Clinical trial NCT04037748
Conditions: Healthy
Keywords: Eutirox® Puran T4® Levothyroxine
Sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Start date: 2019-06-25; Completion date: 2019-09-11
Enrollment: 72 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The study was to verify if the test formulation of Levothyroxine sodium presents an equivalent rate and extension of absorption to the comparator formulation when administered with the same dosage and under fasting conditions and after baseline correction concentrations.

Detailed description:

Arms: arm 1: Participants received single oral dose of Puran T4® 600 micrograms (mcg) (3 tablets of 200 mcg Levothyroxine sodium) in Treatment Period 1 followed by single oral dose of Eutirox® 600 mcg (3 tablets of 200 mcg Levothyroxine sodium) in Treatment Period 2 under fasting conditions. A wash-out period of 70 days was maintained between the Treatment Periods 1 and 2. arm 2: Participants received single oral dose of Eutirox® 600 mcg (3 tablets of 200 mcg Levothyroxine sodium) in Treatment Period 1 followed by single oral dose of Puran T4® 600 mcg (3 tablets of 200 mcg Levothyroxine sodium) in Treatment Period 2 under fasting conditions. A wash-out period of 70 days was maintained between the Treatment Periods 1 and 2.
Interventions: intervention 1: Puran T4® intervention 2: Eutirox®
Intervention descriptions: intervention 1: Participants who received a single oral dose of Puran T4® 600 mcg tablets (3 tablets of 200 mcg Levothyroxine sodium) in either Treatment Period 1 or 2 under fasting conditions. intervention 2: Participants who received a single oral dose of Eutirox® 600 mcg tablets (3 tablets of 200 mcg Levothyroxine sodium) in either Treatment Period 1 or 2 under fasting conditions.

Protocol documents:
Prot_SAP_000.pdf: 
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
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7
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*

**
33&
7
					
*+

*+

*+
33
*,

*,
3
$"*

*
318
*

*
3&.
*
*
*
3>
$	+
+
+
3?
A	 +

+

+
333
	

+

+
33
-7(-7,
+

+
331
A7*
+

+
33&
6+
*
+
33>
+

	
	
+

+
33
8+

+
3
C	
			
	
+

+

8				
;)		
+*

+*
313
++

++
31
-			

++

++
311
++

$		0$		+,

$	+,
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
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PPD




	
			 		






)	+,

	7	+,

+
3111D
	+

+
31&
$					
+
*
+
*
+
+
+
+
+
,
+
,
+

+

8		+

+
3&
		
	+
*

	,
+
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PROTOCOL | 
 
VERSION 4.0 | October 31st, 2018. 
 
 1 
 
 
 
 
Annex 3 | Free and Informed Consent Form 
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FREE AND INFORMED CONSENT FORM- FICF 
 
 
 
___________________                 _______________              __________________________ 
             Heading of Research Participant               Heading of Physician                      Heading of main investigator 
                             
 
Page 1 of 12                                                     FICF – 
 Version 4.0 Date: October 31st, 2018 
 
Research Title: Pharmaceutical bioequivalence evaluation of the pharmaco Levothyroxine sodium - 
Eutirox®200mcg (Merck, S.A. de C.V.) under tablet form versus Puran T4® 200mcg (Sanofi-Aventis 
Farmacêutica Ltda) under tablet form, in healthy male and female research participants under fasting 
conditions, using techniques Liquid Chromatography. 
Main Investigator: 
 
You are invited to participate in a clinical research as a study participant (an individual who is priorly 
informed and consents to participate in a research voluntarily, or under the clarification and 
authorization of her/his legal responsible). 
Your participation is important, however, you should not participate against your will, and therefore, 
before agreeing to participate in this research, it is important that you read this consent form along with 
the team of 
, as they will be able to assist you in clarifying completely the detailed nature of the 
research which you are being invited to participate, so that you understand the explanation of the 
proposed procedures. Your participation is voluntary (i.e., it depends on your willingness to participate) 
and you have the freedom to withdraw or discontinue participation in this clinical study at the moment 
you want. 
This document is known as an informed consent form (ICF) and its name suggests that you should be 
able to decide whether or not to participate in the study only after having read and understood it. 
Read carefully the information below and ask any questions you want, for all the procedures of this 
research are clarified. 
I, ______________________________________________________, am being invited to participate in 
the clinical study mentioned above, which is under the responsibility of the physician 
 and main investigator 
. 
STUDY OBJECTIVE 
1.
The study objective is to verify through a single dose study, if the test formulation of 
Levothyroxine sodium presents an equivalent rate and extension of absorption to the comparator 
formulation when administered with the same dosage and under fasting conditions and after baseline 
correction concentrations (baseline correction of thyroxine hormone that you already have in your 
body). 
PROCEDURES 
2. Pre-study (defined as the recruitment and selection period): 
Before your participation in the study you were invited to come to 
 to check your health condition. 
Upon arrival at the center you signed the Recruitment Term that allowed the recruitment procedures 
that included medical evaluation, anthropometric data collection, and pre-study exams. So you've been 
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FREE AND INFORMED CONSENT FORM- FICF 
 
 
 
___________________                 _______________              __________________________ 
             Heading of Research Participant               Heading of Physician                      Heading of main investigator 
                             
Page 2 of 12                                                     FICF – 
 Version 4.0 Date: October 31st, 2018 
 
submitted to a thorough examination, checking pulse, temperature and blood pressure. You've been 
subjected to an electrocardiographic examination (examination of the heart). The doctor asked if you 
have or have had a disease and if you are taking any medication.  Samples of Blood, urine and feces 
samples were collected for laboratory tests, including complete blood count (white blood cell count, 
erythrocyte), blood chemistries (blood glucose, total protein, albumin, transaminases, creatinine, urea, 
uric acid, alkaline phosphatase, total bilirubin and fractions, cholesterol and triglycerides), hepatitis B, 
hepatitis C, AIDS (HIV 1 and HIV 2) tests and urinalysic (urine I).  
For your participation in this study, it will be necessary to perform the following tests: TSH (thyroid 
stimulating hormone), free and total T4 (Levotiroxin), free and total T3 for evaluation of your thyrodial 
function (gland responsible for production of two hormones T3 and T4). 
On the day of admission, the following procedures will be performed: 
Pregnancy test will be performed through urine dipstick testing upon patient’s admission in the period 1 
and 2. 
At time of admission (Periods 1 and 2) the drug detection test will be performed through urine dipstick 
test and the alcohol detection test will be performed through the breathalyzer. 
The following drugs can be detected in drug test: Methamphetamine, Opiate, Morphine, 
Tetrahydrocannabinol - THC (Marijuana/Cannabis), Amphetamine, Benzoylecgonine (cocaine), 
benzodiazepine. 
Clinical evaluation for reassessment of your eligibility (if you are fit) to participate in the study. 
Post-study (at the end of the study - after all procedures): 
To check your health condition after you receive the drug, you will be subjected to an 
electrocardiographic examination (heart exam). Blood, urine and feces samples will be collected for 
laboratory tests, including complete blood count (white blood cell count, erythrocyte), blood 
chemistries (blood glucose, total protein, albumin, transaminases, creatinine, urea, uric acid, alkaline 
phosphatase, total bilirubin and fractions, cholesterol and triglycerides), pregnancy test for women. 
 The
will provide you with a copy of the results of the tests performed during the study. 
3.You will be taking a medication that has a Levothyroxine sodium, used in the treatment of hormone 
replacement and in the treatment of hypothyroidism. 
4. During the study, you will participate three times for about 24 hours, with a minimum interval of 65 
days. In each admission (period 1 and 2), in fasting condition, you be taking 600 mcg of Levothyroxine 
sodium, which corresponds to 3 tablets of one of the study drugs, with 200ml of mineral water without 
gas. After administration of the drug you must remain seated (in the 90° position) for a period of 1 hour. 
You must ingest the whole medication and cannot break it or chew it. 
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FREE AND INFORMED CONSENT FORM- FICF 
 
 
 
___________________                 _______________              __________________________ 
             Heading of Research Participant               Heading of Physician                      Heading of main investigator 
                             
 
Page 3 of 12                                                     FICF – 
 Version 4.0 Date: October 31st, 2018 
 
In Period 1 you will receive the test drug or the comparator drug, in period 2 will be reversed, if you 
receive the test drug in period 1 you will receive the comparator drug in period 2 and vice versa At the 
end of the study you will have received 03 tablets of the test drug and 03 tablets of the comparator 
drug. 
5. 54 blood samples of 7,5mL for dose of medication will be collected, two samples of 15mL for 
validation of analytical methodologies and two samples of 15mL for laboratory tests and post-study will 
be collected through a needle inserted into a superficial vein. The total volume of blood will be 
approximately 465mL. At regular intervals and when necessary, your pressure, pulse and temperature 
will be checked. The minimum participation is estimated in 76 days from the date of first admission, 
after the selection process. 
6. It is important to emphasize that you will come to 
 for admission at 7:00pm on the day before drug 
administration and will be released after 12 hours of drug administration, returning to 
 for the 
collection of 24:00, 36:00, 48:00 and 72 hours. You will be observed throughout the study period and 
may contact the doctor on duty by the phone (62) 9299-6754 and / or (62) 3240-1900. 
The collections schedule is shown in the table below. During pre-dose collection (before drug 
administration), 01:00, 02:00, 03:00, 04:00, 05:00, 06:00, 08:00 and 12:00 hours and when required the 
vital signs (temperature, blood pressure and pulse) will be assessed (measured). 
Day 
Tempo (h) 
Time of the day it will be collected 
2nd  
Pool Collection - Before the 
administration of the drug 
From 05:00 am 
 (-) 00:30 Collection 
Approximately at 06:30 am 
 (-) 00:15 Collection 
Approximately at 06:45 am 
00:00 Collection – 5 minutes 
before the administration of the 
drug 
Approximately at 06:55 am 
Drug Administration 
Approximately at 07:00 am 
00:30 Collection 
Approximately at 07:30 am 
01:00 Collection 
Approximately at 08:00 am 
01:30 Collection 
Approximately at 08:30 am 
02:00 Collection 
Approximately at 09:00 am 
02:30 Collection 
Approximately at 09:30 am 
03:00 Collection 
Approximately at 10:00 am 
03:15 Collection 
Approximately at 10:15 am 
03:30 Collection 
Approximately at 10:30 am 
03:45 Collection 
Approximately at 10:45 am 
04:00 Collection 
Approximately at 11:00 am 
04:15 Collection 
Approximately at 11:15 am 
04:30 Collection 
Approximately at 11:30 am 
04:45 Collection 
Approximately at 11:45 am 
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FREE AND INFORMED CONSENT FORM- FICF 
 
 
___________________                 _______________              __________________________ 
             Heading of Research Participant               Heading of Physician                      Heading of main investigator 
                             
 
Page 4 of 12                                                     FICF – 
 Version 4.0 Date: October 31st, 2018 
 
05:00 Collection 
Approximately at 12:00 am 
05:30 Collection 
Approximately at 12:30 am 
06:00 Collection 
Approximately at 13:00 am 
06:30 Collection 
Approximately at 13:30 am 
08:00 Collection 
Approximately at 15:00 am 
10:00 Collection 
Approximately at 17:00 am 
12:00 Collection 
Approximately at 19:00 am 
3rd 
24:00 Collection 
Approximately at 07:00 am 
36:00 Collection 
Approximately at 07:00 pm 
4rd 
48:00 Collection 
Approximately at 07:00 am 
5rd 
72:00 Collection and Post Study 
Collection 
Approximately at 07:00 am 
 
7. You will remain fasting from 11:00 pm of the day you are admitted to the study at 
 until 4 hours 
after the drug administration. This means that you will get a dinner up to 11:00 pm of the day that you 
arrive at
, and will take the medication at around 07:00 am on the day after your arrival and will have 
lunch 4 hours after drug administration, i.e. by 11:00 am. So you will receive the medication after about 
8 hours of fasting and will remain until lunchtime. 
You will be served standardized meals (dinner, lunch, afternoon snack, dinner, breakfast and snack in 
the days of extra collections), drink only in prearranged times whereas after midnight (the day of arrival 
at 
) you must remain without drinking water or any other liquid. The next day, you will receive 200mL 
of water with the medicine, and will only be allowed to drinking unlimited water 2 hours after drug 
administration. 
STORAGE 
 
8. The biological samples will be stored in accordance with Resolution No. 441 of May 12, 2011 of the 
National Health Council, which provides guidelines and conditions to be considered for storing  
biological samples, and will be used to verify through a single-dose study if the two formulations of 
Levothyroxine sodium 200mcg (being the comparator drug: Puran T4® 200mcg of the Sanofi-Aventis 
Farmacêutica Ltda. and the Test drug: Eutirox®200mcg of the Merck, S.A. de C.V.)are bioequivalent 
when administered at the same concentration and in fasting condition. Every new research will be 
submitted for approval of the CEP / CONEP system (National Committee for Research Ethics) and you 
must consent the use of these samples, by signing a new free and informed consent form. 
9. Biological samples will be stored for non-commercial use, under the responsibility of 
 and 
management of the principal investigator and will be discarded after the consent of the sponsor. 
10. Biological samples are stored in storage tubes identified by its research participant number with the 
aim of maintaining confidentiality and secrecy. 
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FREE AND INFORMED CONSENT FORM- FICF 
 
 
 
___________________                 _______________              __________________________ 
             Heading of Research Participant               Heading of Physician                      Heading of main investigator 
                             
 
Page 5 of 12                                                     FICF – 
 Version 4.0 Date: October 31st, 2018 
 
REQUIRED INFORMATION 
11. You will be one of the 72 research participants divided into 02 groups of 36 participants each who 
will take part in this study. 
12. You will receive all necessary information, including the benefits (see section "BENEFITS" below) and 
risks (see "POSSIBLE RISKS"), with conditions to consciously decide on the participation in this clinical 
trial. 
Regardless of your will and permission, your participation in the clinical trial may be suspended due to: 
a) Adverse events that are considered clinically significant by the treating physician and / or harmful to 
your health; 
b) Occurrence of any disease, that at the physician's discretion, restricts your participation in the study; 
c) Non-compliance with established regulations; 
d) Any other reason that according to medical criteria is for your own or other participants’ welfare; 
e) The suspension of the study; 
f) In case you need any prohibited medication during your participation in the study; 
g) Finding out that you do not meet the study requirements; 
h) Abnormal laboratory tests judged clinically significant by the physician; 
i) In case you ingest a medicine containing the same substance that will be used during analysis of 
plasma samples during the study; 
j) In case you eat and/or chew the tablet during drug administration; 
k) You be hypersensitive (oversensitivity) to study medications or chemically related compounds; 
l) If you are a vegetarian or have dietary habits that preclude the intake of the diet offered in the study; 
m) In case you don’t attend the last collection of the periods; 
n) In case of women, present at the time of admission (Period 1 or 2) a positive pregnancy test result; 
o) You present during the pre-admission (Period 1 or 2) testing positive for alcohol and/or drug test; 
p) You have thyroid function tests (free and total TSH, total and free T4 and TSH) outside normal limits; 
q) You do not ingest the 200mL of water during the administration of the drug; 
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FREE AND INFORMED CONSENT FORM- FICF 
 
 
 
___________________                 _______________              __________________________ 
             Heading of Research Participant               Heading of Physician                      Heading of main investigator 
                             
 
Page 6 of 12                                                     FICF – 
 Version 4.0 Date: October 31st, 2018 
 
r)  You use  any prescription or non-prescription medications during the course of the study, including 
multivitamins, nutritional supplements and herbal products that may affect the outcome of the study, 
with the exemption of occasional use of paracetamol not exceeding 1000mg/day for maximum of three 
consecutive days; 
s) If you present episode of vomiting or diarrhea within 8 hours after drug administration. 
RESPONSABILITIES 
13. In order to be able to participate in the clinical trial, you should be in good health condition, and 
cannot be under any medical treatment or taking any kind of drugs or medication. Your collaboration is 
important in the following points: 
9 You cannot  have any drugs or alcohol dependency; 
9 Remain seated (approximately 90 °) for 1 hour after administration of the drug or the time required 
at the discretion of the clinical investigator; 
9 Do not be a smoker within 3 months; 
9 You should avoid the use of other concomitant medications with the study medication whenever 
possible. In case you need to use some medication, you should contact the staff of the 
; 
9 You must not have donated blood or plasma within the three months preceding the study.  
9 You must not have participated in any experimental study or ingested any experimental drugs within 
the six months preceding the beginning of the study 
9 You must not consume alcohol beverages in the 24 hours before admission to the study until the last 
sample collection of each period is performed; 
9 Do not smoke tobacco, cigarettes, or consumed coffee, snuff or ingested beverages containing 
xanthines (coffee, tea, cocoa, chocolate, mate, cola, etc.) such as caffeine, theobromine, 
theophylline or charcoal grills, among others in the 24 hours before the start of the study until the 
last collection of each period; 
9 Do not eat or drink grapefruit (also known as toranja, pomelo, jamboa, laranja-melancia, 
pamplemusa, laranja-vermelha, laranja-roma), orange and cranberry in the 07 days before the 
beginning of each period up to the last collection of each period; 
9 You must not consume chewing gum during the admission period; 
9 You must not consume vitamins or natural products [including garlic supplements (derived from 
garlic and onion)]  in the 7 days prior to drug administration until the last sampling of each study 
period; 
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FREE AND INFORMED CONSENT FORM- FICF 
 
 
 
___________________                 _______________              __________________________ 
             Heading of Research Participant               Heading of Physician                      Heading of main investigator 
                             
 
Page 7 of 12                                                     FICF – 
 Version 4.0 Date: October 31st, 2018 
 
9 Do not consume soy and its derivatives in the 7 days prior to administration of the drug until the last 
collection of each study period; 
9 Do not perform procedures that require the use of iodinated contrast (the iodine base) within 30 
days prior to the start of the study. 
9 You must attend study visits on the appointed dates and times; 
9 You must remain fasting for the predicted time; 
9 Take all the medication provided; 
9 Follow the suggested diet; 
9 Ingest liquids in set times; 
9 In the case of women, do not use hormonal contraceptive methods; 
9 Return to 
 at the appointed date, time and place for the consultation and discharging 
appointment. 
BENEFITS 
14. Your participation in this study is experimental, and it does not have the purpose of subjecting you 
to a treatment. 
By participating in this study you will be assessed and monitored by a qualified medical staff in addition 
to performing a careful and detailed clinical evaluation, including clinical and laboratory examinations, 
which will attest if you are healthy. 
Your participation is very important and thus will contribute effectively in ensuring the quality of the 
medication offered to the general population. 
POSSIBLE RISKS 
15. The administration of medications can cause side effects, anaphylactic (allergic) reactions and other 
serious unpredictable, and in some cases, cause death. 
You should understand that the participation in this study involves risks that may be unexpected, related 
or unrelated to the study. Risks associated with blood collection in your arm may include: pain, 
hematoma (bruise), bleeding at the site where blood was withdrawn, dizziness, fainting and, on rare 
occasions, infection. 
The blood sampling for prolonged times, through a single vein may lead to its inflammation 
(thrombophlebitis), with pain and local swelling (when applicable). 
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FREE AND INFORMED CONSENT FORM- 
 
 
 
___________________                 _______________              __________________________ 
             Heading of Research Participant               Heading of Physician                      Heading of main investigator 
                             
 
Page 8 of 12                                                     FICF – 
 Version 4.0 Date: October 31st, 2018 
 
The risks associated with this medication side effects are: 
Very common reaction (≥ 1/10)  
Common reaction (≥ 1/100 and < 1/10)  
Unusual reaction (≥ 1/1.000 and < 1/100)  
Rare reaction (≥ 1/10.000 and < 1/1.000)  
Very rare reaction (< 1/10.000)  
Unknown reaction (cannot be estimated from the available data)  
In general, the adverse reactions of levothyroxine are associated with an excessive dosage and 
correspond to the symptoms of hyperthyroidism. 
• Heart disorders 
Very common: palpitations. 
Common: tachycardia. 
Unknown: cardiac arrhythmias and angina pain. 
• Skin and subcutaneous disorders 
Unknown: rash, hives and sweating. 
• Psychiatric disorders 
Very common: insomnia. 
Common: nervousness. 
Unknown: excitability. 
• Musculoskeletal and connective tissue disorders 
Unknown: muscle weakness and cramps, osteoporosis in suppressive doses of levothyroxine, 
especially in postmenopausal women, especially when treated for a long period. 
• Vascular disorders 
Unknown: hot flashes, circulatory collapse in preterm low birth weight infants. 
• Disorders of the reproductive system and breast 
Unknown: menstrual irregularities. 
• Gastrointestinal disorders 
Unknown: diarrhea and vomiting. 
• Investigations 
Unknown: weight loss. 
• Nervous system disorders 
Very common: headache. 
Unknown: tremors, benign intracranial hypertension particularly in children. 
• General disorders and administration site conditions 
Unknown: heat intolerance, fever. 
• Endocrine disorders 
Common: hyperthyroidism. 
Such effects generally disappear with reduced dosage or temporary withdrawal of treatment. 
 
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FREE AND INFORMED CONSENT FORM- FICF 
 
 
___________________                 _______________              __________________________ 
             Heading of Research Participant               Heading of Physician                      Heading of main investigator 
                             
 
Page 9 of 12                                                     FICF – 
 Version 4.0 Date: October 31st, 2018 
 
16. Additional risks, unusual or unexpected side effects or previously unreported discomforts may occur. 
Thus, it is important that you tell the study doctor or a staff at 
 who is in charge of your treatment 
about all the symptoms and side effects you have, either if you think or not this has been caused by the 
study medication. 
17. Women of childbearing potential: use of study medication may involve unknown risks to a pregnant 
woman, an embryo, fetus (unborn baby) or child being breastfed. So, if you suspect pregnancy, or if 
you’re planning to become pregnant or are breastfeeding, you cannot participate in this study. 
In order to reduce the risk of pregnancy, you should use an effective method of contraception ( to 
prevent pregnancy ) while participating in this study . If you are already using a contraceptive method 
you should talk to the team of doctors at 
 to ensure that its use is considered acceptable in this study. 
No method to prevent pregnancy will be imposed on you . You can choose the most appropriate 
method , after discussing it with the team of 
 doctors. Some types of birth control include oral 
contraceptives ( pills ) or barrier methods such as condoms or diaphragm . If you do not have sex as a 
lifestyle choice ( eg, sexual abstinence for religious reasons or otherwise) , it will be accepted as a 
method of contraception . In this case , you do not need to use another method . Also, if you have sex 
without reproductive risk , it will not be necessary to use a contraceptive method . Your personal 
decision will be respected . However, if during the study you become sexually active with intent / ability 
to become pregnant , you should inform the study doctor immediately. Along with the study doctor you 
will be able to decide what is the best contraceptive method, which will be provided at no cost to you . 
The pregnancy test will be performed in the pre-study phase, before each admission period (Period 1 
and 2) and after the admission to the 2nd  period . The results of the pregnancy test should be negative 
for you to be able to continue participating in this study. 
If you become pregnant during the study, you should notify 
 staff immediately. In case this happens, 
you will be withdrawn from the study for safety reasons and will receive full assistance, including 
medical care for your needs as a mother and to your baby (since conception). 
WITHDRAWAL, DISRUPTING AND DISMISSAL  
18. Your participation in this study is voluntary (i.e., just depends on your willingness to participate), 
having the freedom to give up when you want without any explanation. If you give up, you should 
immediately notify your decision to the physician or researcher in charge. 
19. Your withdrawal, disrupting or dismissal from the study will not cause harm to your care and medical 
treatment (comprehensive care) by 
 staff. 
CONFIDENTIALITY 
20. The records that might identify you will be kept confidential. 
 will not identify you at the time of 
publication of results. 
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FREE AND INFORMED CONSENT FORM- FICF 
 
 
___________________                 _______________              __________________________ 
             Heading of Research Participant               Heading of Physician                      Heading of main investigator 
                             
 
Page 10 of 12                                                     FICF – 
 Version 4.0 Date: October 31st, 2018 
 
However , the main investigator and team members have access to the original records of your clinical 
data to the extent that is permitted by law and regulations, in order to verify the procedures and test 
data , without violating the condition that your information can not be disclosed . Auditors, study 
sponsor and the members of the Research Ethics Committee will only have access to the results of your 
examinations and your medical history , but not to your personal data . By signing this Consent Form, 
you authorize such access, even if you withdraw from the study. 
The clinical study to which you are being invited to participate can have the results published in 
newspapers and / or magazines and / or scientific articles. If that is the case, the confidentiality of your 
records that perhaps can show your identity will be protected. In case of any publication, it will respect 
the rules of privacy and confidentiality in accordance with applicable standards. 
INTERCURRENCES 
21. In any medical complication arising, directly or indirectly, from your participation in this research, 
you will immediate and comprehensive care, whose costs will be borne by the sponsor or Research 
Center 
 responsible for the clinical study that you are participating. It is therefore very important 
that if you have any unusual symptoms, discomforts Unusual, unexpected or non-reported previously, 
you look IMMEDIATELY 
 medical staff. 
In the period between signing the Consent Form (the moment you accepted the invitation to participate 
in this clinical study) and study completion (last collection of the study), 
 will be responsible for any 
supplying of medication, which manages without any cost to you. 
22. During a period of 120 days from the date of the 1st hospitalization, you will be covered by a life 
insurance policy in relation to possible adverse events that may have stemmed from the administration 
of the drug and in cases of death and permanent disability, related or not to the clinical study. 
23. It is also important that the sponsor and the Research Center 
 responsible for the clinical study 
will be responsible for any and all necessary cost in relation to any adverse events that you may suffer as 
a result of their participation in the study. 
COMPENSATION 
24. By participating in this study, after sample collection post-study, you will be reimbursed in the 
amount of R$ 870,00 (Eight hundred and seventy reals), concerning expenditure and time spent during 
the course of clinical study (reimbursement is the material compensation, exclusively expenditure of the 
research participant and their companions, when necessary, such as transportation and food). The 
relinquishment or waiver before attending for the first hospitalization is not entitled to compensation, 
or if you attended only part of the study you will be reimbursed proportionally. 
 
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FREE AND INFORMED CONSENT FORM- FICF 
 
 
___________________                 _______________              __________________________ 
             Heading of Research Participant               Heading of Physician                      Heading of main investigator 
                             
 
Page 11 of 12                                                     FICF – 
 Version 4.0 Date: October 31st, 2018 
 
CLARIFICATION OF DOUBTS 
25. You can contact 
 Research Ethics Committee for complaints regarding the trial by calling the 
number (62) 3240-1906. 
 CEP (Ethics Committee) business hours are Monday to Friday from 8:00 
am to 12:00 pm.  
26. You have the freedom to contact 
 to receive additional information 
related to research or to your rights as a research participant. 
 has a 24 hours telephone answering 
service to assist you. Phones: 
 and / or 
. 
27. The Institute of Pharmaceutical Sciences will keep you informed, in a timely manner, whenever there 
is any additional information and will provide any clarification regarding the progress of the research, as 
per your request. 
All your biological material will be identified uniquely and unmistakably to maintain the confidentiality 
of your identity and as accept the invitation to participate in this clinical study you authorize the storage, 
use and disposal of this biological material and the principal investigator, team members involved in this 
clinical study, auditors, sponsor of the study, the Research Ethics Committee responsible for approving 
the project to access your health information under the same established conditions. You also authorize 
the publication of the results of this clinical study in magazines, newspapers and books, when necessary. 
After reading this term and clarify all your doubts, you, the responsible researcher and physician shall 
write your initial on all the pages, and you and the doctor responsible for applying the term shall sign 
the respective fields. After signing both copies of the document, you will receive one and the other will 
be filed at
. 
By signing this consent form I have not renounced any legal right that I will have to participate in this 
clinical study. 
I have read carefully this Consent form, after having the opportunity to ask questions about its content, 
receiving explanations about the study and all of my questions have been answered completely. I am 
also sure that all the information provided, including my medical history, is true to the best of my 
knowledge, and I declare that I have received a signed and dated copy of this document. 
I hereby give my consent voluntarily and accept the invitation to participate in this clinical study. 
 
 
 
 
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FREE AND INFORMED CONSENT FORM- FICF 
 
 
 
___________________                 _______________              __________________________ 
             Heading of Research Participant               Heading of Physician                      Heading of main investigator 
                             
 
Page 12 of 12                                                     FICF – 
 Version 4.0 Date: October 31st, 2018 
 
TELEPHONE CONTACTS: 
Investigator responsible for the Clinical Phase:  
 - Phone: 
 – 
24 hours 
Main investigator: 
 - Phone: 
 
Nursing Staff – Phone: 
 – 24 hours 
Research Ethics Committee of the Institute of Pharmaceutical Sciences – Phone number: 
 The CEP‘s (Ethics Committee) business hours are Monday to Friday from 8:00 am to 12:00am. 
Institute of Pharmaceutical Sciences - Clinical Unit - Phone: 
 
Signature of the research subject:__________________________________________ 
Aparecida de Goiânia, ___/___/___. 
PLEASE DATE AND  SIGN IT AT THE SAME TIME 
 
 
 
 
Dactyloscopic Printing (when applicable): 
 
* Signature of impartial witness (1): _________________________________________ 
* Applicable in cases where the research subject cannot read, understand and sign this document. 
Aparecida de Goiânia, ___/___/___ 
PLEASE DATE AND SIGN IT AT THE SAME TIME 
*  Signature of impartial witness (2): _________________________________________ 
* Applicable in cases where the research subject cannot read, understand and sign this document. 
Aparecida de Goiânia, ___/___/___. 
PLEASE DATE AND SIGN IT AT THE SAME TIME 
Doctor’s Signature*: ____________________________________________________ 
Aparecida de Goiânia, ___/___/___. 
PLEASE DATE AND SIGN IT AT THE SAME TIME 
* The physician responsible for the study or other doctor for this delegate  are able to sign this document 
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conditions that may affect the development of pregnancy, ex .: hypertension, eclampsia, diabetes, 
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( ) Normal ( ) Congenital anomaly ( ) others neonatal problems ( ) Unknown 
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