TriangleNCT01915303 · REGISTRY CONDITION SEARCH
Study of the Efficacy and Safety of Pasireotide s.c. +/- Cabergoline in Patients With Cushing's Disease
Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.
- Phase
- PHASE2
- Status at capture
- TERMINATED
- Registry last update
- 2020-09-18
The main purpose of this prospective, multicenter, open-label phase II study, was to evaluate the efficacy and safety of pasireotide alone or in combination with cabergoline in patients with Cushing's disease.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Percentage of Responders With Mean Urinary Free Cortisol (mUFC) ≤ 1.0xULN Collected or Imputed at Week 35
Mean Urinary Free Cortisol (mUFC) at Scheduled Visits
Percentage of Responders With Mean Urinary Free Cortisol (mUFC) ≤ 1.0xULN
Percentage of Participants Who Attain mUFC ≤ 1.0 x ULN or Have at Least 50% Reduction From Baseline in mUFC
Duration (Weeks) of Controlled or Partially Controlled Response
Plasma Adrenocorticotropic Hormone (ACTH)
Serum Cortisol Levels
Sitting Systolic Blood Pressure at Week 35
Sitting Diastolic Blood Pressure at Week 35
Body Weight at Week 35
Body Mass Index at Week 35
Waist Circumference at Week 35
LDL, HDL and Total Cholesterol at Week 35
Mean Scores of Cushing QoL Standardized Score at Week 17 and 35
Mean Scores of SF-12v2 Domain Scores at Week 17 and 35
Number of Participants With Improvement in Clinical Symptom of Hypercortisolism From Baseline - Facial Rubor
Number of Participants With Improvement in Clinical Symptom of Hypercortisolism From Baseline - Hirsutism
Number of Participants With Improvement in Clinical Symptom of Hypercortisolism From Baseline - Striae
Number of Participants With Improvement in Clinical Symptom of Hypercortisolism From Baseline - Supraclavicular Fat Pad
Number of Participants With Improvement in Clinical Symptom of Hypercortisolism From Baseline - Dorsal Fat Pad
Number of Participants With Shift From Mild to Severe in Clinical Signs of Hypercortisolism
Number of Patients With Shift From Standing Easily to Not Being Able to Stand
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Inclusion criteria: 1. Written informed consent obtained prior to screening procedures 2. Adult patients with confirmed diagnosis of ACTH-dependent Cushing's disease as evidenced by all of the following: 1. The mean of three 24-hour urine samples collected within 2 weeks \> 1xULN with 2 out of 3 samples \>ULN 2. Morning plasma ACTH within the normal or above normal range 3. Either MRI confirmation of pituitary adenoma \> 6 mm, or inferior petrosal sinus gradient \>3 after CRH stimulation for those patients with a tumor less than or equal to 6 mm\*. For patients who have had prior pituitary surgery, histopathology confirming an ACTH staining adenoma \*If IPSS had previously been performed without CRH (e.g. with DDAVP), then a central to peripheral pre-stimulation gradient \> 2 was required. If IPSS had not previously been performed, IPSS with CRH stimulation was required. 3. Patients with de novo Cushing's disease could only be included only if they were not considered candidates for pituitary surgery (e.g. poor surgical candidates, surgically unapproachable tumors, patients who refused to have surgical treatment) 4. Male or female patients aged 18 years or greater 5. Karnofsky performance status ≥ 60 (i.e. required occasional assistance, but was able to care for most of their personal needs) 6. Patients on medical treatment for Cushing's disease the following washout periods must have been completed before screening assessments were 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 * Progesterone receptor antagonist (mifepristone): 4 weeks 7. Patients could have been considered to enter the trial if they met any one of the following criteria: 1) They were naive to pasireotide 2) They had received pasireotide in the past and have been discontinued because of lack of efficacy (2 weeks for washout prior to screening for patients treated with pasireotide subcutaneously and 12 weeks of washout prior to screening for patients treated with pasireotide LAR) 3) Patients who were on maximal tolerated dose but had not achieved biochemical control 8. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, if they were using highly effective methods of contraception during dosing and for 30 days after stopping study medication. 9. Male participants in the trial must have agreed to use a condom during intercourse, and not to father a child during the study and for the period of 30 days following stopping of the study treatment. Exclusion criteria: 1. Patients with compression of the optic chiasm that caused any visual field defect that required surgical intervention 2. Diabetic patients with poor glycemic control as evidenced by HbA1c \>8% 3. Patients with risk factors for torsade de pointes, i.e. patients with a baseline QTcF \>450 ms in males, and \> 460 ms in females. hypokalemia, hypomagnesaemia, uncontrolled hypothyroidism, family history of long QT syndrome, or concomitant medications known to prolong QT interval. 4. Patients with clinically significant valvular disease. 5. Patients with Cushing's syndrome due to ectopic ACTH secretion 6. Patients with hypercortisolism secondary to adrenal tumors or nodular (primary) bilateral adrenal hyperplasia 7. Patients who had congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, clinically significant bradycardia, advanced heart block, history of acute MI less than one year prior to study entry or clinically significant impairment in cardiovascular function 8. Patients with liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis, or patients with ALT/AST \> 2 X ULN, serum bilirubin \>2.0 X ULN 9. Patients with serum creatinine \>2.0 X ULN 10. Patients with WBC \<3 X 10e9/L; Hb 90% \< LLN; PLT \<100 X 10e9/L 11. Patients with presence of Hepatitis B surface antigen (HbsAg) 12. Patients with presence of Hepatitis C antibody test (anti-HCV) 13. Patients with severe hepatic impairment (Child Pugh C) and hypersensitivity to pasireotide or cabergoline 14. Patients with lung, pericardial, and retroperitoneal fibrosis; gastro-duodenal ulcer or digestive haemorrhage, galactose intolerance, Parkinson's disease, uncontrolled hypertension and Raynauds syndrome. 15. Pregnant or nursing (lactating) women where pregnancy was defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (\> 5 mIU/ml) 16. Patients with end-stage renal failure and/or hemodialysis 17. Patients with presence of active or suspected acute or chronic uncontrolled infection 18. Patients with a history of non-complance to medical regimens or who were considered potentially unreliable or were unable to complete the entire study 19. Patients with presence of Hepatitis B surface antigen (HbsAg) 20. Patients with presence of Hepatitis C antibody test (anti-HCV) 21. Patients with severe hepatic impairment (Child Pugh C) and hpersensitivity to pasireotide or cabergoline 22. Patients with lung, pericardial, and retroperitoneal fibrosis; gastroduodenal ulcer or digestive haemorrhage, galactose intolerance, Parkinson's disease, uncontrolled hypertension and Raynaud's syndrome 23. Pregnant or nursing (lactating) women where pregnancy was defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (\> 5mIU/mL) 24. Patients with end-stage renal failure and/or hemodialysis
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- pasireotide alone or with cabergoline
- intervention Names
- Drug: Pasireotide with or without cabergoline
- label
- pasireotide +/- cabergoline
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- pasireotide +/- cabergoline
- description
- The trial consisted of Pasireotide-untreated patients who started pasireotide 0.6mg twice a day for 8 weeks. If biochemical control was not achieved by the end of the 8 weeks, and the 0.6mg dose is well-tolerated, the dose was increased to 0.9mg twice a day for another 8 weeks. If biochemical control is not achieved, cabergoline was added and patients began combination treatment with cabergoline at the starting dose of 0.5mg once a day for 8 weeks. If biochemical control is still not achieved at the end of the third 8 week period, the dose of cabergoline was increased to 1.0mg once a day. Patients could also immediately start the combination treatment by adding cabergoline 0.5mg once a day at study entry to their current maximal tolerated dose of pasireotide. Patients continued with the combination treatment for 8 weeks. If biochemical control was not not achieved by the end of the 8 week period, the dose of cabergoline was increased to 1mg once a day.
- name
- Pasireotide with or without cabergoline
- type
- DRUG
Study design
- allocation
- NA
- intervention Model
- SINGLE_GROUP
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 68
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- Participants who attained mUFC ≤ 1.0 x ULN (upper limit of normal) with pasireotide alone or in combination with cabergoline. The 24h-UFC concentration results from three samples, collected during the screening period, were averaged to obtain the Baseline urinary free cortisol level. mean 24h-UFC was determined from two 24-hour urine collections collected on two consecutive days that occurred before the visit. Imputation: subjects who completed the end of treatment visit at Week 35, but had missing evaluation of mean urinary free cortisol (mUFC). The last available mUFC assessment at or after previous visit (week) before last week was carried forward as the last week mUFC assessment.
- measure
- Percentage of Responders With Mean Urinary Free Cortisol (mUFC) ≤ 1.0xULN Collected or Imputed at Week 35
- time Frame
- Baseline up to week 35
- secondary Outcomes
- description
- Mean value of mUFC at each scheduled visit was determined from two 24-hour urine collections collected on two consecutive days that occurred before the visit when UFC was measured.
- measure
- Mean Urinary Free Cortisol (mUFC) at Scheduled Visits
- time Frame
- Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 8 weeks during extension
- description
- Actual mean value of mUFC at each scheduled visit was determined from two 24-hour urine collections collected on two consecutive days that occurred before the visit when UFC was measured.
- measure
- Percentage of Responders With Mean Urinary Free Cortisol (mUFC) ≤ 1.0xULN
- time Frame
- Baseline up to week 235
- description
- Actual mean value of mUFC at each scheduled visit was determined from two 24-hour urine collections collected on two consecutive days that occurred before the visit when UFC was measured.
- measure
- Percentage of Participants Who Attain mUFC ≤ 1.0 x ULN or Have at Least 50% Reduction From Baseline in mUFC
- time Frame
- Baseline up to week 235
- description
- 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% from the first time
- measure
- Duration (Weeks) of Controlled or Partially Controlled Response
- time Frame
- from the date patient's first normalization (mUFC ≤ 1.0xULN) or at least 50% reduction from baseline up to the date when the patient's mUFC > 1.0 x ULN
- description
- A pre-dose blood draw for plasma ACTH sampling was taken at visits. Samples were analyzed by a central laboratory.
- measure
- Plasma Adrenocorticotropic Hormone (ACTH)
- time Frame
- Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 8 weeks during extension
- description
- A pre-dose blood draw for an 8 am fasting serum cortisol measurement were taken at visits. Samples were analyzed by a central laboratory.
- measure
- Serum Cortisol Levels
- time Frame
- Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 8 weeks during extension
- description
- The mean arterial blood pressure determinations were obtained in the sitting position. Three measurements were taken with 5 minute intervals and the mean was used for study specific procedures
- measure
- Sitting Systolic Blood Pressure at Week 35
- time Frame
- Baseline and week 35
- description
- The mean arterial blood pressure determinations were obtained in the sitting position. Three measurements were taken with 5 minute intervals and the mean was used for study specific procedures
- measure
- Sitting Diastolic Blood Pressure at Week 35
- time Frame
- Baseline and week 35
- description
- Weight was was one of the measures of clinical symptoms of CD
- measure
- Body Weight at Week 35
- time Frame
- Baseline and week 35
- description
- Body mass index was one of the measurements of clinical symptoms of CD. Body mass index=weight in kg divided by the square of the body height (in meters)
- measure
- Body Mass Index at Week 35
- time Frame
- Baseline and week 35
- description
- Waist circumference was one of the measurements of clinical signs of CD
- measure
- Waist Circumference at Week 35
- time Frame
- Baseline and week 35
- description
- LDL=Low density lipoprotein, HDL=high density llipoprotein and total protein were analyzed by a central laboratory
- measure
- LDL, HDL and Total Cholesterol at Week 35
- time Frame
- Baseline and week 35
Full study description
- brief Summary
- The main purpose of this prospective, multicenter, open-label phase II study, was to evaluate the efficacy and safety of pasireotide alone or in combination with cabergoline in patients with Cushing's disease.
- detailed Description
- This was an open-label, multi-center, international, non-comparative study with adult patients with confirmed diagnosis of Cushing's disease. Given the fact that CD patients may need a multimodality treatment approach, the trial design aimed to mimic CD treatment by using a medical stepwise approach. Therefore, the whole patient population started treatment with Pasireotide and only in patients within this population who did not achieve biochemical control, cabergoline was added. The whole patient population had never received pasireotide or had received it in the past (reasons of discontinuation not related to safety). Core Phase * Pasireotide naïve patients started pasireotide monotherapy at the dose of 0.6 mg s.c. bid. If at the end of the 8 week treatment period, the biochemical control was not achieved and the 0.6mg bid dose was well tolerated, the pasireotide dose was increased to 0.9mg bid. If the 0.9mg bid dose of pasireotide did not lead to biochemical control, cabergoline was added with a starting dose of 0.5mg qd. If the combination dose of 0.9mg bid of pasireotide plus 0.5mg qd cabergolinedid not achieve biochemical control, the cabergoline dose will be increased to 1.0mg qd. * Patients who were currently being treated with maximal tolerated doses of pasireotide monotherapy for at least 8 weeks at screening without achieving normal mUFC, entered the study with a combination therapy starting with cabergoline 0.5mg qd. Extension Phase • After 35 weeks of treatment in core phase, patients had the option to continue study treatment if pasireotide was not yet approved for commercial use and/or reimbursed - if country reimbursement was applicable - in each respective country, or until 31st December 2017, or once an applicable roll over protocol became available, or whichever occurred first. Novartis had a local transition plan in order to ensure that all trial patients had access to the study medication without any delay in their treatment
Source references
- references
- citation
- Feelders RA, Fleseriu M, Kadioglu P, Bex M, Gonzalez-Devia D, Boguszewski CL, Yavuz DG, Patino H, Pedroncelli AM, Maamari R, Chattopadhyay A, Biller BMK, Pivonello R. Long-term efficacy and safety of subcutaneous pasireotide alone or in combination with cabergoline in Cushing's disease. Front Endocrinol (Lausanne). 2023 Oct 9;14:1165681. doi: 10.3389/fendo.2023.1165681. eCollection 2023.
- pmid
- 37876540
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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Preserved source evidence · Not medical advice