Evaluating the Effectiveness and Safety of Embella (Deoxycholic Acid, Produced by Espad Pharmed Co.) for the Management of Submental Fat
Phase: NA
Conditions: Submental Fullness
Sponsor: Espad Pharmed

1
 
 
 
 
Safety and efficacy assessment of deoxycholic acid (Embella®) 
injectable solution for the reduction of unwanted submental fat  
 
 
 
 
 
 
  Location of study: 
Pharmaceutical, Cosmeceutical and Hygienic Products Clinical Evaluation Lab 
(DermaLab), 
Center for Research and Training in Skin Diseases and Leprosy 
Tehran University of Medical Sciences, Tehran, Iran 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date: 20 November 2022 
 
 
 

2
 
 
 
Contents 
Sponsor: ..................................................................................................................................... 3 
Sponsor Representative:............................................................................................................. 3 
Roles and Responsibilities: ........................................................................................................ 3 
Roles and Responsibilities: ........................................................................................................ 5 
Introduction: ............................................................................................................................... 6 
Objectives .................................................................................................................................. 6 
Study Method ............................................................................................................................. 7 
Inclusion Criteria ....................................................................................................................... 7 
Exclusion Criteria ...................................................................................................................... 7 
Intervention ................................................................................................................................ 8 
Method of administration ........................................................................................................... 8 
WARNINGS AND PRECAUTIONS ...................................................................................... 10 
Endpoints ................................................................................................................................. 10 
Study Timeline ......................................................................................................................... 12 
Visit 0: Screening & eligibility control .................................................................................... 12 
Visit 1 (day 1): ......................................................................................................................... 13 
Visit 2 (4 weeks±2 days): ........................................................................................................ 13 
Visit 3 (8 weeks±4 days): ........................................................................................................ 13 
Visit 4 (12 weeks±4 days): ...................................................................................................... 14 
Visit 5 (16 weeks±4 days) (In people with 2 injections): ....................................................... 14 
Visit 6 (20 weeks±4 days) (In people with 3 injections): ....................................................... 14 
Participants:.............................................................................................................................. 14 
Data Collection ........................................................................................................................ 15 
Adverse Events ........................................................................................................................ 15 
Quality Assurance: ................................................................................................................... 17 
Accordance with GCP: ............................................................................................................ 17 
References: ............................................................................................................................... 18 
 
 
 
 
 
 

3
 
 
 Sponsor: 
•  Espad Pharmed Darou Co. 
Roles and Responsibilities:
 
- 
Providing quality-controlled products for using in the study and transferring them to 
the study site  
- 
All associated costs are the responsibility of the sponsor 
- 
Providing compensation for patients who experience adverse events  
- 
Offering financial support for all activities outlined in the study protocol through a 
contractual agreement with the principal investigator 
Sponsor Representative: 
• Zist Orchid Pharmed Co. 
Roles and Responsibilities: 
- 
Study protocol preparation 
- 
Preparing CRFs 
- 
Obtaining necessary approvals from external organizations for conducting the study 
- 
Providing SOP for the investigators in study centers 
- 
Funding provision for site staffs collaborating in data collection via signing 
contracts with the chief and principal investigators 
- 
Providing necessary training for the staff 
- 
Recruiting necessary workforce to conduct monitoring of the trial and the data 
management 
- 
Planning and conducting statistical analyses. 
- 
Preparing required study reports 
 
Researchers:
 
• Principal Investigator (PI): 
Dr. Alireza Firooz 
- MD, Professor of Center for Research and Training in Skin Diseases and Leprosy; 
Tehran University of Medical Sciences 
- Address: No. 415, Naderi St., Taleghani st., Tehran, Iran 
- Phone No.: +982188972220 
- Email: firozali@tums.ac.ir 
Roles and Responsibilities: 
- 
Preparation of clinical study protocol and other required forms 
- 
Conducting the study according to the approved protocol 
- 
Creating a working team to carry out the study 
- 
Conducting practice sessions for new and current team members whenever needed 
- 
Preparing suitable places for patient enrollment  
- 
Arranging an appropriate storage location for the investigational drugs at the site. 

4
 
 
- 
No part of this study may be published without prior approval from the sponsoring 
company. 
 
• Co-Investigators: 
 
• Dr. Mansour Nassiri Kashani 
- MD, Professor of Center for Research and Training in Skin Diseases and Leprosy; 
Tehran University of Medical Sciences 
- Address: No. 415, Naderi St., Taleghani st., Tehran, Iran 
- Phone No.: +982188972220 
 
• Dr. Amirhooshang Ehsani 
- MD, Professor of Center for Department of Dermatology, Razi Hospital, Tehran 
University of Medical Sciences  
- Address: Razi Dermatology Hospital, Vahdat-e-Eslami St., Vahdat-e-Islami Square, 
Tehran, Iran 
- Phone No.: +982155630553 
 
• Dr. Aniseh Samadi 
- MD, PhD, Center for Research and Training in Skin Diseases and Leprosy; Tehran 
University of Medical Sciences 
- Address: No. 415, Naderi St., Taleghani st., Tehran, Iran 
- Phone No.: +982188972220 
 
• Dr. Taraneh Yazdanparast  
- MD, PhD, Center for Research and Training in Skin Diseases and Leprosy; Tehran 
University of Medical Sciences 
- Address: No. 415, Naderi St., Taleghani st., Tehran, Iran 
- Phone No.: +982188972220 
 
• Dr. Saman Ahmad Nasrollahi  
- PharmD, PhD, Center for Research and Training in Skin Diseases and Leprosy; 
Tehran University of Medical Sciences 
- Address: No. 415, Naderi St., Taleghani st., Tehran, Iran 
- Phone No.: +982188972220 
• Dr. Azin Ayatollahi,  
- MD, Associate Professor of Center for Research and Training in Skin Diseases and 
Leprosy, Tehran University of Medical Sciences 
- Address: No. 415, Naderi St., Taleghani st., Tehran, Iran 
- Phone No.: +982188972220 
 

5
 
 
Roles and Responsibilities: 
- 
Conducting the study in accordance with the protocol approved by the principal 
investigator, ethics committees, and the Food and Drug Administration (FDA). 
- 
Establishing a dedicated team for this purpose at the study site. 
- 
Organizing training sessions for both new and existing team members as needed. 
- 
Arranging appropriate facilities for patient intake. 
- 
Providing suitable storage for the medications used in the study. 
- 
Collaborating with monitors during the course of the study. 
- 
All medical documents related to the study must be sent to Espad Pharmed Darou Co. 
at the conclusion of the study. A copy of these documents may be retained by the 
investigator. 
- 
All medical documents related to the study must be kept by the investigator for the 
duration of the study and for five years following its completion. 
- 
Confidentiality of the protocol and study data must be maintained, with no disclosure 
without written permission from Espad Pharmed Darou Co. and the principal 
investigator, except as necessary for obtaining informed consent from individuals to 
whom the product will be administered. 
 
 

6
 
 
Introduction: 
Submental fat (SMF) is considered aesthetically unappealing and can have a negative 
psychological impact on patients (1). Concerning the increasing demands of people for 
aesthetic prospects like decreasing the unwanted submental fat, evidence supports the 
effectiveness of noninvasive alternative procedures for liposuction and plastic surgery (2). 
Amongst them, injection of deoxycholic acid (DCA) is a minimally invasive procedure. In 
2015, the U.S. Food and Drug Administration (FDA) approved DCA, for treating fat beneath 
the chin (3). The mechanism of action of the drug is through the lysis of fat cell membranes 
and the physical destruction of cells (4)  
The efficacy and safety of DCA in reducing the SMF have been demonstrated in multiple phase 
I to III clinical studies. (5). Phase I studies demonstrated that DCA administration did not 
significantly impact on liver function, kidney function, heart rate, or levels of cholesterol, 
triglycerides, free fatty acids, or proinflammatory cytokines (6,7). Phase II studies examined 
treatment regimens and dosages, revealing that the optimal dose for DCA was 2mg/cm2 
administered via 0.2 ml injections spaced 1 cm apart in the submental area. The recommended 
injection interval was 28 days (8, 9). Phase III studies have shown the efficacy and safety of 
DCA in SMF reduction. Accordingly, in a 12-week double-blind, placebo-controlled study 
including physician examinations, patient satisfaction, and MRI fat mass measurements, the 
clinical evaluation revealed that 70% of the individuals who received the medicine showed one 
grade of improvement in SMF score. Additionally, 13.4% of the subjects demonstrated two 
grades improvement, while no improvement was observed in the placebo group. These findings 
underscore the safety and effectiveness of the drug in treating moderate to severe submental 
fat. In the MRI evaluation, the proportion of responders was significantly higher in the 
intervention group compared to placebo group (46.3% vs. 5.3%; p < 0.001). Researchers 
concluded that DCA is an effective and safe injectable drug in reducing SMF (10). 
The drug is administered to individuals aged 18 to 65. Common adverse events included pain, 
swelling, hematoma, and bruising at the injection site. There were some rare case reports, of 
damage to the mandibular nerve resulting in an asymmetric smile that generally resolves 
without any intervention (11). Another potential side effect is dysphagia, and the drug is 
contraindicated for individuals with a history of dysphagia (12). 
The purpose of this study is the safety and efficacy assessment of Embella® injectable solution 
containing deoxycholic acid (manufactured by Espad Darou Pharmed Company) for the 
reduction of unwanted submental fat. 
Objectives  
 
Primary objective: 
 
- 
Safety and efficacy assessment of Embella® injectable solution in reducing the 
unwanted submental fat. 
Secondary objectives: 

7
 
 
 
• Assessment of the efficacy of Embella® injectable solution, in improving the standard 
grading of submental fat (SMF)  
• Assessment of the efficacy of Embella® injectable solution in reducing the diameter of 
submental fat 
• Patient’s satisfaction with the treatment process 
• Pain assessment during the injection using a 11-point visual analogue scale 
• Safety assessment of Embella® injectable solution  
Study Method 
 
It was a single group, before and after the clinical study. The study protocol as well as other 
essential documents (such as CRF, ICF, etc.) were approved by the Undersecretary of 
Research, Tehran University of Medical Sciences . 
Also, all mentioned documents were approved by the ethics committee of Tehran University 
of Medical Sciences on 17 January 2023 (code: IR.TUMS.TIPS.REC.1401.102). The protocol 
was registered in the Iranian Registry of Clinical Trial Registry (IRCT) with registration 
number IRCT20190210042676N29.  
Inclusion Criteria  
 
• Age between 18 and 65 years old 
• Individuals with any severity of unwanted submental fat 
• Voluntarily signed the informed consent form and consented to the 3-month follow-
up 
• Willing to actively participate in the study and the scheduled visits  
  
Exclusion Criteria  
 
- 
Any previous interventions to treat SMF 
- 
Anatomical features or previous trauma in the injection site which is liable to interfere 
with SMF evaluation or result in an aesthetically unacceptable outcome after treatment 
- 
Evidence of any cause of submental enlargement other than SMF 
- 
Patients with a body mass index (BMI) > 30 kg m2 
- 
Those undergoing or considering a weight-reduction program  
- 
Patients with a history of sensitivity to any components of the study medication or 
topical or local anesthetics 
- 
Patients with a history of dysphagia 
- 
Any inflammation, active infection, unhealed wound, or tissue scar at injection site 
- 
Those using anticoagulants or NSAID or other medications that increase the risk of 
coagulation disorders within 7 days before injection 
- 
Unrealistic expectations 
- 
Pregnant or lactating women  
- 
Those undergoing low sodium diets like hypertensive patients  

8
 
 
 
 
 
Intervention 
 
- 
Minimum 1 and maximum 3 treatment sessions (with at least 4 weeks intervals) with 
2 ml of Embella® injectable solution, which contains 20 mg of DCA.  
- 
4 weeks after the first and second injections, the patient will be evaluated by the 
physician and research team. If necessary, they will receive additional injections; 
otherwise, they will proceed with post-injection follow-up. 
- 
The product is a 2 ml sterile, transparent, and colorless vial containing 20 mg of DCA. 
Additional ingredients include hyaluronic acid, water for injection, sodium chloride, 
sodium hydroxide, hydrochloric acid, and disodium phosphate anhydrous. 
- 
Use of ice/cold packs, topical and/or injectable local anesthesia (e.g., lidocaine) may 
enhance patient comfort. 
 
Method of administration  
 
The product is indicated for subcutaneous administration only. 
EMBELLA® is supplied in ready-to-use, single-use vials. Gently invert the vial several times 
before use. Do not dilute. 
 
EMBELLA® shall be prepared for injections in the following way: 
1. Remove the flip-off cap from the vial and clean the penetrable stopper of the vial with 
an antiseptic. If the vial, seal, or flip-off cap is damaged, do not use it. 
2. Attach a large bore sterile needle to a sterile single-use 1 ml syringe. 
3. Introduce the large bore sterile needle into the stopper of the vial and draw 1ml of 
EMBELLA® into the 1ml syringe. 
4. Replace the large bore needle with a 30 gauge (or smaller)-0.5-inch needle. Expel any 
air bubbles in the syringe barrel before injecting the product into the subcutaneous fat. 
5. To withdraw the remaining contents of the vial, repeat steps 3 and 4. 
For injection, the needle is inserted perpendicular to the skin, and injection should be 
avoided in the area defined by a line 1 to 1.5 cm from the angle of the mandible to the 
mentum (Figure 1). 
 
 
 
 
 

9
 
 
 
 
Figure 1. Avoid the Marginal Mandibular Nerve Area 
 
 
 
Avoid injection into the platysma. Prior to each treatment session, palpate the submental area 
to ensure sufficient submental fat and to identify subcutaneous fat between the dermis and 
platysma (pre-platysmal fat) within the target treatment area (Figure 2) . 
 
 
Figure 2. Sagittal View of Platysma Area 
 
 
 
 
 
 
 

10
 
 
 
 
Outline the planned treatment area with a surgical pen and apply a 1 cm2 injection grid to mark 
the injection sites (Figures 3). 
 
Figure 3. Injection Pattern 
 
 
 
 
 
WARNINGS AND PRECAUTIONS 
 
- 
Embella® should only be injected within the defined parameters. Each vial is intended 
for use in one patient and should be discarded after use. 
- 
Store the product between 15°C and 30°C. 
- 
Use of ice/cold packs, topical and/or injectable local anesthesia, and NSAIDs may 
enhance patient comfort. 
 
Endpoints 
 
Primary and secondary endpoints are evaluated before injection and 4 and 12 weeks after the 
last injection. 
 
Primary Endpoint 

11
 
 
At least one-grade improvement in standard grading of submental fat (SMF) evaluated at 4 
and 12 weeks after the last injection (Figure 4) 
 
 
Figure 4: Standard grading of submental fat (SMF) 
 
 
 
Secondary Endpoints 
 
- 
Submental fat diameter will be measured with the calliper at 4 and 12 weeks after the 
last injection 
- 
Intensity of procedural pain will be assessed using the Visual Analogue Scale (VAS), 
ranges from 0 (complete painlessness) to 10 (maximum pain). 
- 
Patient satisfaction will be assessed using the Visual Analogue Scale (VAS), ranges 
from 0 (not satisfied at all) to 10 (maximum satisfaction).  
- 
Any observed or reported adverse events will be recorded after the injections and at 4 
and 12 weeks follow-up visits, graded as mild [1] moderate [2] and severe [3]. 
 
 
 
 
 
 
 
 
 
 

12
 
 
 
Study Timeline 
 
 
Study Visits : 
Visit 0: Screening & eligibility control 
The following screening procedures will be conducted to determine eligibility: The 
investigator will evaluate each patient against the inclusion and exclusion criteria. If the 
patient is eligible to participate in the study, the study process will be explained to them in an 
understandable and verbal manner, and a consent form will be provided. Once the 
information presented to the patient has been thoroughly reviewed and understood by them, 
and they have received the necessary explanations, the patient will be asked to write their full 
name on the consent form and sign it. Following the completion of these steps, the following 
actions will be carried out: 
• Digital AP and lateral photography of the patient's neck 
• Grading of submental fat based on SMF  
• Measurement of submental fat diameter  
 
Visit No 
0 
1 
2 
3 
4 
5 
6 
 
Day 1 
Week 4 (±2 
days) 
(Injection 2)/ 
Follow-up of 
subjects with 
a satisfactory 
response who 
do not require 
further 
treatment 
Week 8 (±4 
days) 
(Injection 3)/ 
Follow-up of 
subjects with 
a satisfactory 
response who 
do not require 
further 
treatment 
Week 12+4 
day 
Week 16+4 
day 
(In subjects 
with 2 
injections) 
Week 20+4 
day 
(In subjects 
with 3 
injections) 
Time  
Baseline  
Injection 1  
Screening   
X 
 
 
 
 
 
 
eligibility control 
X 
 
 
 
 
 
 
Consent 
X 
 
 
 
 
 
 
Demographic data 
X 
 
 
 
 
 
 
Injection 
 
X 
X 
X 
 
 
 
Pain assessment 
 
X 
X 
X 
 
 
 
Digital Photography 
X 
 
X 
X 
X 
X 
X 
Measurement of 
submental fat 
X 
 
X 
X 
X 
X 
X 
Patients’ satisfaction   
 
 
X 
X 
X 
X 
X 
Physicians’ assessment 
According to SMF  
X 
 
X 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 

13
 
 
Visit 1 (day 1): 
 
• Solution injection by the physician  
• Monitor the patient for up to half an hour after injection 
• Reporting and recording adverse events  
• Pain assessment 
 
Visit 2 (4 weeks±2 days): 
In case of complete recovery with the physician's opinion: 
 
• Digital AP and lateral photography of the patient's neck 
• Grading of submental fat based on SMF 
• Measurement of submental fat diameter  
• Reporting and recording adverse events  
• Evaluation the patient satisfaction 
 
If re-injection is needed: 
 
• Solution injection by the physician  
• Monitor the patient for up to half an hour after injection 
• Digital AP and lateral photography of the patient's neck 
• Pain assessment 
• Reporting and recording adverse events 
Visit 3 (8 weeks±4 days): 
In case of complete recovery with the physician's opinion: 
 
• Digital AP and lateral photography of the patient's neck 
• Grading of submental fat based on SMF 
• Measurement of submental fat diameter  
• Reporting and recording adverse events  
• Evaluation the patient satisfaction 
 
If re-injection is needed: 
 
• Solution injection by the physician  
• Monitor the patient for up to half an hour after injection 
• Digital AP and lateral photography of the patient's neck 
• Pain assessment 
• Reporting and recording adverse events 
 

14
 
 
Visit 4 (12 weeks±4 days): 
 
• Digital AP and lateral photography of the patient's neck 
• Grading of submental fat based on SMF 
• Measurement of submental fat diameter  
• Reporting and recording adverse events  
• Evaluation the patient satisfaction 
 
Visit 5 (16 weeks±4 days) (In subjectswith 2 injections): 
 
• Digital AP and lateral photography of the patient's neck 
• Grading of submental fat based on SMF 
• Measurement of submental fat diameter  
• Reporting and recording adverse events 
• Evaluation the patient satisfaction 
 
Visit 6 (20 weeks±4 days) (In subjectswith 3 injections): 
 
• Digital AP and lateral photography of the patient's neck 
• Grading of submental fat based on SMF 
• Measurement of submental fat diameter  
• Reporting and recording adverse events  
• Evaluation the patient satisfaction 
Participants: 
This study will be conducted in 20 eligible participants. 
 
Early Termination Policy: The decision to terminate the study early, due to safety concerns or to 
protect patient health, will be made by the Principal Investigator (PI) or the sponsor, with mutual 
agreement from both parties. 
Withdrawal of Subjects 
- 
The patients were allowed and free to refuse to cooperate with the study and follow-up 
whenever they want, but the researchers try to collect the maximum information, 
including the reasons for leaving the study and, if possible, the final results of the 
treatment.  
- 
If a patient missed 2 or more consecutively scheduled visits, he/she was dismissed 
from the study.  
- 
Occurrence of any of the exclusion criteria 
- 
Occurrence of serious adverse event (SAE). 

15
 
 
Data Collection 
All required data will be recorded on the (paper) CRFs for this study, which will be designed 
and provided by PI. The reason for any missing data will be explained. All entries must be in 
permanent, blue ink.  Errors will have single lines drawn through them with the correct data, 
recorder’s initials, and date entered above the error.  All errors must remain legible.  Erasure 
or obliteration of errors in the CRF or other permanent study records are strictly prohibited. 
 
Statistical analysis: 
For statistical analysis, we performed descriptive statistics (mean, standard deviation or 
median and range, frequency and percentages). The efficacy of the treatment was assessed by 
comparing the mean/median value of each parameter among visits, using the Paired Sample 
T-test or the nonparametric equivalent, Wilcoxson test. SPSS 24 statistical software was used 
for data analysis. The statistical significance level was defined as p<0.05. 
 
Adverse Events  
Adverse Event (AE) is described as any medical event that occurs in patients participating in 
a study, which differs from the clinical manifestations of the underlying disease progression 
and does not necessarily have a causal relationship with the treatment used in the study. 
Clinical manifestations that will be reported as adverse events include any symptoms, signs 
(such as any abnormal laboratory results), or temporary illness related to the use of the 
product being studied, whether or not these effects are causally related to the product under 
study. 
Very common adverse events of DCA include: 
- 
Pain  
- 
Edema  
- 
Numbness, tingling,  
- 
Swelling 
- 
 Bruising  
- 
Redness of the skin (erythema)  
- 
Itching  
 Common adverse events of DCA include: 
- 
Injection site reaction 
- 
Bleeding  
- 
Pain and discomfort  
- 
Flushing 
- 
Change of skin color  
- 
Nerve injury around the jaw  
- 
Skin tightness  
- 
Difficulties in swallowing (dysphagia) 
- 
Feeling sick (nausea) 
- 
Headache  
 
Uncommon adverse events of DCA include: 
- 
Unusual taste in the mouth  

16
 
 
- 
Difficulties in speaking  
- 
Hair loss (alopecia)  
- 
Hives (urticarial) 
- 
Skin sores (ulcer)  
- 
Scar  
Adverse events of DCA where the frequency is not known include (frequency cannot be 
estimated from the available data) : 
- 
Reduced or abnormal sensation in the area of the mouth (e.q. lip, tongue) 
- 
Reduced sense of touch or altered sensation in the cheek  
- 
Tissue damage and cell-death (necrosis) around the treatment area  
- 
Injury of blood vessels if injected accidentally into artery or vein  
 
The medical conditions that existed prior to the start of the study are only considered as 
adverse events if they have worsened during the course of the study and cannot be attributed 
to the natural progression of the disease. 
Serious Adverse Reaction (SAR) is described as a harmful response to an intervention and 
includes: 
 
• result in death . 
 
• pose a risk of death . 
 
• require hospitalization . 
 
• prolong the duration of hospitalization. 
 
• cause persistent or significant disability. 
 
• result in congenital anomalies or birth defects. 
 
• require medical or surgical intervention to prevent permanent damage 
 
Recording and Reporting of Adverse Events: 
 All adverse events and adverse drug reactions will be recorded in the patient's medical file as 
well as in the designated section of the CRF. They will be classified based on severity, 
relevance, and relation to the treatment used in the study, and in accordance with the 
investigator's criteria and the guidelines outlined below. 
Classification of adverse events based on severity: 
Adverse events will be classified according to their severity into three categories: mild [1], 
moderate [2], and severe [3], based on the following definitions: 
Mild: Any reaction, sign, or symptom that the individual can recognize but does not  
influence performance or functioning. 
Moderate: Any reaction, sign, or symptom(s) of a sufficient severity to make the subject 
uncomfortable. Performance of daily activities is influenced. This may require medical 
intervention. 

17
 
 
Severe: Any reaction, sign, or symptom(s) of a sufficient severity to cause the subject severe 
discomfort. Performance of daily activities/functioning is compromised and causes disability 
and/or poses a specific risk to health. This usually requires medical intervention..   
Note:  Severe AEs are not necessarily serious unless one of the serious outcomes has 
occurred.  
Classification of Adverse Events Based on Association with the Treatment Used in the Study: 
To determine the association between an adverse event or adverse drug reaction and the 
treatment used in the study, the following definitions will be considered: 
 
-Certain: A clinical event involving changes in laboratory tests that are associated with a 
timely logical change in drug administration, and its occurrence cannot be explained by the 
person’s current illness or other medications and substances. The response to drug reduction 
(dechallenge) should be clinically acceptable. This should be done from a pharmacological 
point of view and, if necessary, the drug re-exposure information (rechallenge) should be 
used . 
-Probable: A clinical event involving changes in laboratory tests that are associated with a 
timely logical change in drug administration, and it is unlikely to be associated with a 
person’s current illness or other medications and substances, and a reasonable clinical 
response is observed when the dose is reduced. There is no need for a rechallenge to put an 
undesirable event in this group. 
-Possible: A clinical event involving changes in laboratory tests that are associated with a 
timely logical change in drug administration, but it can be justified by the person’s current 
illness or other medications and substances. Drug reduction information maybe not available 
or may be ambiguous . 
Unlikely: A clinical event involving changes in laboratory tests that are associated with a 
timely logical change in drug administration, and it is acceptable to justify its occurrence 
through current illness of the individual or other drugs and substances . 
Conditional/Unclassified: A clinical event involving changes in laboratory tests, which is 
declared as an adverse reaction and it is necessary to obtain more data or more data are being 
evaluated for its correct evaluation. 
Unassessable/Unclassifiable: A symptom that is probably an adverse reaction, but because 
the information about it is insufficient or inconsistent and related data cannot be confirmed or 
completed, it cannot be judged. 
 
Quality Assurance: 
This study and the accuracy of the tests at intervals were evaluated by Dr. Taraneh 
Yazdanparast; the quality assurance manager based on the relevant SOPs . 
 
Accordance with GCP: 
The study was conducted according to the principles provided by Good Clinical Practice (GCP) 
and the Declaration of Helsinki  
 
  

18
 
 
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