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

• Status: Completed
• Trial end date: 2017-01-17
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: National Institutes of Health Clinical Center (CC)
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Cobicistat; Dabigatran; Ritonavir

Criteria

• INCLUSION CRITERIA:

A subject will be considered eligible for this study only if all of the following criteria are met:

1. Between the ages 18 70 years.

2. 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.

3. Subject agrees to storage of specimens for future research.

4. Negative serum or urine pregnancy test for females of child-bearing potential.

5. 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.

EXCLUSION CRITERIA:

A subject will be ineligible for this study if 1, or more, of the following criteria are met:

1. History of HIV exposure/infection, as determined by positive ELISA/ Western Blot.

2. 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.

3. History or presence of the following:

• bleeding/hematologic disorders (hemophilia, etc.)

• serious/major bleeding event (intracranial, gastrointestinal, as assessed by patient interview)

c. current increased risk of bleeding (as indicated by aPTT >1.5 times ULN], platelets, PLT, <150,000/mm3, or Hgb <11 g/dL)

d. for female subjects, menorrhagia

4. Planned invasive or surgical procedure within (prior to, or following) 28 days of study participation.

5. Fasting total cholesterol >270 mg/dL or fasting triglycerides >270 mg/dL.

6. Fasting glucose >125 mg/dL.

7. Concomitant routine therapy with any prescription, over-the-counter, herbal, or holistic medications, including hormonal contraceptives by any route, or any investigational drugs for 30 days prior to receipt of any study medications (Day 0).

1. Concomitant therapy (chronic or intermittent) with any prescription, over-the-counter, herbal, or holistic medications will not be allowed during the study duration

2. Intermittent use of acetaminophen and loperamide will be allowed to have been taken, according to each manufacturer s recommendations, within 30 days prior to study participation

3. Intermittent use of acetaminophen, loperamide, and/or an antiemetic (as approved by the Principal Investigator) will be allowed to be taken according to each manufacturer s recommendations during the study. As P-gp substrates, loperamide and certain anti-emetics (i.e. ondansetron), should not be taken on the days of pharmacokinetic blood sampling

4. A daily multivitamin with minerals will be allowed during the study

5. Receipt of influenza vaccination will be allowed prior, during,

and/or after the study

6. Use of topical medications that are not significantly absorbed systemically will be allowed if approved by the Principal Investigator

8. Inability to obtain venous access for sample collection.

9. Inability to swallow whole capsules and/or tablets.

10. Positive serum or urine pregnancy test or breastfeeding female.

11. The presence of persistent diarrhea or malabsorption that could interferewith the subject s ability to absorb drugs.

12. Drug or alcohol use that may impair safety or adherence.

13. Use of nicotine-containing tobacco products, including cigarettes and chewing tobacco.

14. History of intolerance or allergic reaction (rash; hives; swollen lips;difficulty breathing) to DE, RTV, or COBI.

15. Organ transplant recipient.