Long-term efficacy and safety of once-monthly pasireotide in Cushing's disease: A Phase III extension study

Maria Fleseriu, Stephan Petersenn, Beverly M.K. Biller, Pinar Kadioglu, Christophe De Block, Guy T'Sjoen, Marie Christine Vantyghem, Libuse Tauchmanova, Judi Wojna, Michael Roughton, André Lacroix, John Newell-Price

Research output: Contribution to journalArticle

Abstract

Objectives: Many patients with Cushing's disease (CD) require chronic pharmacotherapy to control their hypercortisolism. We evaluated the efficacy and safety of long-acting pasireotide during a long-term extension study in patients with CD. Design: Open-label extension to a 12-month Phase III study of long-acting pasireotide in CD (N = 150; NCT01374906). Patients: Patients with mean urinary free cortisol (mUFC) ≤ upper limit of normal (ULN) or receiving clinical benefit at core study end could continue long-acting pasireotide during the extension. Results: Eighty-one of 150 (54.0%) enrolled patients entered the extension. Median overall exposure to pasireotide at study end was 23.9 months; 39/81 (48.1%) patients completed the extension (received ≥ 12 months’ treatment during the extension and could transit to a separate pasireotide safety study). mUFC was ≤ULN in 42/81 (51.9%), 13/81 (16.0%) and 43/81 (53.1%) patients at extension baseline, month (M) 36 and last assessment. Median mUFC remained within normal limits. Median late-night salivary cortisol was 2.6 × ULN at core baseline and 1.3 × ULN at M36. Clinical improvements were sustained over time. Forty-two (51.9%) patients discontinued during the extension: 25 (30.9%) before M24 and 17 (21.0%) after M24. Hyperglycaemia-related AEs occurred in 39.5% of patients. Mean fasting glucose (FPG) and glycated haemoglobin (HbA1c) were stable during the extension, with antidiabetic medication initiated/escalated in some patients. Sixty-six (81.5%) and 71 (88.9%) patients were classified as having diabetes (HbA1c ≥ 6.5%, FPG ≥ 7.0 mmol/L, antidiabetic medication use, or history of diabetes) at extension baseline and last assessment. Conclusions: Long-acting pasireotide provided sustained biochemical and clinical improvements, with no new safety signals emerging, supporting its use as an effective long-term therapy for CD.

Original languageEnglish (US)
JournalClinical Endocrinology
DOIs
StateAccepted/In press - Jan 1 2019

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Pituitary ACTH Hypersecretion
Safety
Hydrocortisone
Hypoglycemic Agents
pasireotide
Cushing Syndrome
Glycosylated Hemoglobin A
Hyperglycemia
Fasting

Keywords

  • Cushing syndrome
  • Cushing's disease
  • extension
  • hypercortisolism
  • pasireotide
  • Phase III
  • pituitary

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Fleseriu, M., Petersenn, S., Biller, B. M. K., Kadioglu, P., De Block, C., T'Sjoen, G., ... Newell-Price, J. (Accepted/In press). Long-term efficacy and safety of once-monthly pasireotide in Cushing's disease: A Phase III extension study. Clinical Endocrinology. https://doi.org/10.1111/cen.14081

Long-term efficacy and safety of once-monthly pasireotide in Cushing's disease : A Phase III extension study. / Fleseriu, Maria; Petersenn, Stephan; Biller, Beverly M.K.; Kadioglu, Pinar; De Block, Christophe; T'Sjoen, Guy; Vantyghem, Marie Christine; Tauchmanova, Libuse; Wojna, Judi; Roughton, Michael; Lacroix, André; Newell-Price, John.

In: Clinical Endocrinology, 01.01.2019.

Research output: Contribution to journalArticle

Fleseriu, M, Petersenn, S, Biller, BMK, Kadioglu, P, De Block, C, T'Sjoen, G, Vantyghem, MC, Tauchmanova, L, Wojna, J, Roughton, M, Lacroix, A & Newell-Price, J 2019, 'Long-term efficacy and safety of once-monthly pasireotide in Cushing's disease: A Phase III extension study', Clinical Endocrinology. https://doi.org/10.1111/cen.14081
Fleseriu, Maria ; Petersenn, Stephan ; Biller, Beverly M.K. ; Kadioglu, Pinar ; De Block, Christophe ; T'Sjoen, Guy ; Vantyghem, Marie Christine ; Tauchmanova, Libuse ; Wojna, Judi ; Roughton, Michael ; Lacroix, André ; Newell-Price, John. / Long-term efficacy and safety of once-monthly pasireotide in Cushing's disease : A Phase III extension study. In: Clinical Endocrinology. 2019.
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abstract = "Objectives: Many patients with Cushing's disease (CD) require chronic pharmacotherapy to control their hypercortisolism. We evaluated the efficacy and safety of long-acting pasireotide during a long-term extension study in patients with CD. Design: Open-label extension to a 12-month Phase III study of long-acting pasireotide in CD (N = 150; NCT01374906). Patients: Patients with mean urinary free cortisol (mUFC) ≤ upper limit of normal (ULN) or receiving clinical benefit at core study end could continue long-acting pasireotide during the extension. Results: Eighty-one of 150 (54.0{\%}) enrolled patients entered the extension. Median overall exposure to pasireotide at study end was 23.9 months; 39/81 (48.1{\%}) patients completed the extension (received ≥ 12 months’ treatment during the extension and could transit to a separate pasireotide safety study). mUFC was ≤ULN in 42/81 (51.9{\%}), 13/81 (16.0{\%}) and 43/81 (53.1{\%}) patients at extension baseline, month (M) 36 and last assessment. Median mUFC remained within normal limits. Median late-night salivary cortisol was 2.6 × ULN at core baseline and 1.3 × ULN at M36. Clinical improvements were sustained over time. Forty-two (51.9{\%}) patients discontinued during the extension: 25 (30.9{\%}) before M24 and 17 (21.0{\%}) after M24. Hyperglycaemia-related AEs occurred in 39.5{\%} of patients. Mean fasting glucose (FPG) and glycated haemoglobin (HbA1c) were stable during the extension, with antidiabetic medication initiated/escalated in some patients. Sixty-six (81.5{\%}) and 71 (88.9{\%}) patients were classified as having diabetes (HbA1c ≥ 6.5{\%}, FPG ≥ 7.0 mmol/L, antidiabetic medication use, or history of diabetes) at extension baseline and last assessment. Conclusions: Long-acting pasireotide provided sustained biochemical and clinical improvements, with no new safety signals emerging, supporting its use as an effective long-term therapy for CD.",
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T1 - Long-term efficacy and safety of once-monthly pasireotide in Cushing's disease

T2 - A Phase III extension study

AU - Fleseriu, Maria

AU - Petersenn, Stephan

AU - Biller, Beverly M.K.

AU - Kadioglu, Pinar

AU - De Block, Christophe

AU - T'Sjoen, Guy

AU - Vantyghem, Marie Christine

AU - Tauchmanova, Libuse

AU - Wojna, Judi

AU - Roughton, Michael

AU - Lacroix, André

AU - Newell-Price, John

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Objectives: Many patients with Cushing's disease (CD) require chronic pharmacotherapy to control their hypercortisolism. We evaluated the efficacy and safety of long-acting pasireotide during a long-term extension study in patients with CD. Design: Open-label extension to a 12-month Phase III study of long-acting pasireotide in CD (N = 150; NCT01374906). Patients: Patients with mean urinary free cortisol (mUFC) ≤ upper limit of normal (ULN) or receiving clinical benefit at core study end could continue long-acting pasireotide during the extension. Results: Eighty-one of 150 (54.0%) enrolled patients entered the extension. Median overall exposure to pasireotide at study end was 23.9 months; 39/81 (48.1%) patients completed the extension (received ≥ 12 months’ treatment during the extension and could transit to a separate pasireotide safety study). mUFC was ≤ULN in 42/81 (51.9%), 13/81 (16.0%) and 43/81 (53.1%) patients at extension baseline, month (M) 36 and last assessment. Median mUFC remained within normal limits. Median late-night salivary cortisol was 2.6 × ULN at core baseline and 1.3 × ULN at M36. Clinical improvements were sustained over time. Forty-two (51.9%) patients discontinued during the extension: 25 (30.9%) before M24 and 17 (21.0%) after M24. Hyperglycaemia-related AEs occurred in 39.5% of patients. Mean fasting glucose (FPG) and glycated haemoglobin (HbA1c) were stable during the extension, with antidiabetic medication initiated/escalated in some patients. Sixty-six (81.5%) and 71 (88.9%) patients were classified as having diabetes (HbA1c ≥ 6.5%, FPG ≥ 7.0 mmol/L, antidiabetic medication use, or history of diabetes) at extension baseline and last assessment. Conclusions: Long-acting pasireotide provided sustained biochemical and clinical improvements, with no new safety signals emerging, supporting its use as an effective long-term therapy for CD.

AB - Objectives: Many patients with Cushing's disease (CD) require chronic pharmacotherapy to control their hypercortisolism. We evaluated the efficacy and safety of long-acting pasireotide during a long-term extension study in patients with CD. Design: Open-label extension to a 12-month Phase III study of long-acting pasireotide in CD (N = 150; NCT01374906). Patients: Patients with mean urinary free cortisol (mUFC) ≤ upper limit of normal (ULN) or receiving clinical benefit at core study end could continue long-acting pasireotide during the extension. Results: Eighty-one of 150 (54.0%) enrolled patients entered the extension. Median overall exposure to pasireotide at study end was 23.9 months; 39/81 (48.1%) patients completed the extension (received ≥ 12 months’ treatment during the extension and could transit to a separate pasireotide safety study). mUFC was ≤ULN in 42/81 (51.9%), 13/81 (16.0%) and 43/81 (53.1%) patients at extension baseline, month (M) 36 and last assessment. Median mUFC remained within normal limits. Median late-night salivary cortisol was 2.6 × ULN at core baseline and 1.3 × ULN at M36. Clinical improvements were sustained over time. Forty-two (51.9%) patients discontinued during the extension: 25 (30.9%) before M24 and 17 (21.0%) after M24. Hyperglycaemia-related AEs occurred in 39.5% of patients. Mean fasting glucose (FPG) and glycated haemoglobin (HbA1c) were stable during the extension, with antidiabetic medication initiated/escalated in some patients. Sixty-six (81.5%) and 71 (88.9%) patients were classified as having diabetes (HbA1c ≥ 6.5%, FPG ≥ 7.0 mmol/L, antidiabetic medication use, or history of diabetes) at extension baseline and last assessment. Conclusions: Long-acting pasireotide provided sustained biochemical and clinical improvements, with no new safety signals emerging, supporting its use as an effective long-term therapy for CD.

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KW - Cushing's disease

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KW - hypercortisolism

KW - pasireotide

KW - Phase III

KW - pituitary

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