An Open-label, Multi-center, Expanded Access Study of Pasireotide s.c. in Patients With Cushing's Disease.
- Registration Number
- NCT01582061
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
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.
- Detailed Description
Purpose of this study was to give access to pasireotide sc for patients with Cushing's disease as no medical treatment for Cushing's disease was approved at the time of the study initiation. The study population consisted of patients with persistent or recurrent Cushing's disease or patients with de novo Cushing's disease that were not considered candidates for pituitary surgery (poor surgery candidates, surgically unapproachable tumor, patients with no visible pituitary tumor, patients who refused surgery). A confirmed Cushing's disease diagnosis was required.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 104
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Pasireotide 600 μg Pasireotide sub-cutaneous 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. Pasireotide 900 μg Pasireotide sub-cutaneous 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 Outcome Measures
Name Time Method Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) Baseline up to approximately 256 weeks 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 Outcome Measures
Name Time Method Percent Change in Cushing's Disease Clinical Signs and Symptoms - Pulse Baseline, week 12, 24 and 48 Change from baseline is shown as: Percent change from baseline (BL) =((Post BL value - BL value)/ BL value)\*100
Percent Change in Cushing's Disease Clinical Signs and Symptoms - Temperature Baseline week 12, 24 and 48 degrees celius
Percent Change in Cushing's Disease Clinical Signs and Symptoms - Muscle Strength Baseline, week 12, 24 and 48 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
Percent Change From Baseline in Insulin Growth Factor - 1 (IGF - 1) Values Baseline, week 12, 24 and 48 Descriptive summary of the effect of pasireotide on IGF-1
Percent Change in Cushing Quality of Life and Work Productivity and Activity Impairment-General Health (WPAI-GH) Scores Baseline, week 12, 24 and 48 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.Percent Change in Cushing's Disease Clinical Signs and Symptoms - Body Mass Index (BMI) Baseline, week 12, 24 and 48 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
Percent Change in Cushing's Disease Clinical Signs and Symptoms - Waist Circumference Baseline, week 12, 24 and 48 Clinically relevant threshold (at any time point). Reduction of ≥ 5%, Reduction of ≥ 10%
Percentage of Patients With Mean Urinary Free Cortisol (UFC) ≤ Upper Limit of Normal (ULN) Baseline, week 12, 24 and 48 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.
Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) Baseline, week 12, 24 and 48 Standing systolic and diastolic BP based on 1 assessment and sitting systolic and diastolic BP was mean of 3 assessments.
Percent Change in Cushing's Disease Clinical Signs and Symptoms - Weight Baseline, week 12, 24 and 48 Clinically relevant threshold (at any time point) was reduction of ≥ 5%
Percent Change From Baseline in Growth Hormone (GH) Values Baseline, week 12, 24 and 48 Descriptive summary of the effect of pasireotide on GH.
Percentage of Patients Achieving a Reduction of Mean UFC ≥ 50% From Baseline Baseline, week 12, 24 and 48 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.
Percent Change in Cushing's Disease Clinical Signs and Symptoms - Hirsutism Baseline, week 12, 24 and 48 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.
Trial Locations
- Locations (18)
Advanced Research, LLC
🇺🇸Peoria, Arizona, United States
Mount Sinai School of Medicine
🇺🇸New York, New York, United States
Diabetes and Endocrinology Associates, PC
🇺🇸Omaha, Nebraska, United States
Oregon Health and Science University OHSU 5
🇺🇸Portland, Oregon, United States
University of New Mexico Hospital UNM
🇺🇸Albuquerque, New Mexico, United States
Novartis Investigative Site
🇹🇭Songkla, Thailand
Swedish Cancer Institute Swedish Cancer Institute (SC)
🇺🇸Seattle, Washington, United States
University of California at Los Angeles UCLA Tiverton
🇺🇸Los Angeles, California, United States
LA Biomedical Research at Harbor UCLA Medical Center
🇺🇸Torrance, California, United States
Emory University School of Medicine
🇺🇸Atlanta, Georgia, United States
John H Stroger Jr Hospital of Cook County
🇺🇸Chicago, Illinois, United States
University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
University of Pennsylvania Medical Center Univ Penn
🇺🇸Philadelphia, Pennsylvania, United States
Allegheny Endocrinology Associates
🇺🇸Pittsburgh, Pennsylvania, United States
St Josephs Hospital & Medical Center St Joes
🇺🇸Phoenix, Arizona, United States
Mid South Endocrine Associates
🇺🇸Nashville, Tennessee, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States