Pasireotide in Patients With Acromegaly Inadequately Controlled With First Generation Somatostatin Analogues
Condition: Acromegaly
MeSH terms: Acromegaly
Intervention: Pasireotide LAR
Intervention description: Pasireotide 40 mg and 60 mg. Pasireotide 20 mg which was allowed for dose decrease in case of adverse event.
Intervention MeSH terms: Pasireotide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 123.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: acromegaly; GH; IGF-1; pasireotide LAR; SOM230; first generation; somatostatin analogues; growth disorder; gigantism; Pituitary adenoma; pituitary gigantism

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.
    

Eligibility criteria:

        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.