Pasireotide in Hyperinsulinemic Hypoglycemia

Sponsor

Montefiore Medical Center (Other)

Overall Status

Withdrawn

CT.gov ID

NCT03053284

Collaborator

Novartis Pharmaceuticals (Industry)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Congenital Hyperinsulinism Insulinoma Hyperinsulinism	Drug: Pasireotide 0.6Mg Solution for Injection Drug: Saline Solution	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Non-Randomized

Intervention Model:

Crossover Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

Pasireotide for Prevention of Hypoglycemia in Patients With Hyperinsulinemic Hypoglycemia

Anticipated Study Start Date :

Apr 1, 2017

Anticipated Primary Completion Date :

Jan 1, 2018

Anticipated Study Completion Date :

Apr 1, 2018

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Hypoglycemia [7 hours]
Occurence, frequency and severity of hypoglycemia (serum glucose < 55 mg/dL)

Secondary Outcome Measures

Serum glucose regulators [7 hours]
Insulin, GLP-1, glucagon and cortisol levels

Other Outcome Measures

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [7 hours]
Collection of safety and adverse event data

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

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
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:

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
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.
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
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.