Efficacy and Safety of Pasireotide Administered Monthly in Patients With Cushing's Disease
Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01374906
Collaborator
(none)
150
82
2
61.6
1.8
0
Study Details
Study Description
Brief Summary
This is a randomized, double-blind, multicenter, phase III study to evaluate the safety and efficacy of 2 dosing regiments of Pasireotide long acting release (LAR) in patients with Cushing's disease.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
150 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-blind, Multicenter, Phase III Study to Evaluate the Efficacy and Safety of Pasireotide LAR in Patients With Cushing's Disease
Actual Study Start Date
:
Nov 4, 2011
Actual Primary Completion Date
:
Dec 21, 2016
Actual Study Completion Date
:
Dec 21, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 10 mg LAR dose Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. |
Drug: pasireotide LAR
Pasireotide long-acting was administered as an intra-muscular depot intragluteal injection once every 28 days (±2 days). Patients were administered pasireotide long-acting 10 mg or 30 mg for four months, followed by either continuation of the starting dose, or dose up-titration (if mUFC was still >1.5xULN unless titration was precluded by safety reasons).
Other Names:
Drug: SOM230 LAR 10 mg
starting does of SOM230 LAR 10 mg i.m. administered once every 28 days for 4 months, followed by dose up-titration or continuation of the starting dose.
|
| Experimental: 30 mg LAR dose Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. |
Drug: pasireotide LAR
Pasireotide long-acting was administered as an intra-muscular depot intragluteal injection once every 28 days (±2 days). Patients were administered pasireotide long-acting 10 mg or 30 mg for four months, followed by either continuation of the starting dose, or dose up-titration (if mUFC was still >1.5xULN unless titration was precluded by safety reasons).
Other Names:
Drug: SOM230 LAR 30 mg
starting dose of 30 mg i.m. administered once every 28 days for 4 months, followed by dose up-titration or continuation of starting dose.
|
Outcome Measures
Primary Outcome Measures
- Percentage Participants That Attained a mUFC ≤ 1.0 x ULN at Month 7 Regardless of Dose Titration [Month 7]
Percentage of participants that attained a mean urinary free cortisol (mUFC) <= 1.0 x upper limit of normal (ULN) at Month 7 regardless of dose up-titration at Month 4. Patients who discontinued before month 4 evaluations classed as non-responders. For patients missing month 7 mUFC assessments, the last available mUFC assessment at or after month 4 was carried forward as the month 7 mUFC assessment value.
Secondary Outcome Measures
- Percentage of Participants That Attained a mUFC ≤ 1.0 x ULN at Month 7 and Had Not Had a Dose Increase at Month 4 [Month 7]
Percentage of participants that attain a mUFC ≤ 1.0×ULN at Month 7 and had not had a dose increase at Month 4. Patients who had a dose increase prior to Month 7 were counted as non-responders in this analysis. Patients who discontinued before month 4 evaluations classed as non-responders. For patients missing month 7 mUFC assessments, the last available mUFC assessment at or after month 4 was carried forward as the month 7 mUFC assessment value. A responder was defined as a patient who attains mUFC ≤1.0 X ULN and had not had a dose increase at Month 4.
- Actual Change in Mean Urinary Free Cortisol (mUFC) From Baseline [baseline, Month 7 (M7), Month 12 (M12), Month 24 (M24) , Month 36 (M36)]
Actual change in mUFC (nmol/24h) from baseline by randomized groups.
- Percentage Change in Mean Urinary Free Cortisol (mUFC) From Baseline [M7, M12, M24, M36]
Percentage change in mUFC (nmol/24h) from baseline by randomized groups.
- Percentage of Patients Who Attain mUFC ≤ 1.0 x ULN [M7, M12, M24, M36]
Controlled responder: mUFC ≤ 1.0×ULN by randomized groups.
- Percentage of Patients Who Attain mUFC ≤1.0 x ULN or Have at Least 50 % Reduction From Baseline in mUFC [M7, M12, M24, M36]
Controlled responder: mUFC ≤ 1.0×ULN. Partially controlled responder: at least 50% reduction in mUFC from Baseline, and mUFC >1.0×ULN.
- Percentage of Patients Who Are Controlled Responders (mUFC ≤ 1.0 xULN) on at Least 4 of the 7 mUFC Assessments by Month 7 & on at Least 7 of the 12 mUFC Assessments by Month 12. [Month 7, Month 12]
Percentage of patients with mUFC ≤ 1.0 x ULN at a minimum of 4 months up to and including Month 7, and at a minimum of 7 months up to and including Month 12 by randomized groups.
- Percentage of Patients With Uncontrolled Response at Month 7 & Month 12 Within the Subset of Patients Who Had Uncontrolled Response at a) Months 1 and 2; b) Months 1, 2, and 3 [Month 7, Month12]
Percentage of patients with mUFC > 1.0 xULN at Month 7 and Month 12 within the subset of patients who were uncontrolled at a) Months 1 & 2, b) Months 1, 2, & 3 by randomized groups.
- Percent of Participants Attaining a mUFC ≤ 1.0 x ULN or at Least a 50% Reduction in mUFC From Baseline at Indicated Time Points [Momth 7, Month 12]
Time to first achievement of attaining a mUFC ≤ 1.0 x ULN or at least a 50% reduction in mUFC from baseline by randomized groups.
- Percent of Participants Attaining a Duration of Controlled or Partially Controlled Response at Indicated Time Points [Month 6, 12, 18]
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% for the first time.
- Percentage Change From Baseline on Plasma Adrenocorticotropic Hormone (ACTH) Over Time [Months 7, 12, 24 & 36]
Percentage change in ACTH (pmol/L) from Baseline by randomized groups.
- Percentage Change From Baseline on Serum Cortisol Over Time [Months 7, 12, 24 & 36]
Percentage change in serum cortisol (nmol/L) from Baseline by randomized groups.
- Actual Change From Baseline in Clinical Signs Over Time: Blood Pressure [Month 7]
Change in blood pressure measurements from Baseline
- Actual Change From Baseline in Clinical Signs Over Time: Body Mass Index (BMI) [Month 7]
Change in BMI measurements from Baseline
- Actual Change From Baseline in Clinical Signs Over Time: Weight [Month 7]
Change in weight measurements from Baseline
- Actual Change From Baseline in Clinical Signs Over Time: Body Composition: Region [Month 7]
Change in body composition: region measurements from Baseline
- Actual Change From Baseline in Clinical Signs Over Time: Waist Circumference [Month 7]
Change in waist circumference measurements from Baseline
- Actual Change From Baseline in Clinical Signs Over Time: Cholesterol & Triglycerides [Month 7]
Change in parameter measurements: cholesterol & triglycerides from Baseline
- Percentage Change From Baseline in Clinical Signs Over Time [Month 7]
Percentage change in parameter measurements: blood pressure, body mass index, waist circumference, fasting serum lipid profile, weight, bone density and body composition (examined by DXA scan) from Baseline
- Percentage of Participants Having a Favorable Shift From Baseline in Clinical Signs [Month 7]
This includes patients with improvements in symptoms from baseline. Clinical signs over time include: facial rubor, fat pads, hirsutism, striae, (via photographs by a second local physician who was blinded to the treatment dose and time point of the photograph) and muscle strength.
- Percentage of Participants That Attained a Mean Urinary Free Cortisol (mUFC) <= 1.0 x Upper Limit of Normal (ULN) at Month 7 Regardless of Dose Up-titration at Month 4. [Month 7]
All of the participants who discontinued prior to month 4 evaluations were classed as non-responders. For participants missing month 7 mUFC assessments, the last available mUFC assessment at or after month 4 was carried forward as the month 7 mUFC assessment value. Analysis split by screening strata of mUFC Stratum 1: mUFC 1.5x to < 2.0 x ULN Stratum 2: mUFC 2.0x to <= 5.0 x ULN
- Percentage of Patients That Attain a Reduction of at Least 50% in mUFC From Baseline [Months 7, 12, 24 & 36]
All of the participants who discontinued prior to month 4 evaluations were classed as non-responders. For participants missing month 7 mUFC assessments, the last available mUFC assessment at or after month 4 was carried forward as the month 7 mUFC assessment value. Analysis split by screening strata of mUFC Stratum 1:
- Percent of Participants Attaining a Time to First Achievement of at Least a 50% Reduction in mUFC From Baseline at Indicated Time Points [every month in the core phase and every 3 months in the extension phase) up to and including the cut-off date for the Month 12 CSR (10-Nov-2015)]
Time to first achievement of a 5by randomized groups.0% reduction in mUFC from baseline
- Percent of Participants With a Duration of at Least 50% Reduction in mUFC From Baseline at Indicated Time Points [Months 6, 12 & 18]
Duration of 50% reduction from baseline is defined as the period starting from the date of patient's first 50% reduction from baseline
- Pharmacokinetic (PK) Parameter: Ctrough [Days 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337]
Pasireotide trough levels (Ctrough) was 1 of the parameters used for PK assessments. Ctrough is the pre-dose PK concentration with an elapsed time from previous injection of 28+/-2 days. All patients randomized to the study had at least 1 PK observation & were therefore included in the pharmacokinetic analysis set. PK observations with missing concentrations, missing dose, missing elapsed time or an elapsed time from previous injection outside of 28 ±2 days window were excluded. Given that SOM230 LAR was administered once a month, Ctrough was collected every 28 days and thus this provides a summary of Ctrough values provided by incident dose (last dose administered prior to PK sample collection), not by randomized dose, hence each column is equivalent to an incident dose & not an arm/group. Patients randomized to either 10mg or 30mg could be titrated down to 5mg due to safety, or titrated up to 40mg, hence the 4 incident doses/columns that were allowed per protocol during this study.
- Pharmacokinetic (PK) Parameter: Cmax [Days 22, 106, 190]
Pasireotide peak levels (Cmax) was one of the parameters used for PK assessments. Cmax is the post-dose PK concentration with an elapsed time from the previous injection of 21+/-2 days. All patients randomized to the study had at least one PK observation and were therefore included in the pharmacokinetic analysis set (PAS). Cmax PK observations ("Day 20" and "Day 104") with an elapsed time from the previous injection outside of 21+/-2 days window were excluded. Given that SOM230 LAR was administered once a month, the Cmax were collected every 28 days in this study, thus this provides a summary of Cmax values provided by incident dose (last dose administered prior to PK sample collection), not by randomized dose, hence each column is equivalent to an incident dose and not an arm/group. Patients randomized to either the 10mg or 30mg could be titrated down to 5mg due to safety, or titrated up to 40mg, hence the 4 incident doses/columns that were allowed per protocol during this study.
- Actual Change in Standardized Score of Cushing's Disease HRQoL (CushingQOL) Score From Baseline [Months 7, 12, 24 & 36]
CushingQol is a disease-specific patient-reported outcome instrument. It is a single-domain 12 item Cushing's disease quality of life instrument. The Cushing's syndrome quality of life (CushingQoL) questionnaire is a single domain questionnaire which includes 12 self-report items scored using a five point Likert scale anchored at (1=always/very much and 5=never/not at all). The patient is asked to report what they think or feel about their Cushing's syndrome and how much the illness has interfered in usual activities over the past 4 weeks. The total score is standardized on a 0-100 scale with lower scores indicating a greater impact on quality of life.
- Actual Change in SF-12v2 Score From Baseline - Mental Component Summary [Months 7, 12 & 24]
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.
- Actual Change in SF-12v2 Score From Baseline - Physical Component Summary [Months 7, 12 & 24]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Karnofsky performance status ≥ 60 (i.e. requires occasional assistance, but is able to care for most of their personal needs)
-
For patients on medical treatment for Cushing's disease the following washout periods must be completed before screening assessments are 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
Exclusion Criteria:
-
Patients who are considered candidates for surgical treatment at the time of study entry
-
Patients who have received pituitary irradiation within the last ten years prior to visit 1
-
Patients who have had any previous pasireotide treatment
-
Patients who have been treated with mitotane during the last 6 months prior to Visit 1
-
Diabetic patients on antihyperglycemic medications with poor glycemic control as evidenced by HbA1c >8%
-
Patients with risk factors for torsade de pointes, i.e. patients with a baseline QTcF
470 ms, hypokalemia, uncontrolled hypothyroidism, family history of long QT syndrome, or concomitant medications known to prolong QT interval
- Female patients who are pregnant or lactating, or are of childbearing potential (defined as all women physiologically capable of becoming pregnant) and not practicing an effective method of contraception/birth control. Sexually active males must use a condom during intercourse while taking the drug and for 2 months after the last dose of study drug and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | ClinTriCo | Phoenix | Arizona | United States | 85381 |
| 2 | University of California at Los Angeles UCLA Tiverton | Los Angeles | California | United States | 90095 |
| 3 | Harbor-UCLA Medical Center LA Biomed | Torrance | California | United States | 90509 |
| 4 | Emory University School of Medicine/Winship Cancer Institute G2304 - C2301 | Atlanta | Georgia | United States | 30322 |
| 5 | Pituitary Center, Division of Endocrinology SC | Baltimore | Maryland | United States | 21287 |
| 6 | University of Michigan Comprehensive Cancer Center SC-2 | Ann Arbor | Michigan | United States | 48109-0944 |
| 7 | Mount Sinai School of Medicine Mt. Sinai Medical Center | New York | New York | United States | 10029 |
| 8 | Oregon Health & Sciences University DeptofOregonHealth&Sciences(2) | Portland | Oregon | United States | 97201 |
| 9 | University of Pennsylvania - Clinical Studies Unit Unniv SC | Philadelphia | Pennsylvania | United States | 19104 |
| 10 | Vanderbilt University Medical Center CSOM230G2304 | Nashville | Tennessee | United States | 37212-3139 |
| 11 | Swedish Medical Center Swedish | Seattle | Washington | United States | 98122-4379 |
| 12 | Medical College of Wisconsin MCW 2 | Milwaukee | Wisconsin | United States | 53226 |
| 13 | Novartis Investigative Site | Buenos Aires | Argentina | C1232AAC | |
| 14 | Novartis Investigative Site | Cordoba | Argentina | X5009BSN | |
| 15 | Novartis Investigative Site | Edegem | Antwerpen | Belgium | 2650 |
| 16 | Novartis Investigative Site | Jette | Brussel | Belgium | 1090 |
| 17 | Novartis Investigative Site | Bruxelles | Belgium | 1070 | |
| 18 | Novartis Investigative Site | Gent | Belgium | 9000 | |
| 19 | Novartis Investigative Site | Leuven | Belgium | 3000 | |
| 20 | Novartis Investigative Site | Fortaleza | CE | Brazil | 60020-181 |
| 21 | Novartis Investigative Site | Rio de Janeiro | RJ | Brazil | 21941-913 |
| 22 | Novartis Investigative Site | Ribeirao Preto | SP | Brazil | 14048-900 |
| 23 | Novartis Investigative Site | São Paulo | SP | Brazil | 05403 000 |
| 24 | Novartis Investigative Site | Halifax | Nova Scotia | Canada | B3H 1V7 |
| 25 | Novartis Investigative Site | Montreal | Quebec | Canada | H2L 4M1 |
| 26 | Novartis Investigative Site | Sherbrooke | Quebec | Canada | J1N 5N4 |
| 27 | Novartis Investigative Site | Beijing | Beijing | China | 100730 |
| 28 | Novartis Investigative Site | Chengdu | Sichuan | China | 610041 |
| 29 | Novartis Investigative Site | Shanghai | China | 200025 | |
| 30 | Novartis Investigative Site | Shanghai | China | 200040 | |
| 31 | Novartis Investigative Site | Besancon cedex | France | 25030 | |
| 32 | Novartis Investigative Site | Caen Cedex9 | France | 14033 | |
| 33 | Novartis Investigative Site | Le Kremlin Bicetre | France | 94275 | |
| 34 | Novartis Investigative Site | Lille Cedex | France | 59037 | |
| 35 | Novartis Investigative Site | Marseille Cédex 5 | France | 13385 | |
| 36 | Novartis Investigative Site | Pessac Cedex | France | 33604 | |
| 37 | Novartis Investigative Site | Berlin | Germany | 10117 | |
| 38 | Novartis Investigative Site | Erlangen | Germany | 91054 | |
| 39 | Novartis Investigative Site | Germering | Germany | 82110 | |
| 40 | Novartis Investigative Site | Wurzburg | Germany | 97080 | |
| 41 | Novartis Investigative Site | Mumbai | Maharashtra | India | 400012 |
| 42 | Novartis Investigative Site | Vellore | Tamil Nadu | India | 632004 |
| 43 | Novartis Investigative Site | New Delhi | India | 110 029 | |
| 44 | Novartis Investigative Site | Petach Tikva | Israel | 49100 | |
| 45 | Novartis Investigative Site | Ancona | AN | Italy | 60126 |
| 46 | Novartis Investigative Site | Milano | MI | Italy | 20149 |
| 47 | Novartis Investigative Site | Milano | MI | Italy | 20162 |
| 48 | Novartis Investigative Site | Padova | PD | Italy | 35128 |
| 49 | Novartis Investigative Site | Napoli | Italy | 80131 | |
| 50 | Novartis Investigative Site | Nagoya | Aichi | Japan | 460-0001 |
| 51 | Novartis Investigative Site | Fukuoka city | Fukuoka | Japan | 812-8582 |
| 52 | Novartis Investigative Site | Maebashi city | Gunma | Japan | 371 8511 |
| 53 | Novartis Investigative Site | Sapporo-city | Hokkaido | Japan | 060-8648 |
| 54 | Novartis Investigative Site | Kobe-city | Hyogo | Japan | 650-0017 |
| 55 | Novartis Investigative Site | Nankoku-city | Kochi | Japan | 783-8505 |
| 56 | Novartis Investigative Site | Kyoto-city | Kyoto | Japan | 612-8555 |
| 57 | Novartis Investigative Site | Suita-city | Osaka | Japan | 565-0871 |
| 58 | Novartis Investigative Site | Bunkyo-ku | Tokyo | Japan | 113-8603 |
| 59 | Novartis Investigative Site | Minato-ku | Tokyo | Japan | 105-8470 |
| 60 | Novartis Investigative Site | Shinjuku-ku | Tokyo | Japan | 162-8666 |
| 61 | Novartis Investigative Site | Osaka | Japan | 534-0021 | |
| 62 | Novartis Investigative Site | Rotterdam | Netherlands | 3015 CE | |
| 63 | Novartis Investigative Site | Jesus Maria | Lima | Peru | 11 |
| 64 | Novartis Investigative Site | Miraflores | Lima | Peru | 18 |
| 65 | Novartis Investigative Site | Gdansk | Poland | 80-952 | |
| 66 | Novartis Investigative Site | Poznan | Poland | 60-355 | |
| 67 | Novartis Investigative Site | Warszawa | Poland | 00-909 | |
| 68 | Novartis Investigative Site | Wroclaw | Poland | 50-367 | |
| 69 | Novartis Investigative Site | Moscow | Russian Federation | 119296 | |
| 70 | Novartis Investigative Site | St.- Petersburg | Russian Federation | 199034 | |
| 71 | Novartis Investigative Site | Sevilla | Andalucia | Spain | 41013 |
| 72 | Novartis Investigative Site | Alzira | Comunidad Valenciana | Spain | 46600 |
| 73 | Novartis Investigative Site | Barcelona | Spain | 08041 | |
| 74 | Novartis Investigative Site | Bangkok | Thailand | 10330 | |
| 75 | Novartis Investigative Site | Bangkok | Thailand | 10700 | |
| 76 | Novartis Investigative Site | Diskapi / Ankara | Ankara | Turkey | 06110 |
| 77 | Novartis Investigative Site | Istanbul | TUR | Turkey | 34098 |
| 78 | Novartis Investigative Site | Izmir | Turkey | 35340 | |
| 79 | Novartis Investigative Site | Salford | Manchester | United Kingdom | M6 8HD |
| 80 | Novartis Investigative Site | Norwich | United Kingdom | NR4 7UY | |
| 81 | Novartis Investigative Site | Sheffield | United Kingdom | S5 7AU | |
| 82 | Novartis Investigative Site | Southampton | United Kingdom | SO16 6YD |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01374906
Other Study ID Numbers:
- CSOM230G2304
- 2009-011128-70
First Posted:
Jun 16, 2011
Last Update Posted:
May 22, 2018
Last Verified:
Apr 1, 2018
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | At least 148 patients (Pts.) were planned & 150 were randomized & analyzed. Pts. were all treated with either pasireotide long-acting 10 mg or pasireotide long-acting 30 mg. 81 Pts. completed the Core phase & entered the Extension phase with 39 completing the Extension phase. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. |
| Period Title: Overall Study | ||
| STARTED | 74 | 76 |
| DC Dur Core Phs at/Prior to Data Cutoff | 24 | 22 |
| Completed Core Phase | 50 | 54 |
| Completed Core/Did Not Enter Ext. Phase | 10 | 13 |
| Completed Core Phase/Entered Ext. Phase | 40 | 41 |
| DC Dur Ext Phs at/Prior to Data Cutoff | 16 | 26 |
| Completed Extension Phase | 24 | 15 |
| COMPLETED | 34 | 28 |
| NOT COMPLETED | 40 | 48 |
Baseline Characteristics
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose | Total |
|---|---|---|---|
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. | Total of all reporting groups |
| Overall Participants | 74 | 76 | 150 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
38.3
(12.52)
|
38.6
(12.99)
|
38.5
(12.72)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
58
78.4%
|
60
78.9%
|
118
78.7%
|
| Male |
16
21.6%
|
16
21.1%
|
32
21.3%
|
| Race/Ethnicity, Customized (Number) [Number] | |||
| Caucasian |
39
52.7%
|
44
57.9%
|
83
55.3%
|
| Asian |
27
36.5%
|
24
31.6%
|
51
34%
|
| Black |
2
2.7%
|
0
0%
|
2
1.3%
|
| Other |
6
8.1%
|
8
10.5%
|
14
9.3%
|
Outcome Measures
| Title | Percentage Participants That Attained a mUFC ≤ 1.0 x ULN at Month 7 Regardless of Dose Titration |
|---|---|
| Description | Percentage of participants that attained a mean urinary free cortisol (mUFC) <= 1.0 x upper limit of normal (ULN) at Month 7 regardless of dose up-titration at Month 4. Patients who discontinued before month 4 evaluations classed as non-responders. For patients missing month 7 mUFC assessments, the last available mUFC assessment at or after month 4 was carried forward as the month 7 mUFC assessment value. |
| Time Frame | Month 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug. |
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. |
| Measure Participants | 74 | 76 |
| Number (95% Confidence Interval) [percentage of participants] |
41.9
56.6%
|
40.8
53.7%
|
| Title | Percentage of Participants That Attained a mUFC ≤ 1.0 x ULN at Month 7 and Had Not Had a Dose Increase at Month 4 |
|---|---|
| Description | Percentage of participants that attain a mUFC ≤ 1.0×ULN at Month 7 and had not had a dose increase at Month 4. Patients who had a dose increase prior to Month 7 were counted as non-responders in this analysis. Patients who discontinued before month 4 evaluations classed as non-responders. For patients missing month 7 mUFC assessments, the last available mUFC assessment at or after month 4 was carried forward as the month 7 mUFC assessment value. A responder was defined as a patient who attains mUFC ≤1.0 X ULN and had not had a dose increase at Month 4. |
| Time Frame | Month 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug. |
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. |
| Measure Participants | 74 | 76 |
| Number (95% Confidence Interval) [percentage of participants] |
28.4
38.4%
|
31.6
41.6%
|
| Title | Actual Change in Mean Urinary Free Cortisol (mUFC) From Baseline |
|---|---|
| Description | Actual change in mUFC (nmol/24h) from baseline by randomized groups. |
| Time Frame | baseline, Month 7 (M7), Month 12 (M12), Month 24 (M24) , Month 36 (M36) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug. |
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. |
| Measure Participants | 74 | 76 |
| M7 |
-192.4
(271.59)
|
-234.3
(362.86)
|
| M12 |
-195.1
(282.46)
|
-247.6
(387.05)
|
| M24 |
-236.2
(292.91)
|
-265.2
(313.47)
|
| M36 |
-398.4
(136.09)
|
-164.6
(66.76)
|
| Title | Percentage Change in Mean Urinary Free Cortisol (mUFC) From Baseline |
|---|---|
| Description | Percentage change in mUFC (nmol/24h) from baseline by randomized groups. |
| Time Frame | M7, M12, M24, M36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug. |
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. |
| Measure Participants | 74 | 76 |
| M7 |
-29.3
(102.76)
|
-33.2
(61.37)
|
| M12 |
-30.3
(79.73)
|
-31.1
(78.41)
|
| M24 |
-50.9
(76.48)
|
-51.2
(35.41)
|
| M36 |
-71.6
(20.44)
|
-48.8
(11.36)
|
| Title | Percentage of Patients Who Attain mUFC ≤ 1.0 x ULN |
|---|---|
| Description | Controlled responder: mUFC ≤ 1.0×ULN by randomized groups. |
| Time Frame | M7, M12, M24, M36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug. |
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. |
| Measure Participants | 74 | 76 |
| M7 - Controlled responder |
39.2
53%
|
40.8
53.7%
|
| M12 - Controlled responder |
35.1
47.4%
|
25.0
32.9%
|
| M24 - Controlled responder |
39.7
53.6%
|
21.3
28%
|
| M36 - Controlled responder |
22.0
29.7%
|
4.0
5.3%
|
| Title | Percentage of Patients Who Attain mUFC ≤1.0 x ULN or Have at Least 50 % Reduction From Baseline in mUFC |
|---|---|
| Description | Controlled responder: mUFC ≤ 1.0×ULN. Partially controlled responder: at least 50% reduction in mUFC from Baseline, and mUFC >1.0×ULN. |
| Time Frame | M7, M12, M24, M36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug. |
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. |
| Measure Participants | 74 | 76 |
| M7 |
44.6
60.3%
|
53.9
70.9%
|
| M12 |
45.9
62%
|
42.1
55.4%
|
| M24 |
46.0
62.2%
|
27.9
36.7%
|
| M36 |
28.0
37.8%
|
6.0
7.9%
|
| Title | Percentage of Patients Who Are Controlled Responders (mUFC ≤ 1.0 xULN) on at Least 4 of the 7 mUFC Assessments by Month 7 & on at Least 7 of the 12 mUFC Assessments by Month 12. |
|---|---|
| Description | Percentage of patients with mUFC ≤ 1.0 x ULN at a minimum of 4 months up to and including Month 7, and at a minimum of 7 months up to and including Month 12 by randomized groups. |
| Time Frame | Month 7, Month 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug. |
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. |
| Measure Participants | 74 | 76 |
| Month 7 |
25.7
34.7%
|
31.6
41.6%
|
| Month 12 |
25.7
34.7%
|
25.0
32.9%
|
| Title | Percentage of Patients With Uncontrolled Response at Month 7 & Month 12 Within the Subset of Patients Who Had Uncontrolled Response at a) Months 1 and 2; b) Months 1, 2, and 3 |
|---|---|
| Description | Percentage of patients with mUFC > 1.0 xULN at Month 7 and Month 12 within the subset of patients who were uncontrolled at a) Months 1 & 2, b) Months 1, 2, & 3 by randomized groups. |
| Time Frame | Month 7, Month12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug. |
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. |
| Measure Participants | 74 | 76 |
| Uncontrolled Resp @ M7: subset: M1 & 2 |
60.6
81.9%
|
60.6
79.7%
|
| Uncontrolled Resp @ M7: subset: M1,2 & 3 |
61.3
82.8%
|
65.5
86.2%
|
| Uncontrolled Resp @ M12: subset: M1 & 2 |
69.7
94.2%
|
69.7
91.7%
|
| Uncontrolled Resp @ M12: subset: M1, 2 & 3 |
74.2
100.3%
|
72.4
95.3%
|
| Title | Percent of Participants Attaining a mUFC ≤ 1.0 x ULN or at Least a 50% Reduction in mUFC From Baseline at Indicated Time Points |
|---|---|
| Description | Time to first achievement of attaining a mUFC ≤ 1.0 x ULN or at least a 50% reduction in mUFC from baseline by randomized groups. |
| Time Frame | Momth 7, Month 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug. |
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. |
| Measure Participants | 74 | 76 |
| Month 7 |
86.2
116.5%
|
83.4
109.7%
|
| Month 12 |
90.1
121.8%
|
94.5
124.3%
|
| Title | Percent of Participants Attaining a Duration of Controlled or Partially Controlled Response at Indicated Time Points |
|---|---|
| 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% for the first time. |
| Time Frame | Month 6, 12, 18 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug. |
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. |
| Measure Participants | 74 | 76 |
| Month 6 |
78.0
105.4%
|
72.9
95.9%
|
| Month 12 |
84.0
113.5%
|
82.8
108.9%
|
| Month 18 |
84.0
113.5%
|
87.1
114.6%
|
| Title | Percentage Change From Baseline on Plasma Adrenocorticotropic Hormone (ACTH) Over Time |
|---|---|
| Description | Percentage change in ACTH (pmol/L) from Baseline by randomized groups. |
| Time Frame | Months 7, 12, 24 & 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug. |
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. |
| Measure Participants | 74 | 76 |
| M7 |
2.7
(57.14)
|
-13.5
(46.75)
|
| M12 |
-10.2
(57.57)
|
-14.5
(38.72)
|
| M24 |
-12.1
(43.51)
|
2.5
(68.69)
|
| M36 |
-15.4
(36.90)
|
-0.6
(48.13)
|
| Title | Percentage Change From Baseline on Serum Cortisol Over Time |
|---|---|
| Description | Percentage change in serum cortisol (nmol/L) from Baseline by randomized groups. |
| Time Frame | Months 7, 12, 24 & 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug. |
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. |
| Measure Participants | 74 | 76 |
| M7 |
-8.2
(37.83)
|
-5.1
(40.20)
|
| M12 |
-12.1
(29.69)
|
-0.4
(35.91)
|
| M24 |
-15.6
(30.67)
|
-7.4
(38.37)
|
| M36 |
0.6
(55.67)
|
-23.2
(31.19)
|
| Title | Actual Change From Baseline in Clinical Signs Over Time: Blood Pressure |
|---|---|
| Description | Change in blood pressure measurements from Baseline |
| Time Frame | Month 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug. |
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. |
| Measure Participants | 74 | 76 |
| Supine systolic blood pressure (SBP) |
-6.8
(15.64)
|
-4.6
(14.51)
|
| Supine diastolic blood (DBP) pressure |
-4.8
(12.06)
|
-3.0
(12.12)
|
| Title | Actual Change From Baseline in Clinical Signs Over Time: Body Mass Index (BMI) |
|---|---|
| Description | Change in BMI measurements from Baseline |
| Time Frame | Month 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug. |
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. |
| Measure Participants | 74 | 76 |
| Mean (Standard Deviation) [kg/m2] |
-0.7
(1.60)
|
-1.8
(2.05)
|
| Title | Actual Change From Baseline in Clinical Signs Over Time: Weight |
|---|---|
| Description | Change in weight measurements from Baseline |
| Time Frame | Month 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug. |
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. |
| Measure Participants | 74 | 76 |
| Mean (Standard Deviation) [kg] |
-1.8
(4.16)
|
-4.6
(5.08)
|
| Title | Actual Change From Baseline in Clinical Signs Over Time: Body Composition: Region |
|---|---|
| Description | Change in body composition: region measurements from Baseline |
| Time Frame | Month 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug. |
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. |
| Measure Participants | 74 | 76 |
| Mean (Standard Deviation) [percentage fat] |
-1.0
(2.64)
|
-1.8
(3.97)
|
| Title | Actual Change From Baseline in Clinical Signs Over Time: Waist Circumference |
|---|---|
| Description | Change in waist circumference measurements from Baseline |
| Time Frame | Month 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug. |
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. |
| Measure Participants | 74 | 76 |
| Mean (Standard Deviation) [cm] |
-1.6
(8.47)
|
-7.1
(11.78)
|
| Title | Actual Change From Baseline in Clinical Signs Over Time: Cholesterol & Triglycerides |
|---|---|
| Description | Change in parameter measurements: cholesterol & triglycerides from Baseline |
| Time Frame | Month 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug. |
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. |
| Measure Participants | 74 | 76 |
| Total cholesterol |
-0.5
(1.07)
|
-0.4
(1.00)
|
| HDL cholesterol |
-0.1
(0.28)
|
0
(0.32)
|
| Triglycerides |
0
(0.53)
|
-0.2
(0.64)
|
| Title | Percentage Change From Baseline in Clinical Signs Over Time |
|---|---|
| Description | Percentage change in parameter measurements: blood pressure, body mass index, waist circumference, fasting serum lipid profile, weight, bone density and body composition (examined by DXA scan) from Baseline |
| Time Frame | Month 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug. |
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. |
| Measure Participants | 74 | 76 |
| SBP |
-4.3
(11.46)
|
-3.0
(10.18)
|
| DBP |
-4.7
(14.19)
|
-2.6
(13.78)
|
| BMI |
-2.6
(5.26)
|
-6.1
(6.94)
|
| Weight |
-2.6
(5.26)
|
-6.1
(6.91)
|
| Waist circumference |
-1.4
(8.60)
|
-6.6
(10.06)
|
| HDL |
-6.7
(15.18)
|
0.3
(20.91)
|
| Total cholesterol |
-7.2
(16.86)
|
-6.6
(16.40)
|
| Triglycerides |
4.2
(39.54)
|
-0.9
(39.61)
|
| Body composition |
-2.4
(6.68)
|
-3.6
(10.47)
|
| Title | Percentage of Participants Having a Favorable Shift From Baseline in Clinical Signs |
|---|---|
| Description | This includes patients with improvements in symptoms from baseline. Clinical signs over time include: facial rubor, fat pads, hirsutism, striae, (via photographs by a second local physician who was blinded to the treatment dose and time point of the photograph) and muscle strength. |
| Time Frame | Month 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug. |
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. |
| Measure Participants | 74 | 76 |
| Facial rubor |
32.7
44.2%
|
53.6
70.5%
|
| Hirsutism (females only) |
22.2
30%
|
32.6
42.9%
|
| Striae |
23.1
31.2%
|
23.6
31.1%
|
| Bruising |
25.0
33.8%
|
14.3
18.8%
|
| Supraclavicular fat pad |
40.4
54.6%
|
28.6
37.6%
|
| Dorsal fat pad |
28.8
38.9%
|
40.0
52.6%
|
| Muscle strength |
8.9
12%
|
4.5
5.9%
|
| Title | Percentage of Participants That Attained a Mean Urinary Free Cortisol (mUFC) <= 1.0 x Upper Limit of Normal (ULN) at Month 7 Regardless of Dose Up-titration at Month 4. |
|---|---|
| Description | All of the participants who discontinued prior to month 4 evaluations were classed as non-responders. For participants missing month 7 mUFC assessments, the last available mUFC assessment at or after month 4 was carried forward as the month 7 mUFC assessment value. Analysis split by screening strata of mUFC Stratum 1: mUFC 1.5x to < 2.0 x ULN Stratum 2: mUFC 2.0x to <= 5.0 x ULN |
| Time Frame | Month 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug. |
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. |
| Measure Participants | 74 | 76 |
| stratum:1.5 x ULN to < 2.0 x ULN |
52.0
70.3%
|
52.0
68.4%
|
| stratum:2.0 x ULN to <= 5.0 x ULN |
36.7
49.6%
|
35.3
46.4%
|
| Title | Percentage of Patients That Attain a Reduction of at Least 50% in mUFC From Baseline |
|---|---|
| Description | All of the participants who discontinued prior to month 4 evaluations were classed as non-responders. For participants missing month 7 mUFC assessments, the last available mUFC assessment at or after month 4 was carried forward as the month 7 mUFC assessment value. Analysis split by screening strata of mUFC Stratum 1: |
| Time Frame | Months 7, 12, 24 & 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug. |
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. |
| Measure Participants | 74 | 76 |
| M7 |
35.1
47.4%
|
43.4
57.1%
|
| M12 |
35.1
47.4%
|
38.2
50.3%
|
| M24 |
83.3
112.6%
|
57.1
75.1%
|
| M36 |
100
135.1%
|
33.33
43.9%
|
| Title | Percent of Participants Attaining a Time to First Achievement of at Least a 50% Reduction in mUFC From Baseline at Indicated Time Points |
|---|---|
| Description | Time to first achievement of a 5by randomized groups.0% reduction in mUFC from baseline |
| Time Frame | every month in the core phase and every 3 months in the extension phase) up to and including the cut-off date for the Month 12 CSR (10-Nov-2015) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug. |
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. |
| Measure Participants | 74 | 76 |
| M7 |
80.5
108.8%
|
73.4
96.6%
|
| M12 |
84.4
114.1%
|
80.7
106.2%
|
| Title | Percent of Participants With a Duration of at Least 50% Reduction in mUFC From Baseline at Indicated Time Points |
|---|---|
| Description | Duration of 50% reduction from baseline is defined as the period starting from the date of patient's first 50% reduction from baseline |
| Time Frame | Months 6, 12 & 18 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug. |
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. |
| Measure Participants | 74 | 76 |
| M6 |
78.4
105.9%
|
77.8
102.4%
|
| M12 |
84.9
114.7%
|
83.7
110.1%
|
| M18 |
84.9
114.7%
|
83.7
110.1%
|
| Title | Pharmacokinetic (PK) Parameter: Ctrough |
|---|---|
| Description | Pasireotide trough levels (Ctrough) was 1 of the parameters used for PK assessments. Ctrough is the pre-dose PK concentration with an elapsed time from previous injection of 28+/-2 days. All patients randomized to the study had at least 1 PK observation & were therefore included in the pharmacokinetic analysis set. PK observations with missing concentrations, missing dose, missing elapsed time or an elapsed time from previous injection outside of 28 ±2 days window were excluded. Given that SOM230 LAR was administered once a month, Ctrough was collected every 28 days and thus this provides a summary of Ctrough values provided by incident dose (last dose administered prior to PK sample collection), not by randomized dose, hence each column is equivalent to an incident dose & not an arm/group. Patients randomized to either 10mg or 30mg could be titrated down to 5mg due to safety, or titrated up to 40mg, hence the 4 incident doses/columns that were allowed per protocol during this study. |
| Time Frame | Days 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic analysis set (PAS): The PAS consists of all randomized patients who have received at least one dose of study drug and had at least one post dosing PK assessment. Patients were analyzed according to incident dose (defined as the last dose prior to the PK sample). |
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose | 5 mg Pasireotide LAR Dose | 40 mg Pasireotide LAR Dose |
|---|---|---|---|---|
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. | These patients were dosed with 5 mg of Pasireotide LAR to assess Pharmacokinetics (PK). | These patients were dosed with 40 mg of Pasireotide LAR to assess Pharmacokinetics (PK). |
| Measure Participants | 65 | 64 | 5 | 44 |
| Day 29 |
2.03
(1.25)
|
7.63
(4.58)
|
||
| Day 57 |
2.35
(1.15)
|
7.82
(4.22)
|
0.83
(NA)
|
|
| Day 85 |
2.39
(1.32)
|
8.56
(4.26)
|
1.03
(0.63)
|
|
| Day 113 |
2.40
(1.11)
|
8.31
(3.87)
|
1.29
(0.24)
|
|
| Day 141 |
2.47
(0.94)
|
7.88
(4.00)
|
1.04
(0.68)
|
10.7
(4.91)
|
| Day 169 |
2.47
(0.95)
|
8.46
(3.51)
|
2.01
(0.22)
|
12.0
(5.08)
|
| Day 197 |
2.88
(1.29)
|
9.13
(4.25)
|
0.72
(0.39)
|
11.9
(5.87)
|
| Day 225 |
2.68
(0.98)
|
8.57
(4.70)
|
1.19
(0.43)
|
11.3
(5.18)
|
| Day 253 |
2.87
(1.57)
|
9.00
(4.93)
|
1.77
(0.88)
|
12.1
(5.21)
|
| Day 281 |
3.36
(1.48)
|
8.18
(4.23)
|
1.24
(0.52)
|
11.4
(5.85)
|
| Day 309 |
2.50
(0.99)
|
9.34
(5.61)
|
0.66
(NA)
|
12.0
(4.58)
|
| Day 337 |
3.07
(1.62)
|
8.90
(4.37)
|
1.91
(1.79)
|
12.6
(6.21)
|
| Title | Pharmacokinetic (PK) Parameter: Cmax |
|---|---|
| Description | Pasireotide peak levels (Cmax) was one of the parameters used for PK assessments. Cmax is the post-dose PK concentration with an elapsed time from the previous injection of 21+/-2 days. All patients randomized to the study had at least one PK observation and were therefore included in the pharmacokinetic analysis set (PAS). Cmax PK observations ("Day 20" and "Day 104") with an elapsed time from the previous injection outside of 21+/-2 days window were excluded. Given that SOM230 LAR was administered once a month, the Cmax were collected every 28 days in this study, thus this provides a summary of Cmax values provided by incident dose (last dose administered prior to PK sample collection), not by randomized dose, hence each column is equivalent to an incident dose and not an arm/group. Patients randomized to either the 10mg or 30mg could be titrated down to 5mg due to safety, or titrated up to 40mg, hence the 4 incident doses/columns that were allowed per protocol during this study. |
| Time Frame | Days 22, 106, 190 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic analysis set (PAS): The PAS consists of all randomized patients who have received at least one dose of study drug and had at least one post dosing PK assessment. Patients were analyzed according to incident dose (defined as the last dose prior to the PK sample). |
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose | 5 mg Pasireptide LAR Dose | 40 mg Pasireotide LAR Dose |
|---|---|---|---|---|
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. | These patients were dosed with 5 mg of Pasireotide LAR to assess Pharmacokinetics (PK). | These patients were dosed with 40 mg of Pasireotide LAR to assess Pharmacokinetics (PK). |
| Measure Participants | 67 | 69 | 3 | 22 |
| Day 22 (M 0.75) |
3.0
(1.50)
|
8.2
(3.99)
|
||
| Day 106 (M 3.75) |
3.3
(1.92)
|
9.4
(3.72)
|
1.7
(0.42)
|
|
| Day 190 (M6.75) |
4.0
(1.73)
|
10.0
(3.91)
|
1.4
(0.78)
|
12.1
(5.21)
|
| Title | Actual Change in Standardized Score of Cushing's Disease HRQoL (CushingQOL) Score From Baseline |
|---|---|
| Description | CushingQol is a disease-specific patient-reported outcome instrument. It is a single-domain 12 item Cushing's disease quality of life instrument. The Cushing's syndrome quality of life (CushingQoL) questionnaire is a single domain questionnaire which includes 12 self-report items scored using a five point Likert scale anchored at (1=always/very much and 5=never/not at all). The patient is asked to report what they think or feel about their Cushing's syndrome and how much the illness has interfered in usual activities over the past 4 weeks. The total score is standardized on a 0-100 scale with lower scores indicating a greater impact on quality of life. |
| Time Frame | Months 7, 12, 24 & 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug. |
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. |
| Measure Participants | 74 | 76 |
| M7 |
5.7
(15.97)
|
7.8
(11.63)
|
| M12 |
6.4
(17.56)
|
6.8
(14.42)
|
| M24 |
5.9
(15.56)
|
8.7
(12.80)
|
| M36 |
1.4
(9.10)
|
14.6
(5.10)
|
| Title | Actual Change in SF-12v2 Score From Baseline - Mental Component Summary |
|---|---|
| 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. |
| Time Frame | Months 7, 12 & 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug. |
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. |
| Measure Participants | 74 | 76 |
| M7 |
4.1
(8.81)
|
4.3
(8.05)
|
| M12 |
2.3
(9.97)
|
3.3
(8.26)
|
| M24 |
3.3
(10.43)
|
6.4
(2.53)
|
| Title | Actual Change in SF-12v2 Score From Baseline - Physical Component Summary |
|---|---|
| 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. |
| Time Frame | Months 7, 12 & 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug. |
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. |
| Measure Participants | 74 | 76 |
| M7 |
1.9
(8.50)
|
-0.8
(7.46)
|
| M12 |
4.9
(5.56)
|
-0.5
(6.73)
|
| M24 |
5.3
(4.32)
|
-1.1
(5.54)
|
Adverse Events
| Time Frame | Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose | All Patients | |||
| Arm/Group Description | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. | All Patients from both the 10 mg and 30 mg groups. | |||
All Cause Mortality |
||||||
| 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose | All Patients | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose | All Patients | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 22/74 (29.7%) | 19/76 (25%) | 41/150 (27.3%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 0/74 (0%) | 1/76 (1.3%) | 1/150 (0.7%) | |||
| Cardiac disorders | ||||||
| Angina pectoris | 0/74 (0%) | 1/76 (1.3%) | 1/150 (0.7%) | |||
| Angina unstable | 1/74 (1.4%) | 0/76 (0%) | 1/150 (0.7%) | |||
| Cardiac arrest | 0/74 (0%) | 1/76 (1.3%) | 1/150 (0.7%) | |||
| Cardiac failure | 0/74 (0%) | 1/76 (1.3%) | 1/150 (0.7%) | |||
| Cardiopulmonary failure | 0/74 (0%) | 1/76 (1.3%) | 1/150 (0.7%) | |||
| Coronary artery occlusion | 0/74 (0%) | 1/76 (1.3%) | 1/150 (0.7%) | |||
| Sinus bradycardia | 0/74 (0%) | 1/76 (1.3%) | 1/150 (0.7%) | |||
| Endocrine disorders | ||||||
| Adrenal insufficiency | 1/74 (1.4%) | 0/76 (0%) | 1/150 (0.7%) | |||
| Hyperadrenocorticism | 1/74 (1.4%) | 0/76 (0%) | 1/150 (0.7%) | |||
| Pituitary-dependent Cushing's syndrome | 2/74 (2.7%) | 1/76 (1.3%) | 3/150 (2%) | |||
| Gastrointestinal disorders | ||||||
| Anogenital dysplasia | 1/74 (1.4%) | 0/76 (0%) | 1/150 (0.7%) | |||
| Gastric ulcer | 0/74 (0%) | 1/76 (1.3%) | 1/150 (0.7%) | |||
| Haemorrhoids | 1/74 (1.4%) | 0/76 (0%) | 1/150 (0.7%) | |||
| Large intestine polyp | 1/74 (1.4%) | 0/76 (0%) | 1/150 (0.7%) | |||
| Oedematous pancreatitis | 1/74 (1.4%) | 0/76 (0%) | 1/150 (0.7%) | |||
| General disorders | ||||||
| Injection site pain | 1/74 (1.4%) | 0/76 (0%) | 1/150 (0.7%) | |||
| Malaise | 0/74 (0%) | 1/76 (1.3%) | 1/150 (0.7%) | |||
| Hepatobiliary disorders | ||||||
| Cholecystitis acute | 2/74 (2.7%) | 0/76 (0%) | 2/150 (1.3%) | |||
| Cholelithiasis | 2/74 (2.7%) | 3/76 (3.9%) | 5/150 (3.3%) | |||
| Infections and infestations | ||||||
| Cellulitis | 0/74 (0%) | 1/76 (1.3%) | 1/150 (0.7%) | |||
| Diverticulitis | 1/74 (1.4%) | 0/76 (0%) | 1/150 (0.7%) | |||
| Pneumonia | 1/74 (1.4%) | 0/76 (0%) | 1/150 (0.7%) | |||
| Sepsis | 0/74 (0%) | 1/76 (1.3%) | 1/150 (0.7%) | |||
| Septic shock | 0/74 (0%) | 1/76 (1.3%) | 1/150 (0.7%) | |||
| Subcutaneous abscess | 1/74 (1.4%) | 0/76 (0%) | 1/150 (0.7%) | |||
| Injury, poisoning and procedural complications | ||||||
| Femoral neck fracture | 1/74 (1.4%) | 0/76 (0%) | 1/150 (0.7%) | |||
| Road traffic accident | 1/74 (1.4%) | 0/76 (0%) | 1/150 (0.7%) | |||
| Stress fracture | 2/74 (2.7%) | 0/76 (0%) | 2/150 (1.3%) | |||
| Investigations | ||||||
| Blood cortisol decreased | 1/74 (1.4%) | 1/76 (1.3%) | 2/150 (1.3%) | |||
| Blood cortisol increased | 1/74 (1.4%) | 0/76 (0%) | 1/150 (0.7%) | |||
| Gamma-glutamyltransferase increased | 1/74 (1.4%) | 0/76 (0%) | 1/150 (0.7%) | |||
| Metabolism and nutrition disorders | ||||||
| Diabetes mellitus | 1/74 (1.4%) | 0/76 (0%) | 1/150 (0.7%) | |||
| Hyperglycaemia | 1/74 (1.4%) | 1/76 (1.3%) | 2/150 (1.3%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthritis | 0/74 (0%) | 1/76 (1.3%) | 1/150 (0.7%) | |||
| Osteoarthritis | 1/74 (1.4%) | 0/76 (0%) | 1/150 (0.7%) | |||
| Osteoporosis | 0/74 (0%) | 1/76 (1.3%) | 1/150 (0.7%) | |||
| Spondylolisthesis | 0/74 (0%) | 1/76 (1.3%) | 1/150 (0.7%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Endometrial cancer | 1/74 (1.4%) | 1/76 (1.3%) | 2/150 (1.3%) | |||
| Pregnancy, puerperium and perinatal conditions | ||||||
| Abortion spontaneous | 0/74 (0%) | 1/76 (1.3%) | 1/150 (0.7%) | |||
| Renal and urinary disorders | ||||||
| Acute kidney injury | 0/74 (0%) | 1/76 (1.3%) | 1/150 (0.7%) | |||
| Nephrolithiasis | 0/74 (0%) | 1/76 (1.3%) | 1/150 (0.7%) | |||
| Reproductive system and breast disorders | ||||||
| Endometrial hyperplasia | 1/74 (1.4%) | 0/76 (0%) | 1/150 (0.7%) | |||
| Ovarian cyst | 1/74 (1.4%) | 0/76 (0%) | 1/150 (0.7%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Dysphonia | 1/74 (1.4%) | 0/76 (0%) | 1/150 (0.7%) | |||
| Dyspnoea | 0/74 (0%) | 1/76 (1.3%) | 1/150 (0.7%) | |||
| Pulmonary artery thrombosis | 0/74 (0%) | 1/76 (1.3%) | 1/150 (0.7%) | |||
| Pulmonary embolism | 0/74 (0%) | 2/76 (2.6%) | 2/150 (1.3%) | |||
| Vascular disorders | ||||||
| Deep vein thrombosis | 0/74 (0%) | 1/76 (1.3%) | 1/150 (0.7%) | |||
| Hypertensive crisis | 1/74 (1.4%) | 0/76 (0%) | 1/150 (0.7%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose | All Patients | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 73/74 (98.6%) | 76/76 (100%) | 149/150 (99.3%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 4/74 (5.4%) | 5/76 (6.6%) | 9/150 (6%) | |||
| Cardiac disorders | ||||||
| Palpitations | 4/74 (5.4%) | 3/76 (3.9%) | 7/150 (4.7%) | |||
| Sinus bradycardia | 4/74 (5.4%) | 5/76 (6.6%) | 9/150 (6%) | |||
| Ear and labyrinth disorders | ||||||
| Vertigo | 5/74 (6.8%) | 0/76 (0%) | 5/150 (3.3%) | |||
| Endocrine disorders | ||||||
| Adrenal insufficiency | 4/74 (5.4%) | 6/76 (7.9%) | 10/150 (6.7%) | |||
| Hypothyroidism | 1/74 (1.4%) | 4/76 (5.3%) | 5/150 (3.3%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal discomfort | 4/74 (5.4%) | 2/76 (2.6%) | 6/150 (4%) | |||
| Abdominal distension | 4/74 (5.4%) | 5/76 (6.6%) | 9/150 (6%) | |||
| Abdominal pain | 11/74 (14.9%) | 13/76 (17.1%) | 24/150 (16%) | |||
| Abdominal pain upper | 3/74 (4.1%) | 8/76 (10.5%) | 11/150 (7.3%) | |||
| Constipation | 5/74 (6.8%) | 5/76 (6.6%) | 10/150 (6.7%) | |||
| Diarrhoea | 26/74 (35.1%) | 35/76 (46.1%) | 61/150 (40.7%) | |||
| Dry mouth | 4/74 (5.4%) | 1/76 (1.3%) | 5/150 (3.3%) | |||
| Flatulence | 3/74 (4.1%) | 5/76 (6.6%) | 8/150 (5.3%) | |||
| Frequent bowel movements | 4/74 (5.4%) | 0/76 (0%) | 4/150 (2.7%) | |||
| Nausea | 17/74 (23%) | 16/76 (21.1%) | 33/150 (22%) | |||
| Vomiting | 7/74 (9.5%) | 2/76 (2.6%) | 9/150 (6%) | |||
| General disorders | ||||||
| Asthenia | 10/74 (13.5%) | 5/76 (6.6%) | 15/150 (10%) | |||
| Fatigue | 13/74 (17.6%) | 15/76 (19.7%) | 28/150 (18.7%) | |||
| Oedema peripheral | 9/74 (12.2%) | 12/76 (15.8%) | 21/150 (14%) | |||
| Pyrexia | 5/74 (6.8%) | 2/76 (2.6%) | 7/150 (4.7%) | |||
| Hepatobiliary disorders | ||||||
| Cholelithiasis | 15/74 (20.3%) | 33/76 (43.4%) | 48/150 (32%) | |||
| Cholestasis | 4/74 (5.4%) | 2/76 (2.6%) | 6/150 (4%) | |||
| Gallbladder cholesterolosis | 2/74 (2.7%) | 4/76 (5.3%) | 6/150 (4%) | |||
| Hepatic function abnormal | 2/74 (2.7%) | 4/76 (5.3%) | 6/150 (4%) | |||
| Hepatic steatosis | 1/74 (1.4%) | 6/76 (7.9%) | 7/150 (4.7%) | |||
| Infections and infestations | ||||||
| Bronchitis | 5/74 (6.8%) | 2/76 (2.6%) | 7/150 (4.7%) | |||
| Gastroenteritis | 7/74 (9.5%) | 2/76 (2.6%) | 9/150 (6%) | |||
| Influenza | 12/74 (16.2%) | 6/76 (7.9%) | 18/150 (12%) | |||
| Nasopharyngitis | 18/74 (24.3%) | 13/76 (17.1%) | 31/150 (20.7%) | |||
| Upper respiratory tract infection | 5/74 (6.8%) | 6/76 (7.9%) | 11/150 (7.3%) | |||
| Urinary tract infection | 10/74 (13.5%) | 9/76 (11.8%) | 19/150 (12.7%) | |||
| Injury, poisoning and procedural complications | ||||||
| Contusion | 4/74 (5.4%) | 1/76 (1.3%) | 5/150 (3.3%) | |||
| Investigations | ||||||
| Alanine aminotransferase increased | 6/74 (8.1%) | 5/76 (6.6%) | 11/150 (7.3%) | |||
| Blood cortisol decreased | 4/74 (5.4%) | 2/76 (2.6%) | 6/150 (4%) | |||
| Blood creatine phosphokinase increased | 1/74 (1.4%) | 6/76 (7.9%) | 7/150 (4.7%) | |||
| Blood glucose increased | 6/74 (8.1%) | 7/76 (9.2%) | 13/150 (8.7%) | |||
| Gamma-glutamyltransferase increased | 7/74 (9.5%) | 6/76 (7.9%) | 13/150 (8.7%) | |||
| Glycosylated haemoglobin increased | 4/74 (5.4%) | 4/76 (5.3%) | 8/150 (5.3%) | |||
| Lipase increased | 2/74 (2.7%) | 4/76 (5.3%) | 6/150 (4%) | |||
| Weight decreased | 4/74 (5.4%) | 3/76 (3.9%) | 7/150 (4.7%) | |||
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 3/74 (4.1%) | 12/76 (15.8%) | 15/150 (10%) | |||
| Diabetes mellitus | 15/74 (20.3%) | 20/76 (26.3%) | 35/150 (23.3%) | |||
| Hypercholesterolaemia | 3/74 (4.1%) | 6/76 (7.9%) | 9/150 (6%) | |||
| Hyperglycaemia | 36/74 (48.6%) | 35/76 (46.1%) | 71/150 (47.3%) | |||
| Hyperlipidaemia | 1/74 (1.4%) | 4/76 (5.3%) | 5/150 (3.3%) | |||
| Hyperuricaemia | 5/74 (6.8%) | 5/76 (6.6%) | 10/150 (6.7%) | |||
| Hypoglycaemia | 10/74 (13.5%) | 12/76 (15.8%) | 22/150 (14.7%) | |||
| Type 2 diabetes mellitus | 3/74 (4.1%) | 4/76 (5.3%) | 7/150 (4.7%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 9/74 (12.2%) | 4/76 (5.3%) | 13/150 (8.7%) | |||
| Back pain | 8/74 (10.8%) | 8/76 (10.5%) | 16/150 (10.7%) | |||
| Muscle spasms | 1/74 (1.4%) | 5/76 (6.6%) | 6/150 (4%) | |||
| Musculoskeletal chest pain | 0/74 (0%) | 4/76 (5.3%) | 4/150 (2.7%) | |||
| Myalgia | 4/74 (5.4%) | 4/76 (5.3%) | 8/150 (5.3%) | |||
| Pain in extremity | 6/74 (8.1%) | 6/76 (7.9%) | 12/150 (8%) | |||
| Nervous system disorders | ||||||
| Dizziness | 10/74 (13.5%) | 8/76 (10.5%) | 18/150 (12%) | |||
| Headache | 18/74 (24.3%) | 10/76 (13.2%) | 28/150 (18.7%) | |||
| Paraesthesia | 1/74 (1.4%) | 4/76 (5.3%) | 5/150 (3.3%) | |||
| Psychiatric disorders | ||||||
| Insomnia | 8/74 (10.8%) | 5/76 (6.6%) | 13/150 (8.7%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Dyspnoea | 2/74 (2.7%) | 4/76 (5.3%) | 6/150 (4%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Alopecia | 2/74 (2.7%) | 5/76 (6.6%) | 7/150 (4.7%) | |||
| Dry skin | 2/74 (2.7%) | 5/76 (6.6%) | 7/150 (4.7%) | |||
| Erythema | 2/74 (2.7%) | 4/76 (5.3%) | 6/150 (4%) | |||
| Pruritus | 5/74 (6.8%) | 6/76 (7.9%) | 11/150 (7.3%) | |||
| Rash | 4/74 (5.4%) | 2/76 (2.6%) | 6/150 (4%) | |||
| Skin exfoliation | 3/74 (4.1%) | 4/76 (5.3%) | 7/150 (4.7%) | |||
| Vascular disorders | ||||||
| Hypertension | 11/74 (14.9%) | 13/76 (17.1%) | 24/150 (16%) | |||
| Hypotension | 4/74 (5.4%) | 5/76 (6.6%) | 9/150 (6%) | |||
Limitations/Caveats
All analyses in this study were descriptive in nature. No comparisons were made between the two arms, and no p-values are reported. For the primary and key-secondary, success was based on estimating the response rate (and 95% CI) in each arm.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
| novartis.email@novartis.com |
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01374906
Other Study ID Numbers:
- CSOM230G2304
- 2009-011128-70
First Posted:
Jun 16, 2011
Last Update Posted:
May 22, 2018
Last Verified:
Apr 1, 2018