Dolutegravir-Lamivudine as Dual Therapy in Naive HIV-Infected Patients: A Pilot Study (PADDLE)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified August 2014 by The Huesped Foundation
Sponsor:
Collaborator:
ViiV Healthcare
Information provided by (Responsible Party):
Pedro Cahn, The Huesped Foundation
ClinicalTrials.gov Identifier:
NCT02211482
First received: August 5, 2014
Last updated: August 6, 2014
Last verified: August 2014
  Purpose

The purpose of this study is to evaluate the antiviral efficacy, safety and tolerability of dual therapy with 3TC and DTG as initial therapy among naïve HIV patients


Condition Intervention Phase
HIV-1 Infection
Drug: dolutegravir, lamivudine
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Dolutegravir-Lamivudine as Dual Therapy in Naive HIV-Infected Patients: A Pilot Study

Resource links provided by NLM:


Further study details as provided by The Huesped Foundation:

Primary Outcome Measures:
  • Efficacy Outcome Measure [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Percentage of Participants with HIV-1 RNA levels of less than 50 copies/mL at week 48 by ITT analysis


Secondary Outcome Measures:
  • safety [ Time Frame: 48 week ] [ Designated as safety issue: Yes ]
    Frequency, type and severity of adverse events and laboratory abnormalities


Other Outcome Measures:
  • efficacy [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Proportion of patients with HIV-RNA <400 at week 24

  • safety [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    change in lipid profile between baseline and week 48.

  • efficacy [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Proportion of patients with HIV-1 RNA <1000 copies/mL at week 12

  • efficacy [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Number and type of resistance mutations in case of virologic failure (defined as a confirmed viral above 400 copies/mL after week 24 copies/mL or viral rebound at any timepoint)

  • efficacy [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Changes in CD4+ lymphocyte count between baseline and 48 weeks


Estimated Enrollment: 20
Study Start Date: October 2014
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Dolutegravir , lamivudine
Dolutegravir 50 mg QD plus lamivudine 300 mg QD
Drug: dolutegravir, lamivudine
single arm
Other Names:
  • dolutegravir
  • lamivudine

Detailed Description:

The purpose of this study is to compare the antiviral efficacy, safety and tolerability of dual therapy with 3TC and DTG as initial therapy among naïve HIV patients.

Data collected in this study would inform the development of larger studies designed to evaluate metabolic and long term safety, impact on inflammatory biomarkers, efficacy, safety and cost effectiveness of this strategy among naïve and suppressed patients.

Primary endpoint:Proportion of patients with HIV-1 RNA levels of less than 50 copies/mL at week 48.

Secondary endpoints: Frequency, type and severity of adverse events and laboratory abnormalities, Proportion of patients with HIV-1 RNA <1000 copies/mL at week 12, Proportion of patients with HIV-RNA <400 at week 24 Number and type of resistance mutations in case of virologic failure (defined as a confirmed viral above 400 copies/mL after week 24 copies/mL or viral rebound at any timepoint) Changes in CD4+ lymphocyte count between baseline and 48 weeks, Estimation of the viral decay compared to historical data.

  Eligibility

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

Inclusion Criteria:

  1. > 18 years of age
  2. Documented HIV-1 infection (positive ELISA plus a confirmatory Western Blot; or plasma HIV-1 RNA ≥10,000 copies/mL)
  3. Voluntarily signed and dated , IRB / IEC approved informed consent form
  4. Agrees not to take any other medication during the study
  5. Screening HIV RNA >5,000 copies/mL and ≤ 100,000 copies/ml
  6. Naïve to ARV therapies
  7. CD4 ≥200 cells/mL
  8. Subjects can comply with protocol requirements
  9. Subject's general medical condition, in the investigator's opinion, does not interfere with assessments and completion of the trial
  10. Patient is a male or a female not breastfeeding or pregnant
  11. A female, may be eligible if she:

    1. is of non-child-bearing potential
    2. is of child-bearing potential with a negative pregnancy test at Screening and Day 1 and agrees to use one of the following methods:

      • Complete abstinence from penile-vaginal intercourse from 2 weeks prior to administration of IP, throughout the study, and for at least 2 weeks after
      • Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide)
      • IUD and male condom
      • Male partner sterilization confirmed and male condom
      • Approved hormonal contraception and male condom
      • Any other method with published data showing that the expected failure rate is <1% per year and use male condom
      • Any contraception method must be used for at least 2 weeks after discontinuation of IP

Exclusion Criteria:

1. Genotypic resistance to lamivudine at screening,as per IAS -USA Panel 2013 2. Alcohol or drug use that might impact on adherence 3. Subjects positive for Hepatitis B at screening (+HBsAg), or anticipated need for Hepatitis C virus (HCV) therapy during the study 4. Lactating, pregnancy or fertile women willing to be pregnant 5. Concomitant use of lowering lipid drugs, interferon, interleukin-2, cytotoxic chemotherapy, Dofetilide (or pilsicainide ) or immunosuppressors at study entry 6. Grade 4 lab abnormalities 7. Primary HIV infection (indeterminate WB or previous negative HIV in the last 6 months.) 8. Opportunistic infection (CDC C category) or other disease and/or clinical condition that, in the investigator's opinion, would compromise the patient's safety or outcome of the study; including malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical intraepithelial neoplasia 9. Subjects who in the investigator's judgment, poses a significant suicidality risk 10. History or presence of allergy to the study drugs or their components or drugs of their class 11. Treatment with any of the following agents within 28 days of Screening: radiation therapy; cytotoxic chemotherapeutic agents; any immunomodulators that alter immune responses or treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening or exposure to an experimental drug or experimental vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of investigational product 12. 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 13. Alanine aminotransferase (ALT) >5 times the upper limit of normal (ULN), or ALT ≥ 3xULN and bilirubin ≥ 1.5xULN (with >35% direct bilirubin) 14. Creatinine clearance of <50 mL/min via Cockcroft-Gault method 15. Subjects with moderate to severe hepatic impairment (Class B or greater) as determined by Child-Pugh classification

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  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: NCT02211482

Contacts
Contact: Pedro Cahn, PhD 5411-49817777 pedro.cahn@huesped.org.ar

Locations
Argentina
Fundacion Huesped Not yet recruiting
Caba, Buenos Aires, Argentina, C1202ABB
Sponsors and Collaborators
The Huesped Foundation
ViiV Healthcare
Investigators
Principal Investigator: Pedro Cahn, PhD Fundacion Huesped
  More Information

No publications provided

Responsible Party: Pedro Cahn, PhD, The Huesped Foundation
ClinicalTrials.gov Identifier: NCT02211482     History of Changes
Other Study ID Numbers: FH-18
Study First Received: August 5, 2014
Last Updated: August 6, 2014
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica

Keywords provided by The Huesped Foundation:
HIV-1 infected patients
dual therapy

Additional relevant MeSH terms:
Lamivudine
Dolutegravir
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents
HIV Integrase Inhibitors
Integrase Inhibitors

ClinicalTrials.gov processed this record on September 30, 2014