Pasireotide in Hyperinsulinemic Hypoglycemia

NCT03053284 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: 2016-7044
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a small controlled pilot study to assess the effect of subcutaneous pasireotide on preventing hypoglycemia due to hyperinsulinism, including congenital hyperinsulinism and insulinoma.

Conditions

Congenital Hyperinsulinism; Insulinoma; Hyperinsulinism

Outcome Measures

Primary Outcomes (1)

• Hypoglycemia

  Occurence, frequency and severity of hypoglycemia (serum glucose \< 55 mg/dL)

  7 hours

Secondary Outcomes (1)

• Serum glucose regulators

  7 hours

Other Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  7 hours

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Normal saline s.c. injection once

Drug: Saline Solution

Pasireotide

EXPERIMENTAL

Pasireotide 0.6mg s.c. once

Drug: Pasireotide 0.6Mg Solution for Injection

Interventions

Pasireotide 0.6Mg Solution for Injection DRUG

Pasireotide 0.6Mg Solution for Injection will be given once per study visit

Also known as: SOM230

Pasireotide

Saline Solution DRUG

Saline Solution injection will be given once per study visit

Also known as: Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged 18 to 70 years old
• Patients with hyperinsulinemic hypoglycemia due to either congenital hyperinsulinemic hypoglycemia or insulinoma, as determined by an endocrinologist
• If no prior diagnosis of either insulinoma or congenital hyperinsulinemic hypoglycemia by an endocrinologist, the participant must meet the following criteria:
• A history of symptoms of hypoglycemia, (with or without a blood glucose \<50mg/dL at time of symptoms)
• Improvement of symptoms with ingestion of carbohydrates
• At least one documented blood glucose \<50mg/dL with concomitant insulin \>3 mmol/L and c-peptide \>0.2nmol/L, with a negative sulfonylurea screen
• At least 1 episode of glucose \<50mg/dL in the last year
• Written informed consent obtained prior to treatment to be consistent with local regulatory requirements
• No evidence of significant liver disease:
• Serum total bilirubin \< 2 x ULN
• INR \< 1.3 unless on anticoagulation
• ALT and AST \< 2 x ULN
• Alkaline phosphatase \< 2.5 x ULN
• Patients receiving anti-hypoglycemic treatment are eligible
• Patients who are treatment naïve, or those who were previously, but not currently, treated with anti-hypoglycemic therapy are also eligible

You may not qualify if:

• Age \<18, age \>70 (for both insulinoma and congenital hyperinsulinism)
• Known hypersensitivity to somatostatin or analogues
• Diabetic patients with poor glycemic control as evidenced by HbA1c \>8%
• Patients who are hypothyroid and not on adequate replacement therapy
• Patients with symptomatic cholelithiasis and acute or chronic pancreatitis
• QTcF at screening \> 450 msec in males and QTcF \> 460 msec in females
• Hypokalaemia, hypomagnesaemia, family history of long QT syndrome or concomitant medications with known risk of Torsades de pointes (TdP)
• Patients who have congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, clinically significant bradycardia, advanced heart block, history of acute MI less than one year prior to study entry or clinically significant impairment in cardiovascular function
• Severe non-malignant medical illness that may be jeopardized by treatment with a single dose of pasireotide
• History of another primary malignancy, with the exception of locally excised non-melanoma skin cancer and carcinoma in situ of uterine cervix unless there is no evidence of disease in the last year
• Patients with serum creatinine \>2.0 X ULN
• Patients with WBC \<3 X 109/L; Hb 90% \< LLN; PLT \<100 X 109/L
• Patients with the presence of active or suspected acute or chronic uncontrolled infection
• Patients who have undergone major surgery/surgical therapy for any cause within 4 weeks prior screening
• History of unexplained syncope or family history of idiopathic sudden death

Sponsors & Collaborators

• Montefiore Medical Center: lead
• Novartis Pharmaceuticals: collaborator

Related Publications (9)

• Schmid HA, Brueggen J. Effects of somatostatin analogs on glucose homeostasis in rats. J Endocrinol. 2012 Jan;212(1):49-60. doi: 10.1530/JOE-11-0224. Epub 2011 Oct 10.

  PMID: 21987782 BACKGROUND

• Braun M. The somatostatin receptor in human pancreatic beta-cells. Vitam Horm. 2014;95:165-93. doi: 10.1016/B978-0-12-800174-5.00007-7.

  PMID: 24559918 BACKGROUND

• Boscaro M, Ludlam WH, Atkinson B, Glusman JE, Petersenn S, Reincke M, Snyder P, Tabarin A, Biller BM, Findling J, Melmed S, Darby CH, Hu K, Wang Y, Freda PU, Grossman AB, Frohman LA, Bertherat J. Treatment of pituitary-dependent Cushing's disease with the multireceptor ligand somatostatin analog pasireotide (SOM230): a multicenter, phase II trial. J Clin Endocrinol Metab. 2009 Jan;94(1):115-22. doi: 10.1210/jc.2008-1008. Epub 2008 Oct 28.

  PMID: 18957506 BACKGROUND

• Yorifuji T. Congenital hyperinsulinism: current status and future perspectives. Ann Pediatr Endocrinol Metab. 2014 Jun;19(2):57-68. doi: 10.6065/apem.2014.19.2.57. Epub 2014 Jun 30.

  PMID: 25077087 BACKGROUND

• de Heide LJ, Laskewitz AJ, Apers JA. Treatment of severe postRYGB hyperinsulinemic hypoglycemia with pasireotide: a comparison with octreotide on insulin, glucagon, and GLP-1. Surg Obes Relat Dis. 2014 May-Jun;10(3):e31-3. doi: 10.1016/j.soard.2013.11.006. Epub 2013 Dec 4. No abstract available.

  PMID: 24448101 BACKGROUND

• Quinn TJ, Yuan Z, Adem A, Geha R, Vrikshajanani C, Koba W, Fine E, Hughes DT, Schmid HA, Libutti SK. Pasireotide (SOM230) is effective for the treatment of pancreatic neuroendocrine tumors (PNETs) in a multiple endocrine neoplasia type 1 (MEN1) conditional knockout mouse model. Surgery. 2012 Dec;152(6):1068-77. doi: 10.1016/j.surg.2012.08.021. Epub 2012 Oct 24.

  PMID: 23102680 BACKGROUND

• Tirosh A, Stemmer SM, Solomonov E, Elnekave E, Saeger W, Ravkin Y, Nir K, Talmor Y, Shimon I. Pasireotide for malignant insulinoma. Hormones (Athens). 2016 Apr;15(2):271-276. doi: 10.14310/horm.2002.1639.

  PMID: 26732164 BACKGROUND

• Eigler T, Ben-Shlomo A. Somatostatin system: molecular mechanisms regulating anterior pituitary hormones. J Mol Endocrinol. 2014 Aug;53(1):R1-19. doi: 10.1530/JME-14-0034. Epub 2014 Apr 29.

  PMID: 24780840 BACKGROUND

• Hansen L, Hartmann B, Mineo H, Holst JJ. Glucagon-like peptide-1 secretion is influenced by perfusate glucose concentration and by a feedback mechanism involving somatostatin in isolated perfused porcine ileum. Regul Pept. 2004 Apr 15;118(1-2):11-8. doi: 10.1016/j.regpep.2003.10.021.

  PMID: 14759551 BACKGROUND

MeSH Terms

Conditions

Congenital Hyperinsulinism; Insulinoma; Hyperinsulinism

Interventions

pasireotide; Solutions; Injections; Saline Solution

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Hypoglycemia; Adenoma, Islet Cell; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations; Drug Administration Routes; Drug Therapy; Therapeutics; Crystalloid Solutions; Isotonic Solutions

Study Officials

• Erika Brutsaert, M.D., M.P.H.

  Montefiore Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2017
• First Posted: February 15, 2017
• Study Start: April 1, 2017
• Primary Completion: January 1, 2018
• Study Completion: April 1, 2018
• Last Updated: May 14, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share