| Eligibility |
Inclusion Criteria:
Patients eligible for inclusion in this Treatment Plan have to meet all of the following
criteria:
1. Male or female patients aged 18 years or older
2. Patients with a confirmed diagnosis of hyperinsulinemic hypoglycemia, if possible by
genetic testing
3. Patients not controlled by medical therapies (e.g. diazoxide or octreotide) and/or
pancreatic surgery or patients not eligible for surgery
4. WHO/ ECOG Performance Status of 0-2.
5. Life expectancy =12 weeks
6. Adequate end organ function as defined by:
No evidence of significant liver disease:
- Serum total bilirubin =1.5 x ULN
- INR < 1.3
- ALT and AST = 2 x ULN,
- Alkaline phosphatase = 2.5 x ULN
7. Written informed consent obtained prior to treatment to be consistent with local
regulatory requirements
8. Is suffering from a serious or life-threatening disease or condition
9. Does not have access to a comparable or satisfactory alternative treatment (i.e.,
comparable or satisfactory treatment is not available or does not exist)
10. Is not eligible for participation in any of the IMP's ongoing clinical trials or has
recently completed a clinical trial that has been terminated and, after considering
other options (e.g., trial extensions, amendments, etc.), the clinical team has
determined that treatment is necessary and there are no other feasible alternatives
for the patient
11. There are meaningful human clinical data to support an assessment that the potential
benefits to patient outweigh risks.
12. Meets any other relevant medical criteria for compassionate use of the investigational
product
13. Is not being transferred from an ongoing clinical trial for which they are still
eligible
Exclusion Criteria:
Patients eligible for this Treatment Plan must not meet any of the following criteria:
1. Patients with a known hypersensitivity to somatostatin analogs or any component of the
pasireotide LAR or s.c. formulations.
2. Patients with abnormal coagulation (PT or aPTT elevated by 30% above normal limits).
3. 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.
4. Patients currently using warfarin / warfarin derivatives
5. Patients with symptomatic cholelithiasis.
6. 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.
7. QT-related exclusion criteria: :
- QTcF at screening > 450 msec in males and QTcF > 460 msec
- History of syncope or family history of idiopathic sudden death
- Sustained or clinically significant cardiac arrhythmias
- Risk factors for Torsades de Pointes such as hypokalemia, hypomagnesemia, cardiac
failure, clinically significant/symptomatic bradycardia, or high-grade AV block
- Concomitant disease(s) that could prolong QT such as autonomic neuropathy (caused
by diabetes, or Parkinson's disease), HIV, cirrhosis, uncontrolled hypothyroidism
or cardiac failure
- Family history of long QT syndrome
- Concomitant medications known to prolong the QT interval.
- Potassium < or = 3.5 mmol/L
8. Patients who have any severe and/or uncontrolled medical conditions :
- Uncontrolled diabetes as defined by HbA1c > 8%,
- Patients with the presence of active or suspected acute or chronic uncontrolled
infection or with a history of immunodeficiency, including a positive HIV test
result (ELISA and Western blot). An HIV test will not be required; however,
previous medical history will be reviewed.
- Non-malignant medical illnesses that are uncontrolled or whose control may be
jeopardized by the treatment with this study treatment.
- Life-threatening autoimmune and ischemic disorders.
9. 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.
10. Patients with history of liver disease, such as cirrhosis or chronic active hepatitis
B or C
11. Presence of Hepatitis B surface antigen (HbsAg)
12. Presence of Hepatitis C antibody (anti-HCV)
13. History of, or current alcohol misuse/abuse within the past 12 months.
14. Known gallbladder or bile duct disease, acute or chronic pancreatitis
15. Patients with hypomagnesaemia (< 0.7 mmol/L)
16. Patients with a history of non-compliance to medical regimens or who are considered
potentially
17. 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
- Male sterilization (at least 6 months prior to screening). For female subjects on
the study the vasectomized male partner should be the sole partner for that
subject.
- Combination of any two of the following (a+b or a+c, or b+c):
1. Use of oral, injected or implanted hormonal methods of contraception or
other forms of hormonal contraception that have comparable efficacy (failure
rate <1%), for example hormone vaginal ring or transdermal hormone
contraception.
2. Placement of an intrauterine device (IUD) or intrauterine system (IUS)
3. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal
suppository
- 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.
18. 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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