UNIVERSITY OF PENNSYLVANIA HEALTH SYSTEM

Transcription

1 Tobira Therapeutics , Amendment 4, 24 February 2012:A Phase 2b Randomized, Double-Blind, Double-Dummy Trial of 100 or 200 mg Once-Daily Doses of Cenicriviroc (CVC, TBR-652) or Once-Daily EFV, Each With Open-Label FTC/TDF in HIV-1-Infected, Antiretroviral Treatment-Naïve, Adult Patients with Only CCR5-Tropic Virus CONSENT TO PARTICIPATE IN A RESEARCH STUDY AND RESEARCH SUBJECT HIPAA AUTHORIZATION Your contacts for this study at the Hospital of the University of Pennsylvania [HUP] are: Principal Investigator: Pablo Tebas, MD (215) Coordinator: Joseph Quinn, RN (215) Study Nurses: John Beaver, RN (215) Hour Emergency Number (215) Ask for the Immunodeficiency Program Doctor on call Introduction: You are being asked to participate in this research study because you are infected with HIV-1. To decide whether or not you want to be part of this research, you should understand the risks and benefits of the study in order to make an informed decision. This process is known as informed consent. This consent form describes the purpose, procedures, possible benefits and risks of the study. This form will also explain how your medical information will be used and who may see it. You are being asked to take part in this study because the study doctor feels that you meet the qualifications of the study. Once you understand the study, you will be asked to sign this form if you wish to participate. You may have a copy of this form to review at your leisure or to ask advice from others. Your decision to take part in the study is voluntary. You are free to choose whether or not you will take part in the study. Your choice does not affect the medical care that you will receive. Why Is This Study Being Done? This research study is being conducted by Tobira Therapeutics. Tobira Therapeutics is the Sponsor of this study. You are being asked to take part in a research study of an investigational drug called cenicriviroc (CVC, TBR-652). An investigational drug is one that has not been approved by the U.S. Food and Drug Administration (FDA). Cenicriviroc (CVC,TBR-652) is being developed for treatment of people with the human immunodeficiency virus type 1 (HIV-1). Your participation in the study will contribute to information about the drug and may benefit patients in the future. The primary purpose of this study is to evaluate how effective, how safe and how well tolerated a range of cenicriviroc (CVC,TBR-652) doses compares to a comparator drug (efavirenz, also called Sustiva) while receiving emtricitabine/tenofovir disoproxil fumarate (also called Truvada) in subjects with HIV-1. A comparator drug is an agent that the investigational drug is being compared to in this study. You will also take a matching placebo tablet and capsule. Placebo is an inactive substance, which may resemble an active agent but has no medical value. Page 1 of 14

2 This is a double-blind study, which means, neither you nor the study doctor, the study staff or the Sponsor will know if you will take cenicriviroc (CVC,TBR-652)/placebo or efavirenz/placebo. However, this information will be available to your study doctor in case of an emergency. If you are eligible for the study, you will be assigned (by chance, i.e. like the toss of a coin) by a computer to one of three treatments. You will have an 80% chance of receiving cenicriviroc (CVC, TBR-652)/placebo at one of two different dosages (100 mg or 200 mg). You will have a 20% chance of receivingefavirenz 600 mg/placebo. All subjects will receive emtricitabine/tenofovir disoproxil fumarate (Truvada) and complete the same study-related procedures regardless of which treatment or treatment dose you receive. Regardless of your assignment group, you will take five tablets and one capsule, daily by mouth. Pharmacokinetic Assessment The first 25 subjects who participate in this study will take part of Pharmacokinetic Assessment (PK). The following procedures will take place: You will need to be able to spend a full day at the study site. You will be asked to come in to the clinic early in the morning while fasting (no food or drink other than water for 8 hours prior to the visit) on the day that the PK Assessment is scheduled. You will be asked not to take any study drug the day the PK testing is scheduled. You will have your blood drawn prior to taking your study drug at the study site. Study drugs will be administrated to you with approximately 240 ml of water 30 minutes after completion of breakfast. You will have your blood drawn at 30 minutes, 1, 2, 3, 4, 6, 8, and 12 hours after taking study drug. Lunch may be provided 5 hours after breakfast, and dinner may be provided 10 to12 hours after breakfast. You may be discharged after the hour 12 PK draw and instructed to return to the clinic 12 hours later for the Hour 24 PK draw. What Do I Have To Do If I Am In This Study? Screening Visits Prior to any clinical procedures or evaluation you must sign the informed consent. An abbreviated Screening Visit 1 will occur within 45 days of the first dose of study drugs and a Screening Visit 2 will occur within 10 days of the first dose of study drugs if your results from Screening Visit 1 meet the requirements to join the study. At Screening Visit 1, the following procedures will be completed: You must have no food or drink except water for 8 hours prior to arriving at the study site. You will be asked questions about your medical history, personal information, and information about any drugs that you are taking or have taken in the recent past. Vital signs (blood pressure and heart rate) will be performed. An electrocardiogram (ECG) will be collected. An ECG is a painless test that measures the electrical signals that control the rhythm of your heartbeat. You will have blood drawn for routine lab work. Page 2 of 14

3 You will have a urine pregnancy test (if you are a female subject of child-bearing potential only) You will be screened for hepatitis, and HIV. At Screening Visit 2, the following procedures will be completed: You will be asked questions about your medical history, and information about any drugs that you are taking from your last visit. A physical exam including your height and weight will be collected to determine your body mass index (BMI). You will have blood drawn for routine lab work. A sample of your urine will be taken for routine lab work. All female subjects of nonchild-bearing potential will have a serum FSH blood test. (This test is done to check your hormone levels in your blood). Day 1 (Baseline/Randomization Visit) At the Baseline/Randomization Visit (Day1) you will be verified for eligibility to be in the study and randomized (like flipping a coin but done by a computer) into one of three treatment groups. You will receive study treatment for 48-weeks, returning for visits at Week 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 after the first dose of study drug. The following procedures will be completed: You must have no food or drink except water for 8 hours prior to arriving at the study site. You will be asked questions about your medical history, and information about any drugs that you are taking from your last visit. A physical exam including vital signs (blood pressure and heart rate), will be performed. Your hips and waist circumferences will be measured by the study doctor or study staff. An electrocardiogram (ECG) will be collected. An ECG is a painless test that measures the electrical signals that control the rhythm of your heartbeat. You will have blood drawn for routine lab work and metabolic testing. A sample of your urine will be taken for routine testing. Women able to have children will have a urine pregnancy test. On-site administration of study drug. Receive study drug, which you will take with you to take until your next visit. Week 1-47 (Treatment Period) The following procedures will be completed: You must have no food or drink except water for 8 hours prior to arriving at the study site. (At Week 2, 4, 12, and 24 ) You will be asked questions about how you are feeling and information about any drugs that you are taking from your last visit. A physical exam will be conducted. (At Week 2, 12, 24, and 36) Page 3 of 14

4 Vital signs (blood pressure and heart rate), will be performed. Your hips and waist circumferences will be measured by the study doctor or study staff. (At week 24 and 48) An electrocardiogram (ECG) will be collected. An ECG is a painless test that measures the electrical signals that control the rhythm of your heartbeat. (At Week 12 and 24) You will have blood drawn for routine lab work and HIV-related tests. You will have blood drawn for the PK assessment. (At Week 2 for the first 25 subjects who participate in this study) A sample of your urine will be taken for routine testing. (At Week 12, 24, and 36) Women able to have children will have a urine pregnancy test. (At Week 4, 12, 24, and 36) On-site administration of study drug. Receive study drug which you will take with you to take until your next visit. Study drug needs to be stored at 77 0 F. Your study doctor will discuss study drug storage requirements and how to take the study drugs with you. Each dose of cenicriviroc (CVC, TBR-652)/placebo should be taken with 240 ml of water (approximately 1 cup plus one teaspoon) following breakfast. Each dose of efavirenz/placebo should be taken with 240 ml of water (approximately one cup plus one teaspoon) at bedtime on an empty stomach for a least the first 4 weeks. Each dose of Truvada may be taken with or without food. (If you are one of the first 25 subjects, your study doctor will discuss timing of when you should take your study drugs and any food restrictions with you. You will need to bring all study-supplied pill bottles with you to all visits. Week 48 (End of Treatment) or Early Termination This is the final on-treatment visit for subjects completing 48 weeks of treatment. Subjects who discontinue study drug before completing 48 weeks of treatment will return for Early Termination procedures as soon as possible after discontinuing study drug. The following procedures will be done during the end of treatment visit or if participation is terminated early: You must have no food or drink except water for 8 hours prior to arriving at the study site. You will be asked questions about how you are feeling and information about any drugs that you are taking from your last visit. A physical exam will be conducted. Vital signs (blood pressure and heart rate) will be performed. An electrocardiogram (ECG) will be collected. An ECG is a painless test that measures the electrical signals that control the rhythm of your heartbeat. You will have blood drawn for routine lab work and HIV-related tests. Page 4 of 14

5 You will have blood drawn for the PK assessment (Week 48 Subjects and Early Termination Subjects only who terminate before Week 40 only). A sample of your urine will be taken for routine testing. Women able to have children will have a urine pregnancy test. You will need to bring all study-supplied pill bottles with you to this visit. You will be administered study drug on-site (Week 48 subjects only) You will be tested for HAV/HBV/HCV (Early Termination Subjects only if discontinued because of elevated Liver Function Tests). If you discontinue the study because of confirmed virologic failure, resistance testing, phenotype and genotype tropism testing will be performed, and the results will be made available to your primary physician(s) to help in the selection of new a new antiretroviral regimen. Week 52 Follow Up Visit The following procedures will be done at Week 52 or approximately 4 weeks after the last dose of study drug: You must have no food or drink except water for 8 hours prior to arriving at the study site. You will be asked questions about how you are feeling and information about any drugs that you are taking from your last visit. A physical exam will be conducted. Vital signs (blood pressure and heart rate), will be performed. An electrocardiogram (ECG) will be collected. An ECG is a painless test that measures the electrical signals that control the rhythm of your heartbeat. You will have blood drawn for routine lab work. A sample of your urine will be taken for routine testing. Women able to have children will have a urine pregnancy test. You may be tested for HBV/HCV/HIV-1 You will need to bring all study supplied pill bottles with you to this visit. Page 5 of 14

6 What will I be expected to do as a Study Subject? Attend the scheduled study visits. Take the study drug as directed by the study doctor or study staff. Return the unused study drugs and packaging. Do not share the study drug with anyone else. Inform the study doctor or study staff of any changes in your health and any changes in prescription and over-the-counter (non-prescription) medications during the course of the study. How Many People Will Take Part in This Study? Approximately 150 subjects will take part in this study at about 50 sites in the United States and Puerto Rico. 5-7 people are expected to participate at the University of Pennsylvania. How Long Will I Be In This Study? If you choose to take part, you will be evaluated for a minimum of 59 weeks from the first Screening Visit through the final follow-up procedures. What Are The Risks Of The Study? You could experience deterioration due to ineffective treatment of the investigational study drug. Your HIV may become resistant to the study drug, cenicriviroc (CVC, TBR-652), and/or the background drugs (efavirenz, emtricitabine, tenofovir disoproxil fumarate), and so limit future treatment options. Throughout the study, your study doctor will monitor your HIV-1 levels for viral rebound (increases in HIV-1 levels after having previous results of lowered HIV-1 levels). Resistant mutations develop most rapidly in people who do not take all of their HIV-1 drugs. Therefore, it is important to take all your study drugs as prescribed by your doctor. All medications can cause unwanted side effects. It is very important that you tell the study doctor or nurse about any symptoms you are having or any changes in your health. The following side effects were observed in patients who have taken cenicriviroc (CVC, TBR-652) : headache nausea vomiting watery stools (diarrhea) constipation tiredness (fatigue) stomach discomfort (cramping/bloating) itching blurred vision abnormal dreams elevated AST and ALT levels without other symptoms. AST and ALT are enzymes found in the liver; increased levels can be early signs of liver toxicity. Page 6 of 14

7 Other side effects seen on earlier studies included: menstrual changes back pain congested nose/ runny nose rash muscle spasms dry mouth recurrence of herpes infection in the mouth (cold sore) memory problems discharge from the vagina dizziness sleepiness/drowsiness heart palpitation It is unknown whether these are related to study drug. In laboratory studies, it was found that cenicriviroc had an effect on a channel that helps regulate the heartbeat. However, in studies in monkeys and two small studies in humans no effect was observed. It is not known whether cenicriviroc has an effect on your heart. The electrical activity of your heart is being monitored with an Electrocardiogram (ECG) test. Since this is an investigational study drug, there may be side effects or unknown risks of cenicriviroc (CVC, TBR-652) that are currently unforeseeable and could be life-threatening. You could experience deterioration due to ineffective treatment of the investigational study drug. Efavirenz (comparator drug) The most common side effects include: Rash, dizziness, nausea, headache, tiredness (fatigue), trouble sleeping and vomiting. Other common side effects include trouble concentrating and/or unusual dreams. For at least the first 4 weeks it is recommended you take your efavirenz/placebo at bedtime to help reduce some of these possible side effects. In a small number of patients, rash may be serious. This is not a complete list of side effects possible with efavirenz (Sustiva). Sustiva may cause other side effects including in some patients serious psychiatric problems, serious liver problems, convulsions, increases in lipid levels, changes in body fat and signs and symptoms of inflammation from previous infections. Emtricitabine/Tenofovir Disoproxil Fumarate (TRUVADA) The most common side effects include: diarrhea, dizziness; headache; nausea, tiredness (fatigue); abnormal dreams; depression; trouble sleeping, and rash. This is not a complete list of side effects possible with emtricitabine/tenofovir disoproxil fumarate (Truvada). Truvada may cause other side effects including in some patients a serious condition called lactic acidosis (a build-up of an acid in the blood), serious liver problems, serious kidney problems, changes in bone mineral density, changes in body fat and signs and symptoms of inflammation from previous infections. Page 7 of 14

8 PROCEDURE RISKS Blood Samples: Blood samples will be taken by single needle-stick or by a tube that is left in your arm. You cannot choose how the blood is taken. The study staff will determine the best method for blood draws. There will be about 17 blood draws. The total amount of blood drawn will be about 6 cups for the duration of the study. For comparison, the standard blood donation is about two cups (480 ml). Risks associated with drawing blood from your arm include: pain bruising or bleeding from the site of the needle puncture lightheadedness or fainting infection Electrocardiogram (ECG): The ECG test is a recording of the electrical activity of your heart and is harmless. The sticky pads used may sometimes cause some discomfort such as redness or itching. If the skin under the patches needs to be shaved, irritation from shaving also could occur. Inpatient Visits: The long time you have to spend at the research site may make you uncomfortable. Precautions: When taking any new medication, you should exercise caution and not drive, operate machinery, or engage in other activities requiring mental alertness until you know how the medication will affect you. In addition to the risks or discomforts listed here, there may be other risks that are currently not known. Also, the risks or discomforts described may occur more often or be more severe than has been seen before. You should discuss carefully with the study doctor before taking any other prescriptions, oral supplements and/or over-the-counter (non-prescription) medications during the study. Certain prescription medications, oral supplements, over-the-counter medications and the consumption of grapefruit juice and star fruit are prohibited while you are in this study. Are There Risks Related To Pregnancy? Prior to participation in this study, all women capable of having children will have a pregnancy test. Women capable of having children include all women except those whose menstrual periods have not occurred for more than 1 year after menopause (change of life) or those who have had sterilization surgery (tubal ligation [tubes tied] or a hysterectomy [removal of the uterus or womb]). Pregnant and breastfeeding women may not participate in this research study. If you decide to take part in this study, you must agree to protect yourself or your partner from becoming pregnant before and during the study and for 3 months after the last dose of the study drug. If a child is conceived (created) when either parent is taking the study drug, birth defects may occur. If you are a female study subject and think that you might be pregnant, you must immediately notify the person in charge of the study. Since harmful effects may occur to a child Page 8 of 14

9 who is breast-feeding from a woman taking a study drug, female study subjects must not breast-feed during the study and for 21 days after the study ends. Acceptable methods of contraception during participation in this study are: Total abstinence (no sexual intercourse), absence of menstrual periods in women for more than one year after menopause (change of life), sterilization surgery including tubal ligation (tubes tied) or hysterectomy (removal of uterus or womb) in women or a vasectomy in men. These methods of preventing pregnancy are the most reliable. Double barrier methods Condom with spermicide and IUD (intrauterine device) Condom with spermicide and diaphragm Birth control patch or vaginal ring Oral, injectable or implanted contraceptives Tubal ligation (tubes tied) If you are a man, you must use birth control if you choose to have sex with women while in this study. Methods of birth control for this study include: Abstinence Vasectomy Two (2) forms of birth control (barrier method) throughout the study and for3 months after your last dose of the study drug If you need more information about this, please ask the research study staff. An Antiretroviral Pregnancy Registry will monitor fetal outcomes of any woman who becomes pregnant during or within 3 months after stopping study drug. These women are encouraged to have their primary physician or obstetrician register them by calling Are There Benefits to Taking Part in This Study? You may not have any personal benefit from being in this study. This study may or may not help your condition. However, even if you do not take part in this study, your study doctor will discuss other alternatives with you. The information gained during this study may help doctors learn more about treating HIV-1 infected patients. This knowledge may help patients in the future. What Other Choices Do I Have Besides This Study? If you do not want to take part in this study, you will receive treatment according to the standard practice. All therapies have risks and benefits which you can discuss with your doctor. Can I Leave the Study Early? Your participation in this research study is voluntary. You may decide not to begin or to stop this study at any time without any penalty or loss of benefits to which you may otherwise be entitled. Your care and relationship with health care workers at the University of Pennsylvania Health System will not be affected in any way. Dr. Tebas may stop the study if the research is not helping you, if you do not follow the research directions, or if you have a serious side effect to the research drug. The sponsor, FDA, or the IRB chair may also stop the study at any time. In addition, the study may be Page 9 of 14

10 stopped at any time for administrative reasons. If you choose to leave the study early, you should let Dr. Tebas know, he may ask you to visit the study site for a final examination for your safety and to return the study drug. You will be told of any new information about the research study that may cause you to change your mind about participation. What About Confidentiality? HIPAA AUTHORIZATION The authorization part of the consent gives more detailed information about how your personal health information may be used and disclosed by the University of Pennsylvania Health System (UPHS), the School of Medicine and the individual Principal Investigator, subject to University of Pennsylvania procedures. What personal health information is collected and used in this study and might also be disclosed? The following personal health information will be collected, used for research, and may be disclosed during your involvement with this research study: Name, address, telephone number, date of birth Personal and family medical history Current and past medications or therapies Information from questionnaires administered in the study Results of tests and procedures you will undergo during this research study Social Security Number An HIV test may be done to confirm you are eligible for this study, by law we have to report the infection to the City of Philadelphia Health Department/PA Department of Health. We would report your name, gender, racial/ethnic background, and the month and year you were born. This is to keep track of how many people in the U.S. have HIV infection. It is also to make sure that states get enough money from the federal government to support the medical care of people living with HIV. The Health Department does not share the names of HIV infected people with anyone else. It removes all personal identifiers, such as your name, before giving information on the number of HIV infections to the federal government. It is likely that this information has already been reported by your care provider. Why is your personal contact and health information being used? Your personal contact information is important for the research team to contact you during the study. Your personal health information and results of tests and procedures are being collected as part of this research study. In some situations, your personal health information might be used to help guide your medical treatment. Which of our personnel may use or disclose your personal health information? The following individuals may use or disclose your personal health information for this research study: The Principal Investigator and the Investigator s study team Authorized members of the workforce of the UPHS and the School of Medicine, and University of Pennsylvania support offices, who may need to access your information in the performance of Page 10 of 14

11 their duties (for example: for research oversight and monitoring, to provide treatment, to manage accounting or billing matters, etc.). Who, outside of UPHS and the School of Medicine, might receive your personal health information? As part of the study, the Principal Investigator, the study team and others listed above, may disclose your personal health information, including the results of the research study tests and procedures. This information may be disclosed to those listed below: Individuals or organizations responsible for administering the study: - Tobira Pharmaceuticals: The company conducting this study. - Representatives Of The Sponsor: Authorized persons assisting with the research (such as the contract research organization, Quintiles, Inc., the study monitors, auditor, and project manager), central laboratory. - Government Agencies: Data from this study will be made available to the Food and Drug Administration for them to evaluate the safety and efficacy of the treatments being used in this study. Regulatory and safety oversight organizations The Food and Drug Administration The Office of Human Research Protections The Study Monitoring Committee Once your personal health information is disclosed to others outside of UPHS or the School of Medicine, it may no longer be covered by federal privacy protection regulations. Data are reported to the sponsor on Case Report Forms that identify you by your unique study number and not your name, date of birth or medical record number. Information regarding your health, such as side effects of the study drug you experience will be reported only by code number. All samples collected for analysis will be labeled with your study number, visit number and date of your visit. The Principal Investigator or study staff will inform you if there are any additions to the list above during your active participation in the trial. Any additions will be subject to University of Pennsylvania procedures developed to protect your privacy. A description of this clinical trial will be available on as required by U.S. Law. This Web site will not include information that can identify you. At most, the Web site will include a summary of the results. You can search this Web site at any time. How long may UPHS and the School of Medicine be able to use or disclose your personal health information? Your authorization for use of your personal health information for this specific study does not expire. Your information may be held in a research database. However, the School of Medicine may not reuse or re-disclose information collected in this study for a purpose other than this study unless: You have given written authorization The University of Pennsylvania s Institutional Review Board grants permission As permitted by law Can I change my mind about giving permission for use of my information? Page 11 of 14

12 Yes. You may withdraw or take away your permission to use and disclose your health information at any time. You must do so in writing to the Principal Investigator at the address on the first page. Even if you withdraw your permission, your personal health information that was collected before we received your written request may still be used and disclosed, as necessary for the study. If you withdraw your permission, you will not be able to stay in this study. What if I decide not to give permission to use and give out my health information? Then you will not be able to be in this research study. You will be given a copy of this Research Subject HIPAA Authorization describing your confidentiality and privacy rights for this study. You will also be given the UPHS and School of Medicine s Notice of Privacy Practices that contains more information about the privacy of your personal health information. What Are the Costs To Me? You will not have to pay for any of the medications, medical examinations, procedures or laboratory tests that are required for your participation in this study. Will I Receive Any Payment? You will be compensated $25 for the first screening visit and then $50 for each of the study required visits. Compensation will be given as cash. Thus if you attend all study scheduled visits, Screening 1, Screening 2, Baseline, Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and off study, the maximum compensation for the study will be $875. If you are required by the study staff to come in for any additional unscheduled visits (usually to check a lab value), you will be compensated $10 for every visit. There is no other form of compensation available such as reimbursements for parking, tokens or child care. Please note that if you receive more than $ compensation in one year for participation in research studies at the University of Pennsylvania, you must provide a Individual Tax Identification number or Social Security Number for tax purposes. What Happens If I Am Injured? If you follow the directions of the doctors in charge of this study, and you are physically injured because of any substance or procedure properly given to you under the plan for this study, Tobira Therapeutics will pay for the treatment and medical expenses of that injury that are not covered by your insurance. If you require immediate medical care and are not a hospitalized patient, you should seek immediate medical treatment (Take your informed consent form with you). Otherwise, the investigator will take care of you or help you get the care you need. You will be sent a bill for whatever medical care you receive. All or part of your bill may be paid by Tobira Therapeutics or by your health insurance. The University of Pennsylvania will not pay for the care. Likewise, the University of Pennsylvania will not pay you for pain, worry, lost income, or non-medical care costs that might occur from taking part in this research study. What is an Electronic Medical Record? An Electronic Medical Record (EMR) is an electronic version of the record of your care within a health system. An EMR is simply a computerized version of a paper medical record. Page 12 of 14

13 If you are receiving care or have received care within the University of Pennsylvania Health System (UPHS) (outpatient or inpatient) and are participating in a University of Pennsylvania research study, results of research-related procedures (i.e. laboratory tests, imaging studies and clinical procedures) may be placed in your existing EMR maintained by UPHS. If you have never received care within UPHS and are participating in a University of Pennsylvania research study that uses UPHS services, an EMR will be created for you for the purpose of maintaining any results of procedures performed as part of this research study. The creation of this EMR is required for your participation in this study. In order to create your EMR, the study team will need to obtain basic information about you that would be similar to the information you would provide the first time you visit a hospital or medical facility (i.e. your name, the name of your primary doctor, the type of insurance you have). Results of research procedures performed as part of your participation in the study (i.e. laboratory tests, imaging studies and clinical procedures) may be placed in this EMR. Once placed in your EMR, these results are accessible to appropriate UPHS workforce members that are not part of the research team. Information within your EMR may also be shared with others who are determined by UPHS to be appropriate to have access to your EMR (e.g. health insurance company, disability provider, etc). What Are My Rights As a Research Subject? Taking part in this study is completely voluntary. You may choose not to take part in this study or leave this study at any time. Your healthcare provider will treat you the same no matter what you decide. We will tell you about new information from this or other studies that may affect your health, welfare, or willingness to stay in this study. If you want the results of the study, let the study staff know. What Do I Do If I Have Questions Or Problems? For questions about this study or a research-related injury, contact: Pablo Tebas, MD ( ) Clinical Trials Unit ( ) For questions about your rights as a research subject, contact: Director of Regulatory Affairs at the University of Pennsylvania by phoning (215) CONSENT When you sign this form, you are agreeing to take part in this research study. This means that you have read the consent form, your questions have been answered, and you have decided to volunteer. Your signature also means that you are permitting the University of Pennsylvania Health System and the School of Medicine to use your personal health information collected about you for research purposes within our institution. You are also allowing the University of Pennsylvania Health System and the School of Medicine to disclose that personal health information to outside organizations or Page 13 of 14

14 people involved with the operations of this study. A copy of this consent form will be given to you. You will also be given the University of Pennsylvania Health System and School of Medicine s Notice of Privacy Practices that contains more information about the privacy of your health information. Name of Subject (Please Print) Signature of Subject Date Name of Person Obtaining Signature Date Consent (Please Print) INVESTIGATOR STATEMENT I certify that the research study has been explained to the above individual by me or my research staff including the purpose, the procedures, the possible risks and the potential benefits associated with participation in this research study. Any questions raised have been answered to the individual s satisfaction. Investigator (Print or Type Name) Signature Date Page 14 of 14