The Raltegravir and Ribavirin Pharmacokinetics (PK) Study

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to look at levels of both a new anti-HIV drug called raltegravir and an existing anti-hepatitis C drug called ribavirin to see if they affect the blood levels of each other when given separately and together. This is a phase I, open-label, prospective, three phase, pharmacokinetic study.

Detailed Description
-----------------
Phase I (study day 1 - 14): 14 healthy volunteers with a documented negative HIV-1 antibody test during screening procedures will be enrolled. On day 1, fasted subjects will be administered ribavirin 800 mg without food (witnessed dosing). This will be followed be a 12 hour detailed pharmacokinetic assessment; blood sampling drawn at 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 and 12 hours. This will be followed by a wash-out period. As steady state pharmacokinetics of ribavirin are not reached for several weeks, single dosing pharmacokinetics will be assessed in this study Phase II (study days 15 - 19): On day 15, subjects will commence raltegravir 400 mg twice daily. Subjects will attend for safety visits and witnessed dosing during this phase. Day 19 - after 4 days of dosing when steady state pharmacokinetics has been reached, subjects will attend for a 12 hour detailed pharmacokinetic visit where following witnessed administration of raltegravir 400 mg without food, blood sampling will be drawn at 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post dose for the assessment of raltegravir plasma exposure. Phase III (study day 20): • Subjects will be administered raltegravir 400 mg and ribavirin 800 mg without food. This will be followed by a 12 hour detailed pharmacokinetic assessment with blood sampling drawn at 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, and 12 hours.

Official Title
-----------------
A Prospective, Open-label, Three Phase Pharmacokinetic Study, to Assess the Pharmacokinetic Profile and Safety of Raltegravir 400 mg Twice Daily and Ribavirin 800 mg Once Daily, When Dosed Separately and Together in Healthy Volunteers

Conditions
-----------------
HIV Infections

Intervention / Treatment
-----------------
* Drug: Ribavirin
* Drug: Raltegravir


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The ability to understand and sign a written informed consent form, prior to participation in any screening procedures and must be willing to comply with all study requirements. Male or non-pregnant, non-lactating female. Between 18 to 60 years, inclusive. Subjects in good health upon medical history, physical exam, and laboratory testing and body mass index below 32. Female subjects who are heterosexually active and of childbearing potential (i.e., not surgically sterile or at least two years post menopausal) must practice contraception as follows from screening through completion of the study including 180 days following last dose of study drug: barrier contraceptives (condom, diaphragm with spermicide) oral combined contraceptive pill, implant or injectable hormonal contraceptive PLUS a barrier contraceptive Intrauterine device (IUD) or intrauterine system (IUS) PLUS a barrier contraceptive (or a partner who has been vasectomized for at least six months). Female subjects of childbearing potential must have a negative urine pregnancy test. Male subjects who are heterosexually active must use two forms of barrier contraception (e.g., condom with spermicide) during heterosexual intercourse, from screening through completion of the study including 180 days following last dose of study drug. Have no serologic evidence of HIV infection. Have no serologic evidence of active hepatitis B virus infection evidenced by negative hepatitis B surface antigen and no serologic evidence of hepatitis C virus infection through antibody testing. Have screening laboratory results (haematology, chemistry) that fall within the normal range of the central laboratory's reference ranges unless the results have been determined by the Investigator to have no clinical significance. Exclusion Criteria: Any serious or active medical or psychiatric illness which, in the opinion of the Investigator, would interfere with subject treatment, assessment, or compliance with the protocol. This would include any active clinically significant renal, cardiac, hepatic, pulmonary, vascular, metabolic (thyroid disorders, adrenal disease), immunodeficiency disorders, active infection, or malignancy. Have a body mass index (BMI) greater than 32 Previous participation in an investigational trial involving administration of any investigational compound within 1 month prior to the study screening. Clinically relevant alcohol or drug use (positive screening drug screen) or history of alcohol or drug use considered by the Investigator to be sufficient to hinder compliance with treatment, follow-up procedures or evaluation of adverse events. Smoking is permitted, but tobacco intake should remain consistent throughout the study. Any medication taken listed in Prior and Concomitant Medication section including over-the-counter medications and herbal products within 21 days of commencing study drug dosing with the exception of vitamins and/or paracetamol and/or hormonal contraceptives including the combined oral contraceptive pill, Depo-Provera and the Mirena intrauterine system. When a concomitant medication is necessary, this will be reviewed by the Investigator and if not contraindicated, may be continued at the same dose and frequency during the study period. History of drug sensitivity or drug allergy.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1_ribavirin<br>Treatment with Single dose ribavirin (800 mg) administered on day 1 | Drug: Ribavirin<br>* 800mg once daily<br>* Other names: Copegus;|
| Experimental: Phase2_raltegravir<br>Treatment with Raltegravir (400 mg twice daily) administered from days 15-19 | Drug: Raltegravir<br>* 400mg twice daily<br>|
| Experimental: Phase3_ribavirin+raltegravir<br>Treatment with Ribavirin (800 mg) and Raltegravir (400 mg) administered day 20 | Drug: Ribavirin<br>* 800mg once daily<br>* Other names: Copegus;Drug: Raltegravir<br>* 400mg twice daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ribavirin Maximum Plasma Concentration | Pharmacokinetic analyses of blood samples | Day 20 | 
| Raltegravir Maximum Plasma Concentration |  | Day 20 | 
| Ribavirin Minimum Plasma Concentration | Ribavirin minimum plasma concentration by pharmacokinetic analyses | Day 20 | 
| Raltegravir Minimum Plasma Concentrations | Raltegravir minimum plasma concentrations by pharmacokinetic analyses | Day 20 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Healthy Volunteers