appropriately select patients for screening or referral to metabolicgenetics.

doi:10.1016/j.clinbiochem.2014.07.083

Treatment-related signs and symptoms among patients withurea cycle disorders (UCDs) during treatment with sodiumphenylbutyrate and glycerol phenylbutyrateSandesh C. Nagamania, George A. Diazb, William J. Rheadc, Sue A.Berryd, Cindy Le Monse, Uta Lichter-Konecki f, James A. Bartleyg,Annette Feigenbaumh, Andreas Schulzeh, Nicola Longoi, William E.Berquist j, Renata Gallagherk, Dennis W. Bartholomewl, Cary O.Hardingm, Mark S. Korsonn, Shawn E. McCandlesso, Wendy E.Smithp, Gerard Vockleyq, David Kronnr, Robert Zori s,Dion F. Coakleyt, Bruce F. Scharschmidt t,Masoud Mokhtarani t, Brendan H. Leea, u

aBaylor College of Medicine, TX, USAbIcahn School of Medicine at Mt. Sinai School of Medicine, NY, NY, USAcMed College of WI, Milwaukee, WI, USAdUniversity of MN, Minneapolis, MN, USAeNational Urea Cycle Disorders Foundation, Pasadena, CA, USAfChildren's National Medical Center, Washington, DC, USAgMiller Children's Hospital, Long Beach, CA, USAhHospital for Sick Children, University of Toronto, Toronto, Ontario, CanadaiUniversity of UT, Salt Lake City, UT, USAjStanford University, Palo Alto, CA, USAkDenver Children's Hospital, Denver, CO, USAlNationwide Children's Hospital, Columbus, OH, USAmOregon Health & Sciences Univ., Portland, OR, USAnTufts Medical Center, Boston, MA, USAoUHCMC and CWRU, Cleveland, OH, USApMaine Medical Ctr., Portland, ME, USAqUniversity of Pittsburgh, Pittsburgh, PA, USArWestchester Medical Ctr., Westchester, NY, USAsUniversity of FL, Gainesville, FL, USAtHyperion Therapeutics, Inc., Brisbane, CA, USAuHoward Hughes Medical Institute, Houston, TX, USA

Objectives: Sodium phenylbutyrate (NaPBA) is life-saving, butassociated with high treatment burden which affects compliance.This abstract presents treatment-related symptoms among UCDpatients who participated in the glycerol phenylbutyrate (GPB) trials.

Methods: 51 adult and 49 pediatric patients treated with NaPBAwere enrolled in four switch-over and three 12-month GPB treatmenttrials. Patients, parents, or caregivers completed a non-validated,questionnaire to record symptoms (abdominal pain, nausea, body odor,burning sensation in mouth, vomiting, heartburn, and headache) atenrollment, while receiving NaPBA, and after 3 months on GPB.

Results: Patients switched fromNaPBA to an equivalent dose of GPBin a single step and 39% and 54% of patients on NaPBA and GPB,respectively, recorded a new AE regardless of treatment. Of 69 patientswith ≥1 pre-existing symptom on NaPBA, 80% indicated an improve-ment, 15% had no change, and 5% had an increase in symptoms withGPB treatment. The average number of symptomsper patient decreasedfrom 2.5 on NaPBA at baseline to 1.1 on GPB at the 3 month visit

(p b 0.0001). The most common symptoms (body odor, abdominalpain, nausea and burning sensation in mouth) decreased significantly(p b 0.001). The frequency of spontaneously reported AEs regardless ofrelation to GPB, decreased at months 9–12 relative to months 0–3.

Conclusions: Patients with UCD on long-term NaPBA therapywere switched to GPB in a single step without difficulty and over3 months of open label GPB dosing, reported a reduction intreatment-related adverse events.

doi:10.1016/j.clinbiochem.2014.07.084

Assessment of barriers to drug adherence in the treatment ofurea cycle disorders in North AmericaOleg A. Shchelochkova, Brendan H. Leeb, Bruce F. Scharschmidt c,Klara A. Dickinsonc, Ellen Herberichd, Scott Hawkinsd,Jasmin Smithd, Cynthia Le MonseaDepartment of Pediatrics, University of Iowa, USAbDepartment of Molecular and Human Genetics, Howard HughesMedical Institute, Baylor College of Medicine, Houston, TX, USAcHyperion Therapeutics, Brisbane, CA, USAdHarris Interactive, New York, NY, USAeNational Urea Cycle Disorders Foundation, Pasadena, CA, USA

Objectives: Treatment burden and palatability issues of nitrogenscavengers and dietary supplements may affect patient compliance andclinical outcomes in UCD patients. We assessed non-adherence as abarrier to successful UCD treatment through a physician and patientsurvey.

Methods: UCD physicians, patients, and caregivers completed asurvey, sponsored by the National Urea Cycle Disorders Foundationand Hyperion Therapeutics and conducted by Harris Interactive,designed to assess their self-reported experience with commonlyused UCD treatments.

Results: 25 physicians, 44 patients and 121 caregivers respondedto the survey. Sodium phenylbutyrate (NaPBA) was perceived aseffective (“effective” or “very effective”) by 100% of physicians and88% of patients/caregivers, yet “somewhat difficult” or “very difficultto take” by physicians (83%) and patients/caregivers (47%). Physi-cians reported 13% of patients as “very compliant”, cited medicationamount (90%) and difficulty swallowing (81%) as reasons for non-compliance, and reported that 25%–33% of patients were taking a“lower than ideal dose” due to tolerability. Sodium benzoate (NaBz)was perceived as effective (93% of physicians and 79% of patients/caregivers), but “somewhat difficult” or “very difficult” to take by80% of physicians and 36% of patients. Arginine was perceived as“effective” by 100% of patients and 84% of physicians and citrullineby 84% and 95% of patients and physicians respectively.

Conclusions: Despite their positive views on NaPBA and NaBz,respondents had difficulty with side effects, palatability and drugvolume. Thesefindings demonstrate adherence to treatment representsa significant barrier to achieve optimal outcome for UCD patients.

doi:10.1016/j.clinbiochem.2014.07.085

Abstracts 153