Skip to content

Trial · Interventional

TerminatedPhase 2Results postedRegistry data

Study of the Efficacy and Safety of Pasireotide s.c. +/- Cabergoline in Patients With Cushing's Disease

NCTNCT01915303 (opens ClinicalTrials.gov in a new tab)Other idCSOM230B2411
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Terminated
Phase
Phase 2
Enrollment
68 participants (actual)
Sponsor
Novartis Pharmaceuticals · Industry
Design
Allocation not applicable · Open label (no masking)
Countries
16 countries

United States, Argentina, Belgium, Brazil, Colombia, France, Germany, Greece, Hungary, India, Italy, Malaysia, Mexico, Netherlands, Spain, Turkey (Türkiye)

Start
6 Mar 2014
Primary completion
5 Sept 2016
Completion
4 Sept 2019
First posted
2 Aug 2013 (estimated)
Last update posted
18 Sept 2020
Conditions
Cushings Disease

Timeline

1 trial · 1 stopped early · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2014201520162017201820192020
  1. Ph 2

    Study of the Efficacy and Safety of Pasireotide s.c. +/- Cabergoline in Patients With Cushing's Disease

    NCT01915303

    6 Mar 2014 to 4 Sept 2019

    Terminated

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • Pasireotide with or without cabergolineDrug

Arms1

  • Experimental

    pasireotide +/- cabergoline

    pasireotide alone or with cabergoline

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Percentage of Responders With Mean Urinary Free Cortisol (mUFC) ≤ 1.0xULN Collected or Imputed at Week 35

    Time frame · Baseline up to week 35

    Registry 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.

Secondary outcomes(20)

  1. 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

    Registry 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.

  2. Percentage of Responders With Mean Urinary Free Cortisol (mUFC) ≤ 1.0xULN

    Time frame · Baseline up to week 235

    Registry 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.

  3. 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

    Registry 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.

  4. 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

    Registry 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

  5. Plasma Adrenocorticotropic Hormone (ACTH)

    Time frame · Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 8 weeks during extension

    Registry description

    A pre-dose blood draw for plasma ACTH sampling was taken at visits. Samples were analyzed by a central laboratory.

  6. Serum Cortisol Levels

    Time frame · Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 8 weeks during extension

    Registry 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.

  7. Sitting Systolic Blood Pressure at Week 35

    Time frame · Baseline and week 35

    Registry 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

  8. Sitting Diastolic Blood Pressure at Week 35

    Time frame · Baseline and week 35

    Registry 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

  9. Body Weight at Week 35

    Time frame · Baseline and week 35

    Registry description

    Weight was was one of the measures of clinical symptoms of CD

  10. Body Mass Index at Week 35

    Time frame · Baseline and week 35

    Registry 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)

  11. Waist Circumference at Week 35

    Time frame · Baseline and week 35

    Registry description

    Waist circumference was one of the measurements of clinical signs of CD

  12. LDL, HDL and Total Cholesterol at Week 35

    Time frame · Baseline and week 35

    Registry description

    LDL=Low density lipoprotein, HDL=high density llipoprotein and total protein were analyzed by a central laboratory

  13. Mean Scores of Cushing QoL Standardized Score at Week 17 and 35

    Time frame · Baseline and week 17 and 35

    Registry description

    Patients who completed nine or more items for the 12-item Cushing's syndrome QoL questionaire were considered evaluable for that assessment. Raw scores were obtained for the 12 items using the following scoring: 1) always or very much, 2) often or quite a bit, 3) sometimes or somewhat, 4) rarely or very little, 5) never or not at all. Then the standardized score, Y, was calculated for each patient as follows: Y = 100\* (X - n) / n\*5 - n\*1) = 100 \* (X - n) / 4\*n where X denoted the raw score and n the number of questions answered by the patient. The higher the score, the better the QoL. The best possible standardized score was 100 and the worst possible standardized score was 0

  14. Mean Scores of SF-12v2 Domain Scores at Week 17 and 35

    Time frame · Baseline, week 17 and 35

    Registry description

    SF-12v2 General Health Survey is a general patient reported outcome instrument over time. It is scored to provide eight health domain scores (Bodily Pain (BP), General Health (GH), Physical Functioning (PF), Role-Physical (RP), Social Functioning (SF), Role-Emotional (RE), Vitality (VT) and Mental Health (MH)). These eight domain scores can be combined to form two summary scores reflecting overall physical and mental health: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). The analyses reported here focus on PCS and MCS scores. The domain scores use a norm-based score, which standardizes the scores with respect to the mean and standard deviation of a nationally representative sample of United States (US) adults. These are the scores on the original scale which have not been transformed in any way. The possible range of scores is 0 to 100, with higher scores representing better outcomes.

  15. Number of Participants With Improvement in Clinical Symptom of Hypercortisolism From Baseline - Facial Rubor

    Time frame · Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 16 weeks during extension

    Registry description

    Clinical symptoms include: facial rubor, hirsutism, striae, and supraclavicular and dorsal fat pad. Two photographs, one frontal and one lateral from the shoulders up were taken to assess facial plethora, supraclavicular and dorsal fat pads. Two photographs, frontal and dorsal of the trunk with patient in standing position were taken to assess striae, and hirsutism. The photographs were assessed by a qualified physician at the site. Improvement=decrease in severity of symptom since baseline

  16. Number of Participants With Improvement in Clinical Symptom of Hypercortisolism From Baseline - Hirsutism

    Time frame · Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 16 weeks during extension

    Registry description

    Clinical symptoms include: facial rubor, hirsutism, striae, and supraclavicular and dorsal fat pad. Two photographs, one frontal and one lateral from the shoulders up were taken to assess facial plethora, supraclavicular and dorsal fat pads. Two photographs, frontal and dorsal of the trunk with patient in standing position were taken to assess striae, and hirsutism. The photographs were assessed by a qualified physician at the site. Improvement=decrease in severity of symptom since baseline

  17. Number of Participants With Improvement in Clinical Symptom of Hypercortisolism From Baseline - Striae

    Time frame · Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 16 weeks during extension

    Registry description

    Clinical symptoms include: facial rubor, hirsutism, striae, and supraclavicular and dorsal fat pad. Two photographs, one frontal and one lateral from the shoulders up were taken to assess facial plethora, supraclavicular and dorsal fat pads. Two photographs, frontal and dorsal of the trunk with patient in standing position were taken to assess striae, and hirsutism. The photographs were assessed by a qualified physician at the site. Improvement=decrease in severity of symptom since baseline

  18. Number of Participants With Improvement in Clinical Symptom of Hypercortisolism From Baseline - Supraclavicular Fat Pad

    Time frame · Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 8 weeks during extension

    Registry description

    Clinical symptoms include: facial rubor, hirsutism, striae, and supraclavicular and dorsal fat pad. Two photographs, one frontal and one lateral from the shoulders up were taken to assess facial plethora, supraclavicular and dorsal fat pads. Two photographs, frontal and dorsal of the trunk with patient in standing position were taken to assess striae, and hirsutism. The photographs were assessed by a qualified physician at the site. Improvement=decrease in severity of symptom since baseline

  19. Number of Participants With Improvement in Clinical Symptom of Hypercortisolism From Baseline - Dorsal Fat Pad

    Time frame · Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 16 weeks during extension

    Registry description

    Clinical symptoms include: facial rubor, hirsutism, striae, and supraclavicular and dorsal fat pad. Two photographs, one frontal and one lateral from the shoulders up were taken to assess facial plethora, supraclavicular and dorsal fat pads. Two photographs, frontal and dorsal of the trunk with patient in standing position were taken to assess striae, and hirsutism. The photographs were assessed by a qualified physician at the site. Improvement=decrease in severity of symptom since baseline

  20. Number of Participants With Shift From Mild to Severe in Clinical Signs of Hypercortisolism

    Time frame · Baseline, weeks 1, 2, 4, every 4 or 5 weeks during core, every 8 weeks during extension

    Registry description

    Facial rubor, hirsutism, striae, and supraclavicular and dorsal fat pad were assessed. Two photographs, one frontal and one lateral from the shoulders up will be taken to assess facial plethora, supraclavicular and dorsal fat pads. Two photographs, frontal and dorsal of the trunk with patient in standing position will be taken to assess striae, and hirsutism. The photographs must be assessed by a qualified physician at the site. Improvement=decrease in severity of symptom since baseline

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeNumber· Baseline up to week 35

Percentage of Responders With Mean Urinary Free Cortisol (mUFC) ≤ 1.0xULN Collected or Imputed at Week 35

GroupValue (percentage of responders)
All Patients50.0
Secondary and other outcome results(7)
Secondary outcomeMean· Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 8 weeks during extension

Mean Urinary Free Cortisol (mUFC) at Scheduled Visits

GroupValue (nmol/24h)Spread
All Patients501.6488.66
Secondary outcomeNumber· Baseline up to week 235

Percentage of Responders With Mean Urinary Free Cortisol (mUFC) ≤ 1.0xULN

GroupValue (percentage of responders)
All Patients4.4
Secondary outcomeNumber· Baseline up to week 235

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

GroupValue (percentage of responders)
All Patients4.4
Secondary outcomeMedian· 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

Duration (Weeks) of Controlled or Partially Controlled Response

GroupValue (weeks)
All Patients13.1
Secondary outcomeMean· Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 8 weeks during extension

Plasma Adrenocorticotropic Hormone (ACTH)

GroupValue (pmol/L)Spread
All Patients16.316.3
Secondary outcomeMean· Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 8 weeks during extension

Serum Cortisol Levels

GroupValue (nmol/L)Spread
All Patients738.6332.53
Secondary outcomeMean· Baseline and week 35

Sitting Systolic Blood Pressure at Week 35

GroupValue (mmHg)Spread
All Patients125.914.3

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
All PatientsPasireotide montherapy (0.6 mg bid to 0.9 mg bid) was administered until the biochemical control was achieved and if not achieved, a combination was administered: pasireotide (0.9 mg bid) + cabergoline (0.5 QD to 1 mg QD). Patients were able to add cabergoline at anytime during core and extension3 / 6815 / 6867 / 68

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies1

Studies that cite this trial.

Studies with results

1 study on this page

Indexing hint: Clinical trial · 2023

2 results

Long-term efficacy and safety of subcutaneous pasireotide alone or in combination with cabergoline in Cushing's disease.

Feelders et al. 2023Frontiers in endocrinologycited by 16

PMID 37876540PMC10593462DOI 10.3389/fendo.2023.1165681PUB-37876540

CC BY2 results
Download PDFSee results (2)

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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

PepBank is a research reference. Talk to a doctor before you use any peptide.