Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase IIIb Multicenter, Open-label, Single Arm Study to Evaluate the Efficacy and Safety of Pasireotide in Patients With Acromegaly Inadequately Controlled With First Generation Somatostatin Analogues
Brief Summary: This is a phase IIIb multicenter, open-label; single arm study to evaluate the efficacy and safety of pasireotide LAR 40 mg and 60 mg in patients with inadequately controlled acromegaly with maximal approved doses of first generation somatostatin analogues. The study will enroll inadequately controlled patients by high doses (maximal approved) of first-generation somatostatin analogues given for at least 3 months. Patients will receive pasireotide LAR 40 mg or 60 mg during the 36 week core study phase. Patients who have completed all visits of core phase and have completed all the assessments at the core phase completion visit can move into the 32-week extension phase. Patients can continue with study treatment until pasireotide LAR is commercially available and reimbursed in their respective country or until the end of the extension phase whichever occurs first.


Options:
A: Inclusion Criteria:

* Written informed consent
* Male and female patients ≥18 years
* Patients with confirmed diagnosis of inadequately controlled acromegaly (mean GH concentration ≥1 μg/L and sex- and age-adjusted IGF-1 \>1.3 x ULN)
* Patients treated with octreotide LAR (30 mg or 40 mg) or lanreotide ATG (120 mg) monotherapy for at least 3 months prior to screening

Exclusion Criteria:

* Concomitant treatment with other medications reducing GH and or IGF-1, unless discontinued 3 months prior to screening
* Patients with compression of the optic chiasm requiring surgical intervention
* Diabetic patients with HbA1c \>8% at screening
* Patients who are hypothyroid and not on adequate replacement therapy
* Patients with symptomatic cholelithiasis and acute or chronic pancreatitis
* Patients with clinically significant valvular disease
* Patients with risk factors for torsade de pointes (TdP)
* Hypokalaemia, hypomagnesaemia, uncontrolled hypothyroidism, family history of long QT syndrome or concomitant medications with known risk of TdP
* Patients with 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.
* Concomitant disease(s) that could prolong the QT interval such as autonomic neuropathy (caused by diabetes or Parkinson's disease), HIV, cirrhosis, uncontrolled hypothyroidism or cardiac failure
* Patients with liver disease or ALT/AST \> 2.0 X ULN, serum bilirubin \>2.0 X ULN - Presence of Hepatitis B surface antigen or Hepatitis C antibody test
* 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 active or suspected acute or chronic uncontrolled infection
* Patients who have undergone major surgery/surgical therapy within 4 weeks prior to screening
* Patients with active malignant disease within the last five years (with the exception of basal cell carcinoma or carcinoma in situ of the cervix)
* Patients with abnormal coagulation (PT and/or APTT elevated by 30% above normal limits) or patients receiving anticoagulants that affect PT (prothrombin time) or APTT (activated partial thromboplastin time)
* History of syncope or family history of idiopathic sudden death
* History of immunocompromise, including a positive HIV test result (ELISA and Western blot)
* Known hypersensitivity to somatostatin analogues or any other component of pasireotide LAR
* Patients who have a history of alcohol or drug abuse in the 6 month period prior to receiving pasireotide
* Patients who have given a blood donation (of 400 ml or more) within 2 months before receiving pasireotide
* Patients who have participated in any clinical investigation with an investigational drug within 1 month prior to dosing
* Patients with any current or prior medical condition interfering with the conduct of the study or the evaluation of the study results
* Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will be unable to complete the entire study.
* Sexually active males unless they use a condom during intercourse while taking drug and for 3 months following last dose of pasireotide
* 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 3 months following the last dose of pasireotide.
B: Inclusion Criteria:

Acromegaly:

* Male or female patients ≥18 years of age
* Acromegaly currently treated with Sandostatin LAR

NET:

* Male or female patients ≥18 years of age
* Functional, well-differentiated (Grade 1 or Grade 2) NET with symptoms of carcinoid syndrome (number of bowel movements and/or flushing)
* Currently treated with Sandostatin LAR for symptom control

Exclusion Criteria:

Acromegaly:

* Inadequate bone marrow function
* Abnormal coagulation or chronic treatment with warfarin or coumarin derivates
* Impaired liver, cardiac and/or renal function
* Known gallbladder, bile duct disease or pancreatitis
* Diabetes with poorly controlled blood glucose levels despite adequate therapy
* Hypothyroidisms not adequately treated

NET:

* Poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, pancreatic islet cell carcinoma, insulinoma, glucagonoma, gastrinoma, goblet cell carcinoid, typical and atypical lung carcinoids, large cell neuroendocrine carcinoma and small cell carcinoma
* Carcinoid syndrome refractory to treatment with conventional doses of somatostatin analogues (SSAs)
* Inadequate bone marrow function
* Abnormal coagulation or chronic treatment with warfarin or coumarin derivates
* Impaired liver, cardiac and/or renal function
* Known gallbladder, bile duct disease or pancreatitis
* Short-bowel syndrome
* Diabetics with poorly controlled blood glucose levels despite adequate therapy
* Hypothyroidism, not adequately treated
C: Inclusion Criteria:

* GH nadir during a standard 75 g OGTT \>= 5.0 mmol/L.
* Pituitary tumor by MRI-scan.

Exclusion Criteria:

* Immediate surgery indicated by usual clinical criteria.
* Pregnant.
* Known adverse effects of octreotide.
* Unfit for participation by any other reason.
D: Inclusion Criteria:

* The patient has given written informed consent prior to any study related procedures
* The patient is male or female and is aged between 18 and 75 years, inclusive,
* Diagnosis of acromegaly defined by i) GH nadir \> 1 ng/mL as assessed by an oral glucose tolerance test for non diabetic patients (central laboratory results) or a mean GH level \> 1 ng/mL based on 5 samples taken every 10 to 15 minutes for diabetic patients ( central laboratory results) AND ii) IGF-1 concentrations elevated above the age- and sex-matched normal range for diabetic and non diabetic patients (central laboratory results),
* The patient has a pituitary adenoma with a diameter greater than or equal to 10 mm based on Magnetic Resonance Imaging (MRI) central reading,
* The patient has no visual field defect identified at the visual evaluation, performed by Goldman Visual Fields Analyser and Automated visual field static perimeter, except visual field abnormality at the time of screening and that is in the investigator's Clinical judgement:

  * Not related to the pituitary adenoma
  * Clinically stable condition not presumed to change during the study period
  * Not modifying the ability to evaluate visual field changes related to the macroadenoma

Exclusion Criteria:

* The patient has a history of hypersensitivity to Lanreotide or drugs with a similar chemical structure,
* The patient has received any unlicensed drug within the 30 days prior to the screening visit or is scheduled to receive an unlicensed drug during the course of the study,
* The patient is likely to require treatment during the study with somatostatin analogues other than Lanreotide Autogel 120 mg, dopamine agonist, GH receptor antagonist (pegvisomant), and Cyclosporine or drugs that are not permitted by the study protocol,
* The patient is a female at risk of pregnancy during the study and is not using acceptable contraceptive methods. Females of childbearing potential must provide a negative pregnancy test at start of study and must be using oral, double barrier (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide), injectable contraception or an intra uterine device. Non childbearing potential is defined as post-menopause for at least 1 year, surgical sterilisation or hysterectomy at least three months before the start of the study,
* The patient is pregnant or lactating,
* The patient has a history of, or known current, problems with alcohol abuse,
* The patient has any mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude.
* The patient has abnormal baseline findings, any other medical condition(s) or laboratory findings that, in the opinion of the Investigator, might jeopardize the patient's safety or decrease the chance of obtaining satisfactory data needed to achieve the objective(s) of the study,
* The patient has undergone pituitary surgery or pituitary radiotherapy prior to study entry,
* The patient has previously been treated with a somatostatin analogue,
* The patient has received a dopamine agonist or a GH receptor antagonist (pegvisomant) prior to study entry,
* The patient is expected to require pituitary surgery (adenomectomy) or to receive radiotherapy during the study period,
* Patients with suspected associated prolactinoma: prolactin level \> 100 ng/mL (central laboratory results),
* Patient is allergic to Gadolinium (MRI contrast agent) or has acute or chronic severe renal insufficiency (glomerular filtration rate \<30 mL/min/1.73m2),
* Patient known by Investigator, to have congenital or acquired optic nerve disease or any visual abnormality with risk of worsening during the course of the study (e.g glaucoma), influencing ability to evaluate Visual Field changes related to the macroadenoma.

Answer: A