Jose M Garcia1, Beverly M K Biller2, Márta Korbonits3, Vera Popovic4, Anton Luger5, Christian J Strasburger6, Philippe Chanson7,8, Milica Medic-Stojanoska9, Jochen Schopohl10, Anna Zakrzewska11, Sandra Pekic4,12, Marek Bolanowski13,14, Ronald Swerdloff15, Christina Wang15, Thomas Blevins16, Marco Marcelli17, Nicola Ammer18, Richard Sachse18, Kevin C J Yuen19. 1. Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, University of Washington and SIBCR, Seattle, Washington. 2. Massachusetts General Hospital, Boston, Massachusetts. 3. Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom. 4. University of Belgrade Faculty of Medicine, Belgrade, Serbia. 5. Vienna General Hospital - Medical University Campus, Vienna, Austria. 6. Charité - Universitatsmedizin, Berlin, Germany. 7. Service d'Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l'Hypophyse, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Le Kremlin Bicêtre, France. 8. Unité Mixte de Recherche S-1185, Faculté de Médecine Paris Sud, Université Paris Sud, Le Kremlin-Bicêtre, France. 9. University of Novi Sad, Faculty of Medicine, Clinical Center of Vojvodina, Novi Sad, Serbia. 10. Medizinische Klinik IV, Ludwig Maximilian University of Munich, Munich, Germany. 11. Angelius Provita Medical Center, Katowice, Poland. 12. Clinic for Endocrinology, University Clinical Center, Belgrade, Serbia. 13. WroMedica, Wrocław, Poland. 14. Medical University Wroclaw, Wrocław, Poland. 15. Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California. 16. Texas Diabetes and Endocrinology, Austin, Texas. 17. Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas. 18. Aeterna Zentaris GmbH, Frankfurt, Germany. 19. Swedish Neuroscience Institute, Seattle, Washington.
Abstract
Purpose: The diagnosis of adult GH deficiency (AGHD) is challenging and often requires confirmation with a GH stimulation test (GHST). The insulin tolerance test (ITT) is considered the reference standard GHST but is labor intensive, can cause severe hypoglycemia, and is contraindicated for certain patients. Macimorelin, an orally active GH secretagogue, could be used to diagnose AGHD by measuring stimulated GH levels after an oral dose. Materials and Methods: The present multicenter, open-label, randomized, two-way crossover trial was designed to validate the efficacy and safety of single-dose oral macimorelin for AGHD diagnosis compared with the ITT. Subjects with high (n = 38), intermediate (n = 37), and low (n = 39) likelihood for AGHD and healthy, matched controls (n = 25) were included in the efficacy analysis. Results: After the first test, 99% of macimorelin tests and 82% of ITTs were evaluable. Using GH cutoff levels of 2.8 ng/mL for macimorelin and 5.1 ng/mL for ITTs, the negative agreement was 95.38% (95% CI, 87% to 99%), the positive agreement was 74.32% (95% CI, 63% to 84%), sensitivity was 87%, and specificity was 96%. On retesting, the reproducibility was 97% for macimorelin (n = 33). In post hoc analyses, a GH cutoff of 5.1 ng/mL for both tests resulted in 94% (95% CI, 85% to 98%) negative agreement, 82% (95% CI, 72% to 90%) positive agreement, 92% sensitivity, and 96% specificity. No serious adverse events were reported for macimorelin. Conclusions: Oral macimorelin is a simple, well-tolerated, reproducible, and safe diagnostic test for AGHD with accuracy comparable to that of the ITT. A GH cutoff of 5.1 ng/mL for the macimorelin test provides an excellent balance between sensitivity and specificity.
RCT Entities:
Purpose: The diagnosis of adult GH deficiency (AGHD) is challenging and often requires confirmation with a GH stimulation test (GHST). The insulin tolerance test (ITT) is considered the reference standard GHST but is labor intensive, can cause severe hypoglycemia, and is contraindicated for certain patients. Macimorelin, an orally active GH secretagogue, could be used to diagnose AGHD by measuring stimulated GH levels after an oral dose. Materials and Methods: The present multicenter, open-label, randomized, two-way crossover trial was designed to validate the efficacy and safety of single-dose oral macimorelin for AGHD diagnosis compared with the ITT. Subjects with high (n = 38), intermediate (n = 37), and low (n = 39) likelihood for AGHD and healthy, matched controls (n = 25) were included in the efficacy analysis. Results: After the first test, 99% of macimorelin tests and 82% of ITTs were evaluable. Using GH cutoff levels of 2.8 ng/mL for macimorelin and 5.1 ng/mL for ITTs, the negative agreement was 95.38% (95% CI, 87% to 99%), the positive agreement was 74.32% (95% CI, 63% to 84%), sensitivity was 87%, and specificity was 96%. On retesting, the reproducibility was 97% for macimorelin (n = 33). In post hoc analyses, a GH cutoff of 5.1 ng/mL for both tests resulted in 94% (95% CI, 85% to 98%) negative agreement, 82% (95% CI, 72% to 90%) positive agreement, 92% sensitivity, and 96% specificity. No serious adverse events were reported for macimorelin. Conclusions: Oral macimorelin is a simple, well-tolerated, reproducible, and safe diagnostic test for AGHD with accuracy comparable to that of the ITT. A GH cutoff of 5.1 ng/mL for the macimorelin test provides an excellent balance between sensitivity and specificity.
Authors: Paulo F Collett-Solberg; Geoffrey Ambler; Philippe F Backeljauw; Martin Bidlingmaier; Beverly M K Biller; Margaret C S Boguszewski; Pik To Cheung; Catherine Seut Yhoke Choong; Laurie E Cohen; Pinchas Cohen; Andrew Dauber; Cheri L Deal; Chunxiu Gong; Yukihiro Hasegawa; Andrew R Hoffman; Paul L Hofman; Reiko Horikawa; Alexander A L Jorge; Anders Juul; Peter Kamenický; Vaman Khadilkar; John J Kopchick; Berit Kriström; Maria de Lurdes A Lopes; Xiaoping Luo; Bradley S Miller; Madhusmita Misra; Irene Netchine; Sally Radovick; Michael B Ranke; Alan D Rogol; Ron G Rosenfeld; Paul Saenger; Jan M Wit; Joachim Woelfle Journal: Horm Res Paediatr Date: 2019-09-12 Impact factor: 2.852
Authors: Michael Lissy; Valentin Demmel; Richard Sachse; Nicola Ammer; Nicky Kelepouris; Vlady Ostrow Journal: Clin Pharmacol Drug Dev Date: 2020-09-22
Authors: Clara O Sailer; Bettina Winzeler; Sandrine A Urwyler; Ingeborg Schnyder; Julie Refardt; Anne Eckert; Nimmy Varghese; Martin Fassnacht; Irina Chifu; Elizabeth A Lawson; Joseph G Verbalis; Wiebke Fenske; Mirjam Christ-Crain Journal: Eur J Endocrinol Date: 2021-08-03 Impact factor: 6.558