A Proof of Concept Study to Evaluate the Antiviral Activity, Safety, and Pharmacokinetics of the CCR5 Antagonist TBR 652 in HIV 1-Infected, Antiretroviral Treatment-Experienced, CCR5 Antagonist-Naïve Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tobira Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT01092104
First received: March 22, 2010
Last updated: July 3, 2013
Last verified: July 2013
  Purpose

A double-blind, randomized, placebo-controlled, dose-escalating study to assess the antiviral activity, safety, tolerability, and pharmacokinetics (PK) of the CCR5 antagonist TBR 652 monotherapy dosed orally once daily (QD) for 10 days in HIV 1-infected, antiretroviral treatment-experienced, CCR5 antagonist-naïve patients.


Condition Intervention Phase
HIV-1 Infection
Drug: TBR-652
Drug: TBR-652 Matching Placebo
Drug: TBR-652 50 mg
Drug: TBR-652 75 mg
Drug: TBR-652 100 mg
Drug: TBR-652 150 mg
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Proof of Concept, Multiple Dose-Escalating Study to Evaluate the Antiviral Activity, Safety, and Pharmacokinetics of the CCR5 Antagonist TBR 652 in HIV 1-Infected, Antiretroviral Treatment-Experienced, CCR5 Antagonist-Naïve Patients

Resource links provided by NLM:


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

Primary Outcome Measures:
  • HIV-1 RNA Change from Baseline [ Time Frame: 10 days ] [ Designated as safety issue: No ]

Enrollment: 52
Study Start Date: February 2009
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TBR-652 25 mg QD
TBR 25 mg QD for 10 days
Drug: TBR-652
TBR-652 25 mg
Placebo Comparator: Placebo
Matching Placebo QD for 10 days
Drug: TBR-652 Matching Placebo
Matching Placebo
Experimental: TBR-652 50 mg QD
TBR-652 50 mg QD for 10 days
Drug: TBR-652 50 mg
TBR-652 50 mg QD for 10 days
Experimental: TBR-652 75 mg QD
TBR-652 75 mg QD for 10 days
Drug: TBR-652 75 mg
TBR-652 75 mg QD for 10 days
Experimental: TBR-652 100 mg QD
TBR-652 100 mg QD for 10 days
Drug: TBR-652 100 mg
TBR-652 100 mg QD for 10 days
Experimental: TBR-652 150 mg
TBR-652 150 mg QD for 10 days
Drug: TBR-652 150 mg
TBR-652 150 mg QD for 10 days

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. No clinically significant findings on Screening evaluations (clinical, laboratory, and ECG), which in the opinion of the Investigator would interfere with the subject's ability to comply with the protocol.
  2. Antiretroviral treatment-experienced; no antiretroviral therapy for at least 6 weeks prior to study entry.
  3. CCR5 antagonist therapy naive.
  4. CD4 cell count >/= 250 cells/mm3 during Screening (within 30 days prior to first dose).
  5. Two separate qualifying plasma HIV 1 RNA levels >/= 5,000 copies/mL within 45 days prior to first dose.
  6. Females who are not of reproductive potential (documented to be surgically sterile or postmenopausal [defined as amenorrhea ≥ 1 year and follicle stimulating hormone {FSH} ≥ 30 mU/mL]).
  7. Females of child-bearing potential may be enrolled following a negative serum pregnancy test. If participating in activity that could lead to pregnancy, males and females shall agree to use two forms of barrier method contraception during the trial and for 2 months after stopping the medication.

Exclusion Criteria:

  1. Presence of CXCR4- or dual/mixed-tropic HIV 1 virus.
  2. Active CDC category C disease (except cutaneous Kaposi's sarcoma not requiring systemic therapy during the trial).
  3. History of infection with hepatitis B or hepatitis C virus, history of cirrhosis, or any known active or chronic liver disease. NOTE: Hepatitis B vaccinated patients are eligible.
  4. Serum ALT or AST values greater than Grade 1 or bilirubin values greater than the upper limit of normal (ULN) at Screening.
  5. History of HIV-2.
  6. Recent history (< 30 days prior to study drug administration) of clinically significant infection.
  7. Pregnant females or females who are breastfeeding.
  8. Treatment with immunomodulating agents (such as systemic corticosteroids, interleukins, interferons) or any agent with known anti-HIV activity within 30 days prior to study drug administration.
  9. Treatment with any vaccine within 30 days of study drug administration.
  10. A positive pre-study drug screen, including amphetamines, barbiturates, cocaine, or PCP.
  11. Anticipated use of antacids during the trial and/or within 7 days prior to first dose of study drug.
  12. Current alcohol or drug use, which in the expert judgment of the investigator, will interfere with the patient's ability to comply with the protocol requirements.
  13. Inability, in the opinion of the investigator, to comply with the dosing schedule and protocol evaluations.
  14. Use of any experimental medications within 4 weeks prior to Screening.
  15. Current (within 30 days prior to the first dose of study drug) or anticipated use of antimetabolites; alkylating agents; or drugs, herbal preparations, and foods (including grapefruit) known to affect the CYP 3A4 or CYP 2C8 enzymes or P-glycoprotein transporters.
  16. History of clinically significant hepatic, metabolic, endocrine, renal, hematologic, pulmonary, gastrointestinal, or cardiovascular disorders (including ECG abnormalities).
  17. Uncontrolled hypertension.
  18. Presence of a malabsorption syndrome affecting drug absorption (e.g., Crohn's disease, chronic pancreatitis).
  19. History of malignancy with exception of cured basal or squamous cell carcinoma of the skin.
  20. Receipt of radiation or cytotoxic chemotherapeutic agents and not recovered from side effects prior to the first dose of study medication.
  21. Subjects who have used any over-the-counter medications (including phytotherapeutic, herbal, or plant-derived preparations) within 14 days prior to the first dose of study medication, unless approved by the Investigator, or who have used St. John's wort within 21 days prior to the first dose of study drug. (St. John's wort is prohibited during the study.)
  22. History or presence of an abnormal ECG.
  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.

No Contacts or Locations Provided
  More Information

Publications:
Responsible Party: Tobira Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT01092104     History of Changes
Other Study ID Numbers: 652-2-201
Study First Received: March 22, 2010
Last Updated: July 3, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 28, 2014