The Interaction of Two HIV Medications With Blood Clot Medications in Healthy Volunteers
- People who have the human immunodeficiency virus (HIV) often take several medications to control their disease. They may also need to take medicine to prevent blood clots. Taking both kinds of medicine together can cause bleeding or other problems. But this might not happen if the medications are taken at different times. Researchers will study two particular HIV drugs (ritonavir and cobicistat) and how they interact with blood clot medications.
-To understand how HIV medicine and blood clot medicine interact, so doctors can choose what to prescribe for people who take both.
- Healthy adults between 18 and 70 years old who are not on any medications.
- Participants will be screened with a physical exam and medical history. Blood samples will be collected. Urine samples will be collected from participants who might become pregnant.
- Participants will visit the National Institutes of Health 7 times after the screening visit. Three visits will last about 12 hours. The other 4 will last about 1 hour.
- Participants will take a daily dose of either study medication for 22 days. They will keep a diary of medicine they take and any side effects.
- Treatment will be monitored with blood tests over about 2 months.
- When the study of one drug is completed, the next drug study will begin with a different group of participants.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||The Influence of Cobicistat or Ritonavir on Dabigatran Pharmacokinetics and Pharmacodynamics in Healthy Volunteers|
- To characterize dabigatran pharmacokinetics alone and in combination with ritonavir or cobicistat, respectively, using 2 different dosing strategies, in healthy volunteers. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
|Study Start Date:||June 2013|
|Estimated Study Completion Date:||January 2014|
|Estimated Primary Completion Date:||January 2014 (Final data collection date for primary outcome measure)|
Advances in antiretroviral (ARV) pharmacotherapy have translated to increased longevity and improved quality of life in people living with HIV; hence, elderly individuals comprise an increasing proportion of today s HIV population. Moreover, HIV infection itself has become recognized as a condition characterized by a hypercoaguable state and premature immunologic aging. Potential interactions between ARVs and anticoagulant medications are of particular concern considering that many elderly, and even non-elderly HIV patients will require short-term or chronic anticoagulation to prevent and/or treat systemic embolism. Dabigatran, administered as dabigatran etexilate, is an oral irreversible, competitive direct thrombin inhibitor, which has been shown to be superior to warfarin, and non-inferior to enoxaparin, in preventing thromboembolism in patients with atrial fibrillation and undergoing orthopedic surgery, respectively.
While dabigatran itself is not a substrate of Permeability-glycoprotein (P-gp), its inactivepro-drug, dabigatran etexilate, is a substrate of P-gp. Co-administration of dabigatran etexilate with P-gp modulators has resulted in significant changes in dabigatran exposure. The pharmacokinetic enhancers, ritonavir and cobicistat, as inhibitors of P-gp, are expected to increase plasma concentrations of dabigatran; however, neither agent has been studied in combination with dabigatran etexilate, to date. Hence, the purpose of this study is to determine whether the separate co-administration of ritonavir or cobicistat with dabigatran etexilate increases the systemic exposure of dabigatran in healthy volunteers, and if so, whether adjusting the administration times of these medications can circumvent this interaction.
In this open-label study, 32 healthy volunteers will be assigned to 1 of 2 groups. Group A will consist of 16 subjects who will take 22 days of ritonavir; Group B will consist of 16 subjects who will take 22 days of cobicistat. All subjects will receive 3 separated single doses of dabigatran etexilate. Pharmacokinetic (PK) and pharmacodynamics (PD) sampling for dabigatran will occur on Days 0 1, Day 19 1 20, and Day 26 1 27.
The PD effects of dabigatran will be characterized via ecarin clotting time (ECT) measurements. Dabigatran PK/PD parameters will be determined using non-compartmental methods with the WinNonlin professional computer program (version 5.2; Pharsight Corporation, Mountain View, CA). The following PK/PD parameters will be compared between the groups: area under the curve from 0 to 24 hours (AUC0-24), maximum total dabigatran plasma concentration (Cmax), area under the curve from 0 to infinity hours (AUC0- ), time to maximum plasma concentration (tmax), terminal half-life (T (Omega)), apparent oral clearance (CL/F), area under the effect curve from 0 to 24 hours (AUEC0-24), and the maximum effect ratio over baseline (ERmax).
|Contact: Maryellen McManus, R.N.||(301) firstname.lastname@example.org|
|Contact: Scott R Penzak, Pharm.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org|
|Principal Investigator:||Scott R Penzak, Pharm.D.||National Institutes of Health Clinical Center (CC)|