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

HIV-infection/AIDS Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01827540
• Other study ID #: TBR 652-1-110
• Status: Completed
• Phase: Phase 1
• First received: March 25, 2013
• Last updated: April 8, 2014
• Start date: March 2013
• Est. completion date: May 2013

Study information

• Verified date: April 2014
• Source: Tobira Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: May 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label

Related Conditions & MeSH terms

• HIV-infection/AIDS

Intervention

Drug:
• Cenicriviroc

• Dolutegravir

• Midazolam

Locations

Country	Name	City	State
United States	SeaView Research, Inc.	Miami	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Tobira Therapeutics, Inc.	ViiV Healthcare

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Secondary	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	Yes