A Multicenter, Non-comparative, Phase IV Clinical Trial Evaluation of the Effect of Cogmax® in the Treatment of Memory Loss in Postmenopausal Women
Phase: NA
Conditions: Memory Disorders, Postmenopausal Symptoms
Sponsor: Eurofarma Laboratorios S.A.

 
eurofarma.com 
 
 
 
 
Study Protocol 
 
Official Title of the study: A Multicenter, Non-
comparative, Phase IV Clinical Trial for 
Evaluation of the Effect of Cogmax® in the 
Treatment of Memory Loss in Postmenopausal 
Women 
 
NCT number: NCT03835325  
 
Date of the document: Draft version 1.0 dated 
June 06, 2018 
 
 
 
 
 
 
 

 
- SYNOPSIS – 
Protocol EF152 – COGMAX Trial® 
Draft version 1.0 dated June 06, 2018 
SYNOPSIS 
Title 
A Multicenter, Non-comparative, Phase IV Clinical Trial for Evaluation 
of the Effect of Cogmax® in the Treatment of Memory Loss in 
Postmenopausal Women 
Study 
Identification 
EF152 – COGMAX Trial 
Sponsor 
Eurofarma Laboratórios S.A. 
Experimental 
Product 
Cogmax® (soybean oil, magnesium bisglycinate, di-magnesium 
malate, choline bitartrate, fish oil, purified water, zinc bisglycinate, 
selenomethionine, 
DL-alpha-Tocopherol 
acetate, 
calcium 
pantothenate, cyanocobalamin, pyridoxine hydrochloride, thiamine 
mononitrate, folic acid, colecalciferol) 
Study Phase 
Phase IV 
Study 
Rationale 
Complaints regarding memory loss are very frequent in women in the 
menopausal transitional period. The effectiveness of estrogen 
replacement therapy in cognitive improvement is controversial.  
Partial positive results were obtained in some studies regarding 
memory improvement; currently, there is no standard of care that is 
considered effective for these cases. 
Effective pharmacological approaches for treatment of memory loss 
associated with menopause comprise an unmet medical need. 
Cogmax® is a polyvitamin and mineral supplement containing several 
essential elements for cognitive function, which may be a safe 
therapeutic option for these cases. 
Objectives 
Primary Objective 
To assess the effect of Cogmax® on subjective memory loss 
observed after menopause. 
Secondary Objectives 
- To assess the effect of Cogmax® on attention of postmenopausal 
women. 
- To assess the safety of Cogmax® on postmenopausal women. 
Study Outline 
A Multicenter, non-comparative, phase IV clinical trial (single arm). 
Study 
Population 
80 participants aged between 45 and 60 years old and with 
complaints of memory loss associated with menopause.  
Eligibility 
Criteria 
Inclusion Criteria 
Female subjects who meet all the criteria below will be included: 

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- SYNOPSIS – 
Protocol EF152 – COGMAX Trial® 
Version 1.0 dated September 19, 2018 
1. Age ≥ 45 years and ≤ 60 years. 
2. Complaint of memory loss associated with menopause. 
3. Score ≤ 3.0 (mean value found in elderly subjects1) related to 
the self-efficacy factor, consisting of the sum of the scores for 
the Capability, Control and Change domains obtained through 
the Metamemory in Adulthood Questionnaire - reduced 
version (MIAr)2. 
4. Amenorrhea for at least 1 year and no more than 6 years. 
5. Dosage of Serum FSH > 30 mIU/mL. 
6. Dosage of serum estradiol < 20 pg/mL. 
7. Knowledge of the Portuguese language sufficient to answer 
the questionnaires. 
8. Signature of the Informed Consent Form (ICF) prior to the 
conduction of any study procedure.  
Exclusion criteria 
Subjects who meet at least one of the criteria below will be excluded: 
1. Complaints of hot flashes, insomnia and/or very intense sleep 
disorders, at the discretion of the investigator. 
2. Presence of moderate to serious depression, with score ≥ 18 
at assessment through the Beck depression inventory.3,4 
3. Presence of moderate to serious anxiety, with score ≥ 30 on 
the Beck anxiety inventory.5,6 
4. Initiation of hormone replacement therapy within 6 months 
prior 
to 
study 
inclusion. 
Patients 
receiving 
hormone 
replacement therapy starting more than 6 months before 
inclusion in the study may be included in the study provided 
that the treatment is regular with the same drug and the same 
dose during the last 6 months before inclusion and provided 
that this treatment is maintained throughout the study. 
5. Use 
of 
psychotropic 
medications 
(anticonvulsants, 
benzodiazepines, 
antipsychotics), 
selective 
serotonin 
reuptake inhibitors (SSRIs) and selective serotonin and 
noradrenaline reuptake inhibitors (SNRIs) 
6. Alcoholism and/or use of other illicit drugs. 
7. History of allergy or intolerance to any component of the 
experimental product formulation. 
8. Diagnosis of neurological diseases associated with cognitive 
deficit (including dementia and mental retardation) or 
psychiatric diseases.  

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- SYNOPSIS – 
Protocol EF152 – COGMAX Trial® 
Version 1.0 dated September 19, 2018 
9. Presence of serious or uncontrolled diseases (such as 
decompensated hypothyroidism), at the discretion of the 
investigator (such as stroke, Parkinson’s disease, etc.). 
10. Participation in clinical research protocol within the previous 
12 months, unless, at the discretion of the investigator, their 
participation in the study may incur direct benefit to the 
research participant. 
11. Presence of any condition that, at the discretion of the 
investigator, makes the patient inadequate to participate in the 
study. 
Study 
Duration 
Recruitment period for the study will begin after the required ethical 
and regulatory approvals and it will have an estimated duration of 4 
months.  
A screening period with the maximum duration of 14 days prior to 
study treatment initiation is expected. Each participant will receive the 
treatment with Cogmax ® during 12 weeks (± 4 days).  
Study 
Treatment 
Experimental Product 
Research participants will receive 2 capsules a day (after lunch) of 
Cogmax®, during 12 weeks.  
Visit and 
assessment 
plan 
Each participant must attend four on-site visits in the clinical trial site. 
During the screening visit (VS), which should occur within no longer 
than 14 days prior to treatment initiation (visit 1), the following 
procedures will be performed after ICF signature: verification of 
Eligibility Criteria, collection of demographics, medical history and 
current use of drugs, relevant previous treatments, assessment of 
vital signs, physical examination, collection of blood samples for FSH, 
serum estradiol, TSH and free T4 tests. The MIAr questionnaire and 
the Stroop color-word test will be used7,8.  
During visit 1 (V1), after eligibility criteria review, experimental 
product dispensing will be performed. A daily contact mechanism will 
be implemented with participants, in order to remind them to use the 
study product. The study discontinuation criteria will be verified and 
the data regarding concomitant treatments and adverse event (AE) 
occurrence will be collected.  
During visit 2 (V2), which will occur 42 (± 4) days after visit 1, the 
following procedures will be performed: implementation of MIAr 
questionnaire, accountability and new dispensing of the experimental 
product. The study discontinuation criteria will also be verified and the 
data regarding concomitant treatments and AEs will be collected. 
During the final visit (VF), which will occur 84 (± 4) days after visit 1, 
the following procedures will be performed: measurement of vital 
signs, physical examination, completion of MIAr questionnaire and 
performance of Stroop test and global efficacy assessment by the 

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- SYNOPSIS – 
Protocol EF152 – COGMAX Trial® 
Version 1.0 dated September 19, 2018 
research participant. Collection and accountability of the experimental 
product will also be performed, collecting data regarding concomitant 
treatments and AE occurrence.  
Endpoints 
Primary efficacy endpoint 
• Score regarding the self-efficacy factor, consisting of the sum of 
the scores for the Capability, Control and Change domains in 
MIAr questionnaire. 
Secondary efficacy endpoints 
• Total score obtained through MIAr questionnaire. 
• Score obtained through Stroop color-word test. 
• Global efficacy assessment by the participant. 
Safety endpoints 
• AE profile and incidence, expressed according to MedDRA code 
(The Medical Dictionary for Regulatory Activities). 
• Change of vital signs at the end of treatment (VF) compared to 
baseline (obtained in VS); 
• Treatment discontinuation rate due to AEs. 
Sample Size 
Sample size calculation was based on the following hypothesis test: 
H0: there is no improvement in memory capacity between initial (VS) 
and final assessments (VF), assessed by MIAr questionnaire self-
efficacy factor. 
Ha: there is an improvement in memory capacity between initial (VS) 
and final assessments (VF), assessed by MIAr questionnaire self-
efficacy factor. 
or 
H0: SELF-EF (VF) – SELF-EF (VS) ≤ 0  
Ha: SELF-EF (VF) – SELF-EF (VS) > 0 
where: 
SELF-EF (VS) = mean score of self-efficacy factor in pre-treatment 
(Vs) 
SELF-EF (VF) = mean score of self-efficacy factor in post-treatment 
(VF) 
Therefore, the sample size required to identify an improvement of at 
least 0.2 point, with a standard deviation of 0.6 points1, in the mean 
score of MIAr questionnaire self-efficacy factor is 56 patients. 
Considering the characteristic of assessment through scores varying 
from 1 to 5, an addition of 15% of patients is recommended for the 
correct use of the nonparametric test9; also, considering a loss of 
approximately 20% of patients, the inclusion of at least 80 patients is 
recommended, so that an improvement in memory capacity may be 
identified (measured by MIAr questionnaire self-efficacy factor), with 

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- SYNOPSIS – 
Protocol EF152 – COGMAX Trial® 
Version 1.0 dated September 19, 2018 
80% power and 5% statistical significance (one-sided test). 
Ethical 
aspects 
The study will be conducted according to ethical standards and 
local/international regulations, and it will be approved by the 
Research Ethics Committee (REC) of each participating institution 
prior to its initiation. 
 

 
- SYNOPSIS – 
Protocol EF152 – COGMAX Trial® 
Draft version 1.0 dated June 06, 2018 
Study Scheme 
 
 
 
 
 
 
Screening 
(D
-14 to D
0) 
ICF 
Eligibility 
Beck (anxiety / depression) 
Blood collection (FSH, estradiol, TSH, T4L [free T4]) 
Demographics 
Medical history 
Vital signs 
Physical examination 
Previous/concomitant drugs 
MIAr Questionnaire 
Stroop test 
Eligibility 
Dispensing 
Discontinuation criteria 
Concomitant drugs 
Adverse events 
MIAr Questionnaire 
Collection and accountability 
Dispensing 
Discontinuation criteria 
Concomitant drugs 
Adverse events 
Vital signs 
Physical examination 
MIAr Questionnaire 
Stroop Test 
Global efficacy assessment 
Collection and accountability 
Concomitant drugs 
Adverse events 

Page 7 of 8 
 
- SYNOPSIS – 
Protocol EF152 – COGMAX Trial® 
Version 1.0 dated September 19, 2018 
Visit and assessment schedule 
 
 
VS 
V1 
V2 
VF 
 
(Day -14 to Day 0) (Day 0) (Day 42 ± 4) (Day 84 ± 4) 
Informed Consent Form 
(ICF) / Assent Form 
X 
 
  
  
Inclusion and exclusion 
criteria 
X 
X 
 
  
Demographics 
X 
 
 
 
Medical history 
X 
 
  
  
Previous / concomitant 
treatments 
X 
X 
X 
X 
Vital signs 
X 
 
 
X 
Physical examination 
X 
 
 
X 
Blood collection for FSH, 
serum estradiol, TSH and 
free T4 testsa 
X 
 
  
 
MIAr questionnaire 
X 
 
X 
X 
Stroop color-word test 
X 
 
 
X 
Experimental product 
dispensing 
  
X 
X 
 
Accountability and 
collection of the 
experimental product 
  
 
X 
X 
Dispensation criteria 
  
X 
 X 
  
Assessment of Adverse 
Events 
  
X 
X 
X 
Global efficacy 
assessment by the 
participant 
 
 
 
X 
a Results from dosage tests of FSH, serum estradiol, TSH and free T4 already available 
collected within no longer than 30 days prior to screening visit (VS) will be accepted. In 
this case, visit 1 procedures (V1) must also be performed at this visit (i.e., VS and V1 will 
be performed at the same on-site visit, and the visit day will be considered as Day 0). 
 
 

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- SYNOPSIS – 
Protocol EF152 – COGMAX Trial® 
Version 1.0 dated September 19, 2018 
References 
 
1 Yassuda MS, Lasca VB, Neri AL et al. Meta-memória e auto-eficácia: um 
estudo de validação de instrumentos de pesquisa sobre memoria e 
envelhecimento. Psicol Reflex Crit. 2005;18(1):78-90. 
2 Campelo G, Zortea M, Saraiva R, et al. A short version of the questionnaire of 
metamemory in Adulthood (MIA) in Portuguese. Psicol Reflex Crit. 2016;29(1): 
37-44. 
3 Beck AT, Ward CH, Mendelson M et al. An inventory for measuring 
depression. Arch Gen Psychiatry. 1961;4:561-71. 
4 Gorestein C, Andrade L. Inventário de depressão de Beck: propriedades 
psicométricas 
da 
versão 
em 
português. 
Disponível 
em: 
file:///C:/Users/Cecilia/Downloads/beck-propriedades-
psicometricasGorensteinAndrade1998%20(1).pdf. Acesso em 22 Julho 2018. 
5 Beck AT, Epstein N, Brown G et al. An inventory for measuring clinical 
anxiety: psychometric properties. J Consult Clin Psychol. 1988;56(6):893-7. 
6 Cunha, J. A. (2001). Manual da versão em português das Escalas 
Beck. São Paulo, SP: Casa do Psicólogo.  
7 Stroop Color Word Test (SCWT), Regard 1981, in Spreen & Strauss 
(1998). Versão Victoria; tradução e adaptação de Camargo et al. 
8 Cunha PJ, Nicastri S, de Andrade AGet al. The frontal assessment battery 
(FAS) reveals neurocognitive Dysfunction in substance-dependent individuals 
indistinct executive domains abstract reasoning, motor programming, and 
cognitive flexibility. Addict Behav, 2010;35(10): 875-81. 
9 Erich L. Lehmann, Nonparametrics: Statistical Methods Based on Ranks, 
Revised, 1998, ISBN=978-0139977350, pages 76-81.