Amgen AMG145 Informational Brochure for Participants
Table of Contents Introduction...1 The Importance of Clinical Trials...2 Information on Cardiovascular Disease and LDL-Cholesterol...4 Information on the Study Drug...6 Auto-Injector Instructions...7 Study Drug Single-Use Prefilled Autoinjector/Pen Frequently Asked Questions and Answers for Study Subjects...9 Contact Information...15
Introduction This brochure is meant to provide you with information that may be useful during your participation in this study. Included, you will find: General information on clinical trials General information on Cardiovascular Disease and LDL- Cholesterol Information on the Study Drug, including instructions for using the autoinjector/pen and frequently asked questions 1
The Importance of Clinical Trials Participants in clinical research studies/trials play an integral role in developing potentially better ways to treat various medical conditions. A clinical research study/trial is a study in human participants to answer specific health-related questions. Some research studies determine whether investigational treatments or new ways of using current treatments are safe and effective. In a clinical research study/trial, participants may receive specific interventions according to a research plan known as a protocol. The protocol is designed to obtain answers to specific research questions as well as safeguard the health of participants. The interventions being studied may be investigational medical products, such as drugs or devices; procedures; or changes to participants behavior, for example, diet. Clinical trials may compare an investigational medical approach to a standard one that is already available or to a placebo that contains no active ingredients or to no intervention. Some clinical trials compare interventions that are already available to each other. When an investigational product or approach is being studied, it is not known whether it will be helpful, harmful, or no different than available alternatives. Clinical research studies/trials are conducted in phases. Each phase has a different purpose and helps scientists answer different questions. The U.S. National Institutes of Health describes the phases of a clinical trial as shown below. In Phase I trials, researchers test an experimental drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, test how the body handles the drug, determine a safe dosage range, and identify side effects. These studies are conducted in healthy volunteers and/or individuals with a specific condition or disease. In Phase II trials, the experimental study drug or treatment is given to a larger group of individuals with a specific condition or disease (100-300) to see if it is effective and to further evaluate its safety. 2
In Phase III trials, the experimental study drug or treatment is given to large groups of individuals with a specific condition or disease (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the experimental drug or treatment to be used safely. Phase IV trials test drugs that have been approved for use in the general population to delineate additional information including the drug s risks, benefits, and optimal use. These trials are also known as post-marketing trials. References 1. U.S. National Institutes of Health. (2007, September 20). Understanding Clinical Trials. Retrieved from http://clinicaltrials.gov/ct2/info/understand 2. U.S. National Institutes of Health. (2008, March 18). Glossary of Clinical Trials Terms. Retrieved from http://www.clinicaltrials.gov/ct2/info/glossary 3. U.S. Food and Drug Administration. (2010, January 4). Clinical Trials of Medical Treatments: Why Volunteer? Retrieved from http:// www.fda.gov/forconsumers/byaudience/forpatientadvocates/ ParticipatinginClinicalTrials/ucm129557.htm 3
Information on Cardiovascular Disease and LDL-Cholesterol Cardiovascular disease (CVD) represents a leading cause of death and disability in the world and is estimated to cause over 10% of the global total disease burden. CVD includes disorders of the heart and blood vessels, such as: Coronary Heart Disease, when the blood vessels supplying the heart muscle are involved Cerebrovascular Disease, when the blood vessels supplying the brain are involved Peripheral Arterial Disease, when the blood vessels in the arms and legs are involved CVD can result in heart attacks or strokes. A heart attack occurs when blood flow to a part of the heart is blocked and that part of the heart muscle is damaged. Symptoms include severe chest pain, often radiating to the left arm, and shortness of breath. Heart attacks are also called myocardial infarction (MI) and are a leading cause of death in many countries Stroke is a blockage of blood flow or rupture of an artery to the brain. Sudden loss of speech, weakness, or paralysis of one side of the body can be symptoms Dyslipidemia, which is an abnormal amount of lipids such as cholesterol in the blood, is a major modifiable risk factor for cardiovascular disease. In 2008, the World Health Organization (WHO) estimated that CVD accounted for over 17 million deaths, nearly 80% of which were due to heart attacks and strokes alone. 4
A common form of dyslipidemia is an elevated level of total cholesterol in the bloodstream (hypercholesterolemia) which is often the result of high levels of low-density lipoprotein cholesterol (LDL-cholesterol), commonly known as bad cholesterol, as compared to high-density lipoprotein cholesterol (HDL-cholesterol), commonly known as good cholesterol. Higher levels of LDL-cholesterol contribute to CVD because the cholesterol joins with fats and other substances to build up in the inner walls of arteries, forming plaques. This accumulation leads to atherosclerosis (a chronic inflammation of the artery walls). Over time, these plaques narrow the arteries, and also may rupture. Blood clots form at the site of the rupture, which may eventually block the artery. This can result in: heart attacks, when a ruptured plaque blocks the arteries that bring blood to the heart muscle strokes, when a ruptured plaque blocks the arteries that bring blood to the brain peripheral vascular disease, when a ruptured plaque blocks arteries to other areas of the body, such as the legs 5
Higher levels of HDL-cholesterol, on the other hand, can help reduce the risk of CVD, since HDL-cholesterol removes cholesterol from plaques and the bloodstream. References 1. American Heart Association. (2012, September 14). About Cholesterol. Retrieved from http://www.heart.org/heartorg/conditions/cholesterol/ AboutCholesterol/About-Cholesterol_UCM_001220_Article.jsp Information on the Study Drug The goal of therapies for dyslipidemia is to lower the risk of cardiac events, such as strokes and heart attacks, which occur in people with cardiovascular disease. While there are already lipid-lowering therapies available today, about two-thirds of patients on these lipid-lowering therapies still have cardiovascular events. The investigational medication (AMG 145) is an antibody (a protein) that will be delivered by injection just below the skin (subcutaneously). The investigational medication is being evaluated to see if it may reduce risk of cardiovascular disease by promoting the transport of low density lipoprotein (LDL) cholesterol out of the bloodstream. 6
Follow these steps for using a study drug prefilled autoinjector/pen Instructions for Use: Study Drug Single-Use Prefilled Autoinjector/Pen Important! Step 1: Gather and inspect materials 1a naturally reach room temperature. Caution: Use special care For clinical trial use only Step 2: Get ready 2a Choose and clean your injection site. that you will use for your dose from the package(s). Put Save the original packaging and return it to your study doctor or his/her staff. the refrigerator (36 F to 46 F [2 C to 8 C]) Upper thigh Upper arm DO NOT remove the white needle cap from the light! autoinjector/pen until you are ready to inject! autoinjector(s)/pen(s) to naturally reach room temperature Belly/ abdomen 1b expiration/expiry date Clean your injection site with an alcohol wipe. DO NOT touch the cleaned area of skin again before injecting. cracked or broken contains a needle cover that is composed of dry natural rubber, which is made from latex. Tell your study doctor or his/her staff if you are allergic to latex 90 The outer area of your upper arm (only if someone else is giving you the injection) 3b your skin at Injections should not be given into areas where the skin is tender, bruised, red, or hard. Avoid injecting into areas with scars or stretch marks. Your belly/abdomen, except for the 2-inch (about 5 cm) area right around your belly button/navel You should choose a different site each time you give yourself an injection. If you want to use the same part of your body, you can. Just make sure it is not the same spot that you used last time. injection sit The upper part of your thigh Let your skin dry using a heat source such as hot water or a microwave. 3a Choose an injection site. You can use: Injection sites refrigerator (36 F to 46 F [2 C to 8 C]) Before you use a study drug prefilled autoinjector/pen, read this important information: autoinjector/pen may be broken even if you cannot see Step 3: Injec The white needle cap is missing or not securely attached Incorrect 2b Cor When you are ready to inject, pull the white needle cap straight off. pen has passed of children your study doctor or his/her staff for help. Call your study doctor or his/her staff with questions or if! autoinjector/pen until you are ready to inject. Make sure the study drug in the window is clear, and colorless to yellow DO NOT inject the study drug if it is cloudy or discolored or contains large lumps, doctor or his/her staff for help. Use a new Blue start button DO NOT twist or bend the white needle cap DO NOT put the white needle cap back into the Gather all of the materials you need for the injection. 3d Count slowl of liquid at the end of the needle or gray needle shield 2c! autoinjector/pen works properly. Wash your hands thoroughly with soap and water On a clean, well-lit work surface, place: pinch method as shown below DO NOT touch the cleaned area of skin. Alcohol wipes Cotton ball or gauze pad Stretch method Adhesive bandage Container(s) for used study drug directions, creating an area about 2 inches (5 cm) wide Stretch Study Drug Pinch method Window Pinch Gray needle shield 7 It is normal to see a drop 1c White needle cap Press the bl your thumb When you are ready to inject, pull the white needle cap straight off Guide to the parts! 3c (Needle is inside.) an area about 2 inches (5 cm) wide Windo turns SECO NOT pen f autom
e a Step 3: Inject 3a 3b 3c Incorrect injection site. 90 your skin at the injection site. Correct pen at a right angle (90 ) on your skin The end with the gray needle shield should be pointed toward the injection site! DO NOT touch the blue start button until you are ready to inject. Use enough pressure to push the gray needle shield into the Needle shield pushed into the Press the blue start button and release your thumb. Click You will hear a click. This sound means that the injection has started The injection will continue automatically autoinjector/pen at a right skin during the injection Step 4: Finish 4a 4b Save the used autoinjector/pen and its original packaging. DO NOT put the white needle cap back into the used autoinjector/pen Place the used autoinjector/pen in the container for used study drug DO NOT reuse the used autoinjector/pen DO NOT recycle or discard the used autoinjector/pen, original packaging, or the container for used study drug Return the original packaging and the container for used study drug to your study doctor or his/her staff Keep the used autoinjector/pen, original packaging, and the container for used study drug out of the reach of children Examine the injection site. If there is blood, press a cotton ball or gauze pad on the injection site. Apply an adhesive bandage if needed Congratulations! You did it. Commonly asked questions What will happen if I press the blue start button before I am ready to do the injection? You will not be able to press the blue start button until the gray needle Will the blue start button pop up after I release my thumb? The blue start button may not pop up after you release your thumb if you held your thumb down during the injection. What do I do if I didn t hear a click after I counted slowly to 15 seconds? You may not always hear a second click. If you counted slowly to 15 seconds but didn t hear a click to signal that your injection was complete, injection by checking that the window has turned yellow. Contact your study doctor or his/her staff if you have questions. 3d Count slowly to 15 seconds for your injection! If the entire window does not turn yellow after you have completed your injection, call your study doctor or his/her Window staff. turns yellow injection is complete when: 15 SECONDS The entire window turns yellow You may hear a second click! autoinjector/pen from your skin. Whom do I contact if I need help with the prefilled autoinjector/pen or my injection? your injection, ask your study doctor or his/her staff for help. NOTE: pen from your skin, the gray needle shield will automatically move down to cover the needle. Amgen Inc., Thousand Oaks, CA 91320-1799 USA Amgen Ltd., Cambridge, CB4 0WD United Kingdom Amgen Canada Inc., Mississauga, L5N 0A4 Amgen Australia Pty Ltd / Amgen (New Zealand) Limited 2012 Amgen Inc. All rights reserved. v1 31 July 2012 AI 1.0 8
Study Drug Single-Use Prefilled Autoinjector/ Pen Frequently Asked Questions and Answers for Study Subjects LIST OF QUESTIONS: 1. What if I have a medical emergency? 2. How do I travel with the prefilled autoinjector/pen? 3. How should I store the prefilled autoinjector/pen? 4. What should I do if I accidently leave the prefilled autoinjector/pen out of the refrigerator for more than six hours? 5. What should I do if I accidently expose the prefilled autoinjector/pen to light for more than six hours? 6. What should I do if the prefilled autoinjectors/pens become frozen? 7. The study drug carton is difficult to open. Is it possible to cut the tape on the exterior of the carton? 8. How do I inject with my autoinjector/pen? 9. Should I let the prefilled autoinjector/pen warm up before I use it? 10. The label on the prefilled autoinjector/pen is bothersome. Is it possible to remove this label? 9
11. How long can I wait from the time I take the needle cap off and inject myself? 12. If there are bubbles visible through the prefilled autoinjector/pen window, will I be injecting the bubble(s) into my skin? 13. Is there a way to clear air bubbles out of the prefilled autoinjector/ pen? 14. What should I do if the study drug looks cloudy or discolored, or contains large lumps, flakes, or particles? 15. What should I do if I cannot remove the white needle cap? 16. What should I do if I cannot activate the blue start button or the blue start button does not work? 17. What if I pressed the blue start button, released my thumb, prematurely lifted the prefilled autoinjector/pen from my skin and saw fluid coming out of the prefilled autoinjector/pen? 18. What should I do if the prefilled autoinjector/pen does not inject the full dose? 19. What should I do if I don t hear the second click after I count for 15 seconds? 20. What if I see an air bubble beneath the skin after I inject with prefilled autoinjector/pen? 21. What should I do if I cannot activate the gray needle shield? 22. What if the gray needle shield does not go into the prefilled autoinjector/pen when I place it against my skin? 23. What should I do if I miss a scheduled injection of the study drug? 24. What should I do with the used prefilled autoinjector/pen? 25. What should I do with the original prefilled autoinjector/pen packaging? 26. What should I do if I think I might be pregnant? Note: If your question is not included in this list, please contact your study doctor or his/her staff. QUESTIONS AND ANSWERS: EMERGENCY 1. What if I have a medical emergency? If you feel you have a medical emergency, please contact your nearest emergency services. As soon as possible, also contact your study doctor or his/her staff. 10
STORAGE/TRAVEL 2. How do I travel with the prefilled autoinjector/pen? As long as the prefilled autoinjector/pen is kept in its original packaging, protected from light, it is stable for 12 hours at room temperature. For additional information, contact your study doctor or his/her staff. 3. How should I store the prefilled autoinjector/pen? The prefilled autoinjector/pen should be stored in its original packaging, in the refrigerator at a temperature of 36 F to 46 F (2 C to 8 C). This is the usual temperature for most refrigerators. The prefilled autoinjector/pen should be protected from exposure to light during storage. Short exposures to light are acceptable but avoid prolonged exposure to light, particularly direct sun light. 4. What should I do if I accidently leave the prefilled autoinjector/pen out of the refrigerator for more than six hours? If you have allowed the prefilled autoinjector/pen to remain un-refrigerated and exposed to light for more than 6 hours you should contact your study doctor or his/her staff before using the product. You may use the prefilled autoinjector/pen if it was un-refrigerated and exposed to light for less than 6 hours. 5. What should I do if I accidently expose the prefilled autoinjector/pen to light for more than six hours? The prefilled autoinjector/pen should be stored in the refrigerator which is considered a dark location. If you have allowed prefilled autoinjector/pen to be exposed to light for more than 6 hours you should contact your study doctor or his/her staff before using the product. You may use the prefilled autoinjector/pen if it was un-refrigerated and exposed to light for less than 6 hours. 6. What should I do if the prefilled autoinjectors/pens become frozen? The prefilled autoinjector/pen should be stored in its original packaging, in the refrigerator at a temperature of 36 F to 46 F (2 C to 8 C). This is the usual temperature for most refrigerators. Do not freeze the prefilled autoinjector/pen. Do not use a prefilled autoinjector/pen that has been frozen. Contact your study doctor or his/ 11
her staff for instructions on what to do if your prefilled autoinjector/pen becomes frozen. ADMINISTRATION 7. The study drug carton is difficult to open. Is it possible to cut the tape on the exterior of the carton? The tape on the carton can be cut or peeled back in order to avoid tearing the carton. The carton contains your prefilled autoinjectors/ pens. 8. How do I inject with my autoinjector/pen? Please refer to the instructions for use provided by your study doctor or his/her staff. 9. Should I let the prefilled autoinjector/pen warm up before I use it? Remove the number of prefilled autoinjectors/pens that you will use for your dose from the package(s). Put any unused prefilled autoinjectors/pens back into the refrigerator. Wait at least 30 minutes to allow the prefilled autoinjector(s)/pen(s) to naturally reach room temperature. Do not remove the needle cap from the prefilled autoinjector(s)/pen(s) while you wait. Do not shake the prefilled autoinjector(s)/pen(s). Do not try to warm the prefilled autoinjector(s)/pen(s) by using a heat source such as hot water or a microwave. While the prefilled autoinjector(s)/pen(s) are warming up, try to minimize its exposure to light by placing it under a towel or other convenient light screen. Tip: Set a timer to remind yourself that 30 minutes has passed. 10. The label on the prefilled autoinjector/pen is bothersome. Is it possible to remove this label? You can either fold the label back into place or gently tear off the paper portion of the label, leaving the sticker portion of the label stuck to the prefilled autoinjector/pen in its original place. Retain any removed portion of the label with the packaging and return to your study doctor or his/her staff at your next visit. 11. How long can I wait from the time I take the needle cap off and inject myself? 12
Do not remove the white needle cap from the prefilled autoinjector/ pen until you are ready to inject. Do not remove the white needle cap while waiting for the prefilled autoinjector/pen to naturally reach room temperature. Once the white needle cap is removed from the device, your injection should occur immediately. 12. If there are bubbles visible through the prefilled autoinjector/pen window, will I be injecting the bubble(s) into my skin? During the injection a small amount of air may be injected into the tissue under the skin. The prefilled autoinjector/pen can still be used to administer the injection when bubbles are visible. 13. Is there a way to clear air bubbles out of the prefilled autoinjector/ pen? No, it is not necessary to remove air bubbles from the prefilled autoinjector/pen prior to the injection. 14. What should I do if the study drug looks cloudy or discolored, or contains large lumps, flakes, or particles? Inspect the prefilled autoinjector/pen. Make sure the study drug in the window of the prefilled autoinjector/pen is clear and colorless to yellow. Do not inject the study drug if it cloudy or discolored, or contains large lumps, flakes, or particles. Contact your study doctor or his/her staff for help. 15. What should I do if I cannot remove the white needle cap? Contact your study doctor or his/her staff for instructions on what to do if you cannot remove the white needle cap from the prefilled autoinjector/pen. 16. What should I do if I cannot activate the blue start button or the blue start button does not work? Contact your study doctor or his/her staff for instructions on what to do if you cannot activate the blue start button or if the blue start button does not work. 17. What if I pressed the blue start button, released my thumb, prematurely lifted the prefilled autoinjector/pen from my skin and saw fluid coming out of the prefilled autoinjector/pen? If you observed fluid that was not injected, the full dose may not have been received. Contact your study doctor or his/her staff with 13
questions or if you need a new prefilled autoinjector/pen. 18. What should I do if the prefilled autoinjector/pen does not inject the full dose? Contact your study doctor or his/her staff for instructions on what to do if your prefilled autoinjector/pen does not inject the full dose. 19. What should I do if I don t hear the second click after I count for 15 seconds? You may not always hear a second click. You can confirm a complete injection by checking that the window has turned yellow. Contact your study doctor or his/her staff if you have questions. 20. What if I see an air bubble beneath the skin after I inject with prefilled autoinjector/pen? If you have any questions about the prefilled autoinjector/pen or about your injection, ask your study doctor or his/her staff for help. 21. What should I do if I cannot activate the gray needle shield? Contact your study doctor or his/her staff for instructions on what to do if the gray needle shield on the prefilled autoinjector/pen cannot be activated. 22. What if the gray needle shield does not go into the prefilled autoinjector/pen when I place it against my skin? The injection site must be firm so that the prefilled autoinjector/pen works properly. Begin the injection process again by placing the prefilled autoinjector/pen firmly on your skin at the injection site. Use enough pressure to push the gray needle shield into the prefilled autoinjector/pen. 23. What should I do if I miss a scheduled injection of the study drug? You have up to 3 days from your target injection date to inject the study drug. If you do not inject within this time frame, please contact your study doctor or his/her staff for instructions on what to do. DISPOSAL 24. What should I do with the used prefilled autoinjector/pen? Do not put the white needle cap back into the used autoinjector/pen. Place the used autoinjector/pen in the container for the used study drug and return to your study doctor or his/her staff at your next visit. 14
25. What should I do with the original prefilled autoinjector/pen packaging? Return the original packaging to your study doctor or his/her staff at your next visit. SPECIAL CONDITIONS 26. What should I do if I think I might be pregnant? Pregnant women and women planning to become pregnant should not participate in this study. If you become pregnant or think you are pregnant during this study, do not take your injection and tell the study doctor or his/her study staff right away. The use of the study drug(s) will be stopped. Contact Information If you have any concerns or questions about the information in this brochure, please contact your study doctor or his/her study staff using the below contact information: 15