Efficacy and Safety of Pasireotide Administered Monthly in Patients With Cushing's Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01374906
• Date of registration: 14/06/2011
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals
• Public title: Efficacy and Safety of Pasireotide Administered Monthly in Patients With Cushing's Disease
• Scientific title: A Randomized, Double-blind, Multicenter, Phase III Study to Evaluate the Efficacy and Safety of Pasireotide LAR in Patients With Cushing's Disease
• Date of first enrolment: November 4, 2011
• Target sample size: 150
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01374906
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Argentina, Belgium, Brazil, Canada, China, France, Germany, India, Israel, Italy, Japan, Netherlands, Peru, Poland, Russian Federation, Spain, Thailand, Turkey, United Kingdom, United States

Contacts

• Name: Novartis Pharmaceuticals
• Affiliation: Novartis Pharmaceuticals

Key inclusion & exclusion criteria

Inclusion Criteria:

- Karnofsky performance status = 60 (i.e. requires occasional assistance, but is able to
care for most of their personal needs)

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

- Inhibitors of steroidogenesis (ketoconazole, metyrapone): 1 week

- Pituitary directed agents: Dopamine agonists (bromocriptine, cabergoline) and
PPAR? agonists (rosiglitazone or pioglitazone): 4 weeks

- Octreotide LAR, Lanreotide SR and Lanreotide autogel: 14 weeks

- Octreotide (immediate release formulation): 1 week

Exclusion Criteria:

- Patients who are considered candidates for surgical treatment at the time of study
entry

- Patients who have received pituitary irradiation within the last ten years prior to
visit 1

- Patients who have had any previous pasireotide treatment

- Patients who have been treated with mitotane during the last 6 months prior to Visit 1

- Diabetic patients on antihyperglycemic medications with poor glycemic control as
evidenced by HbA1c >8%

- Patients with risk factors for torsade de pointes, i.e. patients with a baseline QTcF
>470 ms, hypokalemia, uncontrolled hypothyroidism, family history of long QT syndrome,
or concomitant medications known to prolong QT interval

- Female patients who are pregnant or lactating, or are of childbearing potential
(defined as all women physiologically capable of becoming pregnant) and not practicing
an effective method of contraception/birth control. Sexually active males must use a
condom during intercourse while taking the drug and for 2 months after the last dose
of study drug and 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



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

Health Condition(s) or Problem(s) studied

Cushing's Disease

Intervention(s)

Drug: SOM230 LAR 10 mg

Drug: SOM230 LAR 30 mg

Drug: pasireotide LAR

Primary Outcome(s)

Percentage Participants That Attained a mUFC = 1.0 x ULN at Month 7 Regardless of Dose Titration [Time Frame: Month 7]

Secondary Outcome(s)

Actual Change From Baseline in Clinical Signs Over Time: Body Composition: Region [Time Frame: Month 7]

Percent of Participants With a Duration of at Least 50% Reduction in mUFC From Baseline at Indicated Time Points [Time Frame: Months 6, 12 & 18]

Actual Change in SF-12v2 Score From Baseline - Physical Component Summary [Time Frame: Months 7, 12 & 24]

Percentage Change in Mean Urinary Free Cortisol (mUFC) From Baseline [Time Frame: M7, M12, M24, M36]

Actual Change in SF-12v2 Score From Baseline - Mental Component Summary [Time Frame: Months 7, 12 & 24]

Percentage of Participants Having a Favorable Shift From Baseline in Clinical Signs [Time Frame: Month 7]

Percentage of Patients That Attain a Reduction of at Least 50% in mUFC From Baseline [Time Frame: Months 7, 12, 24 & 36]

Pharmacokinetic (PK) Parameter: Cmax [Time Frame: Days 22, 106, 190]

Actual Change From Baseline in Clinical Signs Over Time: Body Mass Index (BMI) [Time Frame: Month 7]

Actual Change in Mean Urinary Free Cortisol (mUFC) From Baseline [Time Frame: baseline, Month 7 (M7), Month 12 (M12), Month 24 (M24) , Month 36 (M36)]

Percentage of Participants That Attained a mUFC = 1.0 x ULN at Month 7 and Had Not Had a Dose Increase at Month 4 [Time Frame: Month 7]

Percentage of Patients With Uncontrolled Response at Month 7 & Month 12 Within the Subset of Patients Who Had Uncontrolled Response at a) Months 1 and 2; b) Months 1, 2, and 3 [Time Frame: Month 7, Month12]

Actual Change From Baseline in Clinical Signs Over Time: Cholesterol & Triglycerides [Time Frame: Month 7]

Actual Change From Baseline in Clinical Signs Over Time: Waist Circumference [Time Frame: Month 7]

Percent of Participants Attaining a mUFC = 1.0 x ULN or at Least a 50% Reduction in mUFC From Baseline at Indicated Time Points [Time Frame: Momth 7, Month 12]

Percent of Participants Attaining a Time to First Achievement of at Least a 50% Reduction in mUFC From Baseline at Indicated Time Points [Time Frame: every month in the core phase and every 3 months in the extension phase) up to and including the cut-off date for the Month 12 CSR (10-Nov-2015)]

Actual Change From Baseline in Clinical Signs Over Time: Weight [Time Frame: Month 7]

Actual Change in Standardized Score of Cushing's Disease HRQoL (CushingQOL) Score From Baseline [Time Frame: Months 7, 12, 24 & 36]

Percentage of Patients Who Attain mUFC = 1.0 x ULN [Time Frame: M7, M12, M24, M36]

Percentage of Patients Who Attain mUFC =1.0 x ULN or Have at Least 50 % Reduction From Baseline in mUFC [Time Frame: M7, M12, M24, M36]

Percent of Participants Attaining a Duration of Controlled or Partially Controlled Response at Indicated Time Points [Time Frame: Month 6, 12, 18]

Pharmacokinetic (PK) Parameter: Ctrough [Time Frame: Days 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337]

Percentage Change From Baseline on Serum Cortisol Over Time [Time Frame: Months 7, 12, 24 & 36]

Percentage of Participants That Attained a Mean Urinary Free Cortisol (mUFC) <= 1.0 x Upper Limit of Normal (ULN) at Month 7 Regardless of Dose Up-titration at Month 4. [Time Frame: Month 7]

Percentage of Patients Who Are Controlled Responders (mUFC = 1.0 xULN) on at Least 4 of the 7 mUFC Assessments by Month 7 & on at Least 7 of the 12 mUFC Assessments by Month 12. [Time Frame: Month 7, Month 12]

Actual Change From Baseline in Clinical Signs Over Time: Blood Pressure [Time Frame: Month 7]

Percentage Change From Baseline in Clinical Signs Over Time [Time Frame: Month 7]

Percentage Change From Baseline on Plasma Adrenocorticotropic Hormone (ACTH) Over Time [Time Frame: Months 7, 12, 24 & 36]

Secondary ID(s)

2009-011128-70

CSOM230G2304

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 11/04/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01374906