Extension Study to Assess the Safety and Efficacy of Pasireotide in Participants With Cushing's Disease

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Pasireotide

About this trial

This is an interventional treatment trial for Cushing Disease focused on measuring Cushing's disease, ACTH, Cortisol, ACTH dependent Cushing's disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Participants who have completed the 15 days of Pasireotide treatment in the CSOM230B2208 study and have achieved normalization of 24-hour urinary free cortisol. Participants who did not achieve normalization of 24 -hour urinary free cortisol may be enrolled if in the opinion of the investigator the participant is getting significant clinical benefits from treatment with Pasireotide . The participant did not experience any unacceptable adverse events of tolerability issues during the original 15 day treatment. Female participants of childbearing potential who have not undergone clinically documented total hysterectomy and/or ovariectomy or tubal ligation must agree to use barrier contraception throughout the course of the extension study, and for one month after the study has ended. Exclusion Criteria: Participant who have developed poorly controlled diabetes mellitus as indicated by ketoacidosis or hemoglobin (Hgb) A1C (HgbA1C) > 10 since starting [study CSOM230B2208]. Participant with persistent alanine aminotransferase (ALT)/ aspartate transaminase (AST) or alkaline phosphatase levels more than 2.5X upper limit of normal (ULN), serum creatinine > 2.0 X ULN, serum bilirubin > 2 X ULN. Participant with abnormal coagulation (Prothrombin time (PT) and partial thromboplastin time (PTT) elevated by 30% above normal limits), white blood cells (WBC) <3.0x1'000'000'000/L; Hgb <12.0g/dL for females, Hgb <13.0g/dL for males; PLT <100x1'000'000'000/L. Other protocol-defined inclusion / exclusion criteria may apply.

Sites / Locations

Massachusetts General Hospital
Oregon Health & Sciences University Dept.ofOregonHealth&SciencesU.
University of Pennsylvania Medical Center
Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pasireotide 600 μg BID SC or Ramp up Dose 900 μg BID SC

Arm Description

Participants received pasireotide 600 micrograms (μg) twice daily (BID) subcutaneously (SC) to achieve or maintain urinary free cortisol (UFC) normalization. If UFC levels were increased at any time, participants received 900 μg BID SC, until no safety or tolerability concerns were observed as per investigators assessment. If the participant was unable to tolerate the 900 μg BID, dosing of 600 μg three times a day was given.

Outcomes

Primary Outcome Measures

Percentage of Responders With Mean Urinary Free Cortisol (UFC) Within Normal Limits

A participant was considered a responder if the mean UFC from the two 24-hour urine samples collected at Month 6 was within normal limits. The normal range for UFC is 55 to 276 nmol/day.

Change From Baseline in Mean Urinary Free Cortisol (UFC)

24-hour urine samples were collected to obtain mean UFC measurements. A negative mean change from baseline indicates improvement.

Secondary Outcome Measures

Number of Participants Who Had At Least One Adverse Event (AE)

An AE was any undesirable sign, symptom or medical condition occurring after starting study drug even if the event is not considered to be related to study drug. AEs were assessed according to incident dose group: Pasireotide 1200 μg sc total daily dose (TDD), Pasireotide 1800 μg SC TDD and Pasireotide SC Any Dose. The incident dose for an AE was the last total daily dose administered on or prior to the AE onset date.

Change From Baseline in Serum Cortisol Levels

Blood samples were withdrawn to obtain the serum cortisol levels. A negative change from baseline indicates improvement.

Plasma Trough Concentrations (Ctrough) of Pasireotide in UFC Responders

Participants with Cushing's disease were considered responders if mean UFC levels from the 24-hour urine collections at Day 15 (Core study) and at extension Month 6, were within normal limits. Ctrough levels of pasireotide were measured at Day 15 of Core study and Month 6.

Change From Baseline in Plasma Adrenocorticotropic Hormone (ACTH) Levels

Blood samples were withdrawn to obtain the ACTH levels. A negative change from baseline indicates improvement.

Change From Baseline in Gene-expression and Protein in Blood and Urine for Biomarker Development

Full Information

NCT ID

NCT00171951

First Posted

September 13, 2005

Last Updated

May 6, 2021

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT00171951

Brief Title

Extension Study to Assess the Safety and Efficacy of Pasireotide in Participants With Cushing's Disease

Official Title

Extension to a Multicenter, Open-label Study to Assess the Safety and Efficacy of 600 μg SOM230, Administered Subcutaneously, Bid in Patients With Cushing's Disease

Study Type

Interventional

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Completed

Study Start Date

August 13, 2004 (Actual)

Primary Completion Date

July 8, 2013 (Actual)

Study Completion Date

July 8, 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

No

5. Study Description

Brief Summary

Cushing's disease is a rare serious condition that is caused by an adrenocorticotropic hormone (ACTH) secreting pituitary adenoma. This study assessed the long-term safety and efficacy of pasireotide in participants with Cushing's disease.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cushing Disease

Keywords

Cushing's disease, ACTH, Cortisol, ACTH dependent Cushing's disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

19 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Pasireotide 600 μg BID SC or Ramp up Dose 900 μg BID SC

Arm Type

Experimental

Arm Description

Participants received pasireotide 600 micrograms (μg) twice daily (BID) subcutaneously (SC) to achieve or maintain urinary free cortisol (UFC) normalization. If UFC levels were increased at any time, participants received 900 μg BID SC, until no safety or tolerability concerns were observed as per investigators assessment. If the participant was unable to tolerate the 900 μg BID, dosing of 600 μg three times a day was given.

Intervention Type

Drug

Intervention Name(s)

Pasireotide

Other Intervention Name(s)

SOM230

Intervention Description

Pasireotide 600 μg or 900 μg was administered as an SC injection.

Primary Outcome Measure Information:

Title

Percentage of Responders With Mean Urinary Free Cortisol (UFC) Within Normal Limits

Description

A participant was considered a responder if the mean UFC from the two 24-hour urine samples collected at Month 6 was within normal limits. The normal range for UFC is 55 to 276 nmol/day.

Time Frame

Month 6

Title

Change From Baseline in Mean Urinary Free Cortisol (UFC)

Description

24-hour urine samples were collected to obtain mean UFC measurements. A negative mean change from baseline indicates improvement.

Time Frame

Core Baseline, Days 14/15 (Core study), Months 6, 12, 24 and 102

Secondary Outcome Measure Information:

Title

Number of Participants Who Had At Least One Adverse Event (AE)

Description

An AE was any undesirable sign, symptom or medical condition occurring after starting study drug even if the event is not considered to be related to study drug. AEs were assessed according to incident dose group: Pasireotide 1200 μg sc total daily dose (TDD), Pasireotide 1800 μg SC TDD and Pasireotide SC Any Dose. The incident dose for an AE was the last total daily dose administered on or prior to the AE onset date.

Time Frame

Up to approximately 106 months

Title

Change From Baseline in Serum Cortisol Levels

Description

Blood samples were withdrawn to obtain the serum cortisol levels. A negative change from baseline indicates improvement.

Time Frame

Core Baseline, Day 15 (Core study), Months 6, 12, 24, and Month 105 (end of the study)

Title

Plasma Trough Concentrations (Ctrough) of Pasireotide in UFC Responders

Description

Participants with Cushing's disease were considered responders if mean UFC levels from the 24-hour urine collections at Day 15 (Core study) and at extension Month 6, were within normal limits. Ctrough levels of pasireotide were measured at Day 15 of Core study and Month 6.

Time Frame

Day 15 (Core study) and Month 6

Title

Change From Baseline in Plasma Adrenocorticotropic Hormone (ACTH) Levels

Description

Blood samples were withdrawn to obtain the ACTH levels. A negative change from baseline indicates improvement.

Time Frame

Core Baseline, Day 15 (Core study), Months 6, 12, 24 and Month 105 (end of the study)

Title

Change From Baseline in Gene-expression and Protein in Blood and Urine for Biomarker Development

Time Frame

Baseline to end of the study

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: Participants who have completed the 15 days of Pasireotide treatment in the CSOM230B2208 study and have achieved normalization of 24-hour urinary free cortisol. Participants who did not achieve normalization of 24 -hour urinary free cortisol may be enrolled if in the opinion of the investigator the participant is getting significant clinical benefits from treatment with Pasireotide . The participant did not experience any unacceptable adverse events of tolerability issues during the original 15 day treatment. Female participants of childbearing potential who have not undergone clinically documented total hysterectomy and/or ovariectomy or tubal ligation must agree to use barrier contraception throughout the course of the extension study, and for one month after the study has ended. Exclusion Criteria: Participant who have developed poorly controlled diabetes mellitus as indicated by ketoacidosis or hemoglobin (Hgb) A1C (HgbA1C) > 10 since starting [study CSOM230B2208]. Participant with persistent alanine aminotransferase (ALT)/ aspartate transaminase (AST) or alkaline phosphatase levels more than 2.5X upper limit of normal (ULN), serum creatinine > 2.0 X ULN, serum bilirubin > 2 X ULN. Participant with abnormal coagulation (Prothrombin time (PT) and partial thromboplastin time (PTT) elevated by 30% above normal limits), white blood cells (WBC) <3.0x1'000'000'000/L; Hgb <12.0g/dL for females, Hgb <13.0g/dL for males; PLT <100x1'000'000'000/L. Other protocol-defined inclusion / exclusion criteria may apply.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticlas

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Massachusetts General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

Oregon Health & Sciences University Dept.ofOregonHealth&SciencesU.

City

Portland

State/Province

Oregon

ZIP/Postal Code

97239

Country

United States

Facility Name

University of Pennsylvania Medical Center

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104-6149

Country

United States

Facility Name

Novartis Investigative Site

City

Paris

ZIP/Postal Code

75006

Country

France

Facility Name

Novartis Investigative Site

City

Essen

ZIP/Postal Code

45122

Country

Germany

Facility Name

Novartis Investigative Site

City

Muenchen

ZIP/Postal Code

80336

Country

Germany

Facility Name

Novartis Investigative Site

City

Ancona

State/Province

AN

ZIP/Postal Code

60126

Country

Italy

Facility Name

Novartis Investigative Site

City

Belfast

ZIP/Postal Code

BT12 6BA

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

23943009

Citation

Boscaro M, Bertherat J, Findling J, Fleseriu M, Atkinson AB, Petersenn S, Schopohl J, Snyder P, Hughes G, Trovato A, Hu K, Maldonado M, Biller BM. Extended treatment of Cushing's disease with pasireotide: results from a 2-year, Phase II study. Pituitary. 2014 Aug;17(4):320-6. doi: 10.1007/s11102-013-0503-3.

Results Reference

result

Cushing Disease

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial