An Open-Label, 2-Part, Multicenter, Post-marketing Study to Evaluate the Effect of Moderately or Severely Active Ulcerative Colitis or Crohn’s Disease on Cytochrome P-450 Enzyme Substrates Compared to Healthy Subjects and the Effect of Vedolizumab...
Full Study Title: An Open-Label, 2-Part, Multicenter, Post-marketing Study to Evaluate the Effect of Moderately or Severely Active Ulcerative Colitis or Crohn's Disease on Cytochrome P-450 Enzyme Substrates Compared to Healthy Subjects and the Effect of Vedolizumab Treatment on Cytochrome P-450 Enzyme Substrates in Subjects With Ulcerative Colitis or Crohn's Disease.
This study is designed to find out if having the medical conditions Ulcerative Colitis or Crohn’s Disease affects the way commonly used medications are broken down in the body.
- Male or female aged 18 to 55
- Weight at least 110 pounds and BMI 18-30 kg/m2
- Prior to entering the study, patients with UC must have had an endoscopy during screening to confirm active disease, with Mayo score of 6 to 12 and an endoscopic subscore ≥2.
- Patients with CD must have a CDAI score of 220 to 450 to confirm moderate to severe disease on entry (ie, Day -1).
- Steroids are PROHIBITED from 14 days prior to Check-in (Day -1) to Study Exit (Day 2).
- Use of any investigational or approved biologic (e.g. Humira, Remicaide etc) or biosimilar agent in the last 6 months prior to Screening is PROHIBITED
This is an open label, 2 part, multicenter, post-marketing disease drug-drug-interaction study. This study is designed to find out if having the medical conditions UC or CD affects the way commonly used medications are broken down in the body. It is important to know this information so that correct doses of medications can be given to UC or CD patients.
Description of Treatment or Intervention (Mechanism of Action)
This will be done by giving a dose of 5 commonly used oral medications (caffeine, losartan, omeprazole, dextromethorphan and midazolam) to patients with UC or CD and measuring the levels of those medications in the body afterwards at different time points. Results from UC or CD patients will be compared with those from volunteers who do not have UC or CD to see if there are any differences in how the medications are broken down. If we determine there is a difference, then we will continue the study with a 2nd part to get more information. However not all patients with UC or CD will be invited to take part in Part 2. The ability to determine how medications are broken down by people with UC or CD will add to the understanding of UC and CD, it may help to allow for more accurate doses of common medications to be given and it may help with the development of new treatments.
Patient Participation Requirements
- Patients will complete 4 visits which includes: Visit 1 (Screening Visit 1a and Screening Visit 1b); Visit 2 (admission, dosing and a 2-night stay); and Visit 3 (follow-up visit). The total time you will need to stay in the hospital will be less than 3 days (2-night stay).
- The study medications which you will receive by mouth will be a combination of: Caffeine, Losartan, Omeprazole, Dextromethorphan, and Midazolam.
Screening Visit 1a
- Discuss the study and obtain written informed consent to participate. Review of suitability for the study. A review of demographics. A review of medical history and medication history. Physical examination Vital signs Height and weight. You will be tested for hepatitis and human immunodeficiency virus (HIV). DNA test to determine how well your body metabolizes certain medications. Standard blood laboratory tests to check on your general health. Pregnancy test for women who can get pregnant. Urine tests: A urine sample to test for alcohol or recreational drugs. A 12-lead ECG (electrocardiogram). If you have CD you will receive a paper diary to record disease symptoms and instructions on how to use it.
Screening Visit 1b
- This visit will occur within 7 days of planned treatment (Day 1). An assessment of your health. A review of current medications.
- CD patients: The following procedures will be performed: A blood test will be taken. CDAI (Crohn’s Disease Activity Index) score will be assessed from the diary you have been keeping.
- UC patients: The following procedures will be performed: You will have a flexible sigmoidoscopy performed to examine the lower part of the colon. Mayo score to be completed to assess the severity of your UC.
Screening Visit 2 (admission, dosing and 2 night stay)
- Admission: Study Day -1 You will have the following tests and procedures done: Review of your suitability for the study. Physical examination. Vital signs (temperature, pulse, respiratory rate and blood pressure). Weight and height. Review of current medications and your health to determine if your status has changed since your screening visit. Standard blood laboratory tests to check your general health. Urine tests: A urine sample to test for alcohol or recreational drugs. Pregnancy test for women who can get pregnant. A 12-lead ECG
- CD patients: In addition the following procedure performed: Your CDAI (Crohn’s Disease Activity Index) score will be assessed from the diary you have been keeping.
- Dosing: Study Day 1 you will have the following tests and procedures done on the day of dosing with the study medication: Vital signs (temperature, pulse, respiratory rate and blood pressure). Physical examination. Review of your health to determine if your status has changed since Day-1. A cannula will be used to collect blood samples from you at multiple time points to look at the levels in your blood of study medication and cytokines. A 12-lead ECG. The study medication will be administered by mouth with approximately 250ml water.
- Discharge: Study Day 2
- The following tests and procedures will be performed prior to discharge. If any tests are abnormal, you may need to wait a little longer if tests need to be repeated or you may be asked to return for repeat testing. Physical examination. Vital signs. Review of your health to determine if your status has changed since Day 1. Standard blood laboratory tests to check your general health. A final blood sample will be taken to look at the levels of study medication in your blood and for cytokines (24 hours after taking study medication).
Possible Risks & Side Effects
- Caffeine 100mg wakefulness, other side effects include nausea, vomiting, stomach pain, diarrhea, insomnia, headache, anxiety, irritability, restlessness, tremor, and palpitations but these are unlikely following a single 100mg dose.
- Losartan 50mg dizziness, upper respiratory infection, nasal congestion, back pain. Less common adverse reactions include anemia, depression, somnolence, headache, sleep disorders, paresthesia, migraine, palpitations, syncope, atrial fibrillation, CVA, and dyspnea.
- Omeprazole 20mg can cause headache, stomach disturbances, and rash. It can rarely cause dizziness, tiredness, cough, dry mouth, itchy skin or allergic reactions.
- Dextromethorphan 30mg can cause drowsiness, seizures, vomiting, nausea, diarrhea, skin reactions including rash (Dextromethorphan SMPC Boots Dry Cough Relief 2.5mg Lozenges).
- Midazolam 2mg can cause hypersensitivity, anaphylactic shock, angioedema, Confusion, euphoric mood, hallucinations, agitation, hostility, rage, hyperactivity, aggressiveness, excitement, involuntary movements, difficulty walking, amnesia, seizures, slowed heart rate or cardiac arrest, low blood pressure, slowed breathing, nausea, vomiting, constipation, rash urticaria, pruritus.
The following are possible discomforts or risks associated with a colonoscopy:
- Heavy or ongoing bleeding from biopsy or removal of polyp
- Cramping, pain, abdominal bloating
- Peritonitis (inflammation of the lining of the abdominal cavity)
- Perforation (a hole) of the intestinal wall. Surgery may be needed if a perforation occurs.
- Nausea, vomiting, bloating, or rectal irritation caused by the bowel cleanse prep.
- Side effects, like drowsiness following sedative or pain medication