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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. The completion date has passed and the status has not been verified in more than two years.
Verified March 2010 by St. James's Hospital, Ireland.
Recruitment status was:  Recruiting
Sponsor:
ClinicalTrials.gov Identifier:
NCT01105611
First Posted: April 16, 2010
Last Update Posted: July 21, 2011
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by:
St. James's Hospital, Ireland
  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
Intervention Model: Parallel Assignment
Masking: None (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 ]
  • Incidence of grade 3-4 liver function test (LFT) elevations [ Time Frame: 12 weeks ]
  • Incidence of grade 3-4 liver function test (LFT) elevations [ Time Frame: 24 weeks ]
  • Incidence of grade 3-4 liver function test (LFT) elevations [ Time Frame: 36 weeks ]
  • Incidence of grade 3-4 liver function test (LFT) elevations [ Time Frame: 48 weeks ]
  • Incidence of grade 3-4 liver function test (LFT) elevations [ Time Frame: 60 weeks ]
  • Incidence of grade 3-4 liver function test (LFT) elevations [ Time Frame: 72 weeks ]
  • Incidence of grade 3-4 liver function test (LFT) elevations [ Time Frame: 84 weeks ]
  • Incidence of grade 3-4 liver function test (LFT) elevations [ Time Frame: 96 weeks ]
  • Viral suppression [ Time Frame: 24 weeks ]
    Viral suppression is defined as HIV-1 RNA less than 50 copies per mL


Secondary Outcome Measures:
  • Viral suppression [ Time Frame: 48 weeks ]
    Viral suppression is defined as HIV- RNA less than 50 copies per mL.

  • Immunologic response [ Time Frame: 96 weeks ]
    Recovery of CD4 count

  • Overall safety in patients with mild to moderate hepatic impairment [ Time Frame: 48 weeks ]
  • Outpatient retention rates [ Time Frame: 96 weeks ]
  • QTc interval changes [ Time Frame: 4 weeks ]
    Effects of pharmacological intervention on corrected QT interval on electrocardiogram

  • Immunologic response [ Time Frame: 24 weeks ]
  • Immunologic response [ Time Frame: 48 weeks ]

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

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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:
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Lennox JL, DeJesus E, Lazzarin A, Pollard RB, Madruga JV, Berger DS, Zhao J, Xu X, Williams-Diaz A, Rodgers AJ, Barnard RJ, Miller MD, DiNubile MJ, Nguyen BY, Leavitt R, Sklar P; STARTMRK investigators. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial. Lancet. 2009 Sep 5;374(9692):796-806. doi: 10.1016/S0140-6736(09)60918-1. Epub 2009 Aug 3. Erratum in: Lancet. 2009 Dec 19-2010 Jan 1;374(9707):2054. Lancet. 2009 Sep 5;374(9692):786.
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Waldrop-Valverde D, Valverde E. Homelessness and psychological distress as contributors to antiretroviral nonadherence in HIV-positive injecting drug users. AIDS Patient Care STDS. 2005 May;19(5):326-34.
Lucas GM, Cheever LW, Chaisson RE, Moore RD. Detrimental effects of continued illicit drug use on the treatment of HIV-1 infection. J Acquir Immune Defic Syndr. 2001 Jul 1;27(3):251-9.
Lucas GM, Griswold M, Gebo KA, Keruly J, Chaisson RE, Moore RD. Illicit drug use and HIV-1 disease progression: a longitudinal study in the era of highly active antiretroviral therapy. Am J Epidemiol. 2006 Mar 1;163(5):412-20. Epub 2006 Jan 4.
Lucas GM, Mullen BA, Weidle PJ, Hader S, McCaul ME, Moore RD. Directly administered antiretroviral therapy in methadone clinics is associated with improved HIV treatment outcomes, compared with outcomes among concurrent comparison groups. Clin Infect Dis. 2006 Jun 1;42(11):1628-35. Epub 2006 Apr 28.
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Kassahun K, McIntosh I, Cui D, Hreniuk D, Merschman S, Lasseter K, Azrolan N, Iwamoto M, Wagner JA, Wenning LA. Metabolism and disposition in humans of raltegravir (MK-0518), an anti-AIDS drug targeting the human immunodeficiency virus 1 integrase enzyme. Drug Metab Dispos. 2007 Sep;35(9):1657-63. Epub 2007 Jun 25.
Iwamoto M, Wenning LA, Petry AS, Laethem M, De Smet M, Kost JT, Merschman SA, Strohmaier KM, Ramael S, Lasseter KC, Stone JA, Gottesdiener KM, Wagner JA. Safety, tolerability, and pharmacokinetics of raltegravir after single and multiple doses in healthy subjects. Clin Pharmacol Ther. 2008 Feb;83(2):293-9. Epub 2007 Aug 22.
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Iwamoto M, Hanley WD, Petry AS, Friedman EJ, Kost JT, Breidinger SA, Lasseter KC, Robson R, Lunde NM, Wenning LA, Stone JA, Wagner JA. Lack of a clinically important effect of moderate hepatic insufficiency and severe renal insufficiency on raltegravir pharmacokinetics. Antimicrob Agents Chemother. 2009 May;53(5):1747-52. doi: 10.1128/AAC.01194-08. Epub 2009 Feb 17.
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DAD Study Group, Friis-Møller N, Reiss P, Sabin CA, Weber R, Monforte Ad, El-Sadr W, Thiébaut R, De Wit S, Kirk O, Fontas E, Law MG, Phillips A, Lundgren JD. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med. 2007 Apr 26;356(17):1723-35.
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Anson BD, Ackerman MJ, Tester DJ, Will ML, Delisle BP, Anderson CL, January CT. Molecular and functional characterization of common polymorphisms in HERG (KCNH2) potassium channels. Am J Physiol Heart Circ Physiol. 2004 Jun;286(6):H2434-41. Epub 2004 Feb 19.
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Nordin C, Kohli A, Beca S, Zaharia V, Grant T, Leider J, Marantz P. Importance of hepatitis C coinfection in the development of QT prolongation in HIV-infected patients. J Electrocardiol. 2006 Apr;39(2):199-205. Epub 2005 Nov 28.
Iwamoto M, Kost JT, Mistry GC, Wenning LA, Breidinger SA, Marbury TC, Stone JA, Gottesdiener KM, Bloomfield DM, Wagner JA. Raltegravir thorough QT/QTc study: a single supratherapeutic dose of raltegravir does not prolong the QTcF interval. J Clin Pharmacol. 2008 Jun;48(6):726-33. doi: 10.1177/0091270008318007. Epub 2008 Apr 25.

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 ( EudraCT Number )
First Submitted: April 14, 2010
First Posted: April 16, 2010
Last Update Posted: July 21, 2011
Last Verified: March 2010

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
Hepatitis
Hepatitis A
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Lentivirus Infections
Retroviridae Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Ritonavir
Atazanavir Sulfate
HIV Protease Inhibitors
Raltegravir Potassium
Protease Inhibitors
Methadone
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents


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