Study Drug Risks. The study drug has been administered in a limited number of healthy participants in this study with no additional risks identified. The safety of the study drug has been studied in healthy participants and animals. In these animal studies, no significant risks or safety events of concern were identified, and the study drug did not cause side effects at any of the dose levels that will be used in clinical studies. Based on the studies done in animals with moderate to high doses of the study drug, potential risks from treatment with the study drug include: Increased respiratory rate (number of breaths per minute) Small reductions in heart rate Small increases in blood pressure Vomiting Changes in movement Small changes in some blood laboratory measures that play a role in the blood clotting system or in inflammation There are limited clinical data from the use of the study drug in humans. As of 14 April 2021, the study drug has been given as a single dose and multiple dose (twice daily for 10 days) to a limited number of healthy volunteer participants. Although only preliminary data are available, the early data in the healthy participant study did not show significant safety concerns when participants were given up to 500 mg of the study drug twice daily with 100 mg ritonavir twice daily, for 10 days. A few participants had slight increase in the thyroid stimulating hormone (TSH) laboratory test with no increase in free thyroxine (T4), the active thyroid hormone. None of these participants developed any clinical symptoms. The laboratory change was reversible and returned to a normal value. You may be monitored for changes in breathing rate, heart rate or blood pressure, as well as for the occurrence of other symptoms or side effects. Blood and urine samples will be taken on a regular basis to measure and evaluate for any changes in laboratory test results. Since the use of the study drug is investigational for the treatment of COVID-19 when taken alone or in combination with other medications, there may be other risks or side effects that are unknown. Human clinical and animal studies do not always predict the side effects of experimental medicines that people may experience.
Study Drug Risks. You may experience risks or discomforts when taking part in this study. The most common discomforts described are change in sense of taste, diarrhea, headache, and vomiting. This is not a complete list of risks or discomforts. A comprehensive list of risks and discomforts is provided further below in this consent document. However, there may be other risks or side effects that are unknown. Human clinical studies do not always predict the side effects of experimental drugs that people may experience. There may be rare and unknown side effects, including reactions that may be life threatening and could result in sickness or death. The study drug, taken with ritonavir, has been studied in more than 1,200 adults. This includes healthy participants and non-hospitalized participants with COVID-19. As of December 11, 2021, safety information is available from a large clinical trial in participants with COVID-19. A total of 1,109 participants received the study drug with ritonavir. A total of 1,115 participants received placebo (contains no active drug). Participants received study drug with ritonavir, or placebo, twice a day for 5 days. The most common side effects that occurred in greater than 1% (more than 1 participant in every 100 participants) of the participants with COVID-19 who received study drug with ritonavir were: • Change in sense of taste • Headache • Diarrhea • Nausea • Vomiting • Abnormal laboratory test results including: o Increased liver function tests o Decreased kidney function tests o Abnormal clotting tests Of the most commonly reported side effects, the following were reported more frequently in participants who received the study drug and ritonavir compared with participants who received placebo: • Change in sense of taste • Headache • Diarrhea • Vomiting Because the study drug is given with ritonavir, which is used to treat HIV, there is a risk for participants with HIV that has not been diagnosed or is not well controlled to develop resistance to some antiretroviral drugs used to treat HIV. This means that some antiretroviral drugs may not work properly to treat HIV. Some medicines interact with ritonavir. The study investigator will review these medicines with you.
Study Drug Risks. This is the first time that the study drug will be given to people. The possible risks and discomforts detailed below are based on information collected in animals and information available on other drugs that work in a similar way to the study drug. The study drug is similar to some injectable drugs that are available to patients by prescription. These prescriptions drugs are associated with side effects such as: • Low blood sugar • Nausea • Vomiting • Diarrhea • Headache • Constipation • Decreased appetite • Heartburn Potential risks of these marketed drugs in humans also include: • Thyroid tumors • Inflammation of the pancreas or gallbladder • Worsening of diabetic eye disease • Effects on kidney function These effects were not seen in the animal studies for the study drug. The study drug has been given to rats and monkeys for up to 8 weeks. While animal studies do not always predict the side effects that people may experience, the data from these animals are summarized below. All noteworthy findings in these animal studies were seen at high doses. The highest dose of the study drug that you will receive in this study may be up to 300 mg. At the highest dose level in the 8-week rat studies, there was evidence of damage to: • Heart • Liver • Stomach • Lungs Some of the rats did not survive to the end of the dosing period, The average drug levels in rats at this highest dose were about 152 times higher than the average drug levels at the highest dose planned in this study. There were no serious findings at any other dose level tested. There were changes in blood chemistry tests and in the liver of some rats across the dose levels tested. At the highest dose level given in the 8-week monkey study, 2 monkeys did not survive to the end of the dosing period. These monkeys ate less food and had low body weights and a worsened overall body condition. The average drug levels at the highest dose tested in monkeys were about 28 times higher than the average drug levels at the highest dose planned in this study. There were no serious findings in any other monkeys at this very high dose level, or at any other dose level tested. There were changes in blood chemistry tests of some monkeys across the dose levels tested. These changes were not considered to be serious due to their small extent and because there were no negative clinical effects. Aside from the 2 monkeys that did not survive to the end of the 8-week dosing period, some monkeys also ate slightly less food...
Study Drug Risks. The safety of the study drug has been studied in humans and animals. In studies in rats and dogs, the study drug was given at various doses for up to 28 days. At the high doses given to rats for up to 14 days, there was evidence of tissue inflammation and/or damage to the following: • Bile duct • Heart • Kidney • Blood vessel of the lungs • Trachea (windpipe) At the high doses given to dogs, when treated up to 28 days, the following occurred: • Vomiting • Loose stools • Evidence of inflammation in the gastrointestinal tract (for example the gall bladder and liver) At the high dose in both rats and dogs treated up to 28 days there was evidence of reduced size of the thymus. The thymus is a small gland that makes immune cells to fight infection. These events occurred in animals that received doses 4 to 33 times higher than what will be dosed in humans. In a previous study, the study drug was given at a lower dose and for a shorter period of time than was given in the animal studies. Animal studies do not always predict the side effects that people may experience. The safety of the study drug has been studied in 201 healthy adult participants in clinical studies. And as of 3 October 2021, 24 pediatric patients hospitalized with RSV infection have received a single dose of the study drug. Doses have ranged from 10 to 525 mg in adults. Overall, the study drug was well tolerated at all doses. The most frequently reported side effects in adults who received more than one dose of study were: • Nausea • Diarrhea • Abdominal pain Vomiting was the most frequent side effect in children who received 1 dose. These side effects were mild to moderate and resolved without any after effects. The vomiting in children happened when the study drug was given orally in water. It did not happen when the study drug was given in formula or breast milk together with a sweetened gel. There has been one serious side effect, a case of fever, reported in a child hospitalized with RSV infection who received a single dose of study drug. The study investigator assessed the event as not related to the study drug. Moxifloxacin Risks In clinical trials, the most commonly reported side effects were nausea, diarrhea, and dizziness. However, moxifloxacin, and other drugs in the same class, have been associated with disabling and potentially irreversible serious side effects including: • Tendinitis and tendon rupture (seen in trials of other meds in same class as moxifloxacin) • Cardiac: o Palpit...
Study Drug Risks. This will be the first time that these study drugs will be given to humans. The study drugs have been tested in rats. They were given orally (by mouth) for up to 6 weeks. The expected side effects from animal studies are: • Skin irritation • Changes in the immune system • Changes in hematolymphopoietic (blood and lymph) system The highest doses of study drugs to be applied in this study were found to be safe based on 6-week studies in minipigs (miniature pigs) where the same formulations were applied topically. Animal studies do not always predict the side effects that humans may experience. Based on clinical experience with oral medications similar to these study drugs, potential risks include: • Serious infections • Cancer • Thromboembolism (blockage of a blood vessel by a blood clot that has become dislodged from another site in the body’s circulation) • Changes in lab tests o Neutrophil (a type of white blood cell) count o Lymphocyte (a type of white blood cell) count o Lipid (fats) profile Also, to avoid reactions that may be life-threatening, various clinical and laboratory safety assessments and skin irritation assessments will be done. Until you know how the study drug(s) will affect you, you should use caution by: • Avoiding stairs • Not driving a car • Not swimming or bathing in a tub • Not working with machinery or at heights Other Risks Because the study drug is investigational, all of its side effects are not known. There may be rare and unknown side effects. These include reactions that may be life-threatening. All drugs have a potential risk of an allergic reaction. If an allergic reaction is not treated quickly, it could become life-threatening. You should get medical help (by calling 911 or immediately going to an emergency room) right away if you think you have any of the following symptoms: • Trouble breathing • Wheezing • Difficulty swallowing • Swelling of the face, mouth, lips, gums, tongue, or neck Other allergic reactions may include: • Itchiness • Rash • Hives • Blisters • Palpitations (racing heart) • Chest discomfort/tightness • Muscle pains/stiffness At times, the following may also be symptoms of an allergic reaction: • Diarrhea • Nausea • Vomiting • Abdominal pain If a significant side effect occurs, the following may be done: • Tests or treatment may be given as needed for your safety • Depending on how severe your symptoms are, you may be seen by outside medical providers or a hospital. This would be for further evaluation a...
Study Drug Risks. The study drug is a new type of antibody. An antibody is a protein that the body uses to fight infection. It targets 3 proteins, known as cytokines, that are believed to be important in causing the inflammation seen in skin diseases such as AD (eczema) and related diseases. inhibition (restricting) of these cytokines alone have been shown to be safe and well tolerated in humans and to have benefit in treating AD and /or asthma. However, the safety and effectiveness of inhibiting all 3 cytokines at the same time have not been studied in people. The study drug has never been given to people before. Therefore, the safety, toleration, and side effects in humans are not known. Studies have been done in animals to identify the risks that may occur in people given the study drug. The study drug has been tested in monkeys for months to see if it would likely be safe to give to people and to identify any possible undesirable side effects. No side effects were identified in this study even at the highest dose tested that produced levels of the study drug in the blood over 10 times the maximum predicted blood levels planned in human clinical trials. Animal studies cannot entirely predict symptoms that may arise after administration of the study drug. There may be rare and unknown side effects, including reactions that may be life- threatening. Based on a test in which blood cells were exposed to the study drug in a test tube (that is, outside of the body), the study drug may have a low risk of causing release of certain proteins (known as cytokines) that could result in a condition known as cytokine release syndrome (CRS). CRS is a serious condition that could result in the need for hospitalization. CRS is easily monitored in the clinic. Other studies have shown that the study drug has a low risk of binding to proteins (known as complement) that start a process normally used by the body to fight infection and destroy germs. If this process is started when there is no infection, there is a risk that the proteins will attack normal cells. To minimize the possible risks of CRS and complement binding, we are only giving the study drug to people in a controlled clinical setting in early clinical studies. Dosing in this first clinical trial will start at a very low dose level. Doses in this first study will be increased gradually and only if the lower dose is well- tolerated. The study drug can cause the body to form antibodies (proteins in the blood that identify and help...
