Study of Dolutegravir (DTG) on PK of Cenicriviroc (CVC), and CVC on PK of DTG & on a Single Dose of Midazolam

Study Overview
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Brief Summary
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To evaluate the PK, safety and tolerability of Cenicriviroc (CVC) administered with and without Dolutegravir (DTG) and CVC with and without a single dose of Midazolam in healthy subjects.

Detailed Description
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Primary Objectives To evaluate the steady-state PK of CVC administered with and without DTG . To evaluate the steady-state PK of DTG administered with and without CVC . To evaluate the PK of a single dose of Midazolam administered with and without steady state CVC when both are administered orally. Secondary Objectives To evaluate the safety and tolerability of CVC administered with and without DTG. To evaluate the safety and tolerability of CVC administered with and without Midazolam.

Official Title
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A Phase I, Multiple-Dose, Open-Label, Crossover Study in Healthy Subjects to Assess the Effect of Dolutegravir (DTG) on the Pharmacokinetics (PK) of Cenicriviroc (CVC) and the Effect of CVC on the PK of DTG and on a Single Dose of Midazolam

Conditions
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HIV-infection/AIDS

Intervention / Treatment
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* Drug: Cenicriviroc
* Drug: Dolutegravir
* Drug: Midazolam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide written informed voluntary consent Adult male and female healthy volunteers Body mass index (BMI) ≥ 18.0 and ≤ 30.0 kg/m2. Be in good general health with no clinically relevant abnormalities Agree to comply with study procedures and restrictions Exclusion Criteria: Any disease or condition that might affect drug absorption, metabolism, or excretion, or clinically significant cardiovascular as determined by investigator History of stomach or intestinal surgery, except for fully healed appendectomy and/or cholecystectomy which will be allowed Clinically significant illness or clinically significant surgery within 4 weeks before the administration of study medication Known or suspected hypersensitivity or allergic reaction to any of the components of CVC or DTG tablets, or midazolam syrup Serum ALT, AST, or bilirubin values greater than or equal to Division of Acquired Immunodeficiency Syndrome (DAIDS) grade 1 at screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cenicriviroc + Midazolam, and CVC + DTG<br>Grp 1: CVC 150mg qd alone from Days 1-10; CVC 150mg qd + DTG 50mg qd from Days 11-20. A single dose of midazolam 5mg administered alone on Day -1 & w/ CVC 150mg on Day 9. | Drug: Cenicriviroc<br> <br> * Other names: CVC;Drug: Dolutegravir<br> <br> * Other names: DTG;Drug: Midazolam<br> <br> * Other names: Versed;|
| Experimental: Dolutegravir , and DTG + CVC<br>Grp 2: DTG 50 mg qd alone from Days 1-10, DTG 50 mg qd + CVC 150 mg qd from Days 11-20. | Drug: Cenicriviroc<br> <br> * Other names: CVC;Drug: Dolutegravir<br> <br> * Other names: DTG;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Assessment of Cenicriviroc | PK profile will be calculated based on CVC exposure. Trough (predose) CVC plasma samples will be obtained prior to dosing on Days 2-9 & 12-19. | 0 (predose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, & 24 hours postdose on Days 10 and 20 | 
| Pharmacokinetic Assessment of Dolutegravir | PK profile will be calculated based on DTG exposure. Trough (predose) DTG plasma samples will be obtained prior to dosing on Days 2-9 & 12-19. | 0 (predose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, & 24 hours postdose on Days 10 and 20 | 
| Pharmacokinetic Assessment of Midazolam and alpha-hydroxymidazolam | PK profile will be calculated (Group 1 only) based on plasma midazolam & alpha-hydroxymidazolam exposure. | 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 & 18 hours postdose on Day -1 and Day 9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events | Physical examinations, vital signs, ECGs, clinical laboratory tests, and AEs or serious AEs (SAEs) will be assessed at specified time points according to the Schedule of Procedures in the protocol. In addition, arterial oxygen saturation will be monitored by pulse oximetry for at least 2 hours after administration of midazolam on Days -1 and 9 in Group 1. For both groups, a final follow-up visit will occur 14 days (±3 days) after the last dose of study medication, or at the time of early termination (if applicable) to evaluate any remaining safety issue(s). | Participants will be followed upon taking first dose of study medication until the follow-up visit, an expected average of 5 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV/AIDS, Cenicriviroc (CVC), Dolutegravir (DTG), Midazolam, Healthy Subjects