Sunflower_TTS_Test

[Audio] Thank you for coming in today. This session is designed to give you a thorough overview of the objectives and goals of this research study, as well as your role as a participant and the rights that you have. This study is titled Sunflower The study is being sponsored by Shenzen Sungening Biological Co. LTD.

[Audio] Goal To evaluate the safety and tolerability of multiple doses of SG1001 tablets in healthy adult participants. To evaluate the pharmacokinetic (PK) characteristics of multiple doses of SG1001 Tablets in healthy adult participants. Your Principal Investigator will be Dr. Al-Ibrahim.

[Audio] Introduction Participation in this study is voluntary. This session will give you an overview of the goals and the objectives of this research. During your individual consent session, please ask any questions you have before signing the Consent form. Do not sign your consent form until your individual consenting session with a member of the study staff..

[Audio] About the Investigational Product Study Drug: SG1001 Possible treatment for Invasive Fungal Disease (IFD) Subjects will undergo a screening period, baseline period, dosing (study drug or placebo) and observation period, early withdrawal/end of the study. An investigational drug is one that has not been approved by the US Food and Drug Administration (FDA).

[Audio] Study Purpose The purpose of this study is to learn about how SG1001 is processed by the body after it is given by mouth as a tablet. This will help to determine how the Study Drug behaves inside the human body. Examining the blood samples collected during this study will provide pharmacokinetic, also referred to as PK, (PK: the study of how a drug behaves in the body) data that show how the human body: Takes the Study Drug into the blood Delivers the Study Drug through the blood Breaks down or processes the Study Drug Removes the Study Drug from the body The study is also designed to help determine the safety and tolerability (can people comfortably use) the Study Drug, and to evaluate the pharmacokinetic characteristics of multiple doses in healthy adult participants.

[Audio] Study Design This study is looking to enroll approximately 20 healthy volunteers between the ages of 18 and 45 20 subjects will be assigned to 1 of 2 groups. It is expected that 16 subjects will receive SG1001 and 4 will receive placebo. This is a randomized double-blind study where you and the Study Doctors will not know which treatment you receive, and the treatment assignment will be made randomly (like a flip of a coin)..

[Audio] Study Duration Screening period: Approximately 28 days to determine if you are eligible to participate. Baseline Period: Eligibility will be rechecked Study period: Multiple-dose administration and observation period (Day 1 to Day 17).

[Audio] Participant Restrictions Participants with any of the following significant diseases that are judged by the investigator as unsuitable for participation in this trial, including but not limited to: neurological/psychiatric disorders, respiratory disorders, cardiovascular and cerebrovascular disorders, gastrointestinal disorders (any history of gastrointestinal diseases that may affect drug absorption), hematological and lymphatic disorders, urinary disorders, endocrine disorders, immune system disorders, etc.; Participants who develop acute diseases from the screening period until before the first dose of the study drugs are judged by the investigator as unsuitable for further participation in the study; Participants with dysphagia; Participants who are potentially or definitely allergic to the study drugs or any of their excipients as judged by the investigator; or participants with a clinically significant allergic constitution (≥ two serious allergic histories to drugs or foods, where anaphylaxis is defined in Appendix 2) or a history of allergic diseases as judged by the investigator; Participants who have a history or presence of cardiac disease, including clinically significant abnormal electrocardiogram (ECG) and/or QTcF > 450 milliseconds.

[Audio] Participants who have evidence of hepatic dysfunction with abnormal laboratory parameters at screening or participants with a history of chronic liver diseases including chronic hepatitis or cirrhosis Participants who have undergone abdominal or gastrointestinal surgery and may affect drug absorption, distribution, metabolism, or excretion as judged by the investigator, those with significant postoperative sequelae, or those planning to undergo surgery during the study; Participants who have donated blood or experienced non-physiological massive blood loss (≥400 mL, including trauma, blood sampling, blood donation, etc., excluding physiological blood loss in females) within 3 months prior to screening, those who have donated ≥2 units of blood components or received a blood transfusion, or those who plan to donate blood during the study or within 3 months after the end of the study; Participants who have received any study drug or participated in any interventional clinical study within 3 months prior to the first dose of the study drugs; Participants who have smoked more than 5 cigarettes per day on average within 3 months prior to screening, or those who cannot stop using any tobacco products during the trial;.

[Audio] Participants who have consumed more than 14 units of alcohol per week on average (1 unit of alcohol ≈ 360 mL of beer, 45 mL of spirits with 40% alcohol content, or 150 mL of wine) within 3 months prior to screening, those who cannot stop using any alcohol-containing products during the trial, or those with a positive breath and/or serum alcohol test result before administration of the study drugs; Participants who have consumed excessive tea, coffee, and/or caffeinated beverages (more than 8 cups on average, 1 cup ≈ 250 mL) per day within 3 months prior to screening, or those who cannot stop drinking tea, coffee, and/or caffeinated beverages during the trial; Participants who have received any prescription drugs, over-the-counter drugs, herbal medicines, vaccines, vitamins, or health supplements within 28 days prior to the first dose of the study drugs or 5 half-lives of the drug (whichever is longer); Female participants who are pregnant or lactating, or those with a positive result in any blood/urine pregnancy test before the first dose of the study drugs; Participants with positive results or results exceeding the upper limit of the reference range for any of the three blood screening tests: hepatitis B surface antigen, hepatitis C virus antibody, and human immunodeficiency virus-p24 (HIV-p24) antigen/antibody test (S);.

[Audio] Participants with a positive result in COVID-19 PCR test before the first dose of the investigational products; Participants with a positive result in drug abuse screening test (morphine, tetrahydrocannabinol acid, methamphetamine, methylenedioxymethamphetamine and ketamine, barbiturates, benzodiazepines, cocaine, cotinine, etc.) at screening, or those with a history of drug abuse or use of illicit drugs within 2 years prior to the trial; Participants who have consumed or drunk dragon fruit, mango, pomelo, carambola, or foods or beverages prepared from them, or foods or beverages containing xanthine, caffeine, or alcohol (including chocolate, tea, coffee, cola, cocoa, etc.), or other special diets that may affect drug absorption, distribution, metabolism, or excretion within 72 h prior to the first dose of the study drugs; Participants with special dietary requirements (e.g., vegan diet), lactose intolerance, or those who cannot accept a standardized meal; Participants who are unsuitable for participation in this trial as judged by the investigator; Participants with difficulty in collecting blood samples or intolerance to venipuncture, or those with a history of needle or blood phobia..

[Audio] Screening Period (Day -28 to Day -1) If you sign this consent form, it means that you have decided to participate in this study. You will be required to undergo screening examinations and procedures to determine whether you are eligible to participate in this study; Your demographic information, such as sex, ethnicity, date of birth, etc., will be inquired; Your past medical history will be asked, including disease history, smoking history, drinking history, drug allergy history, blood donation history, blood transfusion history, surgical history, clinical study history, etc. Information on any drugs you have used in the past, are currently using, or may use in the near future (including prescription drugs, over-the-counter drugs, Chinese patent medicines, Chinese herbal medicines, vaccines, vitamins or health products, etc.) will also be inquired, and your current health status will be understood; A physical examination will be conducted for you to measure your height, weight and vital signs (blood pressure, pulse, body temperature, respiratory rate); You will undergo a 12-lead electrocardiogram (ECG) examination;.

[Audio] Screening Period (Day -28 to Day -1) Continued Your blood and urine will be collected for the following examinations: hematology, blood biochemistry, urinalysis, coagulation function, fasting blood glucose, β2-microglobulin, N-acetyl-β-glucosaminidase (NAG), four items related to hemodialysis examination and hormone examination (adrenocorticotropic hormone (ACTH), cortisol and aldosterone). If you are a female with the potential to become pregnant, you will undergo a serum (blood) pregnancy test (it must be negative to enter the study. You must agree to have no fertility plan during the entire study period and within 3 months after the last dose of the study drug and voluntarily take effective contraceptive measures required by the investigator); Regardless of male or female participants, the contraceptive measures you have taken will be inquired, and the investigator will discuss with you the acceptable contraceptive measures in the study; Based on the results of your various examinations, the inclusion/exclusion criteria will be checked to ensure that you meet the inclusion criteria of this study and do not meet the exclusion criteria..

[Audio] Screening Period (Day -28 to Day -1) Continued Inclusion criteria (Participants who meet all of the following criteria can be included in this study): Healthy male or female participants aged 18 to 45 years (inclusive) at the time of signing the informed consent form (ICF); Weight shall be ≥50.0 kg for male participants and ≥45.0 kg for female participants, with a body mass index (BMI) = weight (kg)/height2 (m2) of falling within 19.0 to 32.0 kg/m2 (inclusive); Women of childbearing potential (WOCBP) or female partners of male participants must have no plans for pregnancy from 4 weeks prior to screening to 3 months after the last dose of the study drugs and must voluntarily take effective contraceptive measures (including one or more non-pharmacological contraceptive measures, as detailed in Appendix 1). Additionally, there should be no plans for sperm or egg donation; Participants without a history of significant diseases, with normal results of physical examination, vital signs, 12-lead ECG, and laboratory tests at screening, or abnormal but not clinically significant as judged by the investigator; Participants who can maintain good communication with the investigator, comply with all clinical trial requirements, and voluntarily sign the ICF..

[Audio] Screening Period (Day -28 to Day -1) Continued Exclusion criteria (Participants who meet any of the following criteria will not be included in this study): Participants with any of the following significant diseases that are judged by the investigator as unsuitable for participation in this trial, including but not limited to: neurological/psychiatric disorders, respiratory disorders, cardiovascular and cerebrovascular disorders, gastrointestinal disorders (any history of gastrointestinal diseases that may affect drug absorption), hematological and lymphatic disorders, urinary disorders, endocrine disorders, immune system disorders, etc.; Participants who develop acute diseases from the screening period until before the first dose of the study drugs are judged by the investigator as unsuitable for further participation in the study; Participants with dysphagia; Participants who are potentially or definitely allergic to the study drugs or any of their excipients as judged by the investigator; or participants with a clinically significant allergic constitution (≥ two serious allergic histories to drugs or foods, where anaphylaxis is defined in Appendix 2) or a history of allergic diseases as judged by the investigator; Participants who have a history or presence of cardiac disease, including clinically significant abnormal electrocardiogram (ECG) and/or QTcF > 450 milliseconds；.

[Audio] Screening Period (Day -28 to Day -1) Continued Participants who have evidence of hepatic dysfunction with abnormal laboratory parameters at screening or participants with a history of chronic liver diseases including chronic hepatitis or cirrhosis; Participants who have undergone abdominal or gastrointestinal surgery and may affect drug absorption, distribution, metabolism, or excretion as judged by the investigator, those with significant postoperative sequelae, or those planning to undergo surgery during the study; Participants who have donated blood or experienced non-physiological massive blood loss (≥400 mL, including trauma, blood sampling, blood donation, etc., excluding physiological blood loss in females) within 3 months prior to screening, those who have donated ≥2 units of blood components or received a blood transfusion, or those who plan to donate blood during the study or within 3 months after the end of the study; Participants who have received any study drug or participated in any interventional clinical study within 3 months prior to the first dose of the study drugs; Participants who have smoked more than 5 cigarettes per day on average within 3 months prior to screening, or those who cannot stop using any tobacco products during the trial;.

[Audio] Screening Period (Day -28 to Day -1) Continued Participants who have consumed more than 14 units of alcohol per week on average (1 unit of alcohol ≈ 360 mL of beer, 45 mL of spirits with 40% alcohol content, or 150 mL of wine) within 3 months prior to screening, those who cannot stop using any alcohol-containing products during the trial, or those with a positive breath and/or serum alcohol test result before administration of the study drugs; Participants who have consumed excessive tea, coffee, and/or caffeinated beverages (more than 8 cups on average, 1 cup ≈ 250 mL) per day within 3 months prior to screening, or those who cannot stop drinking tea, coffee, and/or caffeinated beverages during the trial; Participants who have received any prescription drugs, over-the-counter drugs, herbal medicines, vaccines, vitamins, or health supplements within 28 days prior to the first dose of the study drugs or 5 half-lives of the drug (whichever is longer); Female participants who are pregnant or lactating, or those with a positive result in any blood/urine pregnancy test before the first dose of the study drugs; Participants with positive results or results exceeding the upper limit of the reference range for any of the three blood screening tests: hepatitis B surface antigen, hepatitis C virus antibody, and human immunodeficiency virus-p24 (HIV-p24) antigen/antibody test (S);.

[Audio] Screening Period (Day -28 to Day -1) Continued Participants with a positive result in COVID-19 PCR test before the first dose of the investigational products; Participants with a positive result in drug abuse screening test (morphine, tetrahydrocannabinol acid, methamphetamine, methylenedioxymethamphetamine and ketamine, barbiturates, benzodiazepines, cocaine, cotinine, etc.) at screening, or those with a history of drug abuse or use of illicit drugs within 2 years prior to the trial; Participants who have consumed or drunk dragon fruit, mango, pomelo, carambola, or foods or beverages prepared from them, or foods or beverages containing xanthine, caffeine, or alcohol (including chocolate, tea, coffee, cola, cocoa, etc.), or other special diets that may affect drug absorption, distribution, metabolism, or excretion within 72 h prior to the first dose of the study drugs; Participants with special dietary requirements (e.g., vegan diet), lactose intolerance, or those who cannot accept a standardized meal; Participants who are unsuitable for participation in this trial as judged by the investigator; Participants with difficulty in collecting blood samples or intolerance to venipuncture, or those with a history of needle or blood phobia..

[Audio] Baseline period (Day -1, 1 day before administration) If you pass the screening period examination and meet the inclusion requirements, we will promptly notify you to participate in the baseline period examination. You will be admitted to the clinical study unit (hereinafter referred to as the "study site") 1 day before administration (Day -1 of the study). Upon admission, the following assessments will be carried out: Any new or changed medical history/treatment history since entering the screening period will be inquired; Your vital signs (blood pressure, pulse, body temperature, respiratory rate) will be measured; You will undergo a 12-lead ECG examination; COVID-19 PCR test;.

[Audio] Baseline period (Day -1, 1 day before administration) Continued Your blood and urine will be collected for the following examinations: hematology, blood biochemistry, urinalysis, coagulation function, fasting blood glucose, β2-microglobulin, NAG, blood pregnancy or urine pregnancy test (only for female participants with fertility potential), hormone examination (blood ACTH, cortisol and aldosterone), drug abuse screening breath and/or serum alcohol test; Based on the results of your various examinations, the inclusion/exclusion criteria will be checked to ensure that you meet the inclusion criteria of this study and do not meet the exclusion criteria. Note: 1)Blood pregnancy test is preferred. If the blood pregnancy result cannot be obtained on Day -1 or there is no condition for blood pregnancy test, it can be replaced by urine pregnancy test. (If the screening period coincides with D-1, only 1 test will be performed)..

[Audio] Dosing and Observation Period: Day 1 to Day 17 According to the randomization table, you will be arranged to take the medicine and receive a series of examinations and collect blood or other samples for the study. If you experience any significant discomfort at any time, please contact the clinical research physician or other staff in the study site as soon as possible. You need to comply with the activities such as taking medicine, examinations, and sample collection arranged by the investigator for you. The specific process of the study is as follows:.

[Audio] Dosing and Observation Period: Day 1 to Day 14 Vital signs: 0 h before administration (within 2 h before administration) on D1, D5, D8, D11, D14 and D16; 12-lead ECG: Within 2 h before administration on D1, D5, D8, D11, D14 and D16; Laboratory examinations (hematology, blood biochemistry, urinalysis, coagulation function, fasting blood glucose, β2-microglobulin, n-acetyl-β-glucosaminidase (NAG)): Days 8, D14 and D16; Hormone tests (plasma ACTH, cortisol and aldosterone): Day 14; PK blood sample collection: Day 1 to Day 17; Collect information on combined medications; Record adverse events;.

[Audio] Early Withdrawal/ End of the Study: Day 18 Physical examination; Vital signs; 12-lead ECG; Laboratory examinations (hematology, blood biochemistry, urinalysis, coagulation function, fasting blood glucose, β2-microglobulin, n-acetyl-β-glucosaminidase (NAG)); Hormone tests (plasma ACTH, cortisol and aldosterone); Blood/urine pregnancy test; PK blood sample collection; Collect information on combined medications; Record adverse events; You will leave the study site after completing the above study procedures. Note: 1) If a participant has already undergone physical examination, vital signs, 12- lead ECG, laboratory tests, hormone tests, or blood/urine pregnancy test on the day of early withdrawal, these tests do not need to be repeated..

[Audio] Blood Sample Collection Day 1: Blood samples will be collected at 0 h before the first dose (within 1 h before administration) and at 0.5 h, 1.0 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h and 12 h post-dose; Day5, Day 8, Day11: Blood samples will be collected at 0 h pre-dose (within 1 h before administration); Day 14: Blood samples will be collected at 0 h before last dose (within 1 h before administration) and at 0.5 h, 1.0 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h, and 96 h post-dose. The volume of each PK blood sample collected is approximately 4.0 mL. During the process of multiple blood collections, if an indwelling catheter is used for blood collection, approximately 1 mL of blood containing the tube-sealing fluid will be removed before each blood collection. In the MAD study, PK blood samples will be collected at 27 time points. It is estimated that the blood collection volume for each dose group during the study cycle is approximately 108 mL..

[Audio] Blood Sample Collection continued If you participate in this study, in addition to the above blood collections, you will also need to have blood collected for four items related to hemodialysis, laboratory examinations, and hormone examinations according to the protocol requirements. Among them, the volume of blood collected is approximately 2 mL each time for the hematology, approximately 2 mL each time for fasting blood glucose, approximately 6 mL each time for blood biochemistry, approximately 4 mL each time for coagulation function, approximately 4 mL each time for three items related to hemodialysis, approximately 2 mL each time for hormone examinations, and female participants also need to have a blood pregnancy test with approximately 4 mL of blood collected each time..

[Audio] Blood sample collection continued Please review the following table at your convenience.

[Audio] Risks/Side Effects SG1001 is an innovative chemical drug, the first-in-human study, has been completed in China. A total of 77 healthy participants were enrolled, the single SAD cohort with the dose cohorts range from 15 mg to 360 mg and the multiple cohort with the dose cohorts range from 45 mg BID to 180 mg BID. Overall, the safety profile is good and well-tolerated. In the currently completed study, among the adverse events that occurred in healthy participants after orally administered, all TRAEs were mild in severity, and most resolved without intervention. No SAEs, deaths, or TEAEs leading to withdrawal or treatment discontinuation were reported. There were no significant differences in the incidence of TEAEs/ TRAEs between the study drug and placebo. The most frequently reported TRAEs included: abdominal pain, diarrhea, changes in blood fat levels, changes in liver function tests, changes in hormone levels, changes in blood cell counts, increased uric acid, changes in Electrocardiogram, etc..

[Audio] Risks/Side Effects continued Non-clinical toxicological studies suggest that high doses of SG1001 may cause abnormal liver biochemistry, adrenal toxicity, dyslipidemia, and gastrointestinal reactions. The overall tolerance in animals is good and there are no significant toxicological reactions, supporting that the use of SG1001 in humans is expected to be safe. It is expected that the adverse events that need to be paid attention to in the clinical study of SG1001 tablets include abnormal liver biochemistry and gastrointestinal reactions. The following results of animal studies are provided for your reference. Since all of these findings were discovered in animal studies, the relevance of these findings to humans is still unclear..

[Audio] Risks/Side Effects continued In vitro safety pharmacology studies have shown that SG1001 had a certain inhibitory effect on hERG potassium channel, and the inhibition rate of test sample was 64.80% at 15.000 µM, with a corresponding IC50 of 7.651 µM. The single-dose toxicity study of Sprague-Dawley (SD) rats showed that animals in the ≥600 mg/kg dose groups showed perianal soiling, and those in the 1200 mg/kg dose group also had hunched posture. These symptoms lasted for a maximum of 3 days before resolving, which were considered as non-serious, test sample-related toxic reactions. The single-dose toxicity study of Beagle dogs showed that animals in the 900 mg/kg dose group had salivation, vomiting (yellow), perianal soiling, discoloration stool (yellow), watery stool and soft stool, all of which recovered within 1-3 days and were considered to be related to the test sample..

[Audio] Risks/Side Effects continued The repeated-dose toxicity study in SD rats showed that animals in the ≥30 mg/kg dose group had increased levels of total bilirubin (TBIL), total cholesterol (TCHO), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C); adrenal fascicular zone hypertrophy and hepatocyte hypertrophy (mainly centrilobular); significant increases in the weights of the liver and adrenal glands, as well as the organ/body and organ/brain coefficients. All of the above abnormalities disappeared four weeks after drug withdrawal. The repeated-dose toxicity study of Beagle dogs showed that increased TBIL, GLU, TCHO, LDL-C and HDL-C were observed in animals at ≥10 mg/kg; also, adrenal fascicular zone hypertrophy, degeneration/atrophy of the zona glomerulosa, cortical fibrosis and/or cortical mineralization were noted; at 10 mg/kg, a significant increase in organ weight and organ-to-body weight ratio of adrenal glands was also observed in female animals; at 20 mg/kg, hepatocyte hypertrophy was also induced; these abnormalities were recovered after the 4-week recovery period..

[Audio] Risks/Side Effects continued As of October 21, 2023, the drug with the same target, F901318 (Olorofim), has obtained Phase II data, and F901318 was well-tolerated in this study. The results of safety studies showed that liver biochemical changes in 9.9% of patients were considered to be possibly caused by F901318, but they could be controlled by dose reduction/suspension. Only 2.5% of patients had permanent drug discontinuation due to liver biochemical changes. Other non-serious adverse events observed included diarrhea, nausea and vomiting. Gastrointestinal intolerance to F901318 was observed in 9.9% of patients, which was typically self-limiting. ACM (all-cause mortality) was 11.4% and 15.8% (IA: 17.8% and 25.7%; non-IA infections: 5.0% and 5.9%) on Day 42 and Day 84, respectively..

[Audio] Risks/Side Effects continued In addition, F901318 had no serious adverse events reported in a single-ascending dose Phase I clinical study in healthy male volunteers (NCT02142153); the frequency of non-serious adverse events is as follows: Musculoskeletal pain occurred in 0/30 in the F901318 group and 1/10 in the placebo group; paresthesia or headache occurred in 2/30 in the F901318 group and 0/10 in the placebo group; epistaxis occurred in 2/30 in the F901318 group and 1/10 in the placebo group; eczema occurred in 1/30 in the F901318 group and 0/10 in the placebo group. Finally, in the F901318 group, infusion related reactions were reported, including dizziness (67%), infusion site pain (44%) and phlebitis (39%); these adverse events were reported by 17% of participants in the placebo group..

[Audio] Risks/Side Effects continued It is also necessary to pay attention to the possible risks of blood sample collection and the placement of indwelling needles: Blood sample collection may cause slight pain, and occasionally may lead to local bruising or edema; the placement of indwelling needles may carry risks of infection and blood coagulation disorders. We will try to be as gentle as possible when collecting blood to reduce pain and avoid local bruising. Before using indwelling needles, we will disinfect the blood collection site to minimize the risk of infection..

[Audio] Risks/Side Effects continued The Phase I Clinical Study Office is equipped with medical rescue equipment and first-aid drugs. During the study, you will receive medical monitoring from experienced medical staff, who will carefully monitor any adverse events that may occur to you. To ensure your safety, during the entire study period, if you feel any discomfort, please inform your clinical research physician in a timely and truthful manner. The clinical research physician will take corresponding treatment or handling measures. Once an adverse event occurs, you will receive timely and appropriate treatment. Your physician will closely observe or follow up on any adverse events that occur during your hospitalization and follow-up period until you recover to normal. The sponsor will bear and pay for the relevant examination and treatment costs as well as appropriate compensation expenses..

[Audio] Risks/Side Effects continued If you have any questions about the above adverse events and risks, you can also consult our medical staff, and they will give you detailed explanations. During the study process, if there is any updated safety information or risks regarding the study drug that may affect your decision on whether to continue participating in the study, we will notify you in a timely manner, and it will be up to you to decide whether to continue participating in this study..

[Audio] Participant's Restrictions You cannot be in this study if you use tobacco- or nicotine-containing products (such as cigarettes, cigars, e-cigarettes, hookah, etc.) or are taking any drugs of abuse (illegal and/or prescription) prior to your Screening visit. A urine test will be performed to check for the use of these drugs: Amphetamine Opiate. Cocaine. Barbiturates. Benzodiazepines. Marijuana [tetrahydrocannabinol (THC)] Cannabinoids Methadone Methamphetamine MDMA Morphine Oxycodone Phencyclidine Tri-cyclic antidepressants Buprenorphine Cotinine (Nicotine) It is very important you inform the Study Doctor of any medications you take including prescription, over the counter, herbal remedies or vitamins..

[Audio] Participant's Restrictions continued In order to be eligible, you will be questioned about the following restrictions and your eligibility will be determined by the study staff. These restrictions apply throughout the study: Tobacco or nicotine use Bone marrow or stem cell donation Blood donation Plasma donation Medication use Alcohol use Strenuous exercise In addition, you cannot be in this study if: You are in another research study or if you have participated and received any study medication within 12 weeks or prior to Screening. You have taken weight loss drugs within 12 weeks prior to Screening. You have participated in an investigational device study within 12 weeks prior to Screening..

[Audio] Participant's Expectations While participating in this research study, you will need to: Be willing and able to follow the study directions and procedures. Be willing to be tested for SARS-CoV-2. Tell the study staff about any side effects or problems. Ask questions as you think of them. Tell the Study Doctor or the study staff if you change your mind about staying in the study. Complete all your study visits and study procedures as scheduled..

[Audio] Participants expectations continued Provide a complete and truthful medical history. If you are a man, you must follow the birth control requirements discussed in the Birth Control section. You must also agree to not donate sperm for at least 3 months after your last dose of Study Drug. If you are a woman, you must be non-pregnant, non-lactating and have negative pregnancy test results at Screening (serum) and Admission (serum or urine). Birth control requirements are discussed in the Birth Control section. You must also agree to not donate eggs for at least 3 months after your last dose of Study Drug. Remain on the inpatient research unit during scheduled in patient periods of the study until you meet discharge criteria and are discharged. Follow the inpatient research unit rules during scheduled inpatient periods of the study. Contact the study staff or doctor right away if you are not feeling well or feel concerned about symptoms..

[Audio] Study Treatment After you have checked into the inpatient unit, you will not be allowed to leave until you are eligible for discharge, or you decide to leave the study. There are strict rules that you must be willing to follow during your stay: You cannot have visitors or deliveries. We will provide all your meals and snacks. You will not be allowed to smoke, have drugs or alcohol, or to exercise strenuously. 1.5 hours later, you will receive a second dose of study drug as an infusion, with a small amount of radioactive 14C so that the study doctor can identify the study drug and its breakdown by products in your blood..

[Audio] After Study Treatment Because this is a research study, the Study Drug will be given to you only during this study and not after the study is over. After your end of study visit, you will have completed your participation in this study. If needed, you may be asked by the Study Doctor to stay or return for additional time for safety and monitoring. Early Termination/Early Discharge If you leave the study early, we will ask you to complete all of the procedures scheduled for the End-of-Study visit before you leave the research unit. You will also be asked for updated contact information..

[Audio] Alternatives to Participation Please talk to the Study Doctor about your options before you decide whether or not you will take part in this study. This research study is for research purposes only. The only alternative is to not participate in this study..

[Audio] Pregnancy Precautions SG1001 tablets have undergone 28-day repeated-dose toxicity studies in rats and dogs, and no adverse effects on the reproductive systems of female and male animals were found. The results of genetic toxicity tests indicated that SG1001 did not show genetic toxicity. However, SG1001 tablets have not yet undergone a complete reproductive toxicity study, and there is no available human data or reproductive toxicity information on similar compounds. Therefore, there are unknown risks of SG1001 tablets to embryos or fetuses..

[Audio] Pregnancy precautions Pregnancy is a personal behavior of the participant and his/her spouse. In the case where the investigator has fulfilled the obligation to inform, if the participant or his/her spouse still has an unexpected pregnancy during the study, neither the investigator nor the sponsor has the obligation and responsibility to compensate. Once an unexpected pregnancy occurs to the participant or his/her spouse, the investigator is responsible for reporting it to the sponsor and, based on the previous study data of the study drug, informing the participant of the reproductive toxicity of the study drug. Whether to continue the pregnancy will be decided by the participant and his/her spouse on their own. Please refer to Appendix 1 on the next page for effective contraceptive methods..

[Audio] Effective Contraceptive Methods (Appendix 1) Please note that the definition of fertility described in this appendix is broader than the general sense of fertility. This is to minimize the risk of pregnancy in the study as much as possible. As long as a participant has the possibility of getting pregnant or causing his/her partner to get pregnant, he/she will be defined as fertile in this study. The definition of fertility in this study is as follows: Women of non-childbearing potential are postmenopausal women and premenopausal women who have undergone sterilization surgery. Postmenopausal is defined as the cessation of menstruation for ≥12 consecutive months without alternative medical measures. Sterilization surgery includes bilateral tubal ligation or bilateral oophorectomy or hysterectomy. Women of childbearing potential (WOCBP) are women who have experienced menarche but have not yet reached menopause, or have not undergone sterilization surgery, and are anatomically and physiologically capable of pregnancy..

[Audio] Effective Contraceptive Methods Cont'd If necessary, your clinical research physician will discuss effective contraceptive measures with you. Contraceptive requirements The pregnancy test results for female participants of childbearing potential during the screening period must be negative. If you need to have sexual intercourse, you must agree to use at least one highly effective contraceptive method and an additional effective contraceptive method at the same time. The contraceptive period is from the screening period to within 3 months after the last administration of the study product. At the same time, you must avoid donating eggs or sperm or undergoing in vitro fertilization during the study period and within 3 months after drug administration..

[Audio] Effective Contraceptive Methods Cont'd Female participants of childbearing age and male participants must also agree to one of the following operations: If acceptable to you, complete abstinence is the most effective means to avoid pregnancy. Periodic abstinence methods (e.g., calendar method, ovulation method, symptothermal method, or post-ovulation method) are not permitted. One of the right contraceptive methods with the failure rate below 1%: Intrauterine device (IUD) or hormone-releasing intrauterine system with the annual failure rate below 1%; Vasectomy of male partner; Double barrier method: Condom and/or occlusive cap (diaphragms or cervical cap/vault cap), with the barrier method of spermicide (foam/gel/diaphragm/cream/suppository) as a supplement..

[Audio] Confidentiality Your medical records are protected by privacy standards. However, this research study will produce medical record information about you and follow your medical progress during the course of the study. The information collected will be placed in your medical records. Your study center is required to protect the privacy of your personal health information. If you agree to take part in this study, your personal health information will be used and shared with others involved in this study. Also, any new personal health information about you that comes from tests or other parts of this study will be shared with those involved in this study..

[Audio] Confidentiality Cont'd When your medical records are shared with the Sponsor, they will not include your name or personal contact information and will only be identified by a study identifier and your unique participant code number. However, some of your information that will be shared, such as your year of birth or the location of your study center, could have the potential to be linked to you. Your records of being in the study will be kept private except when ordered by law. The following people will have access to your study records: The investigator The sponsor company or research institution including monitors and auditors The United States Food and Drug Administration (FDA) Other state or federal regulatory agencies Advarra IRB, the Research Ethics Committee that approved this study and any other committees responsible for overseeing the research. Please review your ICF for more information concerning Use and Disclosure of Medical Information and Confidentiality..

[Audio] Termination from the Study The investigator, the sponsor company, Advarra, or the FDA may take you out of the study without your permission, at any time, for the following reasons: If you do not follow the investigator's instructions. If we find out, you should not be in the study. If the study is stopped. If it becomes harmful to your health..