – Safety set 
Table 5.30 – Summary of treatment-emergent ocular IMP-related SAEs for LT4032 or Lumigan per SOC 
and PT – Safety set 
Table 5.31 – Summary of treatment-emergent ocular AEs for LT4032 or Lumigan leading to premature 
IMP drug withdrawal per SOC and PT – Safety set 
 
Same as Table 5.27 
 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 157/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 5.32 – Summary of treatment-emergent ocular AEs for LT4032 or Lumigan per SOC, PT and 
severity – Safety set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
 
Nb of AEs 
Nb (%) of 
patients 
Nb of AEs 
Nb (%) of 
patients 
At least one AE 
xx 
x (xx.x%) 
xx 
x (xx.x%) 
 
 
 
 
 
Body system 1 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
      Mild 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
      Moderate 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
      Severe 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
Preferred term 1 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
      Mild 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
      Moderate 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
      Severe 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
       … 
 
 
 
 
Preferred term n 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
      Mild 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
      Moderate 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
      Severe 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
…. 
 
 
 
 
Body system n 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
      Mild 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
      Moderate 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
      Severe 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
Preferred term 1 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
      Mild 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
      Moderate 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
      Severe 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
       … 
 
 
 
 
Preferred term n 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
      Mild 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
      Moderate 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
      Severe 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
 
 
 
 
 
Nb of AEs: Number of adverse events – Each AE is counted once per System Organ 
Class / Preferred Term 
Nb (%) of patients: Number (%) of patients with at least one AE - Each patient is 
counted once per Preferred Term then per System Organ Class 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 158/163 
 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 5.33 – Summary of treatment-emergent ocular AEs for LT4032 or Lumigan per SOC, PT and 
relationship with the IMP – Safety set 
 
 
T4032 
(N=XX) 
Lumigan 
(N=XX) 
 
Nb of AEs 
Nb (%) of 
patients 
Nb of AEs 
Nb (%) of 
patients 
At least one AE 
xx 
x (xx.x%) 
xx 
x (xx.x%) 
 
 
 
 
 
Body system 1 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
      Related 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
      Not related 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
Preferred term 1 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
      Related 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
      Not related 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
       … 
 
 
 
 
Preferred term n 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
      Related 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
      Not related 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
…. 
 
 
 
 
Body system n 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
      Related 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
      Not related 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
Preferred term 1 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
      Related 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
      Not related 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
       … 
 
 
 
 
Preferred term n 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
      Related 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
      Not related 
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
 
 
 
 
 
Nb of AEs: Number of adverse events – Each AE is counted once per System Organ 
Class / Preferred Term 
Nb (%) of patients: Number (%) of patients with at least one AE - Each patient is 
counted once per Preferred Term then per System Organ Class 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 159/163 
 
 
 
 
 
 
 
 
 
Study: LT4030-201  
Page X / N 
Population: Safety set 
 
Table 5.34 – Summary of treatment-emergent ocular AEs for T4032 per SOC, PT and maximal severity – 
Safety set 
 
 
Mild 
Moderate 
Severe 
 
Nb (%) of 
patients 
Nb (%) of 
patients 
Nb (%) of 
patients 
Body system 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Preferred term 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Preferred term 2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
       … 
 
 
 
Preferred term n 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Body system 2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Preferred term 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Preferred term 2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
       … 
 
 
 
Preferred term n 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
…. 
 
 
 
Body system n 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Preferred term 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Preferred term 2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
       … 
 
 
 
Preferred term n 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
Nb (%) of patients: Number (%) of patients with at least one AE - Each patient is 
counted once per Preferred Term then per System Organ Class 
 
Name of SAS program: B:\THEA\LT4030-201\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4030-201  
Page X / N 
Population: Safety set 
 
Table 5.35 – Summary of treatment-emergent ocular AEs for Lumigan per SOC, PT and maximal 
severity –Safety set  
Same as Table 5.34 
 
Name of SAS program: B:\THEA\LT4030-201\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021  
Page 160/163 
 
 
 
 
 
 
 
 
 
Study: LT4030-201  
Page X / N 
Population: Safety set 
 
Table 5.36 – Summary of treatment-emergent ocular AEs for T4032 per SOC, PT and strongest 
relationship –Safety set 
 
 
Not related 
Related 
 
Nb (%) of 
patients 
Nb (%) of 
patients 
Body system 1 
xx (xx.x%) 
xx (xx.x%) 
Preferred term 1 
xx (xx.x%) 
xx (xx.x%) 
Preferred term 2 
xx (xx.x%) 
xx (xx.x%) 
       … 
 
 
Preferred term n 
xx (xx.x%) 
xx (xx.x%) 
Body system 2 
xx (xx.x%) 
xx (xx.x%) 
Preferred term 1 
xx (xx.x%) 
xx (xx.x%) 
Preferred term 2 
xx (xx.x%) 
xx (xx.x%) 
       … 
 
 
Preferred term n 
xx (xx.x%) 
xx (xx.x%) 
…. 
 
 
Body system n 
xx (xx.x%) 
xx (xx.x%) 
Preferred term 1 
xx (xx.x%) 
xx (xx.x%) 
Preferred term 2 
xx (xx.x%) 
xx (xx.x%) 
       … 
 
 
Preferred term n 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Nb (%) of patients: Number (%) of patients with at least one AE - 
Each patient is counted once per Preferred Term then per System 
Organ Class 
 
Name of SAS program: B:\THEA\LT4030-201\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4030-201  
Page X / N 
Population: Safety set 
 
Table 5.37 – Summary of treatment-emergent ocular AEs for Lumigan per SOC, PT and strongest 
relationship –Safety set 
Same as Table 5.36 
 
Name of SAS program: B:\THEA\LT4030-201\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021 
Page 161/163 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Safety set 
 
Table 5.38 – Overview of systemic treatment-emergent adverse events for Azopt – Azopt Safety set 
Table 5.39 – Overview of systemic treatment-emergent adverse events for LT4032 or Lumigan –  
Safety set 
 
Table 5.40 – Summary of treatment-emergent systemic AEs for Azopt per SOC and PT – Azopt Safety set 
Table 5.41 – Summary of treatment-emergent systemic SAEs for Azopt per SOC and PT –  
Azopt Safety set 
Table 5.42 – Summary of treatment-emergent systemic IMP-related AEs for Azopt per SOC and PT – 
Azopt Safety set 
Table 5.43 – Summary of treatment-emergent systemic AEs for Azopt leading to premature IMP drug 
withdrawal per SOC and PT – Azopt Safety set 
 
Table 5.44 – Summary of treatment-emergent systemic AEs for LT4032 or Lumigan per SOC and PT – 
Safety set 
Table 5.45 – Summary of treatment-emergent systemic SAEs for LT4032 or Lumigan per SOC and PT – 
Safety set 
Table 5.46 – Summary of treatment-emergent systemic IMP-related AEs for LT4032 or Lumigan per 
SOC and PT – Safety set 
Table 5.47 – Summary of treatment-emergent systemic IMP-related SAEs for LT4032 or Lumigan per 
SOC and PT – Safety set 
Table 5. 48 – Summary of treatment-emergent systemic AEs for LT4032 or Lumigan leading to 
premature study drug withdrawal per SOC and PT – Safety set 
 
Table 5.49 – Summary of treatment-emergent systemic AEs for LT4032 or Lumigan per SOC, PT and 
severity – Safety set 
Table 5.50 – Summary of treatment-emergent systemic AEs for LT4032 or Lumigan per SOC, PT and 
relationship with the IMP – Safety set 
Table 5.51 – Summary of treatment-emergent systemic AEs for T4032 per SOC, PT and maximal severity 
–Safety set 
Table 5.52 – Summary of treatment-emergent systemic AEs for Lumigan per SOC, PT and maximal 
severity –Safety set 
Table 5.53 – Summary of treatment-emergent systemic AEs for T4032 per SOC, PT and strongest 
relationship –Safety set 
Table 5.54 – Summary of treatment-emergent systemic AEs for Lumigan per SOC, PT and strongest 
relationship –Safety set 
 
Same as Tables 5.23 to 5.37 
 
 
Table 5.55 – Summary of treatment-emergent non-serious AEs for LT4032 or Lumigan per SOC and PT 
– Safety set 
Table 5.56 – Summary of treatment-emergent non-serious AEs for LT4032 or Lumigan per SOC and PT 
with PT is ≥5% for one group – Safety set 
 
Same as Table 5.27 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021 
Page 162/163 
 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Enrolled patients 
 
Listing 5.6 – Listing of Non emergent AEs – Enrolled patients 
 
Actual 
group 
Patient’s 
identifier 
– Gender 
– Age at 
baseline 
Worse 
Eye 
Diagnosis 
(verbatim) SOC / PT Localisation 
Date-Time 
of 
occurence / 
Date-Time 
of recovery 
or death 
Time 
to 
occu-
rence 
(days) 
AE 
duration 
(days) 
Outcome 
Frequency 
and details Severity 
Action taken 
regarding 
the IMP 
Requirement 
for therapy 
adaptation / 
modification 
Requirement 
for surgical / 
medical 
procedure 
Serious
ness 
Relationship 
with  IMP / 
with procedure 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Listing 5.7 – Listing of treatment-emergent AEs for Azopt – Azopt Safety Set 
Listing 5.8 – Listing of treatment-emergent SAEs for Azopt – Azopt Safety Set 
Listing 5.9 – Listing of treatment-emergent IMP-related AEs for Azopt – Azopt Safety Set 
Listing 5.10 – Listing of treatment-emergent systemic AEs for Azopt leading to premature IMP drug withdrawal – Azopt Safety Set 
 
Listing 5.11 – Listing of treatment-emergent AEs for T4032 or Lumigan – Safety Set 
Listing 5.12 – Listing of treatment-emergent SAEs for T4032 or Lumigan – Safety Set 
Listing 5.13 – Listing of treatment-emergent IMP-related AEs for T4032 or Lumigan – Safety Set 
Listing 5.14 – Listing of treatment-emergent systemic AEs for T4032 or Lumigan leading to premature IMP drug withdrawal – Safety Set 
Listing 5.15 – Listing of AEs for T4032 or Lumigan occur after the day of the maximal date between last IMP instillation and Visit 4 (Week 12) –Safety Set 
 
Same as Listing 5.6 
 


Laboratoires THÉA  
Protocol n° LT4032-301 
Statistical Analysis Plan 
Final Amendment V01 
20APR2021 
Page 163/163 
 
 
 
 
 
 
 
Study: LT4032-301  
Page X / N 
Population: Enrolled patients 
 
Listing 5.16 – Listings of COVID-19 AEs – Enrolled patients 
 
Actual 
group 
Patient’s 
identifier 
– Gender 
– Age at 
baseline 
Worse 
Eye 
Diagnosis 
(verbatim) SOC / PT Localisation 
Date-Time 
of 
occurence / 
Date-Time 
of recovery 
or death 
Time 
to 
occu-
rence 
(days) 
Treatment-
emergence 
AE 
duration 
(days) 
Outcome 
Frequency 
and details Severity 
Action taken 
regarding 
the IMP 
Requirement 
for therapy 
adaptation / 
modification 
Requirement 
for surgical / 
medical 
procedure 
Serious
ness 
Relationship 
with  IMP / 
with procedure 
 
 
 
 
 
 
 
 
No / 
TEAE 
Azopt / 
TEAE 
T4032 or 
Lumigan / 
Post AE 
 
 
 
 
 
 
 
 
 
 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM 
 
 
Study: LT4032-301  
Page X / N 
Population: Enrolled patients 
 
Listing 5.17 – Listings of Deaths, Other Serious adverse events, discontinuations due to adverse events and other adverse events of special interest 
(for narratives)– Enrolled patients 
Same as Table 5.16 
 
Name of SAS program: B:\THEA\LT4032-301\Analyse\Pgm\nom_du_programme.sas 
Date and time program was run: JJMMMYYYY HH:MM