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

April 8, 2014 updated by: Tobira Therapeutics, Inc.

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Miami, Florida, United States, 33126
        • SeaView Research, Inc.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / 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: Midazolam
Other Names:
  • Versed
  • Dormicum
  • Hypnovel
Drug: Dolutegravir
Other Names:
  • DTG
Drug: Cenicriviroc
Other Names:
  • CVC
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: Dolutegravir
Other Names:
  • DTG
Drug: Cenicriviroc
Other Names:
  • CVC

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetic Assessment of Cenicriviroc
Time Frame: 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.
0 (predose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, & 24 hours postdose on Days 10 and 20
Pharmacokinetic Assessment of Dolutegravir
Time Frame: 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.
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
Time Frame: 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.
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
Time Frame: 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).
Participants will be followed upon taking first dose of study medication until the follow-up visit, an expected average of 5 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tobira Therapeutics, Inc.

Collaborators

ViiV Healthcare

Investigators

  • Principal Investigator: Audrey Martinez, MD, SeaView Research, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2013

Primary Completion (Actual)

May 1, 2013

Study Completion (Actual)

May 1, 2013

Study Registration Dates

First Submitted

March 25, 2013

First Submitted That Met QC Criteria

April 4, 2013

First Posted (Estimate)

April 9, 2013

Study Record Updates

Last Update Posted (Estimate)

April 9, 2014

Last Update Submitted That Met QC Criteria

April 8, 2014

Last Verified

April 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TBR 652-1-110

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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