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

Sponsor

Tobira Therapeutics, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01827540

Collaborator

ViiV Healthcare (Industry)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV-infection/AIDS	Drug: Cenicriviroc Drug: Dolutegravir Drug: Midazolam	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

Non-Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Official Title:

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

Study Start Date :

Mar 1, 2013

Actual Primary Completion Date :

May 1, 2013

Actual Study Completion Date :

May 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cenicriviroc + Midazolam, and CVC + DTG 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 Other Names: CVC Drug: Dolutegravir Other Names: DTG Drug: Midazolam Other Names: Dormicum Hypnovel Versed
Experimental: Dolutegravir , and DTG + CVC 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 Other Names: CVC Drug: Dolutegravir Other Names: DTG

Arm

Intervention/Treatment

Experimental: Cenicriviroc + Midazolam, and CVC + DTG

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

Other Names:

CVC

Drug: Dolutegravir

Other Names:

DTG

Drug: Midazolam

Other Names:

Dormicum

Hypnovel

Versed

Experimental: Dolutegravir , and DTG + CVC

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

Other Names:

CVC

Drug: Dolutegravir

Other Names:

DTG

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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