A Phase 3 interventional study of pasireotide LAR and SOM230 LAR 30 mg in Cushing's Disease, sponsored by Novartis Pharmaceuticals. Completed at 82 sites in 20 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-05-22.
Sponsored by Novartis Pharmaceuticals (part of Novartis) · Phase 3, Interventional, and Treatment
Among 37 studies in Pituitary ACTH Hypersecretion with a site in United States — 8 open to participants now, 10 under way, none of them phase 3. Pituitary ACTH Hypersecretion · United States.
Among the 37 studies in Pituitary ACTH Hypersecretion with a site in United States, this one is the 5th largest by enrollment of the 29 interventional ones, is one of 4 that started in 2011, is one of 11 in phase 3, and was the 12th registered.
64 studies on the registry are indexed under Pituitary ACTH Hypersecretion; 16 are open to participants now.
This study's enrollment of 150 is above the median of 44 across 40 interventional studies indexed under Pituitary ACTH Hypersecretion.
Browse Pituitary ACTH Hypersecretion studies →8 of the 37 studies in Pituitary ACTH Hypersecretion with a site in United States are open now, in 1 country. Each count lists the studies.
Of the 12 Pituitary ACTH Hypersecretion studies recruiting now, 7 (58%) set no upper age limit and 2 (17%) stop at 75 or younger; 6 take children under 18; 5 take healthy volunteers.
This study: 18 Years and older · all sexes · no healthy volunteers.
The full table on the hub →37 studies; the count open now beside each. This study's row is marked.
First in 1997; this study’s year is marked. 4 started in 2011.
Median enrollment 31 across the 29 interventional studies, 196 across the 8 observational. Of the 24 that completed or were terminated, 18 (75%) have results posted.
23 of 37 have an industry lead sponsor. The 10 most frequent:
Novartis Pharmaceuticals is the lead sponsor of 2,718 studies on the registry; 221 are open to participants now.
Of its 585 completed or terminated interventional studies of FDA-regulated products, 438 (75%) have results posted.
Novartis Pharmaceuticals has 8 studies filed under Pituitary ACTH Hypersecretion — fewer than ten, so there is no comparison to draw.
4 of the studies in Pituitary ACTH Hypersecretion with a site in United States that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT03364803Memorial Sloan Kettering Cancer CenterCollecting Information About Treatment Results for Patients With Cushing's Syndrome | 2026-11-28 |
| NCT03604198Corcept TherapeuticsExtension Study to Evaluate the Safety of Long-Term Use of Relacorilant in Patients With Cushing Syndrome | 2026-12 |
| NCT07335315Mayo ClinicEvaluation of Intraoperative Contrast Enhanced Ultrasound for the Identification of Pituitary Adenoma in Cushing's Disease Compared to Other Pituitary Tumors | 2027-01 |
| NCT06471829H. Lundbeck A/SA Trial of Lu AG13909 in Adult Participants With Cushing's Disease | 2027-08-10 |
Among the 37 studies in Pituitary ACTH Hypersecretion with a site in United States, from their registry updates:
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.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
For patients on medical treatment for Cushing's disease the following must be completed before screening assessments are performed
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Karnofsky performance status (KPS)
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Washout period
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms.
Drug: pasireotide LAR · Drug: SOM230 LAR 10 mg
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms.
Drug: pasireotide LAR · Drug: SOM230 LAR 30 mg
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).
Also known as: SOM230
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.
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.
Percentage Participants That Attained a mUFC ≤ 1.0 x ULN at Month 7 Regardless of Dose Titration
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
Percentage of Participants That Attained a mUFC ≤ 1.0 x ULN at Month 7 and Had Not Had a Dose Increase at Month 4
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
Actual Change in Mean Urinary Free Cortisol (mUFC) From Baseline
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)
Percentage Change in Mean Urinary Free Cortisol (mUFC) From Baseline
Percentage change in mUFC (nmol/24h) from baseline by randomized groups.
Time frame: M7, M12, M24, M36
Percentage of Patients Who Attain mUFC ≤ 1.0 x ULN
Controlled responder: mUFC ≤ 1.0×ULN by randomized groups.
Time frame: M7, M12, M24, M36
Percentage of Patients Who Attain mUFC ≤1.0 x ULN or Have at Least 50 % Reduction From Baseline in mUFC
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
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.
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
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
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
Percent of Participants Attaining a mUFC ≤ 1.0 x ULN or at Least a 50% Reduction in mUFC From Baseline at Indicated Time Points
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
Percent of Participants Attaining a Duration of Controlled or Partially Controlled Response at Indicated Time Points
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
Percentage Change From Baseline on Plasma Adrenocorticotropic Hormone (ACTH) Over Time
Percentage change in ACTH (pmol/L) from Baseline by randomized groups.
Time frame: Months 7, 12, 24 & 36
Percentage Change From Baseline on Serum Cortisol Over Time
Percentage change in serum cortisol (nmol/L) from Baseline by randomized groups.
Time frame: Months 7, 12, 24 & 36
Actual Change From Baseline in Clinical Signs Over Time: Blood Pressure
Change in blood pressure measurements from Baseline
Time frame: Month 7
Actual Change From Baseline in Clinical Signs Over Time: Body Mass Index (BMI)
Change in BMI measurements from Baseline
Time frame: Month 7
Actual Change From Baseline in Clinical Signs Over Time: Weight
Change in weight measurements from Baseline
Time frame: Month 7
Actual Change From Baseline in Clinical Signs Over Time: Body Composition: Region
Change in body composition: region measurements from Baseline
Time frame: Month 7
Actual Change From Baseline in Clinical Signs Over Time: Waist Circumference
Change in waist circumference measurements from Baseline
Time frame: Month 7
Actual Change From Baseline in Clinical Signs Over Time: Cholesterol & Triglycerides
Change in parameter measurements: cholesterol \& triglycerides from Baseline
Time frame: Month 7
Percentage Change From Baseline in Clinical Signs Over Time
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
Percentage of Participants Having a Favorable Shift From Baseline in Clinical Signs
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
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.
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
Percentage of Patients That Attain a Reduction of at Least 50% in mUFC From Baseline
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
Percent of Participants Attaining a Time to First Achievement of at Least a 50% Reduction in mUFC From Baseline at Indicated Time Points
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)
Percent of Participants With a Duration of at Least 50% Reduction in mUFC From Baseline at Indicated Time Points
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
Pharmacokinetic (PK) Parameter: Ctrough
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
Pharmacokinetic (PK) Parameter: Cmax
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
Actual Change in Standardized Score of Cushing's Disease HRQoL (CushingQOL) Score From Baseline
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
Actual Change in SF-12v2 Score From Baseline - Mental Component Summary
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
Actual Change in SF-12v2 Score From Baseline - Physical Component Summary
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
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.
| Milestone | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| 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 |
| Withdrew: Abnormal laboratory value(s) | 0 | 3 |
| Withdrew: Administrative problems | 2 | 2 |
| Withdrew: Adverse event | 10 | 11 |
| Withdrew: Death | 0 | 2 |
| Withdrew: Protocol violation | 2 | 2 |
| Withdrew: Withdrawal by subject | 15 | 9 |
| Withdrew: Unsatisfactory therapeutic effect | 11 | 19 |
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.
| percentage of participants | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Percentage Participants That Attained a mUFC ≤ 1.0 x ULN at Month 7 Regardless of Dose Titration | 41.9 (30.51 to 53.94) | 40.8 (29.65 to 52.67) |
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.
| percentage of participants | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Percentage of Participants That Attained a mUFC ≤ 1.0 x ULN at Month 7 and Had Not Had a Dose Increase at Month 4 | 28.4 (18.50 to 40.05) | 31.6 (21.39 to 43.25) |
Actual change in mUFC (nmol/24h) from baseline by randomized groups.
| nmol/24h | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| 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 |
Percentage change in mUFC (nmol/24h) from baseline by randomized groups.
| percentage change | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| 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 |
Controlled responder: mUFC ≤ 1.0×ULN by randomized groups.
| percentage of participants | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| M7 - Controlled responder | 39.2 (28.04 to 51.23) | 40.8 (29.65 to 52.67) |
| M12 - Controlled responder | 35.1 (24.39 to 47.11) | 25.0 (15.77 to 36.26) |
| M24 - Controlled responder | 39.7 (27.57 to 52.80) | 21.3 (11.86 to 33.68) |
| M36 - Controlled responder | 22.0 (11.53 to 35.96) | 4.0 (0.49 to 13.71) |
Controlled responder: mUFC ≤ 1.0×ULN. Partially controlled responder: at least 50% reduction in mUFC from Baseline, and mUFC \>1.0×ULN.
| percentage of participants | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| M7 | 44.6 (33.02 to 56.61) | 53.9 (42.13 to 65.45) |
| M12 | 45.9 (34.29 to 57.93) | 42.1 (30.86 to 53.98) |
| M24 | 46.0 (33.39 to 59.06) | 27.9 (17.15 to 40.83) |
| M36 | 28.0 (16.23 to 42.49) | 6.0 (1.25 to 16.55) |
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 participants | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Month 7 | 25.7 (16.22 to 37.16) | 31.6 (21.39 to 43.25) |
| Month 12 | 25.7 (16.22 to 37.16) | 25.0 (15.77 to 36.26) |
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.
| percentage of participants | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Uncontrolled Resp @ M7: subset: M1 & 2 | 60.6 | 60.6 |
| Uncontrolled Resp @ M7: subset: M1,2 & 3 | 61.3 | 65.5 |
| Uncontrolled Resp @ M12: subset: M1 & 2 | 69.7 | 69.7 |
| Uncontrolled Resp @ M12: subset: M1, 2 & 3 | 74.2 | 72.4 |
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.
| Percentage of participants | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Month 7 | 86.2 (76.1 to 93.5) | 83.4 (72.6 to 91.8) |
| Month 12 | 90.1 (80.7 to 96.2) | 94.5 (81.0 to 99.4) |
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 of participants | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Month 6 | 78.0 (66.5 to 87.7) | 72.9 (61.2 to 83.4) |
| Month 12 | 84.0 (73.1 to 92.2) | 82.8 (71.5 to 91.5) |
| Month 18 | 84.0 (73.1 to 92.2) | 87.1 (74.6 to 95.3) |
Percentage change in ACTH (pmol/L) from Baseline by randomized groups.
| Percentage change | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| 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 |
Percentage change in serum cortisol (nmol/L) from Baseline by randomized groups.
| Percentage change | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| 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 |
Change in blood pressure measurements from Baseline
| mmHg | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| 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 |
Change in BMI measurements from Baseline
| kg/m2 | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Actual Change From Baseline in Clinical Signs Over Time: Body Mass Index (BMI) | -0.7 ± 1.60 | -1.8 ± 2.05 |
Change in weight measurements from Baseline
| kg | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Actual Change From Baseline in Clinical Signs Over Time: Weight | -1.8 ± 4.16 | -4.6 ± 5.08 |
Change in body composition: region measurements from Baseline
| percentage fat | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Actual Change From Baseline in Clinical Signs Over Time: Body Composition: Region | -1.0 ± 2.64 | -1.8 ± 3.97 |
Change in waist circumference measurements from Baseline
| cm | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Actual Change From Baseline in Clinical Signs Over Time: Waist Circumference | -1.6 ± 8.47 | -7.1 ± 11.78 |
Change in parameter measurements: cholesterol \& triglycerides from Baseline
| mmol/L | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| 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 |
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 change | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| 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 |
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 | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| Facial rubor | 32.7 | 53.6 |
| Hirsutism (females only) | 22.2 | 32.6 |
| Striae | 23.1 | 23.6 |
| Bruising | 25.0 | 14.3 |
| Supraclavicular fat pad | 40.4 | 28.6 |
| Dorsal fat pad | 28.8 | 40.0 |
| Muscle strength | 8.9 | 4.5 |
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 participants | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| stratum:1.5 x ULN to < 2.0 x ULN | 52.0 (31.31 to 72.20) | 52.0 (31.31 to 72.20) |
| stratum:2.0 x ULN to <= 5.0 x ULN | 36.7 (23.42 to 51.71) | 35.3 (22.43 to 49.93) |
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:
| percentage of participants | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| M7 | 35.1 (24.39 to 47.11) | 43.4 (32.08 to 55.29) |
| M12 | 35.1 (24.39 to 47.11) | 38.2 (27.25 to 50.02) |
| M24 | 83.3 (62.62 to 95.26) | 57.1 (28.86 to 82.34) |
| M36 | 100 (63.06 to 100.00) | 33.33 (0.84 to 90.57) |
Time to first achievement of a 5by randomized groups.0% reduction in mUFC from baseline
| Percentage of participants | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| M7 | 80.5 (69.7 to 89.3) | 73.4 (62.4 to 83.4) |
| M12 | 84.4 (74.0 to 92.3) | 80.7 (69.4 to 89.8) |
Duration of 50% reduction from baseline is defined as the period starting from the date of patient's first 50% reduction from baseline
| Percentage of participants | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| M6 | 78.4 (66.6 to 88.3) | 77.8 (66.0 to 87.7) |
| M12 | 84.9 (73.7 to 93.1) | 83.7 (72.6 to 92.1) |
| M18 | 84.9 (73.7 to 93.1) | 83.7 (72.6 to 92.1) |
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.
| ng/mL | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose | 5 mg Pasireotide LAR Dose | 40 mg Pasireotide LAR Dose |
|---|---|---|---|---|
| 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 |
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.
| ng/mL | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose | 5 mg Pasireptide LAR Dose | 40 mg Pasireotide LAR Dose |
|---|---|---|---|---|
| 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 |
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.
| scores on a scale | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| 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 |
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.
| scores on a scale | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| 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 |
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.
| scores on a scale | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose |
|---|---|---|
| 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 |
Collected over 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.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| 10 mg Pasireotide LAR Dose | — | 22/74 (29.7%) | 73/74 (98.6%) |
| 30 mg Pasireotide LAR Dose | — | 19/76 (25%) | 76/76 (100%) |
| All Patients | — | 41/150 (27.3%) | 149/150 (99.3%) |
| Event | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose | All Patients |
|---|---|---|---|
| CholelithiasisHepatobiliary disorders | 2/74 | 3/76 | 5/150 |
| Pituitary-dependent Cushing's syndromeEndocrine disorders | 2/74 | 1/76 | 3/150 |
| Cholecystitis acuteHepatobiliary disorders | 2/74 | 0/76 | 2/150 |
| Stress fractureInjury, poisoning and procedural complications | 2/74 | 0/76 | 2/150 |
| Pulmonary embolismRespiratory, thoracic and mediastinal disorders | 0/74 | 2/76 | 2/150 |
| Angina unstableCardiac disorders | 1/74 | 0/76 | 1/150 |
| Adrenal insufficiencyEndocrine disorders | 1/74 | 0/76 | 1/150 |
| HyperadrenocorticismEndocrine disorders | 1/74 | 0/76 | 1/150 |
| Anogenital dysplasiaGastrointestinal disorders | 1/74 | 0/76 | 1/150 |
| HaemorrhoidsGastrointestinal disorders | 1/74 | 0/76 | 1/150 |
| Event | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose | All Patients |
|---|---|---|---|
| HyperglycaemiaMetabolism and nutrition disorders | 36/74 | 35/76 | 71/150 |
| DiarrhoeaGastrointestinal disorders | 26/74 | 35/76 | 61/150 |
| CholelithiasisHepatobiliary disorders | 15/74 | 33/76 | 48/150 |
| Diabetes mellitusMetabolism and nutrition disorders | 15/74 | 20/76 | 35/150 |
| NasopharyngitisInfections and infestations | 18/74 | 13/76 | 31/150 |
| HeadacheNervous system disorders | 18/74 | 10/76 | 28/150 |
| NauseaGastrointestinal disorders | 17/74 | 16/76 | 33/150 |
| FatigueGeneral disorders | 13/74 | 15/76 | 28/150 |
| Abdominal painGastrointestinal disorders | 11/74 | 13/76 | 24/150 |
| HypertensionVascular disorders | 11/74 | 13/76 | 24/150 |
Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug.
| Age, Continuous(years) | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose | Total |
|---|---|---|---|
| Mean | 38.3 ± 12.52 | 38.6 ± 12.99 | 38.5 ± 12.72 |
| Sex: Female, Male(Participants) | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose | Total |
|---|---|---|---|
| Female | 58 | 60 | 118 |
| Male | 16 | 16 | 32 |
| Race/Ethnicity, Customized(Participants) | 10 mg Pasireotide LAR Dose | 30 mg Pasireotide LAR Dose | Total |
|---|---|---|---|
| Caucasian | 39 | 44 | 83 |
| Asian | 27 | 24 | 51 |
| Black | 2 | 0 | 2 |
| Other | 6 | 8 | 14 |
Plan to share: Undecided — Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Ran from Nov 2011 to primary completion in Dec 2016, 61 months.
Results were first posted in Apr 2018, 1 year 3 months after primary completion.
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Pituitary ACTH Hypersecretion →