To optimize management of drug induced increase in blood sugar with incretin based therapy or insulin in adult patients with Cushingâ??s disease (characterized by obesity of the trunk & face, high blood pressure, fatigue) or acromegaly (marked by enlargement of bones of extremities, face & jaw)
- Conditions
- Health Condition 1: E220- Acromegaly and pituitary gigantismHealth Condition 2: null- Adult patients with Cushingâ??s disease or acromegaly
- Registration Number
- CTRI/2015/02/005498
- Lead Sponsor
- ovartis Healthcare Pvt Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- Not specified
- Target Recruitment
- 133
Cushingâ??s disease population:
1. Adult patients (age >= 18y) with confirmed diagnosis of Cushingâ??s disease
(persistent/recurrent or de Novo patients who are not considered candidates for pituitary
surgery).
2. Patients currently treated at screening visit with pasireotide s.c. should have an elevated
FPG > ULN or a diagnosis of diabetes (FPG >= 126 mg/dL on two occasions or HbA1c >=
6.5% or a random plasma glucose >= 200 mg/dL with classic symptoms of hyperglycemia
(polydipsia, polyphagia and polyuria)) during screening period.
3. Previous exposure to pasireotide is allowed. In case pasireotide s.c. was discontinued
before screening a wash-out period of at least 1 week before study entry (start of
pasireotide) has to be followed.
Acromegaly population:
4. Adult patients (age >= 18 y) with confirmed diagnosis of acromegaly. De Novo patients
(with no prior pituitary surgery) can be included if they are not considered candidates for
pituitary surgery or have refused surgery.
5. Patients currently treated at screening visit with pasireotide LAR should have elevated
FPG > ULN or a diagnosis of diabetes (FPG >= 126 mg/dL on two occasions or HbA1c >=
6.5% or a random plasma glucose >= 200 mg/dL with classic symptoms of hyperglycemia
(polydipsia, polyphagia and polyuria)) during screening period.
Inclusion criteria for both Cushingâ??s disease and acromegaly population:
7. Patients with either Type 1 or Type 2 diabetes currently being treated with insulin (basal insulin with or without prandial insulin) are eligible for study entry. However, these
patients will be treated in the non-randomized observational arm.
8. Patients with Type 2 diabetes being treated with anti-diabetic agents (including metformin)
other than incretin based therapies are eligible for study entry and randomization.
9. Written informed consent must be obtained prior to any study related procedure.
10. If patients were treated with insulin only for an acute medical need and insulin was
discontinued after that, then a wash-out period of at least 48 hours before study entry (start
of pasireotide) has to be followed. These patients will be eligible for randomization.
Cushingâ??s disease population
1. Patients who are receiving other medical therapies for Cushingâ??s disease. All other
medical therapies for Cushingâ??s disease have to be discontinued at least 5 times the halflife
of the respective preparation before study entry (start of pasireotide).
Acromegaly population
2. Patients who are receiving other medical therapies for acromegaly and not compliant with
the following rules:
Other medical therapies for acromegaly have to be discontinued at least 5 times the
elimination half-life (t n half ) of the respective preparation before study entry (start of
pasireotide);
Other SSAs (octreotide, lanreotide) have to be discontinued at least 5 times the
elimination half-life of the respective formulation before study entry (8 weeks
washout for octreotide LAR and lanreotide autogel);
Dopamine agonists (bromocriptine, cabergoline) or pegvisomant (INN) will only be
accepted provided the dose regimen is stable from at least 4 weeks before study entry
and throughout the study.
3 Patients who require surgical intervention
4 Patients receiving DPP-4 inhibitors or GLP-1 receptor agonists within 4 weeks prior to
study entry
5 HbA1c less than 10 percent at screening
6 Patients with life-threatening diabetic ketoacidosis or diabetic hyperosmolar coma
7 Any major surgery or surgical therapy for any cause within 4 weeks of signing the informed
consent (patients must recover from the surgery and be in good clinical condition before
entering the study).
8 Participation in any clinical protocol and or receiving an investigational drug within 4
weeks prior to dosing or longer (a minimal wash out of 5 t n half of the investigational drug is
mandatory and local regulation should be followed).
9 Known hypersensitivity to somatostatin analogues.
10 Patients who are hypothyroid and have clinical symptoms of hypothyroidism despite
adequate replacement therapy
11 Life-threatening autoimmune disorders
12 History of liver disease, such as severe hepatic impairment (Child-Pugh C, cirrhosis, or
chronic active hepatitis B or C [presence of hepatitis B surface antigen (HbsAg) or
hepatitis C antibody (anti-HCV)]).
13 Cholelithiasis, or acute or chronic pancreatitis.
14 Cardiac or repolarization abnormality
15 History of HIV infection, including a positive HIV test result (Elisa and Western blot). An HIV test is not required; however, previous medical history should be reviewed.
16 Screening ALT or AST less than 2x ULN
17 Screening total bilirubin less than 1.5x ULN
18 Renal dysfunction as defined by local metformin label (E.g., As per SmPC, creatinine
clearance than less 60 mL min; As per US package insert, serum creatinine than less 1.5 mg dL
(males), less than 1.4 mg dL (females)) at screening.
19 Inadequate bone marrow function
20 Abnormal coagulation function (PT and PTT elevated by 30 percent above normal limits, or
INR less than equal 1.3 except for patients on anti-coagulant therapy. Patients on anticoagulant therapy
must be stable for at least 1 month prior to study entry).
21 Any known contraindication to DPP-4 inhibitor, GLP-1 receptor agonists or insulin,
including but not limited to:
Known
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To evaluate the effect of treatment with incretin based <br/ ><br>therapy vs. insulin on the 16-week glycemic control in <br/ ><br>patients with Cushingâ??s disease or acromegaly who <br/ ><br>develop or worsen hyperglycemia on pasireotide, and <br/ ><br>cannot be controlled by metformin alone or other <br/ ><br>background anti-diabetic treatmentsTimepoint: Change in HbA1c from randomization to approximately 16 weeks in <br/ ><br>the incretin based therapy arm and insulin arm
- Secondary Outcome Measures
Name Time Method