Pasireotide in Hyperinsulinemic Hypoglycemia

May 12, 2021 updated by: Montefiore Medical Center

Pasireotide for Prevention of Hypoglycemia in Patients With Hyperinsulinemic Hypoglycemia

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Pasireotide is a somatostatin analog with affinity for several somatostatin receptors including those on pancreatic beta cells; when activated these receptors affect the secretion of glucagon and insulin. Pasireotide is also known to decrease glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP) secretion. Hyperglycemia is a well-documented adverse effect of pasireotide in its approved indications for treatment of Cushing's disease and acromegaly.

In light of this, the investigators hypothesize that pasireotide may be an effective therapy for hypoglycemia due to hyperinsulinism. Therefore a small controlled pilot study to assess the effect of subcutaneous (s.c.) pasireotide on preventing hypoglycemia due to hyperinsulinism over 7 hours of observation in both fasting and fed states is proposed.

Study Type

Interventional

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  1. Male or female patients aged 18 to 70 years old
  2. Patients with hyperinsulinemic hypoglycemia due to either congenital hyperinsulinemic hypoglycemia or insulinoma, as determined by an endocrinologist

  3. 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
  4. Written informed consent obtained prior to treatment to be consistent with local regulatory requirements

  5. 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
  6. Patients receiving anti-hypoglycemic treatment are eligible
  7. Patients who are treatment naïve, or those who were previously, but not currently, treated with anti-hypoglycemic therapy are also eligible
  8. Patients with insulinoma who are operative candidates are eligible if surgery is not emergently needed, and study participation would not delay the timing of a surgical intervention

Exclusion criteria:

  1. Age <18, age >70 (for both insulinoma and congenital hyperinsulinism)
  2. Known hypersensitivity to somatostatin or analogues
  3. Diabetic patients with poor glycemic control as evidenced by HbA1c >8%
  4. Patients who are hypothyroid and not on adequate replacement therapy
  5. Patients with symptomatic cholelithiasis and acute or chronic pancreatitis
  6. QTcF at screening > 450 msec in males and QTcF > 460 msec in females
  7. Hypokalaemia, hypomagnesaemia, family history of long QT syndrome or concomitant medications with known risk of Torsades de pointes (TdP)
  8. 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
  9. Severe non-malignant medical illness that may be jeopardized by treatment with a single dose of pasireotide
  10. 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
  11. Patients with serum creatinine >2.0 X ULN
  12. Patients with WBC <3 X 109/L; Hb 90% < LLN; PLT <100 X 109/L
  13. Patients with the presence of active or suspected acute or chronic uncontrolled infection
  14. Patients who have undergone major surgery/surgical therapy for any cause within 4 weeks prior screening
  15. History of unexplained syncope or family history of idiopathic sudden death
  16. Sexually active males unless they use a condom during intercourse while taking drug and for 3 months following last dose of pasireotide and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.
  17. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test
  18. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and 30 days following last dose of pasireotide.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
PLACEBO_COMPARATOR: Placebo
Normal saline s.c. injection once
Drug: Saline Solution
Saline Solution injection will be given once per study visit
Other Names:
  • Placebo
EXPERIMENTAL: Pasireotide
Pasireotide 0.6mg s.c. once
Drug: Pasireotide 0.6Mg Solution for Injection
Pasireotide 0.6Mg Solution for Injection will be given once per study visit
Other Names:
  • SOM230

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hypoglycemia
Time Frame: 7 hours
Occurence, frequency and severity of hypoglycemia (serum glucose < 55 mg/dL)
7 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum glucose regulators
Time Frame: 7 hours
Insulin, GLP-1, glucagon and cortisol levels
7 hours

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame: 7 hours
Collection of safety and adverse event data
7 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Montefiore Medical Center

Collaborators

Novartis Pharmaceuticals

Investigators

  • Principal Investigator: Erika Brutsaert, M.D., M.P.H., Montefiore Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

April 1, 2017

Primary Completion (ANTICIPATED)

January 1, 2018

Study Completion (ANTICIPATED)

April 1, 2018

Study Registration Dates

First Submitted

February 9, 2017

First Submitted That Met QC Criteria

February 14, 2017

First Posted (ACTUAL)

February 15, 2017

Study Record Updates

Last Update Posted (ACTUAL)

May 14, 2021

Last Update Submitted That Met QC Criteria

May 12, 2021

Last Verified

May 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2016-7044

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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