Drug Interaction Potential Between Dolutegravir and Simeprevir in HIV/HCV Seronegative Volunteers

Study Overview
=================
Brief Summary
-----------------
The investigator believes simeprevir concentrations are unchanged when administered in combination with dolutegravir relative to administration alone. The investigator believes dolutegravir concentrations are unchanged when administered in combination with simeprevir. Additionally, the investigator believes simeprevir and dolutegravir are safe when administered alone and in combination.

Detailed Description
-----------------
To investigate the potential for drug interactions between simeprevir and dolutegravir, participants will receive each drug alone and the drugs in combination for 7 days. The pharmacokinetics of simeprevir and dolutegravir when given in combination vs. alone will be compared.

Official Title
-----------------
Drug Interaction Potential Between Dolutegravir and Simeprevir in HIV/Hepatitis C Virus (HCV) Seronegative Volunteers

Conditions
-----------------
HIV, Hepatitis C

Intervention / Treatment
-----------------
* Drug: dolutegravir
* Drug: simeprevir


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and women ages 18-60 years Absence of HIV-1 and HCV antibodies at screening, Ability and willingness to give written informed consent before the first trial-related activity. Exclusion Criteria: Pregnancy Breastfeeding Active alcohol or drug abuse that, in the opinion of the investigators, would interfere with adherence to study requirements Participation in any investigational drug study within 30 days prior to study entry Currently active or chronic gastrointestinal, cardiovascular, neurologic, psychiatric, metabolic, renal, hepatic, respiratory, inflammatory, or infectious disease or malignancy requiring pharmacologic treatment, and/or if in the opinion of the investigator, would affect study participation, safety, or integrity of results Use of concomitant medication, including investigational, prescription, and over-the-counter products and dietary supplements with the following exceptions: aspirin, acetaminophen, ibuprofen, hormonal oral contraceptives Concomitant medications other than those listed above must have been discontinued at least 14 days before study entry Currently active dermatitis or urticaria or diagnosis of eczema or psoriasis, History of significant drug allergy (i.e., anaphylaxis and/or angioedema) Subjects with the following laboratory abnormalities at screening as defined by the 2004 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS grading table) and in accordance with the normal ranges of the trial clinical laboratory: serum creatinine grade 1 or greater (≥ 1.1 x upper limit of laboratory normal range (ULN)); hemoglobin grade 1 or greater (≤ 10.9 g/dL); platelet count grade 1 or greater (≤ 124.999 x 109/L); absolute neutrophil count grade 1 or greater (≤ 1.3 x 109/L); aspartate aminotransferase (AST) or alanine aminotransferase (ALT) grade 1 or greater (≥ 1.25 x ULN); total bilirubin grade 1 or greater (≥ 1.1 x ULN), any other laboratory abnormality of grade 2 or above.

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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1a<br>Sequence 1,2,3: simeprevir only, then dolutegravir only, then both simeprevir and dolutegravir. | Drug: dolutegravir<br>* dolutegravir tablets 50mg, once daily x 7 days.<br>Drug: simeprevir<br>* simeprevir tablets 150mg, once daily x 7 days.<br>|
| Experimental: Sequence 1b<br>Sequence 1,3,2: simeprevir only, then both simeprevir and dolutegravir, then dolutegravir only. | Drug: dolutegravir<br>* dolutegravir tablets 50mg, once daily x 7 days.<br>Drug: simeprevir<br>* simeprevir tablets 150mg, once daily x 7 days.<br>|
| Experimental: Sequence 2a<br>Sequence 2,1,3: dolutegravir only, then simeprevir only, then both simeprevir and dolutegravir. | Drug: dolutegravir<br>* dolutegravir tablets 50mg, once daily x 7 days.<br>Drug: simeprevir<br>* simeprevir tablets 150mg, once daily x 7 days.<br>|
| Experimental: Sequence 2b<br>Sequence 2,3,1: dolutegravir only, then both simeprevir and dolutegravir, then simeprevir only. | Drug: dolutegravir<br>* dolutegravir tablets 50mg, once daily x 7 days.<br>Drug: simeprevir<br>* simeprevir tablets 150mg, once daily x 7 days.<br>|
| Experimental: Sequence 3a<br>Sequence 3,1,2: both simeprevir and dolutegravir, then simeprevir only, then dolutegravir only. | Drug: dolutegravir<br>* dolutegravir tablets 50mg, once daily x 7 days.<br>Drug: simeprevir<br>* simeprevir tablets 150mg, once daily x 7 days.<br>|
| Experimental: Sequence 3b<br>Sequence 3,2,1: Both simeprevir and dolutegravir, then dolutegravir only, then simeprevir only. | Drug: dolutegravir<br>* dolutegravir tablets 50mg, once daily x 7 days.<br>Drug: simeprevir<br>* simeprevir tablets 150mg, once daily x 7 days.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Simeprevir AUC Pharmacokinetics | Determine simeprevir area-under-the concentration time curve (AUC) when administered alone and when being co-administered with Dolutegravier. | Pre-dose and, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose on day 7 | 
| Dolutegravir AUC Pharmacokinetics | Determine Dolutegravir area-under-the concentration time curve (AUC) when administered alone and when co-administered with simeprevir. | Pre-dose and, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose on day 7 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
dolutegravir, simeprevir, HIV, HCV