An Open-label, Multi-center, Expanded Access Study of Pasireotide s.c. in Patients With Cushing's Disease.

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01582061
• Date of registration: 12/04/2012
• Prospective Registration: No
• Primary sponsor: Novartis Pharmaceuticals
• Public title: An Open-label, Multi-center, Expanded Access Study of Pasireotide s.c. in Patients With Cushing's Disease. SEASCAPE
• Scientific title: An Open-label, Multi-center, Expanded Access Study of Pasireotide s.c. in Patients With Cushing's Disease (Seascape).
• Date of first enrolment: August 16, 2011
• Target sample size: 104
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01582061
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Brazil, Czech Republic, Czechia, Egypt, Germany, Greece, Korea, Republic of, Lebanon, Netherlands, Romania, Russian Federation, Spain, Thailand, United States

Contacts

• Name: Novartis Pharmaceuticals
• Affiliation: Novartis Pharmaceuticals

Key inclusion & exclusion criteria

Inclusion criteria:

1. Written informed consent obtained prior to any screening procedures

2. Male or female patients aged 18 years or greater

3. Patients with confirmed diagnosis of Cushing's disease as evidenced by mean urinary
free cortisol of three 24-hour urine samples collected during the 3-week screening
period above the upper limit of the laboratory normal range morning plasma ACTH within
the normal or above normal range either MRI confirmation of pituitary adenoma (greater
than or equal to 0.6 cm), or inferior petrosal sinus gradient >3 after CRH stimulation
for those patients with a microadenoma less than 0.6 cm, or for patients who have had
prior pituitary surgery, histopathology confirming an ACTH staining adenoma.

4. Patients with de novo Cushing's disease must not be considered as candidates for
pituitary surgery (i.e. poor surgical candidates, surgically unapproachable tumors,
patients with no visible pituitary tumor, patients who refuse to have surgical
treatment)

5. Karnofsky performance status >60 (i.e. requires occasional assistance, but is able to
care for most of his personal needs)

6. For patients on previous medical treatment for Cushing's disease the following washout
periods must be completed before screening assessments are performed

- Inhibitors of steroidogenesis (e.g. ketoconazole, metyrapone, rosiglitazone): 1
week

- Dopamine agonists (e.g. bromocriptine, cabergoline): 4 weeks

- Mitotane: 6 months

- Octreotide LAR and Lanreotide autogel: 8 weeks

- Lanreotide SR: 4 weeks

- Octreotide (immediate release formulation): 1 week

- Glucocorticoid receptor inhibitor (mifepristone): 4 weeks

Exclusion criteria:

1. Radiotherapy of the pituitary <4 weeks before screening or patient who has not
recovered from side effects

2. Patients with compression of the optic chiasm causing acute clinically significant
visual field defect

3. Patients with Cushing's syndrome due to ectopic ACTH secretion

4. Patients with hypercortisolism secondary to adrenal tumors or nodular (primary)
bilateral adrenal hyperplasia

5. Patients who have a known inherited syndrome as the cause for hormone over secretion
(i.e. Carney Complex, McCune-Albright syndrome, MEN-1)

6. Patients with a diagnosis of glucocorticoid-remedial aldosteronism (GRA)

7. Patients who have undergone major surgery within 1 month prior to screening

8. Patients with known gallbladder or bile duct disease, acute or chronic pancreatitis
(patients with asymptomatic cholelithiasis and asymptomatic bile duct dilation can be
included)

9. Diabetic patients whose blood glucose is poorly controlled as evidenced by HbA1C >8%

10. Patients who have clinically significant impairment in cardiovascular function or are
at risk thereof, as evidenced by congestive heart failure (NYHA Class III or IV),
unstable angina, sustained ventricular tachycardia, clinically significant
bradycardia, high grade AV block, history of acute MI less than one year prior to
study entry

- QTcF >450 msec at screening

- History of syncope or family history of idiopathic sudden death

- Risk factors for Torsades de Pointes such as uncorrected hypokalemia, uncorrected
hypomagnesemia, cardiac failure

- Concomitant disease(s) that could prolong the QT interval such as autonomic
neuropathy (caused by diabetes or Parkinson's disease), HIV, cirrhosis,
uncontrolled hypothyroidism, concomitant medication(s) with known risk for TdP

11. Patients with liver disease or history of liver disease such as cirrhosis, chronic
active hepatitis B and C, or chronic persistent hepatitis, or patients with ALT or AST
more than 2 x ULN, serum creatinine >2.0 x ULN, serum bilirubin >1.5 x ULN, serum
albumin < 0.67 x LLN at screening

12. Patients who have any current or prior medical condition that can interfere with the
conduct of the study or the evaluation of its results, such as

- History of immunocompromise, including a positive HIV test result (Elisa and
Western blot). An HIV test will not be required, however, previous medical
history will be reviewed

- Presence of active or suspected acute or chronic uncontrolled infection

- History of, or current alcohol misuse/abuse in the 12 month period prior to
screening

13. Female patients who are pregnant or lactating, or are of childbearing potential and
not practicing a medically acceptable method of birth control. If a woman is
participating in the trial then one form of contraception is sufficient (pill or
diaphragm) and the partner should use a condom. If oral contraception is used in
addition to condoms, the patient must have been practicing this method for at least
two months prior to screening and must agree to continue the oral contraceptive
throughout the course of the study and for one month after the study has ended. Male
patients who are sexually active are required to use condoms during the study and for
three month afterwards as a precautionary measure (available data do not suggest any
increased reproductive risk with the study drugs)

14. Patients who have participated in any clinical investigation with an investigational
drug within 1 month prior to screening or patients who have previously been treated
with pasireotide

15. Known hypersensitivity to somatostatin analogues

16. 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

17. Patients with presence of Hepatitis B surface antigen (HbsAg)

18. Patients with presence of Hepatitis C antibody test (anti-HCV)



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Cushing's Disease

Intervention(s)

Drug: Pasireotide sub-cutaneous

Primary Outcome(s)

Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) [Time Frame: Baseline up to approximately 256 weeks]

Secondary Outcome(s)

Percent Change in Cushing's Disease Clinical Signs and Symptoms - Pulse [Time Frame: Baseline, week 12, 24 and 48]

Percent Change From Baseline in Growth Hormone (GH) Values [Time Frame: Baseline, week 12, 24 and 48]

Percent Change in Cushing's Disease Clinical Signs and Symptoms - Hirsutism [Time Frame: Baseline, week 12, 24 and 48]

Percentage of Patients With Mean Urinary Free Cortisol (UFC) = Upper Limit of Normal (ULN) [Time Frame: Baseline, week 12, 24 and 48]

Percent Change in Cushing's Disease Clinical Signs and Symptoms - Muscle Strength [Time Frame: Baseline, week 12, 24 and 48]

Percent Change From Baseline in Insulin Growth Factor - 1 (IGF - 1) Values [Time Frame: Baseline, week 12, 24 and 48]

Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) [Time Frame: Baseline, week 12, 24 and 48]

Percent Change in Cushing's Disease Clinical Signs and Symptoms - Waist Circumference [Time Frame: Baseline, week 12, 24 and 48]

Percentage of Patients Achieving a Reduction of Mean UFC = 50% From Baseline [Time Frame: Baseline, week 12, 24 and 48]

Percent Change in Cushing Quality of Life and Work Productivity and Activity Impairment-General Health (WPAI-GH) Scores [Time Frame: Baseline, week 12, 24 and 48]

Percent Change in Cushing's Disease Clinical Signs and Symptoms - Body Mass Index (BMI) [Time Frame: Baseline, week 12, 24 and 48]

Percent Change in Cushing's Disease Clinical Signs and Symptoms - Temperature [Time Frame: Baseline week 12, 24 and 48]

Percent Change in Cushing's Disease Clinical Signs and Symptoms - Weight [Time Frame: Baseline, week 12, 24 and 48]

Secondary ID(s)

CSOM230B2406

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 19/06/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01582061