Phase III, Randomized, Multicenter, Open-label Clinical Trial to Evaluate the Efficacy and Safety of the Aurora® Digital Medical Device With Conventional Drug Treatment, Compared to Conventional Drug Treatment Alone, in Adult Patients With Moderate to Severe Generalized Anxiety Disorder
Phase: PHASE3
Conditions: General Anxiety Disorder
Sponsor: Psicofarma, S.A. De C.V.

Study: 
INNOVA 2024-01 
Version: 1.2   
Date: July 3rd of 2025 
COFEPRIS  
Registered 
Number: 
253300410C1001/2025 
 
 
 
 
Pag 1 of 8 
 
 
 
 
 
 
 
 
 
 
 
 
 
Phase III, randomized, multicenter, open-label clinical trial to 
evaluate the efficacy and safety of the Aurora® digital 
medical device with conventional drug treatment, compared 
to conventional drug treatment alone, in adult patients with 
moderate to severe generalized anxiety disorder. 
 
STUDY INNOVA 2024-01 
 
 
 
COFEPRIS Mexico Authorization number registered:  
253300410C1001/2025 

Study: 
INNOVA 2024-01 
Version: 1.2   
Date: July 3rd of 2025 
COFEPRIS  
Registered 
Number: 
253300410C1001/2025 
 
 
 
 
Pag 2 of 8 
 
Phase III, randomized, multicenter, open-label clinical trial to evaluate the efficacy and safety of the 
Aurora® digital medical device with conventional drug treatment, compared to conventional drug 
treatment alone, in adult patients with moderate to severe generalized anxiety disorder. 
SUMMARY STUDY INNOVA 2024-01 
Title of the study 
Phase III, randomized, multicenter, open-label clinical trial to evaluate the 
efficacy and safety of the Aurora® digital medical device with conventional 
drug treatment, compared to conventional drug treatment alone, in adult 
patients with moderate to severe generalized anxiety disorder. 
Methodology 
Phase III clinical trial, controlled (with active comparator), randomized, 
open-label, longitudinal, analytical, experimental, prospective, multicenter. 
Duration 
8 months 
Objective 
Primary 
To evaluate the superiority of cognitive behavioral therapy using the 
Aurora® digital medical device + conventional drug treatment, compared 
to conventional drug treatment alone, in reducing anxiety symptoms, as 
assessed by the change in the GAD-7 scale at 12 weeks of treatment, relative 
to baseline. 
Secondary 
- Evaluate the effect of Aurora® + conventional drug treatment, 
compared to conventional drug treatment alone, on the reduction of 
anxiety symptoms, assessed using the GAD-7 scale at 4, 8, and 12 weeks 
of treatment, compared to baseline. 
- 
Evaluate the effect of Aurora® + conventional drug treatment 
versus conventional drug treatment on the reduction of symptoms 
of concern, according to the PSWQ, at 4, 8, and 12 weeks of 
treatment, compared to baseline. 
- 
Evaluate the effect of Aurora® + conventional drug treatment 
versus conventional drug treatment on depressive symptoms, 
according to the PHQ-9 scale, at 4, 8, and 12 weeks of treatment, 
compared to baseline. 
- 
Determine the frequency of psychiatric emergency events at 12 
weeks of treatment in both treatment groups. 
- 
Determine the frequency and characteristics of adverse events and 
incidents during the subjects' participation in the study. 

Study: 
INNOVA 2024-01 
Version: 1.2   
Date: July 3rd of 2025 
COFEPRIS  
Registered 
Number: 
253300410C1001/2025 
 
 
 
 
Pag 3 of 8 
 
- 
Determine the percentage of patients who required a switch from 
SSRIs to SNRIs during the study in both treatment groups. 
- 
Determine the percentage of patients who required a dose increase, 
both those treated with SSRIs and those treated with SNRIs. 
Selection criteria 
Inclusion Criteria: 
1. Men and women aged ≥18 and ≤65 years. 
2. Diagnosis of generalized anxiety disorder (GAD) based on DSM-5-
TR criteria. 
3. Score ≥10 on the GAD-7 (Generalized Anxiety Disorder Scale) 
instrument 
4. That they agree to participate in the study by signing the informed 
consent form. 
 
Exclusion Criteria: 
 
1. Concomitant alcohol use disorder or recreational drug use disorder. 
Consumption of energy drinks. 
2. Excessive caffeine consumption (more than 150 mg per day). 
Patients with hypersensitivity to escitalopram (Selective®) or 
duloxetine (Arquera®) and/or any component of the formulation. 
 
3. Having received psychiatric drug treatment within the 6 months 
prior to inclusion in this protocol, including but not limited to 
prescription drugs such as SSRIs, SNRIs, benzodiazepines, herbal 
medicines, or unauthorized substances such as cannabis, 
microdoses of LSD, CBD, ayahuasca, or any other recreational 
psychotropic substance. 
- 
Having received psychotherapy or having been part of support 
groups, meditation, mindfulness, or equivalent groups will not 
be grounds for exclusion, provided that this has not been 
accompanied by medication aimed at modifying any psychiatric 
disorder. 
4. Any clinical or sociodemographic condition that prevents the use of 
the Aurora® digital medical device as established in this protocol; 
for example, severe visual impairment, complete lack of knowledge 
about the use of personal electronic devices such as cell phones or 
tablets, among others. 
5. Presence of other psychiatric comorbidities, with the exception of 
depressive disorders not induced by substances or medications. 

Study: 
INNOVA 2024-01 
Version: 1.2   
Date: July 3rd of 2025 
COFEPRIS  
Registered 
Number: 
253300410C1001/2025 
 
 
 
 
Pag 4 of 8 
 
6. Patients who, at the time of the selection assessment, present any 
psychiatric emergency (psychosis, catatonia, manic episode, risk of 
self-harm or harm to others, etc.). 
7. Diagnosis or suspicion of bipolar disorder. 
8. History of seizures, even while undergoing anti-seizure treatment. 
9. Identification of prolonged QT interval length on the initial 
assessment electrocardiogram. 
10. Previous diagnosis of chronic liver failure, Child-Pugh class B or C. 
11. Previous diagnosis of chronic kidney disease stage KDIGO 3 or 
higher. 
12. Diagnosis of NYHA functional class III/IV heart failure. 
13. Diagnosis of pheochromocytoma. 
14. Diagnosis of acute or chronic degenerative diseases that are not 
included in control targets, or that, in the investigator's opinion, 
represent an additional risk to the patient. 
15. Patients requiring concomitant treatment with medications 
contraindicated with the use of escitalopram (Selective®) or 
duloxetine (Arquera®), such as the following: monoamine oxidase 
inhibitors 
(MAOIs), 
tricyclic 
antidepressants, 
class 
I 
antiarrhythmics or sodium channel blockers, acetylsalicylic acid, 
cimetidine, 
beta-adrenergic 
blockers, 
buspirone, 
digoxin, 
carbamazepine, lithium, sumatriptan, theophylline, warfarin, 
vortioxetine, 
bupropion, 
mirtazapine, 
agomelatine, 
and 
phentermine. 
16. Any other clinical condition that, in the investigator's opinion, 
contraindicates the use of conventional treatment. 
17. Pregnant or breastfeeding women. 
18. Any alteration in laboratory tests that, in the opinion of the 
Investigator, is considered clinically relevant and represents a risk 
to the patient. 
19. Patients who have received or are scheduled to receive any 
investigational product from another clinical study within 90 days 
prior to the selection process. 
20. Patients who, in the investigator's opinion, are unable to comply 
with the protocol activities or whose inclusion poses a risk to their 
health. 
21. Patients who are receiving cognitive behavioral therapy prior to or 
at the time of study entry. 
 
Elimination Criteria: 

Study: 
INNOVA 2024-01 
Version: 1.2   
Date: July 3rd of 2025 
COFEPRIS  
Registered 
Number: 
253300410C1001/2025 
 
 
 
 
Pag 5 of 8 
 
1. Serious adverse events during the study. 
2. Adverse events that pose a serious threat to public health. 
3. Presence of a psychiatric emergency (psychosis, catatonia, manic 
episode, risk of self-harm or harm to others, etc.) during the study. 
4. Presence of other conditions that, in the opinion of the Investigator, 
may put the patient at risk. 
5. Voluntary withdrawal of the study subject. 
6. Low adherence to treatment (less than 80%). 
Sample size 
The sample size calculation was based on the methodological design 
established as a clinical superiority trial; that is, to determine whether 
Aurora® Digital Therapy for 12 weeks plus conventional drug treatment is 
superior to conventional drug treatment alone. To this end, the following 
superiority hypothesis is considered: H0: μA – μB ≤ δ vs. H1: μA – μB>δ. 
The calculation used the formula recommended by Flight L et al (2015), 
taking as a reference the calculation values published in the study by 
Richards D et al (2020), which determined the efficacy of cognitive 
behavioral therapy using a digital medical device compared to placebo 
using the GAD-7 scale, reporting a detectable mean difference (δ) of 2.59 
points and a standard deviation (σ) of 5.31 points. Considering a value of α 
= 0.05, a value of β = 0.20, and a proportion k = 1, a sample of 134 patients 
was determined to be adequate, with 67 patients per treatment arm. 
However, after considering an approximate loss rate of 20% of the sample 
(26.8 patients), it was deemed appropriate to add 28 more patients to recruit 
a total of 162 patients, 81 patients per treatment arm. 
The calculation was performed with the support of the Epidat statistical 
program: Program for epidemiological data analysis Version 4.2 (2016) 
endorsed by the Pan American Health Organization. 
Intervention 
Test arm: 
Escitalopram (Selective®) 10 mg Tablet (days 1 to 28, 1 tablet/day; at the 
discretion of the principal investigator based on tolerance and therapeutic 
response, increase in dose to 2 tablets per day, from day 29 to the end of the 
study) or Duloxetine (Arquera®) 30 mg 1 capsule/day (with the possibility 
of increasing to 60 mg per day at the discretion of the principal investigator 
based on tolerance and therapeutic response) from day 29 to the end of the 
study + Aurora® digital medical device. 
Comparator arm: 

Study: 
INNOVA 2024-01 
Version: 1.2   
Date: July 3rd of 2025 
COFEPRIS  
Registered 
Number: 
253300410C1001/2025 
 
 
 
 
Pag 6 of 8 
 
Escitalopram (Selective®) 10 mg Tablet (days 1 to 28, 1 tablet/day; at the 
discretion of the principal investigator based on tolerance and therapeutic 
response, increase the dose to 2 tablets per day, from day 29 to the end of 
the study) or Duloxetine (Arquera®) 30 mg 1 capsule/day (with the 
possibility of increasing to 60 mg per day at the discretion of the principal 
investigator based on tolerance and therapeutic response) from day 29 to 
the end of the study. 
Switching to Duloxetine (Arquera®) in cases of intolerance or lack of 
response to escitalopram (Selective®) will not be considered a rescue 
medication and will be considered part of the standard treatment for GAD, 
as indicated in the literature and clinical practice guidelines. based on 
current evidence, it is estimated that switching to another first-line option 
may be necessary in 40 to 50% of patients with GAD after the initial 
therapeutic trial. 
Outcome variables 
Primary Superiority Variable: 
Change in GAD-7 scale score at week 12 compared to baseline, value used 
to determine the primary efficacy variable and evaluate the superiority of 
treatment A over treatment B. 
Other variables of interest for secondary objectives:   
• 
GAD-7 scale score at baseline, week 4, week 8, and week 12. 
• 
PSWQ score at baseline, week 4, week 8, and week 12. 
• 
PHQ-9 scale score at baseline, week 4, week 8, and week 12. 
• 
Percentage of patients switching from SSRIs to SNRIs. 
• 
Percentage of treatment adherence at visits 3 to 5. 
• 
Presence of psychiatric urgency. 
• 
Adverse events. 
• 
Concomitant medications. 
 
Sociodemographic variables and other variables: 
Age, sex, weight, body mass index, vital signs, body mass index, history of 
smoking. 

Study: 
INNOVA 2024-01 
Version: 1.2   
Date: July 3rd of 2025 
COFEPRIS  
Registered 
Number: 
253300410C1001/2025 
 
 
 
 
Pag 7 of 8 
 
Statistical methods 
The analysis of the primary efficacy variable (change in GAD-7 score) will 
be performed using a covariance analysis model (ANCOVA) on the per-
protocol population. 
 
Dependent variable: 
Change from baseline = GAD-7 post-treatment − GAD-7 baseline 
Predictors: Treatment (categorical variable [A vs. B]), GAD-7 baseline 
(continuous covariate [adjusted to reduce standard error]), research center 
(fixed effect [to control for heterogeneity between sites]). 
Taking the above into account, and given that the minimum clinically 
significant change on the GAD-7 scale is 3 points, as established by Kroenke 
et al. (2019), the following hypotheses aimed at testing superiority of efficacy 
will be considered for this protocol: 
• 
H0: μA – μB ≤ 3 (Treatment A is not clinically superior to B at 12 
weeks). 
•    H1: μA − μB > 3 (Treatment A is clinically superior to B at 12 weeks). 
 
Inference and Success Criteria: 
– 
Effect estimate: The adjusted difference β1 (A vs. B) and its 
standard error will be calculated using least squares. 
– 
Superiority test: One-tailed t-statistic, p-value (Ho will be rejected 
if p < 0.025 [one-tailed α level]). 
– 
Confidence interval: One-tailed 97.5% CI for β1: 
 
– 
Clinical superiority will be declared only if p-value < 0.025 and 
lower limit (LL) of the 97.5% CI > 3. 

Study: 
INNOVA 2024-01 
Version: 1.2   
Date: July 3rd of 2025 
COFEPRIS  
Registered 
Number: 
253300410C1001/2025 
 
 
 
 
Pag 8 of 8 
 
For descriptive statistics, measures of central tendency will be used for 
numerical variables with parametric distribution, such as mean and 
standard deviation, and measures of position will be used for numerical 
variables with nonparametric distribution, such as median and 
interquartile range. Rates and proportions will be used for categorical 
variables. Inferential statistics will be determined with a 95% confidence 
interval, and p<0.05 will be considered significant for all tests. Based on the 
parametric distribution of the variables, differences between numerical 
variables will be determined using Student's t-test or Mann-Whitney's U 
test. Where appropriate, the numerical correlation of variables will be 
evaluated using Spearman's test if the distribution is non-parametric, and 
Pearson's test if it is parametric. The association between categorical 
variables will be evaluated using the χ² test, and if necessary, the association 
of numerical variables with categorical variables will be evaluated using 
logistic regression. 
Keywords 
Generalized anxiety disorder, digital therapy, cognitive behavioral therapy, 
pharmacological treatment.