Safety and Efficacy Study Comparing Raltegravir to a Protease Inhibitor in Treatment-naïve, HIV/Hepatitis C Drug Users

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2010 by St. James's Hospital, Ireland.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
St. James's Hospital, Ireland
ClinicalTrials.gov Identifier:
NCT01105611
First received: April 14, 2010
Last updated: July 20, 2011
Last verified: March 2010
  Purpose

The purpose of this study is to compare how safe, tolerable, and effective a novel drug, raltegravir, is to a commonly used combination, atazanavir/ritonavir, as initial treatment in HIV/Hepatitis C co-infected injecting drug users on a methadone program.


Condition Intervention Phase
HIV Infections
Hepatitis C
Drug: Raltegravir
Drug: Atazanavir/Ritonavir
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Randomised Pilot Study Comparing the Efficacy, Safety and Tolerability of Raltegravir With Protease Inhibitor-based Therapy in Treatment-naïve, HIV/Hepatitis C Co-infected Injecting Drug Users Receiving Methadone

Resource links provided by NLM:


Further study details as provided by St. James's Hospital, Ireland:

Primary Outcome Measures:
  • Incidence of grade 3-4 liver function test (LFT) elevations [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
  • Incidence of grade 3-4 liver function test (LFT) elevations [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Incidence of grade 3-4 liver function test (LFT) elevations [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • Incidence of grade 3-4 liver function test (LFT) elevations [ Time Frame: 36 weeks ] [ Designated as safety issue: Yes ]
  • Incidence of grade 3-4 liver function test (LFT) elevations [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Incidence of grade 3-4 liver function test (LFT) elevations [ Time Frame: 60 weeks ] [ Designated as safety issue: Yes ]
  • Incidence of grade 3-4 liver function test (LFT) elevations [ Time Frame: 72 weeks ] [ Designated as safety issue: Yes ]
  • Incidence of grade 3-4 liver function test (LFT) elevations [ Time Frame: 84 weeks ] [ Designated as safety issue: Yes ]
  • Incidence of grade 3-4 liver function test (LFT) elevations [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
  • Viral suppression [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Viral suppression is defined as HIV-1 RNA less than 50 copies per mL


Secondary Outcome Measures:
  • Viral suppression [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Viral suppression is defined as HIV- RNA less than 50 copies per mL.

  • Immunologic response [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
    Recovery of CD4 count

  • Overall safety in patients with mild to moderate hepatic impairment [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Outpatient retention rates [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
  • QTc interval changes [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    Effects of pharmacological intervention on corrected QT interval on electrocardiogram

  • Immunologic response [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Immunologic response [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: August 2010
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Raltegravir
Raltegravir in combination with Tenofovir/Emtricitabine
Drug: Raltegravir
400mg orally twice daily. Number of cycles: unless toxicity or treatment failure occurs, there will be no anticipated treatment discontinuation.
Other Name: Isentress™
Active Comparator: Atazanavir/Ritonavir
Atazanavir 300mg orally once daily with Ritonavir 100mg orally once daily; together with combination of Tenofovir/Emtricitabine
Drug: Atazanavir/Ritonavir
Atazanavir 300mg orally once daily boosted with Ritonavir orally 100mg once daily. Number of cycles: unless toxicity or treatment failure occurs, there will be no anticipated treatment discontinuation.
Other Name: Reyataz™ (Atazanavir), Norvir™ (Ritonavir)

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  • Male or Female Patients Age ≥ 18 years old.
  • Naïve to antiretroviral treatment.
  • Subject must be willing and able to understand and provide written, informed consent prior to participation in the study.
  • Subjects must be on concurrent methadone maintenance therapy.
  • Documented HIV infection (antibody positive).
  • Documented Hepatitis C co-infection (PCR positive).
  • HIV RNA > 5,000.
  • Indication for starting ART according to guidelines.
  • Documented resistance profile taken at baseline and includes investigational medicinal products.
  • Females may be eligible for enrolment in the study if she is of:

    1. Non-childbearing potential; or, Child-bearing potential females must have a negative pregnancy test at initial screening and agree to an acceptable barrier and/or hormonal method of contraception; Sterilization

Exclusion Criteria:

  • Subject is in the initial acute phase of a CDC Clinical Category C infection at Baseline. Subjects may be enrolled provided they are receiving treatment for such infections and are clinically improving at the Baseline visit.
  • Concurrent treatment with an investigational drug or participation in another clinical trial.
  • Use of an investigational drug within 4 weeks or 5 half-lives, whichever is longer, preceding the first dose of investigational medicinal product.
  • Subject is, in the opinion of the investigator, unable to complete the study dosing period and protocol evaluations and assessments.
  • Subject has evidence of genotypic (as defined by the current ANRS AC-11 algorithm) resistance to raltegravir, atazanavir and ritonavir at screening.
  • Patients with alcohol and drug use problems that in the view of investigator will compromise participation in the study.
  • Elevated alanine aminotransferase (ALT) > 5 times upper limit of normal (ULN)
  • Subjects with severe hepatic impairment (Child-Pugh score > 9).
  • Subjects receiving treatment for HCV.
  • Subjects with concurrent HBV infection.
  • Subject is pregnant or breast feeding.
  • Subject suffers from any serious medical condition which would compromise the safety of the subject.
  • Subject has a pre-existing mental, physical, or substance abuse disorder that may interfere with the subject's ability to comply with the dosing schedule and protocol evaluations and assessments.
  • Subject has a condition or disorder which may interfere with drug absorption or render the subject unable to take oral medication.
  • Subject has any acute laboratory abnormality at screening, which, in the opinion of the Investigator, would preclude the subject's participation in the study of an investigational compound. Any verified Grade 4 laboratory abnormality would exclude a subject from study participation.
  • Subject has an estimated creatinine clearance < 50 mL/min via the Cockcroft-Gault method [Cockcroft, 1976].
  • Subject is receiving, or has received within 14 days prior to screen, any drug that has been classified as 'contraindicated' from use with RAL or ATV/RTV.
  • Subject has received treatment with radiation therapy or cytotoxic chemotherapeutic agents within 28 days prior to Screening, or has an anticipated need for these agents within the study period.
  • Subject has received treatment with an HIV-1 immunotherapeutic vaccine or any agents with documented activity against HIV-1 in vitro within 28 days prior to screening, or an anticipated need during the study.
  • Subjects who require treatment with any contraindicated medications within 14 days of commencement of investigational medicinal product, or an anticipated need during the study.
  • Subject has a history of allergy to any of the investigational medicinal products or any excipients therein.
  • Subject has prolonged QTc interval on screening electrocardiogram (repeated demonstration of a QTc interval >450ms in men and >470ms in women).
  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: NCT01105611

Contacts
Contact: Colm Bergin, MD, FRCPI +35314162507 cbergin@stjames.ie
Contact: James Woo, MB, MRCPI +353868108086 wooj@tcd.ie

Locations
Ireland
Department of Genitourinary Medicine and Infectious Diseases, St. James's Hospital Recruiting
Dublin, Ireland
Contact: Colm Bergin, MD, FRCPI    +35314162507    cbergin@stjames.ie   
Contact: James Woo, MB, MRCPI    +353868108086    wooj@tcd.ie   
Principal Investigator: Colm Bergin, MD, FRCPI         
Sub-Investigator: James Woo, MB, MRCPI         
Mater Misericordiae University Hospital Not yet recruiting
Dublin, Ireland
Contact: Patrick Mallon, MB FRCPI PhD    +35317166311    Paddy.Mallon@ucd.ie   
Principal Investigator: Patrick Mallon, MB FRCPI PhD         
Sponsors and Collaborators
St. James's Hospital, Ireland
Investigators
Principal Investigator: Colm Bergin, MD, FRCPI Department of Genitourinary Medicine and Infectious Diseases, St. James's Hospital, Dublin, Ireland
  More Information

Publications:

Responsible Party: Professor Colm Bergin, St. James's Hospital, Dublin, Ireland
ClinicalTrials.gov Identifier: NCT01105611     History of Changes
Other Study ID Numbers: CB-2010-01, 2010-018326-39
Study First Received: April 14, 2010
Last Updated: July 20, 2011
Health Authority: Ireland: Research Ethics Committee
Ireland: Irish Medicines Board

Keywords provided by St. James's Hospital, Ireland:
HIV
Hepatitis C
Co-infection
Intravenous drug users
Treatment-naïve
Methadone

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Hepatitis
Hepatitis A
Hepatitis C
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
Flaviviridae Infections
Methadone
Protease Inhibitors
Ritonavir
Atazanavir
HIV Protease Inhibitors
Analgesics, Opioid
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 22, 2014