Mol Genet Metab. 2015 Sep-Oct;116(1-2):29-34. doi: 10.1016/j.ymgme.2015.08.002. Epub 2015 Aug 5.

Self-reported treatment-associated symptoms among patients with urea cycle disorders participating in glycerol phenylbutyrate clinical trials.

Nagamani SC¹, Diaz GA², Rhead W³, Berry SA⁴, Le Mons C⁵, Lichter-Konecki U⁶, Bartley J⁷, Feigenbaum A⁸, Schulze A⁹, Longo N¹⁰, Berquist W¹¹, Gallagher R¹², Bartholomew D¹³, Harding CO¹⁴, Korson MS¹⁵, McCandless SE¹⁶, Smith W¹⁷, Vockley J¹⁸, Kronn D¹⁹, Zori R²⁰, Cederbaum S²¹, Merritt JL 2nd²², Wong D²¹, Coakley DF²³, Scharschmidt BF²³, Dickinson K²⁴, Marino M¹⁴, Lee BH²⁵, Mokhtarani M²³.

Author information

1: Baylor College of Medicine, One Baylor Plaza, Room R814, Houston, TX 77030, USA. Electronic address: Nagamani@bcm.edu.
2: Icahn School of Medicine at Mount Sinai, Department of Genetics and Genomic Sciences, Department of Pediatrics, 1428 Madison Avenue, New York, NY 10029, USA.
3: The Medical College of Wisconsin, MS 716, 9000 W. Wisconsin Avenue, Milwaukee, WI 53226, USA.
4: University of Minnesota, 420 Delaware St. SE, MMC 75, Minneapolis, MN 55455, USA.
5: National Urea Cycle Disorders Foundation, 75 S. Grand Ave, Pasadena, CA 91105, USA.
6: Drexel University, 3141 Chestnut Street, Philadelphia, PA, 19104, USA.
7: Long Beach Memorial Hospital, 2801 Atlantic Avenue, Long Beach, CA 90806, USA.
8: Rady Children's Hospital, 3020 Children's Way, San Diego, CA 92123, USA.
9: The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G1X8, Canada.
10: The University of Utah, Division of Medical Genetics, 2C412 SOM, 50 North Mario Capecchi Drive, Salt Lake City, UT 84132, USA.
11: Stanford University, 750 Welch Road, #116, Palo Alto, CA 94305, USA.
12: UCSF School of Medicine, 550 16th Street, San Francisco, CA 94158, USA.
13: Nationwide Children's Hospital, 545 South 18th Street, TH485, Columbus, OH 43205, USA.
14: Oregon Health & Science University, 3181 SW Sam Jackson Park Road, A036/B198, Mail code L103, Portland, OR 97239, USA.
15: Tufts Medical Center, Floating Building, 3rd Floor, 800 Washington Street, Boston, MA 02111, USA.
16: Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
17: Maine Medical Center, 1577 Congress Street, 2nd Floor, Portland, ME 04102, USA.
18: Children's Hospital of Pittsburgh, One Children's Hospital Drive, 4401 Penn Avenue, Rangos Floor 5, Pittsburgh, PA 15224, USA.
19: Westchester Medical Center, 503 Grasslands Road, Valhalla, NY 10595, USA.
20: University of Florida, UFHSC Box 100296, Gainesville, FL 32610, USA.
21: University of California, Los Angeles, 10833 Le Conte Avenue CHS 32-225, Los Angeles, CA 90095, USA.
22: Seattle Children's Hospital, 4800 Sand Point Way NE M/S W-65945, Seattle, WA 98105, USA.
23: Horizon Therapeutics Inc., 2000 Sierra Point Parkway Suite 400, Brisbane, CA 94005, USA.
24: Anthera Pharmaceuticals, 25801 Industrial Blvd. Suite B, Hayward, CA 94545, USA.
25: Baylor College of Medicine, One Baylor Plaza, Room R814, Houston, TX 77030, USA.

Abstract

BACKGROUND:

Health care outcomes have been increasingly assessed through health-related quality of life (HRQoL) measures. While the introduction of nitrogen-scavenging medications has improved survival in patients with urea cycle disorders (UCDs), they are often associated with side effects that may affect patient compliance and outcomes.

METHODS:

Symptoms commonly associated with nitrogen-scavenging medications were evaluated in 100 adult and pediatric participants using a non-validated UCD-specific questionnaire. Patients or their caregivers responded to a pre-defined list of symptoms known to be associated with the use of these medications. Responses were collected at baseline (while patients were receiving sodium phenylbutyrate [NaPBA]) and during treatment with glycerol phenylbutyrate (GPB).

RESULTS:

After 3 months of GPB dosing, there were significant reductions in the proportion of patients with treatment-associated symptoms (69% vs. 46%; p<0.0001), the number of symptoms per patient (2.5 vs. 1.1; p<0.0001), and frequency of the more commonly reported individual symptoms such as body odor, abdominal pain, nausea, burning sensation in mouth, vomiting, and heartburn (p<0.05). The reduction in symptoms was observed in both pediatric and adult patients. The presence or absence of symptoms or change in severity did not correlate with plasma ammonia levels or NaPBA dose.

CONCLUSIONS:

The reduction in symptoms following 3 months of open-label GPB dosing was similar in pediatric and adult patients and may be related to chemical structure and intrinsic characteristics of the product rather than its effect on ammonia control.