Cushing DiseasePhase 2NCT00171951
Extension Study to Assess the Safety and Efficacy of Pasireotide in Participants With Cushing's Disease
A Phase 2 study testing Pasireotide in people with Cushing Disease, run by Novartis Pharmaceuticals at 8 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cushing Disease
- What is being tested?
- Pasireotide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 8 sitesin 5 countries
- Study dates
- 13 Aug 2004to 8 Jul 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
8 sites in 5 countries.
8 sites in 5 countries
United States3 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
University of Pennsylvania Medical Center
Philadelphia, Pennsylvania, 19104-6149
Oregon Health & Sciences University Dept.ofOregonHealth&SciencesU.
Portland, Oregon, 97239
Germany2 sites
Novartis Investigative Site
Essen, 45122
Novartis Investigative Site
München, 80336
About this study
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
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.
- Conditions
- Cushing Disease
- Being tested
- Pasireotide
- Keywords
- Cushing's disease, ACTH, Cortisol, ACTH dependent Cushing's disease
- Medical subject headings
- Pituitary ACTH Hypersecretion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PasireotideDrug
Also called SOM230
Pasireotide 600 μg or 900 μg was administered as an SC injection.
| Study group | Role | What they receive |
|---|---|---|
| Pasireotide 600 μg BID SC or Ramp up Dose 900 μg BID SC | Experimental | 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. Receives: Drug: Pasireotide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Month 6
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.
Measured: Core Baseline, Days 14/15 (Core study), Months 6, 12, 24 and 102
Secondary outcomes (5)
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.
Measured: Up to approximately 106 months
Change From Baseline in Serum Cortisol Levels
Blood samples were withdrawn to obtain the serum cortisol levels. A negative change from baseline indicates improvement.
Measured: Core Baseline, Day 15 (Core study), Months 6, 12, 24, and Month 105 (end of the study)
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.
Measured: Day 15 (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.
Measured: Core Baseline, Day 15 (Core study), Months 6, 12, 24 and Month 105 (end of the study)
Change From Baseline in Gene-expression and Protein in Blood and Urine for Biomarker Development
Measured: Baseline to end of the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2005 (estimated)
- Study start13 Aug 2004
- Primary completion8 Jul 2013
- Study completion8 Jul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cushing DiseaseStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticlas, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00171951
- Sponsor's protocol ID
- CSOM230B2208E1
- Other IDs
- 2004-002407-32, 2004
- Status last verified
- May 2021
- First submitted
- 13 Sep 2005
- Last updated
- 2 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 23943009
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00171951
- Acronym / sponsor ID
- CSOM230B2208E1
- Conditions
- Cushing Disease
- Keywords
- Cushing's disease, ACTH, Cortisol, ACTH dependent Cushing's disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 13 Aug 2004 (actual)
- Primary completion
- 8 Jul 2013 (actual)
- Study completion
- 8 Jul 2013 (actual)
- First posted
- 15 Sep 2005 (estimated)
- Results
- Posted 2 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pasireotide 600 μg BID SC or Ramp up Dose 900 μg BID SC | Experimental | Drug: PasireotideParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PasireotideAlso: SOM230Pasireotide 600 μg or 900 μg was administered as an SC injection. | Drug | Pasireotide 600 μg BID SC or Ramp up Dose 900 μg BID SC |
Primary outcome
Percentage of Responders With Mean Urinary Free Cortisol (UFC) Within Normal Limits
Time frame: Month 6
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)
Time frame: Core Baseline, Days 14/15 (Core study), Months 6, 12, 24 and 102
24-hour urine samples were collected to obtain mean UFC measurements. A negative mean change from baseline indicates improvement.
5 secondary outcomes
Number of Participants Who Had At Least One Adverse Event (AE)
Time frame: Up to approximately 106 months
Change From Baseline in Serum Cortisol Levels
Time frame: Core Baseline, Day 15 (Core study), Months 6, 12, 24, and Month 105 (end of the study)
Plasma Trough Concentrations (Ctrough) of Pasireotide in UFC Responders
Time frame: Day 15 (Core study) and Month 6
Change From Baseline in Plasma Adrenocorticotropic Hormone (ACTH) Levels
Time frame: Core Baseline, Day 15 (Core study), Months 6, 12, 24 and Month 105 (end of the study)
Change From Baseline in Gene-expression and Protein in Blood and Urine for Biomarker Development
Time frame: Baseline to end of the study
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23943009Boscaro 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticlas study director
Novartis Pharmaceuticals
8 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pasireotide in people with Cushing Disease, run by Novartis Pharmaceuticals at 8 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Germany, France, Italy, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Responders With Mean Urinary Free Cortisol (UFC) Within Normal Limits (time frame: Month 6). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00171951, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2021.