A Scintigraphic Study to Evaluate the Localization and Delivery Function of a Drug Delivery System 2 (DDS2) Capsule in Subjects with Ulcerative Colitis (UC) in a Fasted State
Published: 03/25/2022
General Information:
To evaluate the safety, tolerability, and localization and delivery function of the DDS2 Capsule using gamma scintigraphy in people with active UC in a fasted state. The DDS2 capsule features proprietary localization technology designed to enable precise study drug delivery at the site of disease in the GI tract. Safety and tolerability of the DDS2 capsule has previously been tested in healthy participants. In this study, the DDS2 capsule will deliver a saline solution containing a small amount of non-absorbed radioactive tracer upon entry into the colon of people with ulcerative colitis in a fasted state. Gamma scintigraphy will be used to assess the localization and delivery function of the capsule.
Eligibility:
Inclusion Criteria
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Male and non-pregnant female participants between ≥ 18 and ≤ 75 years of age who are willing to adhere to contraception and sperm donation criteria.
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The participant can demonstrate the ability to swallow a capsule about the size of a large vitamin.
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The participant has a documented diagnosis of UC confirmed by endoscopy and histology.
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The participant has active UC within one (1) month of screening
Exclusion Criteria
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The participant has a history of achalasia or any other esophageal disorder such as esophageal strictures.
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The participant is diagnosed with Crohn’s disease or indeterminate colitis or clinical findings suggestive of Crohn’s disease (e.g., stricture, fistula, or granulomas on biopsy).
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The participant has current evidence of fulminant colitis (e.g., toxic megacolon or bowel perforation).
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The participant has a current or anticipated need (within 3 months) for colostomy or ileostomy.
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The participant had current evidence of colonic dysplasia or past evidence of colonic dysplasia that had not been definitively treated.
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The participant has a history of increased risk for bowel obstruction, including individuals.
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The participant has an active or chronic latent bacterial or viral infection, including evidence of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
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Female participants that are currently lactating or breastfeeding.
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The participant is implanted with a pacemaker or any other electronic medical device.
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The participant is unwilling to undergo an abdominal x-ray or other medical intervention if considered necessary by the Investigator, if the DDS2 is not recovered within 7 days of administration.
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The participant is unwilling to abstain from alcohol for 24 hours prior to screening and 24 hours prior to dosing until the final image is collected during each dosing period.
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The participant has a clinically significant history of illicit drug use in the past year or is unwilling to refrain from using illicit drugs while participating in the study.
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The participant is unwilling to abstain from caffeine- or xanthine-containing foods or beverages for 24 hours prior to screening and 24 hours prior to dosing until collection of the final image during each dosing period.
Study Details:
The purpose of this study is to look at how the DDS2 Capsule moves through the stomach of a person with active ulcerative colitis (UC) and the time and location where the DDS2 Capsule releases an inactive solution (does not contain drug) in their digestive tract. This study will not treat the participant's ulcerative colitis and will not stop or change their current management of their ulcerative colitis.
The participant’s participation in this study will include one (1) outparticipant screening visit (within 4 weeks of their study capsule dose), one Study Treatment Period (which requires up to 2 days and 3 nights of continuous in-clinic confinement), and a follow-up visit on or within 2 weeks after the last day of the Study Treatment Period.
Description of treatment or intervention (mechanism of action):
The DDS2 ingestible capsule is 0.45 x 1.03 inches, which is slightly larger than a typical large vitamin pill. The outside of the capsule is made of polycarbonate plastic that is safe for use in devices that go in the human body. The capsule has rounded ends for ease of swallowing. In this study, the DDS2 Capsule contains a liquid with a radioactive marker, but the capsule does not contain any active medicines. The liquid in the capsule reservoir is automatically released when the DDS2 Capsule localization technology determines it has reached the colon.
The participant will be given, by mouth, one study capsule in the fasted state. After the participant takes the study capsule, they will have gamma scintigraphy imaging performed to determine the capsule location. This will be repeated as often as every 15 minutes. After taking the study capsule, the participant will be asked to stay at the study site and will be discharged from the study site no sooner than 48 hours after taking the study capsule, and after all study procedures are complete.
Participation Requirements:
Responsibilities as a study participant include the following:
- Must be able to provide written informed consent. Legally authorized representatives may not provide consent for the participant’s participation in this study.
- Complete all required visits to the study center.
- Tell the truth about their medical history, current conditions and any prescription medicine or non-prescription medicine the participant uses
- Tell the study investigator about any problems they have during the study.
- Take the study capsule as directed by the study investigator and study staff.
- Inform the study investigator or study staff if they decide to withdraw from the study. The participant will then be asked to return to the study investigator for a final visit.
- The participant must refrain from alcohol, tobacco, nicotine, and strenuous activity (no more than their usual activity level, including competitive sports) for at least 24 hours before screening, Day 1, while they are confined to the study site (approximately 2 days), and at least 24 hours before the Follow-up Visit safety lab blood sample.
- Adhere to provided diet while at the clinic. All food will be provided by the clinic and no other food will be permitted. The participant should tell the study investigator about any special dietary requirements (for example: vegetarian, vegan, gluten sensitivity, allergies, dislike of certain foods) before agreeing to participate.
Possible risks and side effects:
The following risks are noted:
- The participant should not go into a room that has an MRI machine after swallowing the study capsule until the DDS2 has been recovered. The magnet may cause the capsule to move inside them, which may cause pain or damage. For their safety, the participant should not have an MRI done for 14 days after ingesting the capsule unless capsule exit has been verified.
- The participant may experience choking when the capsule is swallowed that may include labored breathing, wheezing, and involuntary coughing.
- If the participant or the study staff have not visually verified the capsule upon exit and if the participant experiences unexplained stomach pain, vomiting, loss of appetite, nausea, constipation, inability to have bowel movements or pass gas, or swelling of the stomach occurs, they should contact the study investigator. If the capsule has not passed, an x-ray of their digestive system may be done, which would involve additional radiation exposure. It may also be necessary to either take medication or have an additional procedure or surgery to treat a possible complication.
- Although extremely unlikely, there is a risk of the capsule going down the wrong pipe and entering the airways or lungs when trying to swallow. This will cause the urge to cough, wheezing and feel like it’s hard to breathe, which may lead to choking. The study investigator will be present when the participant swallows the capsule to prevent any serious problem.
Similar versions of the DDS2 Capsule have been administered to approximately 50 people. There is a large amount of evidence showing that a similar capsule does not present a serious risk to the health, safety, or welfare of participants. The capsule device we are investigating is similar in material and profile to the commercially available PillCam endoscopy capsules (11.6 x 31.5 mm). As of December 31, 2012, over 1.9 million PillCam capsules have been sold.
Since the use of the DDS2 Capsule is investigational in this study, there may be other risks and side effects that are not known at this time. Some of these may be life threatening.
Radiation Dose Risks
The participant will receive a maximum whole-body radiation dose equivalent to about ¾ of the yearly dose normally received from background radiation (natural radiation present in the environment). The risk of radiation exposure of this size is difficult to compare to everyday risks.
The possible effects of low level radiation dose on future generations are not entirely known, but it is known that the added risk (the risk over and above environmental, hereditary, and other factors that cause birth defects and genetic mutations) is within generally acceptable limits for the dose levels the participant will receive by taking part in this study.
Although unlikely, an x-ray image of the participant’s digestive system may be needed if they do not pass the capsule. Such x-rays also involve exposure to radiation. The amount of additional radiation exposure they may receive from such standard diagnostic tests is considered small.
If the participant needs an x-ray, they may be exposed to more radiation because they are taking part in the study. At exposure levels much higher than they might receive from a diagnostic x-ray, radiation is known to increase the risk of developing cancer after many years. At the exposure level the participant may receive from diagnostic x-rays as a result of participating in this study, it is very likely that they will see no effects at all.
Blood Draw Risks
In this study, the amount of blood collected during this study will be 59 ml (about 4 tablespoons). This is less than the amount of blood donated during a routine blood donation (450-500ml).
Blood samples will be drawn by separate direct needle sticks into a vein in the participant’s arm.
During the collection of blood samples by direct needle sticks, there is a chance of:
- Swelling
- Pain
- Dizziness
- Bruising
- Infection
- Redness at the site(s) where blood is taken
Nasal Swab Risk
The participant will be tested for COVID-19 using nasal swabs. They may have minor discomfort from the insertion of the nasal swab(s). This irritation will be brief. They may experience discomfort, eyes watering, sneezing, or bleeding.
General Discomfort Risks
The participant will be asked to fast for about 10 hours or more during this study. They will not be able to utilize tobacco or nicotine containing products, consume beverages or products containing caffeine, nor engage in strenuous exercise for 24 hours before screening, Day 1, while they are at the clinic, and before their Follow-up blood sample. They will not be able to drink alcohol or use products containing alcohol for 24 hours before screening, Day 1, while they are at the clinic, and before their Follow-up blood sample. These restrictions may cause the participant some discomfort. Withdrawal from caffeine can cause severe headaches. They may experience minimal discomfort from the ECG during the attachment and removal of the ECG leads to and from the skin.
Allergic Reaction Risks
There is a risk of allergic reaction. If the participant has a very serious allergic reaction, they may be at risk of death. Some symptoms of allergic reactions are:
- Rash
- Wheezing and difficulty breathing
- Dizziness and fainting
- Swelling around the mouth, throat or eyes
- A fast pulse
- Sweating
The participant could experience an allergic reaction during the study. Allergic reactions are serious and could be life threatening. If they have previously had an allergic reaction to other drug products, they will be asked to let the study investigator know.
The participant could experience a side effect or an allergic reaction that has not been reported with the use of the DDS2. Serious allergic reactions can be life threatening. Other medicines the participant may be taking could cause a bad reaction when taken with the DDS2. The participant must tell the study investigator or study staff right away if they have any of these side effects, allergic reactions, or changes in the way they feel during the study.
Unknown Risks
The participant might have side effects or discomforts that are not listed above. Some side effects may not be known yet.
Progress to date:
The DDS2 Capsule is a non-invasive ingestible capsule that operates as an autonomous drug delivery system designed to deliver a bolus dose of a therapeutic compound to a defined and detected location within the gastrointestinal (GI) tract. The safety and localization technology of a prototype device has successfully been evaluated in 58 participants across 3 clinical studies. In addition, the safety and device functionality assessment of current device had also found to be safe and tolerable with a high precision to localize and deliver in the colon using gamma scintigraphy in 12 normal healthy participants (PM-601-DDS2-Delivery). This study is intended to assess for safety, localization, and delivery functionality of the DDS2 Capsule in the active Ulcerative Colitis (UC) patient population.