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Congenital hyperinsulinism is a rare condition that can cause life-threatening hypoglycemia. Current treatment for congenital hyperinsulinism is often suboptimal, and such individuals may respond to a new somatostatin analog, pasireotide. This is a compassionate use study of the effects of pasireotide on individuals with suboptimally treated congenital hyperinsulinism.
Full description
Congenital hyperinsulinism is a rare condition that can cause life-threatening hypoglycemia. Current treatment for congenital hyperinsulinism is often suboptimal, with diazoxide as the mainstay of treatment. Individuals who are not adequately treated with diazoxide may undergo pancreatectomy. Octreotide has been used with some success in congenital hyperinsulinism but there is limited data on pasireotide, the newest somatostatin receptor agonist, which, compared to octreotide, has 30-40 times greater affinity for somatostatin receptors 1 (SSTR1) and 5 (SSTR5), 5 times greater for somatostatin receptor 3 (SSTR3) and a comparable affinity for somatostatin receptor 2 (SSTR2).
In human islets, SSTR2 & SSTR5 are present in beta cells. Therefore, there is reason to believe that pasireotide may have greater effectiveness than octreotide in preventing hypoglycemia due to hyperinsulinism. Indeed hyperglycemia is a known effect of pasireotide when used for treatment of Cushing's disease and Acromegaly. The current study is of compassionate use for prevention of hypoglycemia in individuals with congenital hyperinsulinemic hypoglycemia who are not adequately treated with diazoxide.
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Inclusion criteria
Male or female patients aged 18 years or older
Patients with a confirmed diagnosis of hyperinsulinemic hypoglycemia, if possible by genetic testing
Patients not controlled by medical therapies (e.g. diazoxide or octreotide) and/or pancreatic surgery or patients not eligible for surgery
World Health Organization/ Eastern Cooperative Oncology Group Performance Status of 0-2.
Life expectancy ≥12 weeks
Adequate end organ function as defined by:
No evidence of significant liver disease:
Written informed consent obtained prior to treatment to be consistent with local regulatory requirements
Is suffering from a serious or life-threatening disease or condition
Does not have access to a comparable or satisfactory alternative treatment (i.e., comparable or satisfactory treatment is not available or does not exist)
Is not eligible for participation in any of the investigators ongoing clinical trials or has recently completed a clinical trial that has been terminated and, after considering other options (for example., trial extensions, amendments, etc.), the clinical team has determined that treatment is necessary and there are no other feasible alternatives for the patient
There are meaningful human clinical data to support an assessment that the potential benefits to patient outweigh risks.
Meets any other relevant medical criteria for compassionate use of the investigational product
Is not being transferred from an ongoing clinical trial for which they are still eligible
Exclusion criteria
Patients with a known hypersensitivity to somatostatin analogs or any component of the pasireotide long acting release (LAR) or subcutaneous. formulations.
Patients with abnormal coagulation (prothrombin time or activated partial thromboplastin time elevated by 30% above normal limits).
Patients on continuous anticoagulation therapy. Patients who were on anticoagulant therapy must complete a washout period of at least 10 days and have confirmed normal coagulation parameters before study inclusion.
Patients currently using warfarin / warfarin derivatives
Patients with symptomatic cholelithiasis.
Patients who are not biochemically euthyroid. Patients with known history of hypothyroidism are eligible if they are on adequate and stable replacement thyroid hormone therapy for at least 3 months.
QT-related exclusion criteria: :
Patients who have any severe and/or uncontrolled medical conditions :
Patients who have a history of another primary malignancy, with the exception of locally excised non-melanoma skin cancer and carcinoma in situ of uterine cervix. Patients who have had no evidence of disease from another primary cancer for 1 or more years are allowed to participate in the study.
Patients with history of liver disease, such as cirrhosis or chronic active hepatitis B or
Presence of Hepatitis B surface antigen (HbsAg)
Presence of Hepatitis C antibody (anti-HCV)
History of, or current alcohol misuse/abuse within the past 12 months.
Known gallbladder or bile duct disease, acute or chronic pancreatitis
Patients with hypomagnesaemia (< 0.7 mmol/L)
Patients with a history of non-compliance to medical regimens or who are considered potentially
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. Highly effective contraception methods include:
Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
Combination of any two of the following (a+b or a+c, or b+c):
In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment.
If the patient is a sexually active male he is excluded unless he agrees to use a condom during intercourse while taking pasireotide and for 3 months after stopping pasireotide medication . They 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
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Data sourced from clinicaltrials.gov
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