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

A Randomized, Double-blind, Multicenter, Phase III Study to Evaluate the Efficacy and Safety of Pasireotide LAR in Patients With Cushing's Disease

This is a randomized, double-blind, multicenter, phase III study to evaluate the safety and efficacy of 2 dosing regiments of Pasireotide long acting release (LAR) in patients with Cushing's disease.

Study Overview

• Status: Completed
• Conditions: Cushing's Disease
• Intervention / Treatment: Drug: pasireotide LAR; Drug: SOM230 LAR 10 mg; Drug: SOM230 LAR 30 mg

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1232AAC
    • Novartis Investigative Site
  • Cordoba, Argentina, X5009BSN
    • Novartis Investigative Site
• Belgium
  • Bruxelles, Belgium, 1070
    • Novartis Investigative Site
  • Gent, Belgium, 9000
    • Novartis Investigative Site
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
  • Antwerpen
    • Edegem, Antwerpen, Belgium, 2650
      • Novartis Investigative Site
  • Brussel
    • Jette, Brussel, Belgium, 1090
      • Novartis Investigative Site
• Brazil
  • CE
    • Fortaleza, CE, Brazil, 60020-181
      • Novartis Investigative Site
  • RJ
    • Rio de Janeiro, RJ, Brazil, 21941-913
      • Novartis Investigative Site
  • SP
    • Ribeirao Preto, SP, Brazil, 14048-900
      • Novartis Investigative Site
    • São Paulo, SP, Brazil, 05403 000
      • Novartis Investigative Site
• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Novartis Investigative Site
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
      • Novartis Investigative Site
    • Sherbrooke, Quebec, Canada, J1N 5N4
      • Novartis Investigative Site
• China
  • Shanghai, China, 200025
    • Novartis Investigative Site
  • Shanghai, China, 200040
    • Novartis Investigative Site
  • Beijing
    • Beijing, Beijing, China, 100730
      • Novartis Investigative Site
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Novartis Investigative Site
• France
  • Besancon cedex, France, 25030
    • Novartis Investigative Site
  • Caen Cedex9, France, 14033
    • Novartis Investigative Site
  • Le Kremlin Bicetre, France, 94275
    • Novartis Investigative Site
  • Lille Cedex, France, 59037
    • Novartis Investigative Site
  • Marseille Cédex 5, France, 13385
    • Novartis Investigative Site
  • Pessac Cedex, France, 33604
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 10117
    • Novartis Investigative Site
  • Erlangen, Germany, 91054
    • Novartis Investigative Site
  • Germering, Germany, 82110
    • Novartis Investigative Site
  • Wurzburg, Germany, 97080
    • Novartis Investigative Site
• India
  • New Delhi, India, 110 029
    • Novartis Investigative Site
  • Maharashtra
    • Mumbai, Maharashtra, India, 400012
      • Novartis Investigative Site
  • Tamil Nadu
    • Vellore, Tamil Nadu, India, 632004
      • Novartis Investigative Site
• Israel
  • Petach Tikva, Israel, 49100
    • Novartis Investigative Site
• Italy
  • Napoli, Italy, 80131
    • Novartis Investigative Site
  • AN
    • Ancona, AN, Italy, 60126
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20162
      • Novartis Investigative Site
    • Milano, MI, Italy, 20149
      • Novartis Investigative Site
  • PD
    • Padova, PD, Italy, 35128
      • Novartis Investigative Site
• Japan
  • Osaka, Japan, 534-0021
    • Novartis Investigative Site
  • Aichi
    • Nagoya, Aichi, Japan, 460-0001
      • Novartis Investigative Site
  • Fukuoka
    • Fukuoka city, Fukuoka, Japan, 812-8582
      • Novartis Investigative Site
  • Gunma
    • Maebashi city, Gunma, Japan, 371 8511
      • Novartis Investigative Site
  • Hokkaido
    • Sapporo-city, Hokkaido, Japan, 060-8648
      • Novartis Investigative Site
  • Hyogo
    • Kobe-city, Hyogo, Japan, 650-0017
      • Novartis Investigative Site
  • Kochi
    • Nankoku-city, Kochi, Japan, 783-8505
      • Novartis Investigative Site
  • Kyoto
    • Kyoto-city, Kyoto, Japan, 612-8555
      • Novartis Investigative Site
  • Osaka
    • Suita-city, Osaka, Japan, 565-0871
      • Novartis Investigative Site
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8603
      • Novartis Investigative Site
    • Minato-ku, Tokyo, Japan, 105-8470
      • Novartis Investigative Site
    • Shinjuku-ku, Tokyo, Japan, 162-8666
      • Novartis Investigative Site
• Netherlands
  • Rotterdam, Netherlands, 3015 CE
    • Novartis Investigative Site
• Peru
  • Lima
    • Jesus Maria, Lima, Peru, 11
      • Novartis Investigative Site
    • Miraflores, Lima, Peru, 18
      • Novartis Investigative Site
• Poland
  • Gdansk, Poland, 80-952
    • Novartis Investigative Site
  • Poznan, Poland, 60-355
    • Novartis Investigative Site
  • Warszawa, Poland, 00-909
    • Novartis Investigative Site
  • Wroclaw, Poland, 50-367
    • Novartis Investigative Site
• Russian Federation
  • Moscow, Russian Federation, 119296
    • Novartis Investigative Site
  • St.- Petersburg, Russian Federation, 199034
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08041
    • Novartis Investigative Site
  • Andalucia
    • Sevilla, Andalucia, Spain, 41013
      • Novartis Investigative Site
  • Comunidad Valenciana
    • Alzira, Comunidad Valenciana, Spain, 46600
      • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10330
    • Novartis Investigative Site
  • Bangkok, Thailand, 10700
    • Novartis Investigative Site
• Turkey
  • Izmir, Turkey, 35340
    • Novartis Investigative Site
  • Ankara
    • Diskapi / Ankara, Ankara, Turkey, 06110
      • Novartis Investigative Site
  • TUR
    • Istanbul, TUR, Turkey, 34098
      • Novartis Investigative Site
• United Kingdom
  • Norwich, United Kingdom, NR4 7UY
    • Novartis Investigative Site
  • Sheffield, United Kingdom, S5 7AU
    • Novartis Investigative Site
  • Southampton, United Kingdom, SO16 6YD
    • Novartis Investigative Site
  • Manchester
    • Salford, Manchester, United Kingdom, M6 8HD
      • Novartis Investigative Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85381
      • ClinTriCo
  • California
    • Los Angeles, California, United States, 90095
      • University of California at Los Angeles UCLA Tiverton
    • Torrance, California, United States, 90509
      • Harbor-UCLA Medical Center LA Biomed
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine/Winship Cancer Institute G2304 - C2301
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Pituitary Center, Division of Endocrinology SC
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0944
      • University of Michigan Comprehensive Cancer Center SC-2
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine Mt. Sinai Medical Center
  • Oregon
    • Portland, Oregon, United States, 97201
      • Oregon Health & Sciences University DeptofOregonHealth&Sciences(2)
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania - Clinical Studies Unit Unniv SC
  • Tennessee
    • Nashville, Tennessee, United States, 37212-3139
      • Vanderbilt University Medical Center CSOM230G2304
  • Washington
    • Seattle, Washington, United States, 98122-4379
      • Swedish Medical Center Swedish
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin MCW 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 PPARγ 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 10 mg LAR dose; Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms.	Drug: pasireotide LAR; Pasireotide long-acting was administered as an intra-muscular depot intragluteal injection once every 28 days (±2 days). Patients were administered pasireotide long-acting 10 mg or 30 mg for four months, followed by either continuation of the starting dose, or dose up-titration (if mUFC was still >1.5xULN unless titration was precluded by safety reasons).; Other Names: SOM230; Drug: SOM230 LAR 10 mg; starting does of SOM230 LAR 10 mg i.m. administered once every 28 days for 4 months, followed by dose up-titration or continuation of the starting dose.
Experimental: 30 mg LAR dose; Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms.	Drug: pasireotide LAR; Pasireotide long-acting was administered as an intra-muscular depot intragluteal injection once every 28 days (±2 days). Patients were administered pasireotide long-acting 10 mg or 30 mg for four months, followed by either continuation of the starting dose, or dose up-titration (if mUFC was still >1.5xULN unless titration was precluded by safety reasons).; Other Names: SOM230; Drug: SOM230 LAR 30 mg; starting dose of 30 mg i.m. administered once every 28 days for 4 months, followed by dose up-titration or continuation of starting dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Participants That Attained a mUFC ≤ 1.0 x ULN at Month 7 Regardless of Dose Titration	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. Patients who discontinued before month 4 evaluations classed as non-responders. For patients missing month 7 mUFC assessments, the last available mUFC assessment at or after month 4 was carried forward as the month 7 mUFC assessment value.	Month 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants That Attained a mUFC ≤ 1.0 x ULN at Month 7 and Had Not Had a Dose Increase at Month 4	Percentage of participants that attain a mUFC ≤ 1.0×ULN at Month 7 and had not had a dose increase at Month 4. Patients who had a dose increase prior to Month 7 were counted as non-responders in this analysis. Patients who discontinued before month 4 evaluations classed as non-responders. For patients missing month 7 mUFC assessments, the last available mUFC assessment at or after month 4 was carried forward as the month 7 mUFC assessment value. A responder was defined as a patient who attains mUFC ≤1.0 X ULN and had not had a dose increase at Month 4.	Month 7
Actual Change in Mean Urinary Free Cortisol (mUFC) From Baseline	Actual change in mUFC (nmol/24h) from baseline by randomized groups.	baseline, Month 7 (M7), Month 12 (M12), Month 24 (M24) , Month 36 (M36)
Percentage Change in Mean Urinary Free Cortisol (mUFC) From Baseline	Percentage change in mUFC (nmol/24h) from baseline by randomized groups.	M7, M12, M24, M36
Percentage of Patients Who Attain mUFC ≤ 1.0 x ULN	Controlled responder: mUFC ≤ 1.0×ULN by randomized groups.	M7, M12, M24, M36
Percentage of Patients Who Attain mUFC ≤1.0 x ULN or Have at Least 50 % Reduction From Baseline in mUFC	Controlled responder: mUFC ≤ 1.0×ULN. Partially controlled responder: at least 50% reduction in mUFC from Baseline, and mUFC >1.0×ULN.	M7, M12, M24, M36
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.	Percentage of patients with mUFC ≤ 1.0 x ULN at a minimum of 4 months up to and including Month 7, and at a minimum of 7 months up to and including Month 12 by randomized groups.	Month 7, Month 12
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	Percentage of patients with mUFC > 1.0 xULN at Month 7 and Month 12 within the subset of patients who were uncontrolled at a) Months 1 & 2, b) Months 1, 2, & 3 by randomized groups.	Month 7, Month12
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 to first achievement of attaining a mUFC ≤ 1.0 x ULN or at least a 50% reduction in mUFC from baseline by randomized groups.	Momth 7, Month 12
Percent of Participants Attaining a Duration of Controlled or Partially Controlled Response at Indicated Time Points	Duration of controlled or partially controlled response is defined as the period starting from the date of patient's first normalization (mUFC≤ 1.0 x ULN) or at least 50% reduction from baseline up to the date when the patient's mUFC >1.0 x ULN and the reduction from baseline falls to less than 50% for the first time.	Month 6, 12, 18
Percentage Change From Baseline on Plasma Adrenocorticotropic Hormone (ACTH) Over Time	Percentage change in ACTH (pmol/L) from Baseline by randomized groups.	Months 7, 12, 24 & 36
Percentage Change From Baseline on Serum Cortisol Over Time	Percentage change in serum cortisol (nmol/L) from Baseline by randomized groups.	Months 7, 12, 24 & 36
Actual Change From Baseline in Clinical Signs Over Time: Blood Pressure	Change in blood pressure measurements from Baseline	Month 7
Actual Change From Baseline in Clinical Signs Over Time: Body Mass Index (BMI)	Change in BMI measurements from Baseline	Month 7
Actual Change From Baseline in Clinical Signs Over Time: Weight	Change in weight measurements from Baseline	Month 7
Actual Change From Baseline in Clinical Signs Over Time: Body Composition: Region	Change in body composition: region measurements from Baseline	Month 7
Actual Change From Baseline in Clinical Signs Over Time: Waist Circumference	Change in waist circumference measurements from Baseline	Month 7
Actual Change From Baseline in Clinical Signs Over Time: Cholesterol & Triglycerides	Change in parameter measurements: cholesterol & triglycerides from Baseline	Month 7
Percentage Change From Baseline in Clinical Signs Over Time	Percentage change in parameter measurements: blood pressure, body mass index, waist circumference, fasting serum lipid profile, weight, bone density and body composition (examined by DXA scan) from Baseline	Month 7
Percentage of Participants Having a Favorable Shift From Baseline in Clinical Signs	This includes patients with improvements in symptoms from baseline. Clinical signs over time include: facial rubor, fat pads, hirsutism, striae, (via photographs by a second local physician who was blinded to the treatment dose and time point of the photograph) and muscle strength.	Month 7
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.	All of the participants who discontinued prior to month 4 evaluations were classed as non-responders. For participants missing month 7 mUFC assessments, the last available mUFC assessment at or after month 4 was carried forward as the month 7 mUFC assessment value. Analysis split by screening strata of mUFC Stratum 1: mUFC 1.5x to < 2.0 x ULN Stratum 2: mUFC 2.0x to <= 5.0 x ULN	Month 7
Percentage of Patients That Attain a Reduction of at Least 50% in mUFC From Baseline	All of the participants who discontinued prior to month 4 evaluations were classed as non-responders. For participants missing month 7 mUFC assessments, the last available mUFC assessment at or after month 4 was carried forward as the month 7 mUFC assessment value. Analysis split by screening strata of mUFC Stratum 1:	Months 7, 12, 24 & 36
Percent of Participants Attaining a Time to First Achievement of at Least a 50% Reduction in mUFC From Baseline at Indicated Time Points	Time to first achievement of a 5by randomized groups.0% reduction in mUFC from baseline	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)
Percent of Participants With a Duration of at Least 50% Reduction in mUFC From Baseline at Indicated Time Points	Duration of 50% reduction from baseline is defined as the period starting from the date of patient's first 50% reduction from baseline	Months 6, 12 & 18
Pharmacokinetic (PK) Parameter: Ctrough	Pasireotide trough levels (Ctrough) was 1 of the parameters used for PK assessments. Ctrough is the pre-dose PK concentration with an elapsed time from previous injection of 28+/-2 days. All patients randomized to the study had at least 1 PK observation & were therefore included in the pharmacokinetic analysis set. PK observations with missing concentrations, missing dose, missing elapsed time or an elapsed time from previous injection outside of 28 ±2 days window were excluded. Given that SOM230 LAR was administered once a month, Ctrough was collected every 28 days and thus this provides a summary of Ctrough values provided by incident dose (last dose administered prior to PK sample collection), not by randomized dose, hence each column is equivalent to an incident dose & not an arm/group. Patients randomized to either 10mg or 30mg could be titrated down to 5mg due to safety, or titrated up to 40mg, hence the 4 incident doses/columns that were allowed per protocol during this study.	Days 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337
Pharmacokinetic (PK) Parameter: Cmax	Pasireotide peak levels (Cmax) was one of the parameters used for PK assessments. Cmax is the post-dose PK concentration with an elapsed time from the previous injection of 21+/-2 days. All patients randomized to the study had at least one PK observation and were therefore included in the pharmacokinetic analysis set (PAS). Cmax PK observations ("Day 20" and "Day 104") with an elapsed time from the previous injection outside of 21+/-2 days window were excluded. Given that SOM230 LAR was administered once a month, the Cmax were collected every 28 days in this study, thus this provides a summary of Cmax values provided by incident dose (last dose administered prior to PK sample collection), not by randomized dose, hence each column is equivalent to an incident dose and not an arm/group. Patients randomized to either the 10mg or 30mg could be titrated down to 5mg due to safety, or titrated up to 40mg, hence the 4 incident doses/columns that were allowed per protocol during this study.	Days 22, 106, 190
Actual Change in Standardized Score of Cushing's Disease HRQoL (CushingQOL) Score From Baseline	CushingQol is a disease-specific patient-reported outcome instrument. It is a single-domain 12 item Cushing's disease quality of life instrument. The Cushing's syndrome quality of life (CushingQoL) questionnaire is a single domain questionnaire which includes 12 self-report items scored using a five point Likert scale anchored at (1=always/very much and 5=never/not at all). The patient is asked to report what they think or feel about their Cushing's syndrome and how much the illness has interfered in usual activities over the past 4 weeks. The total score is standardized on a 0-100 scale with lower scores indicating a greater impact on quality of life.	Months 7, 12, 24 & 36
Actual Change in SF-12v2 Score From Baseline - Mental Component Summary	SF-12v2 General Health Survey is a general patient reported outcome instrument over time. It is scored to provide eight health domain scores (Bodily Pain (BP), General Health (GH), Physical Functioning (PF), Role-Physical (RP), Social Functioning (SF), Role-Emotional (RE), Vitality (VT) and Mental Health (MH)). These eight domain scores can be combined to form two summary scores reflecting overall physical and mental health: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). The analyses reported here focus on PCS and MCS scores. The domain scores use a norm-based score, which standardizes the scores with respect to the mean and standard deviation of a nationally representative sample of United States (US) adults. These are the scores on the original scale which have not been transformed in any way. The possible range of scores is 0 to 100, with higher scores representing better outcomes.	Months 7, 12 & 24
Actual Change in SF-12v2 Score From Baseline - Physical Component Summary	SF-12v2 General Health Survey is a general patient reported outcome instrument over time. It is scored to provide eight health domain scores (Bodily Pain (BP), General Health (GH), Physical Functioning (PF), Role-Physical (RP), Social Functioning (SF), Role-Emotional (RE), Vitality (VT) and Mental Health (MH)). These eight domain scores can be combined to form two summary scores reflecting overall physical and mental health: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). The analyses reported here focus on PCS and MCS scores. The domain scores use a norm-based score, which standardizes the scores with respect to the mean and standard deviation of a nationally representative sample of United States (US) adults. These are the scores on the original scale which have not been transformed in any way. The possible range of scores is 0 to 100, with higher scores representing better outcomes.	Months 7, 12 & 24

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Lacroix A, Bronstein MD, Schopohl J, Delibasi T, Salvatori R, Li Y, Barkan A, Suzaki N, Tauchmanova L, Ortmann CE, Ravichandran S, Petersenn S, Pivonello R. Long-acting pasireotide improves clinical signs and quality of life in Cushing's disease: results from a phase III study. J Endocrinol Invest. 2020 Nov;43(11):1613-1622. doi: 10.1007/s40618-020-01246-0. Epub 2020 May 8.
• Newell-Price J, Pivonello R, Tabarin A, Fleseriu M, Witek P, Gadelha MR, Petersenn S, Tauchmanova L, Ravichandran S, Gupta P, Lacroix A, Biller BMK. Use of late-night salivary cortisol to monitor response to medical treatment in Cushing's disease. Eur J Endocrinol. 2020 Feb;182(2):207-217. doi: 10.1530/EJE-19-0695.
• Fleseriu M, Petersenn S, Biller BMK, Kadioglu P, De Block C, T'Sjoen G, Vantyghem MC, Tauchmanova L, Wojna J, Roughton M, Lacroix A, Newell-Price J. Long-term efficacy and safety of once-monthly pasireotide in Cushing's disease: A Phase III extension study. Clin Endocrinol (Oxf). 2019 Dec;91(6):776-785. doi: 10.1111/cen.14081. Epub 2019 Oct 1.
• Lacroix A, Gu F, Gallardo W, Pivonello R, Yu Y, Witek P, Boscaro M, Salvatori R, Yamada M, Tauchmanova L, Roughton M, Ravichandran S, Petersenn S, Biller BMK, Newell-Price J; Pasireotide G2304 Study Group. Efficacy and safety of once-monthly pasireotide in Cushing's disease: a 12 month clinical trial. Lancet Diabetes Endocrinol. 2018 Jan;6(1):17-26. doi: 10.1016/S2213-8587(17)30326-1. Epub 2017 Oct 12. Erratum In: Lancet Diabetes Endocrinol. 2018 Jan;6(1):e1.
• Silverstein JM. Hyperglycemia induced by pasireotide in patients with Cushing's disease or acromegaly. Pituitary. 2016 Oct;19(5):536-43. doi: 10.1007/s11102-016-0734-1.

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2011
• Primary Completion (Actual): December 21, 2016
• Study Completion (Actual): December 21, 2016

Study Registration Dates

• First Submitted: June 14, 2011
• First Submitted That Met QC Criteria: June 15, 2011
• First Posted (Estimate): June 16, 2011

Study Record Updates

• Last Update Posted (Actual): May 22, 2018
• Last Update Submitted That Met QC Criteria: April 25, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: SOM230; Cushing's Disease; Mean Urinary Free Cortisol; Pasireotide; Pasireotide LAR; Pasireotide long-acting release; secondary hypercortisolism; secondary hypercorticism; Itsenko-Cushing disease; increased secretion of adrenocorticotropic hormone (ACTH); hyperpituitarism
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Hypothalamic Diseases; Hyperpituitarism; Pituitary Diseases; Adenoma; Pituitary Neoplasms; ACTH-Secreting Pituitary Adenoma; Pituitary ACTH Hypersecretion; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pasireotide
• Other Study ID Numbers: CSOM230G2304; 2009-011128-70 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No