1505. Safety and Tolerability of Crofelemer 125 mg Twice Daily in the Treatment of Noninfectious Diarrhea in HIV-Seropositive Patients on Antiretroviral Therapy: Results From a Phase 3, 48-Week Open-Label Study
Session: Poster Abstract Session: HIV and Co-infections
Saturday, October 5, 2013
Room: The Moscone Center: Poster Hall C
Posters
  • 13-SAL-0250 IDWeek 2013 Poster_Final Poster_092713.pdf (106.2 kB)
  • Background: Noninfectious diarrhea is an important health concern in some HIV-seropositive patients on antiretroviral therapy (ART). Crofelemer is a first-in-class, minimally absorbed, botanically derived gastrointestinal drug indicated for symptomatic relief of noninfectious diarrhea in patients with HIV receiving ART. This trial assessed the long-term (48-week) safety and tolerability of crofelemer.

    Methods: HIV-seropositive adults taking ART, with CD4+ counts ≥100 cells/mm3 and self-reported diarrhea necessitating antidiarrheal medication (ADM) use for ≥4 weeks, received crofelemer 125 mg twice daily for up to 48 weeks in a multicenter, open-label trial. Assessments included periodic monitoring of adverse events (AEs) and clinical laboratory tests. Immune status (HIV viral load; CD4+ count) was evaluated at baseline and Month 12/end of treatment. Concomitant ADMs were permitted. 

    Results: The safety population (n=250; 44 from a previous trial [ADVENT] and 206 new patients) was 84.4% male and 53.6% white, with a mean (SD) age of 46.8 (8.3) years. At baseline, 74.4% of patients used concomitant ADMs and 100% reported current ART use; most frequently used ART included ritonavir, tenofovir/emtricitabine, and raltegravir. Median days (range) of crofelemer exposure totaled 335 (7-366), with 78.8% of patients treated for ≥9 months. Most commonly reported AEs were infection- (eg, upper respiratory tract [16.8%], intestinal parasitic [12.4%], Giardia [8.0%]; none drug-related) or gastrointestinal-related (eg, nausea [5.6%], constipation [5.6%]). The majority of AEs (90.5% of patients) were mild or moderate in severity.  Most patients (10 of 14) reporting constipation AE also used ADMs during the study. Only 3.6% of patients reported diarrhea as an AE. No deaths were reported. Although 20 patients (8.0%) experienced serious AEs (including infection in 10 patients), none were drug-related. Change from baseline in CD4+ count (>500 to ≤500 cells/mm3; 9.4% of patients) and viral load (<400 to ≥400 copies/mL; 14.3%) were minimal. 

    Conclusion: In HIV-seropositive patients on ART with noninfectious diarrhea, crofelemer 125 mg twice daily for up to 48 weeks was well tolerated with a low incidence of AEs and no clinical deterioration of immune status.

    Trevor Hawkins, MD1, Rodger Macarthur, M.D.2, Stephen Brown, MD3, Patrick Clay, PharmD, FCCP, CCTI4, Lawrence Waldman, MD5, Andrew Barrett, PhD6, Enoch Bortey, PhD6, Craig Paterson, MD6 and William Forbes, PharmD6, (1)Southwest Care Center, Santa Fe, NM, (2)Department of Infectious Diseases, Wayne State University, Detroit, MI, (3)AIDS Research Alliance, Los Angeles, CA, (4)Pharmacotherapy, University of North Texas System College of Pharmacy, Fort Worth, TX, (5)The Southwest Center for HIV/AIDS, Phoenix, AZ, (6)Salix Pharmaceuticals, Inc., Raleigh, NC

    Disclosures:

    T. Hawkins, Bristol-Myers Squibb: Consultant, Grant Investigator and Speaker's Bureau, Consulting fee, Research grant and Speaker honorarium
    Gilead Sciences: Consultant, Grant Investigator and Speaker's Bureau, Consulting fee, Research grant and Speaker honorarium
    Janssen Pharmaceuticals, Inc.: Consultant, Grant Investigator and Speaker's Bureau, Consulting fee, Research grant and Speaker honorarium
    Vertex Pharmaceuticals: Consultant, Grant Investigator and Speaker's Bureau, Consulting fee, Research grant and Speaker honorarium
    GlaxoSmithKline: Grant Investigator, Research grant
    Salix Pharmaceuticals, Inc.: Grant Investigator, Research grant
    Merck: Speaker's Bureau, Speaker honorarium

    R. Macarthur, Salix Pharmaceuticals, Inc.: Grant Investigator, Research grant

    S. Brown, Salix Pharmaceuticals, Inc.: Grant Investigator, Research grant

    P. Clay, Salix Pharmaceuticals, Inc.: Consultant, Grant Investigator and Speaker's Bureau, Consulting fee, Research grant and Speaker honorarium

    L. Waldman, None

    A. Barrett, Salix Pharmaceuticals, Inc.: Employee and Shareholder, Company Shares and Salary

    E. Bortey, Salix Pharmaceuticals, Inc.: Employee and Shareholder, Company Shares and Salary

    C. Paterson, Salix Pharmaceuticals, Inc.: Employee and Shareholder, Company Shares and Salary

    W. Forbes, Salix Pharmaceuticals, Inc.: Employee, Officer and Shareholder, Company Shares and Salary

    Findings in the abstracts are embargoed until 12:01 a.m. PST, Oct. 2nd with the exception of research findings presented at the IDWeek press conferences.