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

NCT01374906 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: CSOM230G23042009-011128-70
• Study Type: interventional
• Target: 150
• Locations: 20 countries
• Sites: 82

Brief Summary

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.

Conditions

Cushing's Disease

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (28)

• Percentage of Participants That Attained a mUFC ≤ 1.0 x ULN at Month 7 and Had Not Had a Dose Increase at Month 4

  Month 7

• Actual Change in Mean Urinary Free Cortisol (mUFC) From Baseline

  baseline, Month 7 (M7), Month 12 (M12), Month 24 (M24) , Month 36 (M36)

• Percentage Change in Mean Urinary Free Cortisol (mUFC) From Baseline

  M7, M12, M24, M36

• Percentage of Patients Who Attain mUFC ≤ 1.0 x ULN

  M7, M12, M24, M36

• Percentage of Patients Who Attain mUFC ≤1.0 x ULN or Have at Least 50 % Reduction From Baseline in mUFC

  M7, M12, M24, M36

Study Arms (2)

10 mg LAR dose

EXPERIMENTAL

Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms.

Drug: pasireotide LAR; Drug: SOM230 LAR 10 mg

30 mg LAR dose

EXPERIMENTAL

Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms.

Drug: pasireotide LAR; Drug: SOM230 LAR 30 mg

Interventions

pasireotide LAR DRUG

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).

Also known as: SOM230

10 mg LAR dose; 30 mg LAR dose

SOM230 LAR 30 mg DRUG

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.

30 mg LAR dose

SOM230 LAR 10 mg DRUG

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.

10 mg LAR dose

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (82)

ClinTriCo

Phoenix, Arizona, 85381, United States

Location

University of California at Los Angeles UCLA Tiverton

Los Angeles, California, 90095, United States

Location

Harbor-UCLA Medical Center LA Biomed

Torrance, California, 90509, United States

Location

Emory University School of Medicine/Winship Cancer Institute G2304 - C2301

Atlanta, Georgia, 30322, United States

Location

Pituitary Center, Division of Endocrinology SC

Baltimore, Maryland, 21287, United States

Location

University of Michigan Comprehensive Cancer Center SC-2

Ann Arbor, Michigan, 48109-0944, United States

Location

Mount Sinai School of Medicine Mt. Sinai Medical Center

New York, New York, 10029, United States

Location

Oregon Health & Sciences University DeptofOregonHealth&Sciences(2)

Portland, Oregon, 97201, United States

Location

University of Pennsylvania - Clinical Studies Unit Unniv SC

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt University Medical Center CSOM230G2304

Nashville, Tennessee, 37212-3139, United States

Location

Swedish Medical Center Swedish

Seattle, Washington, 98122-4379, United States

Location

Medical College of Wisconsin MCW 2

Milwaukee, Wisconsin, 53226, United States

Location

Novartis Investigative Site

Buenos Aires, C1232AAC, Argentina

Location

Novartis Investigative Site

Córdoba, X5009BSN, Argentina

Location

Novartis Investigative Site

Edegem, Antwerpen, 2650, Belgium

Location

Novartis Investigative Site

Jette, Brussels Capital, 1090, Belgium

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Novartis Investigative Site

Brussels, 1070, Belgium

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Novartis Investigative Site

Ghent, 9000, Belgium

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Novartis Investigative Site

Leuven, 3000, Belgium

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Novartis Investigative Site

Fortaleza, Ceará, 60020-181, Brazil

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Novartis Investigative Site

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

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Novartis Investigative Site

Ribeirão Preto, São Paulo, 14048-900, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 05403 000, Brazil

Location

Novartis Investigative Site

Halifax, Nova Scotia, B3H 1V7, Canada

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Novartis Investigative Site

Montreal, Quebec, H2L 4M1, Canada

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Novartis Investigative Site

Sherbrooke, Quebec, J1N 5N4, Canada

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Novartis Investigative Site

Beijing, Beijing Municipality, 100730, China

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Novartis Investigative Site

Chengdu, Sichuan, 610041, China

Location

Novartis Investigative Site

Shanghai, 200025, China

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Novartis Investigative Site

Shanghai, 200040, China

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Novartis Investigative Site

Besançon, 25030, France

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Novartis Investigative Site

Caen Cedex9, 14033, France

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Novartis Investigative Site

Le Kremlin-Bicêtre, 94275, France

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Novartis Investigative Site

Lille, 59037, France

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Novartis Investigative Site

Marseille Cédex 5, 13385, France

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Novartis Investigative Site

Pessac, 33604, France

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Novartis Investigative Site

Berlin, 10117, Germany

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Novartis Investigative Site

Erlangen, 91054, Germany

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Novartis Investigative Site

Germering, 82110, Germany

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Novartis Investigative Site

Würzburg, 97080, Germany

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Novartis Investigative Site

Mumbai, Maharashtra, 400012, India

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Novartis Investigative Site

Vellore, Tamil Nadu, 632004, India

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Novartis Investigative Site

New Delhi, 110 029, India

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Novartis Investigative Site

Petah Tikva, 49100, Israel

Location

Novartis Investigative Site

Ancona, AN, 60126, Italy

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Novartis Investigative Site

Milan, MI, 20149, Italy

Location

Novartis Investigative Site

Milan, MI, 20162, Italy

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Novartis Investigative Site

Padua, PD, 35128, Italy

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Novartis Investigative Site

Napoli, 80131, Italy

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Novartis Investigative Site

Nagoya, Aichi-ken, 460-0001, Japan

Location

Novartis Investigative Site

Fukuoka, Fukuoka, 812-8582, Japan

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Novartis Investigative Site

Maebashi, Gunma, 371 8511, Japan

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Novartis Investigative Site

Sapporo, Hokkaido, 060-8648, Japan

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Novartis Investigative Site

Kobe, Hyōgo, 650-0017, Japan

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Novartis Investigative Site

Nankoku, Kochi, 783-8505, Japan

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Novartis Investigative Site

Kyoto, Kyoto, 612-8555, Japan

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Novartis Investigative Site

Suita, Osaka, 565-0871, Japan

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Novartis Investigative Site

Bunkyo-ku, Tokyo, 113-8603, Japan

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Novartis Investigative Site

Minato-ku, Tokyo, 105-8470, Japan

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Novartis Investigative Site

Shinjuku-ku, Tokyo, 162-8666, Japan

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Novartis Investigative Site

Osaka, 534-0021, Japan

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Novartis Investigative Site

Rotterdam, 3015 CE, Netherlands

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Novartis Investigative Site

Jesus Maria, Lima region, 11, Peru

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Novartis Investigative Site

Miraflores, Lima region, 18, Peru

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Novartis Investigative Site

Gdansk, 80-952, Poland

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Novartis Investigative Site

Poznan, 60-355, Poland

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Novartis Investigative Site

Warsaw, 00-909, Poland

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Novartis Investigative Site

Wroclaw, 50-367, Poland

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Novartis Investigative Site

Moscow, 119296, Russia

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Novartis Investigative Site

Saint Petersburg, 199034, Russia

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Novartis Investigative Site

Seville, Andalusia, 41013, Spain

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Novartis Investigative Site

Alzira, Valencia, 46600, Spain

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Novartis Investigative Site

Barcelona, 08041, Spain

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Novartis Investigative Site

Bangkok, 10330, Thailand

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Novartis Investigative Site

Bangkok, 10700, Thailand

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Novartis Investigative Site

Diskapi / Ankara, Ankara, 06110, Turkey (Türkiye)

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Novartis Investigative Site

Istanbul, TUR, 34098, Turkey (Türkiye)

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Novartis Investigative Site

Izmir, 35340, Turkey (Türkiye)

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Novartis Investigative Site

Salford, Manchester, M6 8HD, United Kingdom

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Novartis Investigative Site

Norwich, NR4 7UY, United Kingdom

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Novartis Investigative Site

Sheffield, S5 7AU, United Kingdom

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Novartis Investigative Site

Southampton, SO16 6YD, United Kingdom

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Related Publications (5)

• 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.

  PMID: 32385851 DERIVED

• 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.

  PMID: 31804965 DERIVED

• 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.

  PMID: 31465533 DERIVED

• 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.

  PMID: 29032078 DERIVED

• 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.

  PMID: 27405306 DERIVED

MeSH Terms

Conditions

Pituitary ACTH Hypersecretion; Hyperpituitarism

Interventions

pasireotide

Condition Hierarchy (Ancestors)

Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases

Limitations and Caveats

All analyses in this study were descriptive in nature. No comparisons were made between the two arms, and no p-values are reported. For the primary and key-secondary, success was based on estimating the response rate (and 95% CI) in each arm.

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: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2011
• First Posted: June 16, 2011
• Study Start: November 4, 2011
• Primary Completion: December 21, 2016
• Study Completion: December 21, 2016
• Last Updated: May 22, 2018
• Results First Posted: April 11, 2018

Record last verified: 2018-04

Locations

IL (1); BR (4); DE (4); CN (4); ES (3); FR (6); TU (3); IT (5); IN (3); GB (4); PL (4); CA (3); US (12); BE (5); JP (12); TH (2); AR (2); RU (2); NL (1); PE (2)