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Trial · Interventional

CompletedPhase 3Results postedRegistry data

An Open-label, Multi-center, Expanded Access Study of Pasireotide s.c. in Patients With Cushing's Disease.

Short name SEASCAPE

Overview

Status
Completed
Phase
Phase 3
Enrollment
104 participants (actual)
Sponsor
Novartis Pharmaceuticals · Industry
Design
Not randomized · Open label (no masking)
Countries
11 countries

United States, Brazil, Czechia, Germany, Greece, Lebanon, Romania, Russia, South Korea, Spain, Thailand

Start
16 Aug 2011
Primary completion
26 Jan 2017
Completion
26 Jan 2017
First posted
20 Apr 2012 (estimated)
Last update posted
19 Jun 2018
Conditions
Cushing's Disease

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2012201420162018
  1. Ph 3

    SEASCAPE

    NCT01582061

    16 Aug 2011 to 26 Jan 2017

Registry summary

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

This study provided access to pasireotide sc in patients with Cushing's disease.and provided additional information for safety and efficacy of pasireotide s.c.

Interventions

  • Pasireotide sub-cutaneousDrug

Arms2

  • Experimental

    Pasireotide 600 μg

    Pasireotide sub-cutaneous was supplied in 1 ml ampoules containing 600 μg pasireotide per 1 ml of solution and was administered BID. Starting dose was 600 μg for glucose impaired metabolism patients. Mean daily dose category is defined on the mean daily dose considering the following grouping rule: 600 μg bid group includes all patients whose mean daily dose \< 1500 μg /day.

  • Experimental

    Pasireotide 900 μg

    Pasireotide sub-cutaneous was supplied in 1 ml ampoules containing 900 μg pasireotide per 1 ml of solution and was administered BID. Starting dose was 900 μg. Mean daily dose category is defined on the mean daily dose considering the following grouping rule: 900 μg bid group includes all patients whose mean daily dose ≥ 1500 μg /day

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE)

    Time frame · Baseline up to approximately 256 weeks

    Registry description

    Only AEs occurring on or after the start of study treatment and no more than 28 days after the discontinuation of study treatment. A patient with multiple occurrences of an AE under one treatment is counted only once in the AE category for that treatment. A patient with multiple severity grades for an AE while on a treatment, is only counted under the maximum grade.

Secondary outcomes(13)
  1. Percentage of Patients With Mean Urinary Free Cortisol (UFC) ≤ Upper Limit of Normal (ULN)

    Time frame · Baseline, week 12, 24 and 48

    Registry description

    The 24h-UFC concentration results from three samples during screening were averaged to obtain baseline. After baseline, mean 24h UFC was determined at week 24. At Week 4, 8, 16 and 20, mean 24h UFC was determined from two 24 hour urine collections collected on two consecutive days occurring before the visit. At Week 12, 24 and 48, the mean 24h-UFC from three 24 hour urine collections, collected over the week before the visit, was determined. After Week 24, the mean 24h UFC was determined at 12-week intervals until end of study visit, from two 24 hour collections during two consecutive days prior to each respective visit (except at Week 48). UFC was determined by liquid chromatography tandem mass spectroscopy (LC/MS/MS). The normal ranges were determined by the central laboratory's own reference range. All samples, including screening samples, were analyzed by a central laboratory.

  2. Percentage of Patients Achieving a Reduction of Mean UFC ≥ 50% From Baseline

    Time frame · Baseline, week 12, 24 and 48

    Registry description

    The 24h-UFC concentration results from three samples during screening were averaged to obtain baseline. After baseline, mean 24h UFC was determined at week 24. At Week 4, 8, 16 and 20, mean 24h UFC was determined from two 24 hour urine collections collected on two consecutive days occurring before the visit. At Week 12, 24 and 48, the mean 24h-UFC from three 24 hour urine collections, collected over the week before the visit, was determined. After Week 24, the mean 24h UFC was determined at 12-week intervals until end of study visit, from two 24 hour collections during two consecutive days prior to each respective visit (except at Week 48). UFC was determined by liquid chromatography tandem mass spectroscopy (LC/MS/MS). The normal ranges were determined by the central laboratory's own reference range. All samples, including screening samples, were analyzed by a central laboratory.

  3. Percent Change in Cushing Quality of Life and Work Productivity and Activity Impairment-General Health (WPAI-GH) Scores

    Time frame · Baseline, week 12, 24 and 48

    Registry description

    A 12-item Cushing's syndrome HRQoL questionnaire (CushingQoL, cf. Webb et al 2008) was implemented and patients who completed 9 or more items at a visit were considered evaluable for that visit. The standardized scores were calculated as follows: 1) Obtain raw scores, denoted by X, as the sum of all the ratings on all the HRQoL questions for a single patient and the score can range from 12 (worst HRQoL) to 60 points (best HRQoL). Therefore, the lower the score, greater the negative impact on HRQoL and 2) obtain standardized score, Y, for a single patient • Y = 100 (X-12) / (60-12) = 100 (X-12)/48. For example, if a patient answers all 12 items with 'Sometimes' or 'Somewhat', X = 36 and Y = 100 ∙ 24/48 = 50 The WPAI-GH questionnaire was used to assess work productivity and activity impairment. However, there was very limited baseline data and therefore the results and outcomes of the objective, 'change from baseline in WPAI-GH scores' are not included.

  4. Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP)

    Time frame · Baseline, week 12, 24 and 48

    Registry description

    Standing systolic and diastolic BP based on 1 assessment and sitting systolic and diastolic BP was mean of 3 assessments.

  5. Percent Change in Cushing's Disease Clinical Signs and Symptoms - Pulse

    Time frame · Baseline, week 12, 24 and 48

    Registry description

    Change from baseline is shown as: Percent change from baseline (BL) =((Post BL value - BL value)/ BL value)\*100

  6. Percent Change in Cushing's Disease Clinical Signs and Symptoms - Temperature

    Time frame · Baseline week 12, 24 and 48

    Registry description

    degrees celius

  7. Percent Change in Cushing's Disease Clinical Signs and Symptoms - Body Mass Index (BMI)

    Time frame · Baseline, week 12, 24 and 48

    Registry description

    Percent change in patients reducing by at least one class level. Class levels: \<25.0, 25.0 to \<30.0, ≥ 30.0. Percent change from baseline (BL) =((Post BL value - BL value)/ BL value)\*100

  8. Percent Change in Cushing's Disease Clinical Signs and Symptoms - Weight

    Time frame · Baseline, week 12, 24 and 48

    Registry description

    Clinically relevant threshold (at any time point) was reduction of ≥ 5%

  9. Percent Change in Cushing's Disease Clinical Signs and Symptoms - Muscle Strength

    Time frame · Baseline, week 12, 24 and 48

    Registry description

    Direct observation of ability to stand unaided: 0=able to stand easily with arms extended, 1=able to stand after several efforts without using arms as assistance, 2=able to stand only by using arms as assistance 3=completely unable to stand

  10. Percent Change in Cushing's Disease Clinical Signs and Symptoms - Waist Circumference

    Time frame · Baseline, week 12, 24 and 48

    Registry description

    Clinically relevant threshold (at any time point). Reduction of ≥ 5%, Reduction of ≥ 10%

  11. Percent Change in Cushing's Disease Clinical Signs and Symptoms - Hirsutism

    Time frame · Baseline, week 12, 24 and 48

    Registry description

    Change from baseline is shown as: Percent change from baseline (BL) =((Post BL value - BL value)/ BL value)\*100. Ferriman-Gallway scoring was used: 0=minimum and 36 was maximum in females only.

  12. Percent Change From Baseline in Growth Hormone (GH) Values

    Time frame · Baseline, week 12, 24 and 48

    Registry description

    Descriptive summary of the effect of pasireotide on GH.

  13. Percent Change From Baseline in Insulin Growth Factor - 1 (IGF - 1) Values

    Time frame · Baseline, week 12, 24 and 48

    Registry description

    Descriptive summary of the effect of pasireotide on IGF-1

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 approximately 256 weeks

Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE)

GroupValue (percentage of participants)
600 µg Bid - All Grades53.1
600 μg - Grades 3/453.1
900 μg - All Grades29.1
900 μg - Grades 3/427.3
All Patients - All Grades40.4
All Patients - Grades 3/439.4
Secondary and other outcome results(7)
Secondary outcomeNumber· Baseline, week 12, 24 and 48

Percentage of Patients With Mean Urinary Free Cortisol (UFC) ≤ Upper Limit of Normal (ULN)

GroupValue (percentage of participants)
Pasireotide 600 μg77.8
Pasireotide 900 μg38.5
All Patients54.5
Secondary outcomeNumber· Baseline, week 12, 24 and 48

Percentage of Patients Achieving a Reduction of Mean UFC ≥ 50% From Baseline

GroupValue (percentage of participants)
Pasireotide 600 μg74.1
Pasireotide 900 μg48.7
All Patients59.1
Secondary outcomeMean· Baseline, week 12, 24 and 48

Percent Change in Cushing Quality of Life and Work Productivity and Activity Impairment-General Health (WPAI-GH) Scores

GroupValue (percent change in score)Spread
Pasireotide 600 μg21.347.03
Pasireotide 900 μg100.8252.25
All Patients67.1197.09
Secondary outcomeMean· Baseline, week 12, 24 and 48

Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP)

GroupValue (percent change of mmhg)Spread
Pasireotide 600 μg-6.812.04
Pasireotide 900 μg-1.414.40
All Patients-3.813.61
Secondary outcomeMean· Baseline, week 12, 24 and 48

Percent Change in Cushing's Disease Clinical Signs and Symptoms - Pulse

GroupValue (percent change in bpm)Spread
Pasireotide 600 μg2.318.93
Pasireotide 900 μg-7.511.50
All Patients-3.215.87
Secondary outcomeMean· Baseline week 12, 24 and 48

Percent Change in Cushing's Disease Clinical Signs and Symptoms - Temperature

GroupValue (percent change in celius)Spread
600 µg Bid - All Grades0.11.26
900 μg - All Grades-0.31.06
All Patients - All Grades-0.11.17
Secondary outcomeMean· Baseline, week 12, 24 and 48

Percent Change in Cushing's Disease Clinical Signs and Symptoms - Body Mass Index (BMI)

GroupValue (percent change in kg/m2)Spread
Pasireotide 600 μg-4.23.70
Pasireotide 900 μg-4.85.38
All Patients-4.54.69

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
600 µg Bid600 µg bid0 / 4913 / 4949 / 49
900 µg Bid900 µg bid1 / 5517 / 5554 / 55
All PatientsAll patients1 / 10430 / 104103 / 104

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.

More studies

1 study on this page

PubMed tag: none · 2019

Safety and Efficacy of Subcutaneous Pasireotide in Patients With Cushing's Disease: Results From an Open-Label, Multicenter, Single-Arm, Multinational, Expanded-Access Study.

Fleseriu et al. 2019Frontiers in endocrinologycited by 13

PMID 31379734PMC6646464DOI 10.3389/fendo.2019.00436PUB-31379734

CC BY
Download PDF

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 any screening procedures 2. Male or female patients aged 18 years or greater 3. Patients with confirmed diagnosis of Cushing's disease as evidenced by mean urinary free cortisol of three 24-hour urine samples collected during the 3-week screening period above the upper limit of the laboratory normal range morning plasma ACTH within the normal or above normal range either MRI confirmation of pituitary adenoma (greater than or equal to 0.6 cm), or inferior petrosal sinus gradient \>3 after CRH stimulation for those patients with a microadenoma less than 0.6 cm, or for patients who have had prior pituitary surgery, histopathology confirming an ACTH staining adenoma. 4. Patients with de novo Cushing's disease must not be considered as candidates for pituitary surgery (i.e. poor surgical candidates, surgically unapproachable tumors, patients with no visible pituitary tumor, patients who refuse to have surgical treatment) 5. Karnofsky performance status \>60 (i.e. requires occasional assistance, but is able to care for most of his personal needs) 6. For patients on previous medical treatment for Cushing's disease the following washout periods must be completed before screening assessments are performed * Inhibitors of steroidogenesis (e.g. ketoconazole, metyrapone, rosiglitazone): 1 week * Dopamine agonists (e.g. bromocriptine, cabergoline): 4 weeks * Mitotane: 6 months * Octreotide LAR and Lanreotide autogel: 8 weeks * Lanreotide SR: 4 weeks * Octreotide (immediate release formulation): 1 week * Glucocorticoid receptor inhibitor (mifepristone): 4 weeks Exclusion criteria: 1. Radiotherapy of the pituitary \<4 weeks before screening or patient who has not recovered from side effects 2. Patients with compression of the optic chiasm causing acute clinically significant visual field defect 3. Patients with Cushing's syndrome due to ectopic ACTH secretion 4. Patients with hypercortisolism secondary to adrenal tumors or nodular (primary) bilateral adrenal hyperplasia 5. Patients who have a known inherited syndrome as the cause for hormone over secretion (i.e. Carney Complex, McCune-Albright syndrome, MEN-1) 6. Patients with a diagnosis of glucocorticoid-remedial aldosteronism (GRA) 7. Patients who have undergone major surgery within 1 month prior to screening 8. Patients with known gallbladder or bile duct disease, acute or chronic pancreatitis (patients with asymptomatic cholelithiasis and asymptomatic bile duct dilation can be included) 9. Diabetic patients whose blood glucose is poorly controlled as evidenced by HbA1C \>8% 10. Patients who have clinically significant impairment in cardiovascular function or are at risk thereof, as evidenced by congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, clinically significant bradycardia, high grade AV block, history of acute MI less than one year prior to study entry * QTcF \>450 msec at screening * History of syncope or family history of idiopathic sudden death * Risk factors for Torsades de Pointes such as uncorrected hypokalemia, uncorrected hypomagnesemia, cardiac failure * Concomitant disease(s) that could prolong the QT interval such as autonomic neuropathy (caused by diabetes or Parkinson's disease), HIV, cirrhosis, uncontrolled hypothyroidism, concomitant medication(s) with known risk for TdP 11. Patients with liver disease or history of liver disease such as cirrhosis, chronic active hepatitis B and C, or chronic persistent hepatitis, or patients with ALT or AST more than 2 x ULN, serum creatinine \>2.0 x ULN, serum bilirubin \>1.5 x ULN, serum albumin \< 0.67 x LLN at screening 12. Patients who have any current or prior medical condition that can interfere with the conduct of the study or the evaluation of its results, such as * History of immunocompromise, including a positive HIV test result (Elisa and Western blot). An HIV test will not be required, however, previous medical history will be reviewed * Presence of active or suspected acute or chronic uncontrolled infection * History of, or current alcohol misuse/abuse in the 12 month period prior to screening 13. Female patients who are pregnant or lactating, or are of childbearing potential and not practicing a medically acceptable method of birth control. If a woman is participating in the trial then one form of contraception is sufficient (pill or diaphragm) and the partner should use a condom. If oral contraception is used in addition to condoms, the patient must have been practicing this method for at least two months prior to screening and must agree to continue the oral contraceptive throughout the course of the study and for one month after the study has ended. Male patients who are sexually active are required to use condoms during the study and for three month afterwards as a precautionary measure (available data do not suggest any increased reproductive risk with the study drugs) 14. Patients who have participated in any clinical investigation with an investigational drug within 1 month prior to screening or patients who have previously been treated with pasireotide 15. Known hypersensitivity to somatostatin analogues 16. Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will be unable to complete the entire study 17. Patients with presence of Hepatitis B surface antigen (HbsAg) 18. Patients with presence of Hepatitis C antibody test (anti-HCV)

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