HIV-infection/AIDS
Conditions
Keywords
HIV/AIDS, Cenicriviroc (CVC), Dolutegravir (DTG), Midazolam, Healthy Subjects
Brief summary
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
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.
Interventions
Sponsors
ViiV Healthcare
Tobira Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Provide written informed voluntary consent 2. Adult male and female healthy volunteers 3. Body mass index (BMI) ≥ 18.0 and ≤ 30.0 kg/m2. 4. Be in good general health with no clinically relevant abnormalities 5. Agree to comply with study procedures and restrictions
Exclusion criteria
1. Any disease or condition that might affect drug absorption, metabolism, or excretion, or clinically significant cardiovascular as determined by investigator 2. History of stomach or intestinal surgery, except for fully healed appendectomy and/or cholecystectomy which will be allowed 3. Clinically significant illness or clinically significant surgery within 4 weeks before the administration of study medication 4. Known or suspected hypersensitivity or allergic reaction to any of the components of CVC or DTG tablets, or midazolam syrup 5. Serum ALT, AST, or bilirubin values greater than or equal to Division of Acquired Immunodeficiency Syndrome (DAIDS) grade 1 at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Assessment of Cenicriviroc | 0 (predose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, & 24 hours postdose on Days 10 and 20 | 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. |
| Pharmacokinetic Assessment of Dolutegravir | 0 (predose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, & 24 hours postdose on Days 10 and 20 | 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. |
| Pharmacokinetic Assessment of Midazolam and alpha-hydroxymidazolam | 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 | PK profile will be calculated (Group 1 only) based on plasma midazolam & alpha-hydroxymidazolam exposure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with adverse events | Participants will be followed upon taking first dose of study medication until the follow-up visit, an expected average of 5 weeks | 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). |
Countries
United States
Outcome results
None listed