Clinical Trials

MainTitle

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

This study has been completed
Sponsor
The Huesped Foundation

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 10, 2017
Last Verified: August 2017
History of Changes
Purpose

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: Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Dolutegravir-Lamivudine as Dual Therapy in Naive HIV-Infected Patients: A Pilot Study

Further study details as provided by Pedro Cahn, The Huesped Foundation:

Primary Outcome Measures

  • Efficacy Outcome Measure [ Time Frame: 48 weeks ]
    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 ]
    Frequency, type and severity of adverse events and laboratory abnormalities
Other Outcome Measures:
  • efficacy [ Time Frame: 24 weeks ]
    Proportion of patients with HIV-RNA <400 at week 24
  • safety [ Time Frame: 48 weeks ]
    change in lipid profile between baseline and week 48.
  • efficacy [ Time Frame: 12 weeks ]
    Proportion of patients with HIV-1 RNA <1000 copies/mL at week 12
  • 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) [ Time Frame: 48 weeks ]
    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 ]
    Changes in CD4+ lymphocyte count between baseline and 48 weeks

Enrollment: 20
Study Start Date: October 2014
Study Completion Date: April 2017
Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Other: Dolutegravir , lamivudine
Dolutegravir 50 mg QD plus lamivudine 300 mg QD
Drug: dolutegravir, lamivudine

single arm

Other Name:
  • 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

Eligibility

Ages Eligible for Study: 18 Years and older  
Sexes Eligible for Study: All  
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:
  12. Complete abstinence from penile-vaginal intercourse from 2 weeks prior to administration of IP, throughout the study, and for at least 2 weeks after
  13. Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide)
  14. IUD and male condom
  15. Male partner sterilization confirmed and male condom
  16. Approved hormonal contraception and male condom
  17. Any other method with published data showing that the expected failure rate is <1% per year and use male condom
  18. Any contraception method must be used for at least 2 weeks after discontinuation of IP

  • Exclusion Criteria:
  • 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

    contacts and locations

    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

    Locations

    Argentina
    Fundacion Huesped
    Caba, Buenos Aires, Argentina, C1202ABB

    Sponsors and Collaborators

    The Huesped Foundation
    ViiV Healthcare

    Investigators

    Principal Investigator: Pedro Cahn, PhD Fundacion Huesped
    More Information

    More Information


    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 10, 2017  
    Individual Participant Data    
    Plan to Share IPD: Yes  

    Keywords provided by Pedro Cahn, The Huesped Foundation:

    HIV-1 infected patients
    dual therapy

    Additional relevant MeSH terms:
    Lamivudine
    Dolutegravir

    ClinicalTrials.gov processed this data on May 24, 2020
    This information is provided by ClinicalTrials.gov.