The Interaction of Two HIV Medications With Blood Clot Medications in Healthy Volunteers

NCT01896622 | Completed Phase 1

• 2 other identifiers: 13016013-CC-0160
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- 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. Objectives:

• To understand how HIV medicine and blood clot medicine interact, so doctors can choose what to prescribe for people who take both. Eligibility: \- Healthy adults between 18 and 70 years old who are not on any medications. Design:
• 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.

Conditions

HIV

Keywords

Dabigatran Etexilate; Ritonavir; Cobicistat; P-Glycoprotein

Outcome Measures

Primary Outcomes (1)

• To characterize dabigatran pharmacokinetics alone and in combination with ritonavir or cobicistat, respectively, using 2 different dosing strategies, in healthy volunteers.

  Days 0-1, Days 19-20, Days 26-27

Secondary Outcomes (1)

• To characterize dabigatran pharmacodynamics (as measured by ECT) alone and in combination with RTV or COBI, respectively, using 2 different dosing strategies in healthy volunteers

  Days 0-1, Days 19-20, Days 26-27

Study Arms (2)

A

EXPERIMENTAL

Ritonavir

Drug: Ritonavir

B

EXPERIMENTAL

Cobicistat

Drug: Cobicistat

Interventions

Ritonavir DRUG

Impact on dabigatran PK/PD

A

Cobicistat DRUG

Impact on dabigatran PK/PD

B

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A subject will be considered eligible for this study only if all of the following criteria are met:
• Between the ages 18 70 years.
• Judged to be healthy based on medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory tests (liver function tests \[LFTs\] less than or equal to 2 times upper limit of normal \[ULN\], serum creatinine \[sCr\] less than or equal to ULN.
• Subject agrees to storage of specimens for future research.
• Negative serum or urine pregnancy test for females of child-bearing potential.
• For female subjects, willing to prevent pregnancy by (a) practicing abstinence or (b) using effective non-hormonal and/or barrier methods of birth control, during the study period.

You may not qualify if:

• A subject will be ineligible for this study if 1, or more, of the following criteria are met:
• History of HIV exposure/infection, as determined by positive ELISA/ Western Blot.
• History or presence of any of the following:
• gastrointestinal disease, that is uncontrolled or requires daily treatment with medication (pancreatitis, peptic ulcer disease, etc.)
• hepatitis (as assessed by patient interview) or hepatic impairment
• renal impairment (chronic or acute renal failure or insufficiency)
• respiratory disease, that is uncontrolled or requires daily treatment with medication (asthma, chronic obstructive pulmonary disease, etc.)
• cardiovascular disease (hypertension \[systolic blood pressure \>140 mmHg or diastolic blood pressure \>90 mmHg\], heart failure,arrhythmia, etc.)
• metabolic disorders (diabetes mellitus, etc.)
• immunologic disorders
• hormonal disorders
• psychiatric illness, that would interfere with his or her ability to comply with study procedures or that requires daily treatment with medication
• seizure disorder, with the exception of childhood febrile seizures
• malignancy, or P-3 Pharmacoenhancers \& Pradaxa, a P-gp Substrate 26
• any other condition that may interfere with the interpretation of the study results, or not be in the best interest of the subject in the opinion of the Investigator.

Sponsors & Collaborators

• National Institutes of Health Clinical Center (CC): lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Ding R, Tayrouz Y, Riedel KD, Burhenne J, Weiss J, Mikus G, Haefeli WE. Substantial pharmacokinetic interaction between digoxin and ritonavir in healthy volunteers. Clin Pharmacol Ther. 2004 Jul;76(1):73-84. doi: 10.1016/j.clpt.2004.02.008.

  PMID: 15229466 BACKGROUND

• Hartter S, Sennewald R, Nehmiz G, Reilly P. Oral bioavailability of dabigatran etexilate (Pradaxa((R)) ) after co-medication with verapamil in healthy subjects. Br J Clin Pharmacol. 2013 Apr;75(4):1053-62. doi: 10.1111/j.1365-2125.2012.04453.x.

  PMID: 22946890 BACKGROUND

• Lepist EI, Phan TK, Roy A, Tong L, Maclennan K, Murray B, Ray AS. Cobicistat boosts the intestinal absorption of transport substrates, including HIV protease inhibitors and GS-7340, in vitro. Antimicrob Agents Chemother. 2012 Oct;56(10):5409-13. doi: 10.1128/AAC.01089-12. Epub 2012 Jul 30.

  PMID: 22850510 BACKGROUND

• Kumar P, Gordon LA, Brooks KM, George JM, Kellogg A, McManus M, Alfaro RM, Nghiem K, Lozier J, Hadigan C, Penzak SR. Differential Influence of the Antiretroviral Pharmacokinetic Enhancers Ritonavir and Cobicistat on Intestinal P-Glycoprotein Transport and the Pharmacokinetic/Pharmacodynamic Disposition of Dabigatran. Antimicrob Agents Chemother. 2017 Oct 24;61(11):e01201-17. doi: 10.1128/AAC.01201-17. Print 2017 Nov.

  PMID: 28848011 DERIVED

MeSH Terms

Interventions

Ritonavir; Cobicistat

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbamates; Acids, Acyclic; Carboxylic Acids

Study Officials

• Colleen M Hadigan, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2013
• First Posted: July 11, 2013
• Study Start: June 18, 2013
• Primary Completion: January 17, 2017
• Study Completion: January 17, 2017
• Last Updated: July 2, 2017

Record last verified: 2017-01-17

Locations

US (1)