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

This study has been completed.
Sponsor:
Collaborator:
ViiV Healthcare
Information provided by (Responsible Party):
Tobira Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT01827540
First received: March 25, 2013
Last updated: April 8, 2014
Last verified: April 2014
  Purpose

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 Intervention Phase
HIV-infection/AIDS
Drug: Cenicriviroc
Drug: Dolutegravir
Drug: Midazolam
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Tobira Therapeutics, Inc.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 0 (predose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, & 24 hours postdose on Days 10 and 20 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    PK profile will be calculated (Group 1 only) based on plasma midazolam & alpha-hydroxymidazolam exposure.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

    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).



Enrollment: 20
Study Start Date: March 2013
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: CVC
Drug: Dolutegravir
Other Name: 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 Name: CVC
Drug: Dolutegravir
Other Name: DTG

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.
  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01827540

Locations
United States, Florida
SeaView Research, Inc.
Miami, Florida, United States, 33126
Sponsors and Collaborators
Tobira Therapeutics, Inc.
ViiV Healthcare
Investigators
Principal Investigator: Audrey Martinez, MD SeaView Research, Inc.
  More Information

No publications provided

Responsible Party: Tobira Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT01827540     History of Changes
Other Study ID Numbers: TBR 652-1-110
Study First Received: March 25, 2013
Last Updated: April 8, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Tobira Therapeutics, Inc.:
HIV/AIDS
Cenicriviroc (CVC)
Dolutegravir (DTG)
Midazolam
Healthy Subjects

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Dolutegravir
Midazolam
Adjuvants, Anesthesia
Anesthetics
Anesthetics, General
Anesthetics, Intravenous
Anti-Anxiety Agents
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Central Nervous System Agents
Central Nervous System Depressants
Enzyme Inhibitors
GABA Agents
GABA Modulators
HIV Integrase Inhibitors
Hypnotics and Sedatives
Integrase Inhibitors

ClinicalTrials.gov processed this record on October 20, 2014