Efficacy and Safety of Pasireotide Administered Monthly in Patients With Cushing's Disease - Full Text View

Purpose

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.

Condition	Intervention	Phase
Cushing's Disease	Drug: SOM230 LAR 30 mg Drug: SOM230 LAR 10 mg	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Randomized, Double-blind, Multicenter, Phase III Study to Evaluate the Efficacy and Safety of Pasireotide LAR in Patients With Cushing's Disease

Resource links provided by NLM:

Genetics Home Reference related topics: Cushing disease familial isolated pituitary adenoma

Drug Information available for: Pasireotide

Genetic and Rare Diseases Information Center resources: Cushing Disease

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Proportion of responders in each of the two Pasireotide LAR (long acting release)regimens independently [ Time Frame: 7 months ] [ Designated as safety issue: No ]
To assess the efficacy of two Pasireotide LAR (long acting release) regimens independently in patients with Cushing's disease after 7 months of treatment regardless of up titration at month 4. A responder is defined as a patient who attains Mean Urinary Free Cortisol (mUFC) ≤ 1.0 X Upper Limit of Normal (ULN) at month 7 regardless of dose-titration.

Secondary Outcome Measures:

Proportion of responders in each of the Pasireotide LAR (long acting release) 10 mg and 30 mg doses independently in patients with Cushing's disease after 7 months of treatment who did not up titrate the doses of Pasireotide at month 4. [ Time Frame: 7 months ] [ Designated as safety issue: No ]
A responder is defined as a patient who attains mUFC ≤1.0 X ULN and had not had a dose increase at Month 4.
Change in mean urinary free cortisol from baseline at every month in the core and every 3 months in extension within the two Pasireotide LAR regimens [ Time Frame: 26 months ] [ Designated as safety issue: Yes ]
Proportion of responders in the two Pasireotide LAR regimens at every month in the core and every 3 months in the extension phases [ Time Frame: 26 months ] [ Designated as safety issue: No ]
Proportion of responders in the two Pasireotide LAR regimens as measured by controlled and partially controlled mUFC(mean urinary free cortisol) combined responders at every month in the core and every 3 months in the extension [ Time Frame: 26 months ] [ Designated as safety issue: No ]
Controlled mUFC (mean urinary free cortisol)response of the two Pasireotide regimens by month 7 and 12 [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
To evaluate the frequency of controlled mUFC response of the two Pasireotide regimens by month 7 and 12.


Enrollment:	150
Study Start Date:	November 2011
Estimated Study Completion Date:	December 2016
Estimated Primary Completion Date:	December 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 10 mg LAR dose	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	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.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01374906

Show 80 Study Locations

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators


Study Director:	Novartis Pharmaceuticals	Novartis Pharmaceuticals

More Information


Responsible Party:	Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT01374906 History of Changes
Other Study ID Numbers:	CSOM230G2304
Study First Received:	June 14, 2011
Last Updated:	July 28, 2016
Health Authority:	United States: Food and Drug Administration Netherlands: Medicines Evaluation Board (MEB) United Kingdom: Medicines and Healthcare Products Regulatory Agency Russia: Ministry of Health of the Russian Federation Turkey: Ministry of Health China: Food and Drug Administration Belgium: Federal Agency for Medicinal Products and Health Products Germany: Federal Institute for Drugs and Medical Devices France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Italy: The Italian Medicines Agency Spain: Spanish Agency of Medicines Canada: Ministry of Health & Long Term Care, Ontario Brazil: Ministry of Health Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Thailand: Food and Drug Administration Japan: Ministry of Health, Labor and Welfare India: Drugs Controller General of India Israel: Ministry of Health Peru: Instituto Nacional de Salud

Keywords provided by Novartis:


Cushing's Disease Mean Urinary Free Cortisol Pasireotide

Additional relevant MeSH terms:


Pituitary ACTH Hypersecretion ACTH-Secreting Pituitary Adenoma Hyperpituitarism Pituitary Diseases Hypothalamic Diseases Brain Diseases Central Nervous System Diseases Nervous System Diseases	Endocrine System Diseases Adenoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Pituitary Neoplasms Endocrine Gland Neoplasms Neoplasms by Site

ClinicalTrials.gov processed this record on September 27, 2016