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

NCT01582061 | Completed Phase 3 Results

• 1 other identifier: CSOM230B2406
• Study Type: interventional
• Target: 104
• Locations: 11 countries
• Sites: 65

Brief Summary

This study provided access to pasireotide sc in patients with Cushing's disease.and provided additional information for safety and efficacy of pasireotide s.c.

Conditions

Cushing's Disease

Keywords

Cushing's disease; Hormone disorder; Cortisol; Adrenocorticotropic hormone; Pituitary tumor; SOM230; adult

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE)

  Only AEs occurring on or after the start of study treatment and no more than 28 days after the discontinuation of study treatment. A patient with multiple occurrences of an AE under one treatment is counted only once in the AE category for that treatment. A patient with multiple severity grades for an AE while on a treatment, is only counted under the maximum grade.

  Baseline up to approximately 256 weeks

Secondary Outcomes (13)

• Percentage of Patients With Mean Urinary Free Cortisol (UFC) ≤ Upper Limit of Normal (ULN)

  Baseline, week 12, 24 and 48

• Percentage of Patients Achieving a Reduction of Mean UFC ≥ 50% From Baseline

  Baseline, week 12, 24 and 48

• Percent Change in Cushing Quality of Life and Work Productivity and Activity Impairment-General Health (WPAI-GH) Scores

  Baseline, week 12, 24 and 48

• Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP)

  Baseline, week 12, 24 and 48

• Percent Change in Cushing's Disease Clinical Signs and Symptoms - Pulse

  Baseline, week 12, 24 and 48

Study Arms (2)

Pasireotide 600 μg

EXPERIMENTAL

Pasireotide sub-cutaneous was supplied in 1 ml ampoules containing 600 μg pasireotide per 1 ml of solution and was administered BID. Starting dose was 600 μg for glucose impaired metabolism patients. Mean daily dose category is defined on the mean daily dose considering the following grouping rule: 600 μg bid group includes all patients whose mean daily dose \< 1500 μg /day.

Drug: Pasireotide sub-cutaneous

Pasireotide 900 μg

EXPERIMENTAL

Pasireotide sub-cutaneous was supplied in 1 ml ampoules containing 900 μg pasireotide per 1 ml of solution and was administered BID. Starting dose was 900 μg. Mean daily dose category is defined on the mean daily dose considering the following grouping rule: 900 μg bid group includes all patients whose mean daily dose ≥ 1500 μg /day

Drug: Pasireotide sub-cutaneous

Interventions

Pasireotide sub-cutaneous DRUG

Pasireotide sub-cutaneous was supplied in 1 ml ampoules containing 900 μg, 600 μg, or 300 μg pasireotide per 1 ml of solution and was administered BID. Starting dose was 900 μg and 600 μg for glucose impaired metabolism patients

Also known as: SOM230 sub-cutaneous

Pasireotide 600 μg; Pasireotide 900 μg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent obtained prior to any screening procedures
• Male or female patients aged 18 years or greater
• 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.
• 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)
• Karnofsky performance status \>60 (i.e. requires occasional assistance, but is able to care for most of his personal needs)
• 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

You may not qualify if:

• Radiotherapy of the pituitary \<4 weeks before screening or patient who has not recovered from side effects
• Patients with compression of the optic chiasm causing acute clinically significant visual field defect
• Patients with Cushing's syndrome due to ectopic ACTH secretion
• Patients with hypercortisolism secondary to adrenal tumors or nodular (primary) bilateral adrenal hyperplasia
• Patients who have a known inherited syndrome as the cause for hormone over secretion (i.e. Carney Complex, McCune-Albright syndrome, MEN-1)
• Patients with a diagnosis of glucocorticoid-remedial aldosteronism (GRA)
• Patients who have undergone major surgery within 1 month prior to screening
• Patients with known gallbladder or bile duct disease, acute or chronic pancreatitis (patients with asymptomatic cholelithiasis and asymptomatic bile duct dilation can be included)
• Diabetic patients whose blood glucose is poorly controlled as evidenced by HbA1C \>8%
• 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
• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (65)

Advanced Research, LLC

Peoria, Arizona, 85381, United States

Location

St Josephs Hospital & Medical Center St Joes

Phoenix, Arizona, 85013, United States

Location

University of California at Los Angeles UCLA Tiverton

Los Angeles, California, 90095, United States

Location

LA Biomedical Research at Harbor UCLA Medical Center

Torrance, California, 90502, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

John H Stroger Jr Hospital of Cook County

Chicago, Illinois, 60644, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Diabetes and Endocrinology Associates, PC

Omaha, Nebraska, 68131, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

University of New Mexico Hospital UNM

Albuquerque, New Mexico, 87106, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Oregon Health and Science University OHSU 5

Portland, Oregon, 97239, United States

Location

University of Pennsylvania Medical Center Univ Penn

Philadelphia, Pennsylvania, 19104, United States

Location

Allegheny Endocrinology Associates

Pittsburgh, Pennsylvania, 15212, United States

Location

Mid South Endocrine Associates

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

Location

Swedish Cancer Institute Swedish Cancer Institute (SC)

Seattle, Washington, 98104, United States

Location

Novartis Investigative Site

Fortaleza, Ceará, 04636-000, Brazil

Location

Novartis Investigative Site

Londrina, Paraná, 86015-520, Brazil

Location

Novartis Investigative Site

Rio de Janeiro, Rio de Janeiro, 21941-913, Brazil

Location

Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, 90560-030, Brazil

Location

Novartis Investigative Site

Joinville, Santa Catarina, 89201260, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 04029-000, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 05403 000, Brazil

Location

Novartis Investigative Site

Prague, Czech Republic, 128 00, Czechia

Location

Novartis Investigative Site

Aachen, 52074, Germany

Location

Novartis Investigative Site

Augsburg, 86150, Germany

Location

Novartis Investigative Site

Berlin, 10098, Germany

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

Erlangen, 91054, Germany

Location

Novartis Investigative Site

Frankfurt, 60329, Germany

Location

Novartis Investigative Site

Frankfurt, 60590, Germany

Location

Novartis Investigative Site

Göttingen, 37075, Germany

Location

Novartis Investigative Site

Hamburg, 22587, Germany

Location

Novartis Investigative Site

Heidelberg, 69120, Germany

Location

Novartis Investigative Site

Leipzig, 04103, Germany

Location

Novartis Investigative Site

Mainz, 55131, Germany

Location

Novartis Investigative Site

Marburg, 35039, Germany

Location

Novartis Investigative Site

München, 80804, Germany

Location

Novartis Investigative Site

Oldenburg, 26122, Germany

Location

Novartis Investigative Site

Würzburg, 97080, Germany

Location

Novartis Investigative Site

Athens, GR, 115 27, Greece

Location

Novartis Investigative Site

Thessaloniki, GR, 546 42, Greece

Location

Novartis Investigative Site

Athens, 106 76, Greece

Location

Novartis Investigative Site

Thessaloniki, 546 36, Greece

Location

Novartis Investigative Site

El Achrafiyé, 166830, Lebanon

Location

Novartis Investigative Site

Bucharest, 011461, Romania

Location

Novartis Investigative Site

Bucharest, 011863, Romania

Location

Novartis Investigative Site

Cluj-Napoca, 400006, Romania

Location

Novartis Investigative Site

Iași, 700106, Romania

Location

Novartis Investigative Site

Moscow, 129110, Russia

Location

Novartis Investigative Site

Seoul, Korea, 02447, South Korea

Location

Novartis Investigative Site

Seoul, Korea, 06351, South Korea

Location

Novartis Investigative Site

Seoul, 03080, South Korea

Location

Novartis Investigative Site

Seoul, 03722, South Korea

Location

Novartis Investigative Site

Córdoba, Andalusia, 14004, Spain

Location

Novartis Investigative Site

Granada, Andalusia, 18003, Spain

Location

Novartis Investigative Site

Palma de Mallorca, Balearic Islands, 07120, Spain

Location

Novartis Investigative Site

Badalona, Catalonia, 08916, Spain

Location

Novartis Investigative Site

Ourense, Galicia, 32005, Spain

Location

Novartis Investigative Site

Pontevedra, Galicia, 36071, Spain

Location

Novartis Investigative Site

Valencia, Valencia, 46014, Spain

Location

Novartis Investigative Site

Valencia, Valencia, 46026, Spain

Location

Novartis Investigative Site

Bangkok, 10330, Thailand

Location

Novartis Investigative Site

Songkhla, 90110, Thailand

Location

Related Publications (1)

• Fleseriu M, Iweha C, Salgado L, Mazzuco TL, Campigotto F, Maamari R, Limumpornpetch P. Safety and Efficacy of Subcutaneous Pasireotide in Patients With Cushing's Disease: Results From an Open-Label, Multicenter, Single-Arm, Multinational, Expanded-Access Study. Front Endocrinol (Lausanne). 2019 Jul 16;10:436. doi: 10.3389/fendo.2019.00436. eCollection 2019.

  PMID: 31379734 DERIVED

MeSH Terms

Conditions

Pituitary ACTH Hypersecretion; Pituitary Neoplasms

Condition Hierarchy (Ancestors)

Hyperpituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2012
• First Posted: April 20, 2012
• Study Start: August 16, 2011
• Primary Completion: January 26, 2017
• Study Completion: January 26, 2017
• Last Updated: June 19, 2018
• Results First Posted: June 19, 2018

Record last verified: 2018-05

Locations

KR (4); RU (1); LE (1); CZ (1); US (17); GR (4); RO (4); DE (16); ES (8); BR (7); TH (2)