What is the purpose of this study?
The purpose of this study is to evaluate if STX209 (also referred to in this form as the “study drug”), as compared to a placebo capsule (an inactive substance, like a sugar pill), is effective in managing the irritability associated with fragile X syndrome and is safe and able to be tolerated. STX209 is a new investigational form of the drug called baclofen that is approved by the United States Food and Drug Administration (FDA) to treat spasticity (stiff muscles) due to cerebral palsy or other forms of brain or spinal cord injury. An investigational drug is one that is not approved by the FDA. STX209 contains only the more active form of the two drug forms that are in baclofen. There is some evidence that baclofen may help with irritable behavior in people with developmental disabilities. Also, baclofen and STX209 activate a brain chemical (neurotransmitter) system called the GABA system and there is some data suggesting the GABA system is abnormal in mice with fragile X syndrome. Thus STX209 may be helpful for humans with fragile X syndrome. There are currently no medications approved for the treatment of irritable behavior in people who have fragile X syndrome.
All study subjects will receive STX209 during one part of the study and receive placebo capsules during another part. You will be randomly assigned by chance (like the flip of a coin) to first receive either the study drug or placebo capsules. During the second part of the study you will receive the study drug or placebo that you did not receive in the first part. Your study doctor will instruct you on how many capsules to take a day and how often to take them each day. You and the study doctor will NOT know what type of capsule you are receiving. If needed because of an urgent medical problem, your doctor can find out which treatment you were given. If at any time your doctor determines that it is in your best interest, you will be discontinued from the study and the doctor will continue to treat you as usual and customary.
How many people are expected to take part in the study?
If you agree to participate, you will be one of 60 subjects who will be participating in this research study at 8 different hospitals across the United States. Approximately 8-18 subjects will be enrolled at Rush University Medical Center.
What will you be asked to do?
If you agree to be in the study and you are satisfied with the explanations from the research team, you will be asked to sign this consent form. This study has four parts: a screening visit, and two treatment periods, and a follow-up period.
The first part of the study is the Screening Visit at which you will be evaluated to see if you qualify to participate in the study. This entire Visit will take about 2-3 hours. At the Screening Visit the following tests will be carried out to determine if you are eligible for the study:
- A physical examination will be done by one of the research doctors;
- A medical history will be taken, including questions about any past or present medical problems you may have and a review of drugs, vitamins, and dietary supplements you have taken in the past or are taking now;
- Measurement of vital signs will be done (height, weight, blood pressure, heart rate, breathing rate and oral temperature);
- Blood samples will be taken to obtain a chemistry panel that will screen for problems like kidney or liver disease, and CBC (complete blood count). The amount of blood taken will be approximately 2 teaspoonfuls and the blood will be taken from a vein in your arm. This blood will be tested right away and will not be saved.
- A urine sample will be obtained for standard urine analysis to screen for kidney or bladder problems.
- A pregnancy test will be done if you are a female of childbearing potential. The results of the pregnancy test will be shared with you and your parent/guardian, if you are not your own guardian;
- An electrocardiogram (EKG) will be done to monitor your heart (this is a painless procedure where sticky pads are stuck to the chest to measure the activity of the heart);
- You will be asked to complete several behavioral surveys and cognitive (thinking) assessments that will take between 1-2 hours.
Once the study doctor decides if you are able to participate, you will move into the next part of the study and be asked to return to the study doctor’s office to begin the first treatment period within 30 days.
At your visit at the beginning of the first treatment period (Visit 1 at day 1), you will be asked questions and have a brief examination to make sure you still qualify to be in the study. If so, you will be asked to complete several behavioral surveys and cognitive assessments, and if you are female you will have a urine pregnancy test. This visit will take about 2-3 hours and at the end of the visit you will receive either the study drug or placebo capsules. You and your study doctor will not know what type of capsules you have been assigned.
The first treatment period is expected to last 28 days. The number of capsules you are taking and how often you take them will be adjusted periodically by the study doctor. At the end of the 28 days, the study drug or placebo capsules will be slowly lowered, and then you will stop taking all study drug or placebo capsules for at least 7 days, and then return to the doctor’s office to begin the second treatment period.
During this first treatment period you will have 2 additional office visits (Visit 2 at day 14, Visit 3 at day 28) and you will be having 9 scheduled telephone calls with the study doctor or study nurse (on days 3, 6, 10, 18, 21, 24, 33, 38, 42). At the office visits you will be asked to complete the following: a review of your medical history, all drugs, vitamins, dietary supplements you are taking, how you are feeling, and any symptoms or side effects you may have experienced, a brief physical exam, blood pressure, heart rate and breathing rate, and several behavioral surveys and cognitive assessments. At Visit 3, you will also have blood drawn (about 3 teaspoons) to check study drug levels and safety blood checks, and you will give a urine sample. Visit 2 will take about 1-2 hours and Visit 3 about 2-3 hours.
At the scheduled phone calls you will discuss with the study doctor the current drugs, vitamins, dietary supplements you are taking, or if anything has changed. You will also be asked how you are feeling. Your dose of the study drug or placebo capsules may be adjusted during the phone calls or study visits, depending on whether you have shown improvement in symptoms or are having side effects.
To start the second treatment period, you will return for an office visit (Visit 4 at day 50) at which you will complete a review of your medical history, all drugs, vitamins, dietary supplements you are taking, how you are feeling, and any symptoms or side effects you may have experienced, a brief physical exam, blood pressure, heart rate and breathing rate, several behavioral surveys and cognitive assessments, and if you are female you will have a urine pregnancy test. This visit will take about 2-3 hours. You will again receive either the study drug or placebo capsules, depending on what you received in the first treatment period. Again, your study doctor and you will NOT know what type of capsule you are receiving at this time.
The second treatment period is expected to last 28 days and the number of capsules you are taking and how often you take them each day will be adjusted by your study doctor. Again, at the end of this period the amount of medication you are taking will be slowly lowered until you are completely off all study medication.
During this second treatment period you will have 3 additional office visits (Visit 5 at day 63, Visit 6 at day 77, and Visit 7 at day 91) and you will be having 9 scheduled telephone calls with the study doctor or study nurse (on days 52, 55, 59, 67, 70, 73, 82, and 87). At Visit 5 and 6 you will be asked to complete the following: a review of your medical history, all drugs, vitamins, dietary supplements you are taking, how you are feeling, and any symptoms or side effects you may have experienced, a brief physical exam, blood pressure, heart rate and breathing rate, and several behavioral surveys and cognitive assessments. At Visit 6, you will also have blood drawn (about 3 teaspoons) to check study drug levels and safety blood screens, and you will give a urine sample. Visit 5 will take about 1-2 hours and Visit 6 about 2-3 hours. Visit 7 will be on the day you stop taking all study drug or placebo capsules. At this Visit you will be asked questions about symptoms and side effects and have a brief physical exam, blood pressure, heart rate and breathing rate. This visit will take less than 1 hour.
The scheduled phone calls will be similar to those in the first treatment period. As before, your dose of the study drug or placebo capsules may be adjusted during the phone calls or study visits, depending on whether you have shown improvement in symptoms or are having side effects.
This period of the study is expected to last up to 30 days and at this time you will NOT receive any study drug or placebo capsules. The purpose of this period is to gather additional information from you after you are off the study drug or placebo capsules.
During this period you will have 1 scheduled telephone call where you will discuss with the study doctor or nurse the current capsules, vitamins, dietary supplements you are taking, or if anything has changed. You will also be asked how you are feeling.
How long will you be in the study?
The entire study is expected to last up to 151 days. During the study you are expected to come to the doctor’s office a total of 7 times and in addition receive a telephone call from the study doctor a total of 18 times.
You may be removed from this study without your consent for any of the following reasons: the study doctor decides that continued participation in the study will be harmful to you, you will need a treatment not allowed on the study, your disease becomes worse, you are unable to take the treatment as indicated, or the study is canceled by Seaside Therapeutics.
What are the possible risks of the study?
All investigational drugs can cause side effects or other reactions. The most common side effect reported by people taking baclofen (the less active approved version of STX209) is drowsiness. Other common side effects include dizziness, weakness and fatigue (tiredness).
Other side effects reported occasionally are confusion, headache, insomnia (problem sleeping), low blood pressure, nausea, constipation and increased urinary frequency.
It is important to note that on rare occasions, hallucinations and seizures may occur if the drug is stopped without first reducing it slowly. To minimize the risk of seizures, your study drug will be slowly increased to the appropriate dose and then slowly decreased before stopping.
During blood drawing you may experience pain or discomfort, and/or bleeding, and bruising at the site the needle enters the body, and in rare cases, fainting or infection. These risks will be minimized by having a trained professional take your blood.
When the EKG is done it is possible that the stickers to which the EKG is attached will be uncomfortable or could produce a rash due to a skin reaction.
Some of the tests may make you feel anxious but the research staff will do everything they can to make the visits to the clinic as relaxed as possible. If you feel uncomfortable or agitated at any point, you should tell the study doctor or a member of the research staff.
Throughout this study you will be told about any new information that may affect your health, welfare, or willingness to stay in the study.
Since the study drug is investigational there may be other risks that are unknown. All drugs, including the drug used in this study, have a potential risk of an allergic reaction. Signs of an allergic reaction may include redness, itching, swelling or (in rare cases) difficulty with breathing, and light-headedness. If you feel that you are experiencing a severe allergic reaction, you should call 911 and notify the study doctor immediately (Dr. Elizabeth Berry-Kravis, 312-942-4036).
Are there any anticipated pregnancy risks?
Women
STX209 may harm a pregnant woman, an unborn child or a nursing infant. Therefore, if you are pregnant or breastfeeding, you cannot take part in this study. Pregnancy tests are required and will be given at the Screening Visit, Visit 1, and Visit 4. The results of the pregnancy test will be shared with you and your parent/guardian, if you are not your own guardian. You are responsible for using an effective birth control method such as birth control pills, barrier method (such as condoms or diaphragms), intrauterine device (IUD), hormone implants or surgical sterility while you are taking part in this study. Once you have completed treatment, you may discontinue birth control 3 months after completion of treatment. If you become pregnant, you must notify the study doctor immediately.
Men
You are responsible for using an effective birth control method, such as the ones listed above. If you are a male and your female partner becomes pregnant, you must notify your study doctor immediately. Once you have completed treatment, you may discontinue birth control 3 months after completion of treatment.
Are there benefits to taking part in the study?
There may be no direct benefit to you for participating in this study. Your symptoms may be better while you are on the STX209, however you will have to come off the medication at the end of the study. If STX209 proves effective, there may be a general benefit to other people with fragile X syndrome and irritable behavior.
What other options are there?
You cannot be treated with STX209 unless you participate in this study, however there are other drugs your doctor may be able to use to treat your symptoms, and you can discuss these options with the study doctor.
What about confidentiality of your information?
Records of participation in this research study will be maintained and kept confidential as required by law. Study subjects will be given a study number and all data on test scores, behavioral measures, blood tests and exam results, and side effects will be entered into a computer database according to study number. Identifying information will be removed in the computer database. A key to the names that correspond to the study numbers will be in a separate computer file accessible only to study investigators. Only study investigators will be able to connect individual study subjects to their study number. All data will be stored on discs and a computer hard drive in the locked office of Dr. Berry-Kravis. Intake and monitoring forms, raw data from tests, and lab reports generated during the study, which will have subject names on them, will be kept in file folders, also in the office of Dr. Berry-Kravis. You can request that parts of the information from the folder (eg. lab reports) be provided to you at any time if you wish to have these for your records.
In order to conduct the study, the study doctor, Dr. Elizabeth Berry-Kravis,will use and share personal health information about you. This includes information already in your medical record, as well as information created or collected during the study. Examples of the information that may be shared include your medical history, physical exam and laboratory test results. The study doctor will use this information about you to complete this research.
Confidentiality and disclosure of your personal information is further described in the attachment to this form. The attachment is entitled HIPAA Authorization to Share Personal Health Information in Research (2 pages).
Your identity will not be revealed on any report, publication, or at scientific meetings.
The Rush Institutional Review Board (IRB) will have access to your files as they pertain to this research study. The IRB is a special committee that reviews human research to check that the rules and regulations are followed.
What are the costs of your participation in this study?
There is no cost to you or your insurance company for any of the exams, procedures, EKG, laboratory tests or other tests associated with the study, including the study drug or placebo capsules given to you and study visits that you attend. All costs that are part of your usual medical care, such as medical evaluations not required by the study, will be charged to you or your insurance company. You will be responsible for all costs associated with your usual medical care that are not paid by your insurance company.
The study is being conducted for Seaside Therapeutics. Your study doctor is being paid by Seaside Therapeutics to conduct this study. This payment will be used to pay for the costs of the study, which may include such things as tests, drugs, physical exams, etc. Also, a portion of the money will be given to Rush University Medical Center. One example of what this payment will cover would be the cost of rent for office space within the medical center.
Will you be paid?
You will receive a twenty-five dollar compensation for travel and food expenses at each of the scheduled study visits. Your parking expenses at the adjacent Rush Medical Center parking garage will also be covered on these days.
For more information please contact Crystal Hervey at 312-942-7250, or by email at crystal_hervey@rush.edu
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