30 Clinical Trials for Various Conditions
This study will investigate the effect of multiple doses of the strong P450 enzyme inhibitor itraconazole on the pharmacokinetics of Lu AF35700 in healthy subjects.
This is a Phase I study to determine the effect of GW786034 (pazopanib) on P450 enzymes. This study will help determine which types of drugs may interact with GW786034.
Tacrolimus (Prograf) belongs to a class of medications known as the calcineurin inhibitors. It is a maintenance drug that is used to prevent rejection in kidney, liver, and heart transplant recipients. Calcineurin inhibitors display high pharmacokinetic (the body's effects on a drug) variability and necessitate use of blood tests to ensure that adequate drug levels are present to maintain effectiveness and safety. Early after transplant or at times when tacrolimus cannot be taken by mouth, alternative routes of administration are sought. Although an intravenous (through the vein) product is available, it can be toxic to the kidneys and has been associated with allergic reactions. Drug delivery via the oral mucosa is an alternative method of systemic drug administration which offers an alternative when oral administration is impractical (gastrointestinal dysmotility, reduced drug absorption, intestinal failure, difficulty in swallowing, or in those with nausea or vomiting). Administration of tacrolimus by the sublingual route may allow for direct entry into the systemic circulation and bypasses problems associated with drug absorption and breakdown that take place in the small intestine.
Drug-drug interactions play an important role in clinical adverse events due to the prevalence of multi-drug therapy. Co-administration of warfarin and a statin has expanded substantially in the US over the last decades. The purpose of this study is to develop a mechanistic understanding of the role of a drug-metabolizing enzyme, CYP4F2, in the interaction between warfarin and statins. This study will test the hypothesis that lovastatin potentiates the anticoagulant effect of warfarin by inducing vitamin K-metabolizing enzyme CYP4F2 in humans, thus increasing warfarin's anticoagulant effect.
This study will evaluate drug-drug interactions between cannabis extracts containing Tetrahydrocannabinol (THC) and THC+ Cannabinoids (CBD) and probe drugs for select CYP450 pathways including: caffeine (CYP1A2), omeprazole (CYP2C19), losartan (CYP2C9), dextromethorphan (CYP2D6), and midazolam (CYP3A).
The primary objective of this study is to assess the drug-drug interactions of Androxal with cytochrome P450 isoenzymes, CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 in healthy male subjects administered 25 mg Androxal once daily for 3 days. Secondly, the safety and tolerability of Androxal will be determined in healthy male subjects administered Androxal 25 mg daily for 3 days.
The purpose of this clinical trial is to determine how the supplement oregano affects how the body metabolizes pharmaceutical drugs.
This is a Phase 1, open-label, fixed-sequence, 2-part DDI study. Subjects will participate in only 1 study part.
The purpose of this study is to evaluate the effect of the following index inhibitors or inducers of CYP2C8 and/or CYP3A on the single-dose pharmacokinetics (PK) of ozanimod and its major active metabolite, CC112273, in healthy adult subjects: gemfibrozil (strong inhibitor of CYP2C8), rifampin (moderate inducer of CYP2C8 and strong inducer of CYP3A), and itraconazole (strong inhibitor of CYP3A). Study Design This is a Phase 1, randomized, parallel-group, open-label study with two parts, 1 and 2. Forty subjects will be enrolled in Part 1 and will be randomized into 1 of the 2 treatment groups, with 20 subjects in each treatment group. Sixty subjects will be enrolled in Part 2 and will be randomized into 1 of the 3 treatment groups, with 20 subjects in each treatment group. . Study parts and treatment groups are as follow: Part 1: * Treatment Group A (reference): A single dose of ozanimod. * Treatment Group B (test): Gemfibrozil 600 mg twice daily (BID) on Days 1 through 17. On Day 4, a single dose of ozanimod will be coadministered with the morning dose of gemfibrozil. Part 2: * Treatment Group C (reference): A single dose of ozanimod. * Treatment Group D (test): Itraconazole 200 mg once daily (QD) on Days 1 through 17. On Day 4, a single dose of ozanimod will be coadministered with itraconazole. * Treatment Group E (test): Rifampin 600 mg QD on Days 1 through 21. On Day 8, a single dose of ozanimod will be coadministered with rifampin. Study Population Subjects will be healthy men and non-pregnant, non-lactating women, ages 18 to 55 years, inclusive, with a body weight of at least 110 pounds (50 kg); body mass index (BMI) within the range of 18.0 to 30.0 kg/m2, inclusive. Length of Study The study duration ranges from 43 days to 50 days.
This is a Phase 1, single center, fixed sequence, open label, drug-drug interaction study of the effect of multiple doses of rifampin 600 mg daily, a strong CYP3A inducer, on the exposure of mifepristone at 2 dose levels.
This study is aimed to investigate the influence of cenobamate on the activity of CYP3A4/5, CYP2B6, CYP2C19, and CYP2C9 by using drugs recommended by both the FDA and EMA as in vivo probes. In order to avoid a potential pharmacokinetic interaction between the probes, midazolam (CYP3A), warfarin (CYP2C9), and omeprazole (CYP2C19) will be administered together as a validated cocktail and separately from bupropion (CYP2B6) using an adequate washout time period between the 2 assessments. The starting daily dose of cenobamate will be 12.5 mg, which will be administered for 2 weeks. Then, daily cenobamate doses will be increased every 2 weeks to 25 mg, 50 mg, 100 mg, 150 mg, and 200 mg. The CYP probes will be tested before cenobamate administration, at steady state at 100mg/day of cenobamate for midazolam only and finally at steady state at 200mg/day of cenobamate for all CYP probes. The results of this DDI study will provide a basis to make appropriate dose recommendation for a safe use of concomitant drugs with cenobamate using these isoenzymes in their metabolic pathway.
This study aims to evaluate the pharmacokinetics (PK) of apixaban when co-administered with cyclosporine and tacrolimus in healthy volunteers. The study participants will receive apixaban alone, cyclosporine followed by apixaban and tacrolimus followed by apixaban.
This randomized controlled trial will evaluate whether the use of pharmacogenetic testing through a Medication Therapy Management (MTM) program has a beneficial impact on drug therapy problems. More specifically, cytochrome DNA testing, which provides information with regards to participant specific metabolism of medications, will be used in the evaluation of participant medication regimens. The overall aim of the project is to evaluate if the addition of genetic CYP testing to a standardized MTM Program provides increased clinical value. To answer this question, the investigators will look at the drug therapy problems (DTPs) identified by the genetic test compared to those DTPs discovered without the test.
This study will examine the effect of an inhibitor of cytochrome P450 isoenzyme 3A4 (CYP3A4) and permeability glycoprotein 1 (P gp) (200 mg itraconazole) on the PK disposition of a 10 mg tablet of TD- 1211 administered orally to fasted subjects.
The purpose of this research study is to understand whether there is any difference in the amount of midazolam (including its breakdown product) in the blood when midazolam is given with tasimelteon, and whether there is any difference in the amount of rosiglitazone in the blood when rosiglitazone is given with tasimelteon.
This is a 4-week sequential drug interaction study to measure the effects of American ginseng on efavirenz pharmacokinetics using steady-state 24-hour Area Under the Curve (AUC) and Cmax as the primary comparison measures in healthy male volunteers. Efavirenz Cmin, T1/2, tmax, and clearance will also be assessed as secondary outcome measures. This study is a phase I, prospective, within-subject, fixed-order, two-period, multiple dose, open label, drug interaction study, to determine the stead-state plasma pharmacokinetic profile of efavirenz before and after concurrent treatment with American ginseng. The investigators hypothesis is that concurrent oral administration of American ginseng for up to 14 days will not significantly alter the steady-state plasma pharmacokinetic of efavirenz.
Grapefruit juice is an inhibitor of the cytochrome P450 (CYP) 3A4 enzyme system, one of the enzyme systems responsible for the metabolism of colchicine. This study will evaluate the effect of multiple daily consumptions of grapefruit juice on the pharmacokinetic profile of a single 0.6 mg dose of colchicine. A secondary objective is to evaluate the safety and tolerability of this regimen in healthy volunteers. All study subjects will be monitored for adverse events throughout the study period.
Colchicine is a substrate for both cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp). Extended-release diltiazem (diltiazem ER) is a potent inhibitor of both CYP3A4 and P-gp. This study will evaluate the effect of multiple doses of diltiazem ER on the pharmacokinetic profile of a single 0.6 mg dose of colchicine. A secondary objective is to evaluate the safety and tolerability of this regimen in healthy volunteers. All study subjects will be monitored for adverse events throughout the study period.
Ketoconazole is a potent inhibitor of the cytochrome P450 (CYP) 3A4 enzyme system, one of the enzyme systems responsible for the metabolism of colchicine. This study will evaluate the effect of multiple doses of ketoconazole on the pharmacokinetic profile of a single 0.6 mg dose of colchicine. A secondary objective is to evaluate the safety and tolerability of this regimen in healthy volunteers. All study subjects will be monitored for adverse events throughout the study period.
This is an open label non-randomized single sequence, single group two way drug interaction study in healthy adult volunteers to determine the extent to which quinine, an inducer of cytochrome p450 CYP 3A4, affects the pharmacokinetics of midazolam, an accepted probe drug for CYP 3A4. The study will also determine the extent to which midazolam affects the pharmacokinetics of quinine.
Rosiglitazone is predominantly metabolized by cytochrome P450 (CYP) 2C8. Quinine sulfate is an inhibitor of CYP 2C8. This study will evaluate the effect of multiple doses of quinine sulfate at steady-state on the pharmacokinetics of single-dose rosiglitazone in healthy adult subjects.
In a prior in vitro study using human hepatocytes quinine was shown to induce the activity of Cytochrome p450 CYP 1A2. The present study will evaluate the extent to which quinine sulfate-related induction of this enzyme effects the pharmacokinetics of theophylline, a sensitive probe drug for the activity of CYP 1A2. It will also evaluate the effect of single-dose theophylline on the pharmacokinetics of steady-state quinine sulfate.
The purpose of this clinical research study is to assess the effect of Atazanavir 400 mg QD and Atazanavir/Ritonavir 300/100 mg QD at steady state on the single dose pharmacokinetics of RGZ in healthy subjects.
Patients meeting eligibility criteria will be randomized into two groups, one receiving pharmacogenetic testing and the other not receiving pharmacogenetic testing. In this open-label trial, a pharmacist will make medication therapy recommendations using YouScript® Personalized Prescribing System for patients who receive genetic testing and standard drug information resources per usual for patients who do not undergo pharmacogenetic testing.
This multicenter observational study aims to investigate the benefits of providing pharmacogenetic testing with the YouScript Personalized Prescribing System which includes a clinical decision support tool and individualized pharmacist recommendations to elderly polypharmacy patients who are most at risk of adverse drug events. The YouScript system is unique in identifying drug-gene, and drug-drug-gene interactions that are missed by existing systems, and represent over 35% of significant interaction warnings. Data analysis will assess the impact of recommendations for medication changes on clinical decision making, patient outcomes, and healthcare resource utilization to determine which medications, specialties, or patient segments derive the greatest benefit from this intervention. Data gathered from patients enrolled in this study will be compared to patients matched on key characteristics from Inovalon's MORE2 healthcare database.
Adverse events due to drug-drug and/or herb-drug interactions are of serious concern and a major cause of morbidity and mortality. Resveratrol is a polyphenol antioxidant that has been identified in over 70 species and is suggested to be the constituent in red wine responsible for cardioprotective effects. The potential health benefits of resveratrol supplements are highly extolled in the alternative medicine industry and daily doses are up to 5 grams are being studied. While there are potential health benefits of high doses of resveratrol, for patients taking other drugs metabolized by CYP3A4, such as transplant medications, chemotherapies and HMG-CoA reductase inhibitors, there may be a clinically significant herb-drug interaction. We, the investigators, have shown in vitro that resveratrol is a mechanism-based inhibitor of cytochrome P450 3A4 (CYP3A4). Based on our in vitro evidence and literature reports of the pharmacokinetics of resveratrol, we hypothesize that resveratrol will be a potent in vivo mechanism-based inhibitor of intestinal CYP3A4 enzymes. To date, there are no clinical studies that address the potential for a resveratrol-drug interaction. We propose to test whether single and multiple doses of resveratrol alter the pharmacokinetics of midazolam, a prototypic CYP3A4 probe drug.
The purpose of this study is to see if administration of medicines and genetic differences affects the activity of a liver enzyme called CYP2B6 in healthy volunteers.
The two purposes of this study are 1. to determine what effect the chronic and moderate/heavy drinking of alcoholic beverages has 1. on the blood level of bupropion and chlorzoxazone and their major breakdown products in the blood and 2. on the stimulant effect of bupropion and 2. to determine what effect a normal and common (25% frequency) genetic variation of a specific liver enzyme (that breaks down bupropion) has 1. on the blood levels of bupropion and its major breakdown products in the blood and 2. on the stimulant effect of bupropion. Two groups of volunteers will be recruited for this study: 1. volunteers who drink moderate to heavy amounts of alcohol frequently and 2. volunteers who usually do not drink alcohol. Volunteers will NOT be asked to change their drinking (or nondrinking) habits during the study.
This study will evaluate the effects of genetics on metabolism of the anti-HIV medicine efavirenz (Sustiva) and will see if Efavirenz interacts with bupropion (Zyban or Wellbutrin), a drug commonly used to treat depression and to help people quit smoking. Efavirenz is metabolized by an enzyme called CYP2B6, which is thought to be more active in some people than in others, depending on their genetic makeup. The rate of metabolism of the drug can affect how the body responds it and perhaps the ability of the HIV virus to develop resistance to it. Healthy volunteers between 18 and 55 years of age who are non-smokers and HIV-infected men and women 18 years of age and older who are taking efavirenz along with two or three nucleoside reverse transcriptase inhibitors may be eligible for this study. Candidates are screened with a medical history and physical examination and blood tests, including tests to determine which genes they have for four different proteins or enzymes (CYP2B6, CYP3A4, CYP3A5, and MDR1) that metabolize drugs. Participants are assigned to one of three groups for the following procedures: -HIV-infected individuals: Blood samples are drawn to measure efavirenz levels, as follows: On the last day of taking efavirenz, the subject skips his or her usual evening efavirenz dose the night before sampling. The next morning at clinic, a catheter (flexible plastic tube) is inserted into a vein in the subject's arm for collecting blood samples. After the first sample is drawn, the subject takes a dose of efavirenz. Eight more blood samples are collected at 1, 2, 4, 6, 8, 12, 24 and 48 hours after taking the efavirenz tablet. (The catheter is removed after the 12-hour sample and the subject is discharged home, and then returns to the clinic for the 24- and 48-hour samples, which are collected through a needle inserted into an arm vein.) The subject returns to the clinic four more times for a single blood draw at 7, 14, 21 and 28 days after stopping efavirenz. HIV-infected patients whose HIV viral load reaches 1,000 copies/L or more within 12 months after completing the study are asked to return to the clinic for a blood draw to check the genotype of the virus for drug resistance. * Healthy Volunteers - Group 1: Blood samples are drawn to measure efavirenz levels, as follows: Participants take one efavirenz tablet once a day for 13 to 15 days. On the last day of taking efavirenz, the subject takes his/her last dose of efavirenz in clinic, where blood is then collected as described above for HIV-infected individuals. * Healthy Volunteers - Group 2: A catheter is inserted into a vein in the subject's arm and a blood sample is drawn through the catheter. The subject then takes a single bupropion tablet and additional blood samples are drawn at 1,2, 2.5, 3, 3.5, 4, 6, 8, 12, 24 and 48 hours after the dose to measure the amount of drug in the blood. Subjects begin taking efavirenz 0 to 6 days after the last bupropion blood level is measured. As above, subjects will take one efavirenz tablet once a day for 13 to 15 days. On the last day of taking efavirenz, a catheter is inserted into the subject's arm. Two blood samples are drawn through the catheter, the subject takes the daily dose of efavirenz along with a bupropion tablet. Eleven additional blood samples are drawn at 1, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours after taking the pills to measure blood levels of bupropion. Eight additional samples are collected at 1, 2, 4, 6, 8, 12, 24, and 48 hours to measure efavirenz blood levels. (The catheter is removed after the 12-hour sample and the subject is discharged home; the 24- and 48-hour samples are collected through a needle inserted into an arm vein.)
This study will examine whether and how levothyroxine (Synthroid, a synthetic thyroid hormone) affects the way the body handles other drugs. If levothyroxine does affect the metabolism of other drugs, the dose of those medications may need to be increased to enhance their action or decreased to avoid adverse reactions. Patients 18 years of age and older with thyroid cancer who are participating in NIH protocol #77-DK-0096 and are receiving long-term suppression therapy with levothyroxine may be eligible for this study. This is not a study of thyroid cancer or of potential new drugs to treat it. Thyroid cancer patients are being studied because their treatment regimen provides an opportunity to study drug metabolism while patients are both on and off levothyroxine therapy. Participants come to the NIH Clinical Center on two occasions: once while they are regularly taking their levothyroxine, and once while they are off the medication in preparation for their radioactive iodide diagnostic scan for the procedures outlined below. The time interval between the two clinic visits depends on whether the first visit is while the patient is on or off medication. Participants are asked to fast overnight before each visit and to abstain from certain foods and beverages for 48 to 72 hours before the visit. At each visit, patients undergo the following procedures: * Medication history, limited physical examination, and blood draw for laboratory tests, including a test to look for genes important in eliminating medications from the body. * Insertion of a catheter (thin plastic tube) into an arm vein for collecting blood samples. * Shave skin biopsy (optional) to explore how proteins in the skin that metabolize and transport drugs are affected by thyroid hormone. For this procedure, the skin is cleaned, numbed with medicine, and a small sample of the top layer is removed with a razor blade. The wound heals in 2 to 3 days. * Medication dosing. Participants take all of the following substances by mouth at the same time: 1) 200 mg of caffeine, a compound commonly found in chocolate, soda/pop, coffee, tea and non-prescription products to prevent sleep; 2) 30 mg of dextromethorphan, a non-prescription cough suppressant; 3) 40 mg of omeprazole, a prescription drug for heartburn and stomach ulcers; 4) 8 mg of midazolam, a prescription drug used to cause relaxation and drowsiness; and 5) 120 mg of fexofenadine, a non-sedating prescription antihistamine used to treat allergies. * Blood and urine sampling. Fifteen blood samples of about 5 mL (1 teaspoon) each are collected through the catheter and urine is collected over the next 24 hours to determine what happens to the test drugs in the body. Participants may resume their normal diet 4 hours after taking the study medications.