Dumping Syndrome
Conditions
Keywords
Dumping syndrome, SOM230, pasireotide LAR
Brief summary
multi-center, phase II study evaluating efficacy, safety and pharmacokinetics of pasireotide in patients with dumping syndrome
Detailed description
43 adult patients with dumping syndrome received pasireotide s.c. during the dose escalation phase (3 months dose could be increased based on the presence of hypoglycemia during OGTT). After completing Month 3, patients were switched to pasireotide LAR for 3 months (up to Month 6). The core phase of the study was completed at the end of Month 6. Patients were allowed to enter the 6 month extension phase if they experienced benefit with pasireotide LAR treatment.
Interventions
DRUGSOM230
Pasireotide (SOM230) sc injection was provided as solution for injection in individual 1-point-cut 1 mL ampule, containing nominally 200 μg of pasireotide (as free base). Doses: 50, 100, 150 and 200 μg. Pasireotide im LAR depot injection was provided as micro particles powder in vials containing nominally 10, 20, 40 & 60 mg of pasireotide (as free base) & solvent for suspension for injection in ampules for the reconstitution of the LAR micro particles. Doses: 10, 20, 30, 40 or 60 mg
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
. * Male or female patients ≥ 18 years of age. * Post-gastric or esophageal bypass surgery, matching one of the criteria below: * Bariatric surgery: more than 6 months before signing the informed consent * Esophageal cancer surgery: were disease free at study entry * Gastric cancer surgery: were at stage 0 or I and were disease free at study entry * Patient with a documented diagnosis of Dumping Syndrome defined as having: * History of/or active symptoms associated with dumping syndrome (e.g. post-prandial tachycardia, bloating, diarrhea) and * Documented history of hypoglycemia based on either: * glucose \<50 mg/dL or 2.8 mmol/L on a sporadic or scheduled blood analysis -or * glucose value \<60 mg/dL or ≤ 3.3 mmol/L at 90, 120, 150 or 180 min during an OGTT * Patients had at least one glucose level \<60 mg/dL (or ≤ 3.3 mmol/L) at 90, 120, 150 or 180 min during the 3-hour OGTT at screening. * Patients with esophageal cancer with a negative computed tomography (CT) or Magnetic resonance imaging (MRI) scan (neck, thoracic, and upper abdominal) and albumin ≥ 3.5 g/dl at baseline. * Patients with gastric cancer with a negative CT or MRI scan (total abdomen). * Karnofsky Performance Status ≥ 60 (i.e. required occasional assistance, but was able to care for most of their personal needs) * Patients who received other therapies for dumping syndrome (such as acarbose, gama guar, pectin) must have stopped all treatments and had a wash out period prior to signing the informed consent (i.e. at least 2 weeks between last previous therapy and first dose of study medication in this study). * Patients who had provided signed written informed consent prior to study participation.
Exclusion criteria
* Bariatric patients who had lap band. * Patients with a current diagnosis of diabetes mellitus. * Patients who had failed treatment with somatostatin analogues for dumping syndrome in the past. * Patients who had been treated with somatostatin analogues in the past, must have had an appropriate interval between the last administration of somatostatin analogues treatment and the study drug as follows * Octreotide sc for ≥ 72 hours * Octreotide LAR for ≥ 56 days (8 weeks) * Lanreotide Autogel for ≥ 98 days (14 weeks) * Lanreotide SR ≥ 28 days (4 weeks) * Patients who were already treated with pasireotide. * Patients who had a known hypersensitivity to somatostatin analogues. * Patients who were receiving anti-cancer therapy (chemotherapy and/or radiotherapy). * Patients who had any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: * Patients with the presence of active or suspected acute or chronic uncontrolled infection or with a history of immunodeficiency, including a positive human immunodeficiency virus (HIV) test result (ELISA and Western blot). An HIV test was not required; however, previous medical history was reviewed. * Non-malignant medical illnesses that were uncontrolled or whose control may have been jeopardized by the treatment with this study treatment. * Life-threatening autoimmune and ischemic disorders. * Patients with the presence of active or suspected acute or chronic uncontrolled infection. Inadequate end organ function as defined by: * Inadequate bone marrow function: * White blood cells (WBC) \<2.5 x 109/L * Absolute neutrophil count \<1.5 x 109/L * Platelets \<100 x 109/L * Hemoglobin \<9 g/dL * International normalized ratio (INR) ≥ 1.3 * Serum creatinine \>2.0 mg/dL * Alkaline phosphatase (ALP) \>2.5 x upper limit of normal (ULN) * Serum total bilirubin \>1.5 x ULN * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \>2 x ULN * History of liver disease, such as cirrhosis or chronic active hepatitis B and C. * Presence of Hepatitis B surface antigen (HbsAg) and/ or presence of Hepatitis C antibody test (anti-Hepatitis C Virus).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate in Plasma Glucose Level | at Month 3 (M3) | Response rate is defined as percentage of patients with no glucose values \< 60 mg/dL at 90,120, 150 and 180 min during the Oral Glucose Tolerance Test (OGTT) at the end of s.c. dose escalation phase |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate in Pulse Rate | at baseline, M3, M6, M12 | Pulse rate was defined as percentage of patients with change in pulse rate \>=10 bpm from pre-OGTT to 30 minutes post OGTT. |
| Response Rate in Hematocrit Levels | M3, M6, M12 | Percentage of patients with change in hematocrit \>= 3% from pre-OGTT to 30 minutes post OGTT. |
| Glucagon-like Peptide 1 (GLP-1) Levels During OGTT | M3, M6, M12 | Absolute Glucagon-like peptide 1 (GLP-1) levels at the end of at the end of Months 3, 6 and 12 at different time points. |
| Gastric Inhibitory Polypeptide (GIP) Levels at During OGTT | M3, M6, M12 | Absolute Gastric Inhibitory Polypeptide (GIP) levels at the end of Months 3, 6 and 12 at different time points. |
| Insulin Levels During OGTT | M3, M6, M12 | Absolute insulin levels at the end of M3, M6, M12 |
| Glucagon Levels During OGTT | M3, M6, M12 | Absolute glucagon levels at the end of Months 3, 6 & 12 |
| Health-related Quality of Live (HRQoL) Short Form- 36 (SF-36) Score(s) | M3, M6, M12 | Absolute HRQoL SF-36 Scores at end of the Months 3, 6 and 12 from s.c. baseline. SF-36, a 36-Item Short Form Health Survey (SF-36) is a set of generic, coherent, and easily administered quality-of-life measures. These measures rely upon patient self-reporting. Items are scored so that a high score defines a more favorable health state. In addition, each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively. |
| Dumping Severity Score (DSS) at the End of Months 3, 6 and 8 | M3, M6, M8 | Absolute Dumping Severity Score (DSS) scores at end of M3, M6 & M8. At study start patients were assessed using DSS (older version of DSQ); however after the implementation of protocol amendment 2, all patients were expected to use DSQ. No results available for M12 as last patient that answered the DSS was at M8. DSS = disease-specific patient (Pt.) reported outcome (PRO) questionnaire uses a 4-point Likert scale (0, absent; 1, mild; 2, relevant; 3, severe; 4) to ask Pt. to evaluate intensity of early dumping symptoms (within 30 minutes (\<30 minutes) after food ingestion). The questionnaire also evaluates 65 late dumping symptoms (more than 1.5 hours (\>90 minutes) after food ingestion). Early & late dumping score calculated by adding the scores of the respective questions. Cumulative dumping score is obtained by adding early & late scores. DSS Range (min (absent) - max (severe)): Early dumping: 0-24; Late Dumping: 0-18; Cumulative: 0-42. Lower scores represent a better outcome. |
| Response Rate in Plasma Glucose Level | at Month 6 (M6), Month 12 (M12) | Response rate is defined as percentage of patients with no glucose values \< 60 mg/dL at 90,120, 150 and 180 min during the Oral Glucose Tolerance Test (OGTT) at the end of 6 months (end of LAR/Core phase) and at the end of 12 months (extension phase) |
| Patient Global Assessment at the End of Months 3, 6 and 12 | M3, M6, M12 | Treatment with pasireotide LAR (both early and late dumping scores), was assessed by patient global assessment. Patient Global Assessment served as an additional approach to symptom based measurement by DSQ. It incorporated a patient global assessment question: Considering all the ways that your disease affects you, rate how you are feeling during the last 7 days compared with your situation before starting the study .Patients Global Assessment was measured utilizing a 7 point scale (from 1=a lot worse to 7= a lot better). |
| Plasma Pharmacokinetic (PK) Parameter of Pasireotide: Cmax, ss (Steady State) and Ctrough, ss, After s.c. Injection | M1 to M3 | A pre-dose PK blood sample was collected before the morning pasireotide s.c. dose of 50 μg, 100 ug, 150 ug and 200 ug. OGTT was performed right after the morning s.c. dose (Time point zero); additional PK blood samples were collected at the same time points as the OGTT evaluation at 30, 60, 90, 120, 150 and 180 minutes. 'n' = number of subjects with non-missing values |
| Plasma Pharmacokinetic (PK) Parameter of Pasireotide: AUC0-3h, ss, After s.c. Injection | M1 to M3 | A pre-dose PK blood sample was collected before the morning pasireotide s.c. dose of 50 μg, 100 ug, 150 ug and 200 ug. OGTT was performed right after the morning s.c. dose (Time point zero); additional PK blood samples were collected at the same time points as the OGTT evaluation at 30, 60, 90, 120, 150 and 180 minutes. |
| Plasma Pharmacokinetic (PK) Parameter of Pasireotide: Tmax, ss, After s.c. Injection | M1 to M3 | A pre-dose PK blood sample was collected before the morning pasireotide s.c. dose of 50 μg, 100 ug, 150 ug and 200 ug. OGTT was performed right after the morning s.c. dose (Time point zero); additional PK blood samples were collected at the same time points as the OGTT evaluation at 30, 60, 90, 120, 150 and 180 minutes. |
| Plasma PK Parameter of AUC0-3h, d21, End _inj and AUC0-3h, d28, 3rd_inj Associated With LAR (LAR Core Phase) | M4 to M6 | — |
| Summary of LAR PK Parameters by Dose | M4 to M6 | Summary of plasma PK parameter Cmax, p2 , 2nd injection and Ctrough, d28 associated with LAR injection (LAR Core phase) |
| Pasireotide Concentrations in LAR Phase | M7 to M12 | Summary of pasireotide concentrations following monthly i.m. injections of pasireotide LAR by incident dose (LAR Pharmacokinetic set) |
| LAR PK Parameter: Ctrough - at Steady State (ss) by Dose | M4 to M12 | In the LAR treatment phase, monthly injections of pasireotide LAR 10, 20, 30 and 40 mg were given to participants and trough concentration at steady state (Ctrough,ss) were obtained but due to only 1 participant in the 40mg arm, standard deviation could not be calculated. |
| Dumping Score Questionnaire (DSQ) at the End of Months 3, 6 and 12 | M3, M6, M12 | Absolute Dumping Score Questionnaire (DSQ) scores at end of Months 3, 6 & 12 from s.c. baseline. DSQ = disease-specific PRO scale. The questionnaire uses a 5-point Likert scale (0, none; 1, mild; 2, moderate; 3, severe; 4, very severe) to ask Pt. to evaluate intensity of 10 early dumping symptoms (within 30 minutes (\<30 minutes) after food ingestion). The questionnaire also evaluates 5 late dumping symptoms (more than 1.5 hours (\>90 minutes) after food ingestion). Early & late dumping score calculated by adding the scores of respective questions. A cumulative dumping score is obtained by adding early & late scores. At study start patients were assessed using DSS (older version of DSQ); however after the implementation of protocol amendment 2, all patients used DSQ. DSQ Range: (min (None) - max (Very severe)): Early dumping: 0-40; Late Dumping: 0-20; Cumulative: 0-60. Lower scores represent a better outcome. |
Countries
Belgium, France, Germany, Netherlands, United States
Participant flow
Recruitment details
43 patients were enrolled as planned; 33 patients completed the core sc phase, 31 patients completed the core LAR phase. Of the 31 patients who completed core LAR phase, 27 patients entered the extension phase. Of the 27 patients who entered the extension phase, 23 patients completed the study.
Pre-assignment details
All patients underwent an OGTT (75g of glucose) and were evaluated at different time points. If the glucose level was \<60 mg/dL at 90, 120, 150 or 180 min during the OGTT and all the other eligibility criteria were met, patients were allowed to start study medication. The study was divided in 2 phases, core phase and extension phase.
Participants by arm
| Arm | Count |
|---|---|
| SOM230 Subjects with dumping syndrome treated with pasireotide | 43 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative problems | 1 |
| Overall Study | Adverse Event | 6 |
| Overall Study | completed core, did not enter ext. phase | 4 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Unsatisfactory therapeutic effect | 2 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | SOM230 |
|---|---|
| Age, Continuous | 45.9 Years STANDARD_DEVIATION 9.99 |
| Sex: Female, Male Female | 38 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 31 / 43 | 25 / 33 |
| serious Total, serious adverse events | 6 / 43 | 10 / 33 |
Outcome results
Primary
Response Rate in Plasma Glucose Level
Response rate is defined as percentage of patients with no glucose values \< 60 mg/dL at 90,120, 150 and 180 min during the Oral Glucose Tolerance Test (OGTT) at the end of s.c. dose escalation phase
Time frame: at Month 3 (M3)
Population: The sc full analysis set (sc FAS) consisted of all patients who received at least one dose of pasireotide sc during core sc phase.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOM230 - 3 Months (sc) | Response Rate in Plasma Glucose Level | 60.5 percentage of participants |
Secondary
Dumping Score Questionnaire (DSQ) at the End of Months 3, 6 and 12
Absolute Dumping Score Questionnaire (DSQ) scores at end of Months 3, 6 & 12 from s.c. baseline. DSQ = disease-specific PRO scale. The questionnaire uses a 5-point Likert scale (0, none; 1, mild; 2, moderate; 3, severe; 4, very severe) to ask Pt. to evaluate intensity of 10 early dumping symptoms (within 30 minutes (\<30 minutes) after food ingestion). The questionnaire also evaluates 5 late dumping symptoms (more than 1.5 hours (\>90 minutes) after food ingestion). Early & late dumping score calculated by adding the scores of respective questions. A cumulative dumping score is obtained by adding early & late scores. At study start patients were assessed using DSS (older version of DSQ); however after the implementation of protocol amendment 2, all patients used DSQ. DSQ Range: (min (None) - max (Very severe)): Early dumping: 0-40; Late Dumping: 0-20; Cumulative: 0-60. Lower scores represent a better outcome.
Time frame: M3, M6, M12
Population: The sc full analysis set (sc FAS) consisted of all patients who received at least one dose of pasireotide sc during core sc phase. The LAR full analysis set (LAR FAS) consisted of all patients who received at least one dose of pasireotide LAR during core LAR phase.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOM230 - 3 Months (sc) | Dumping Score Questionnaire (DSQ) at the End of Months 3, 6 and 12 | Late symptoms (n=15, 20, 23) | 4.9 scores on a scale | Standard Deviation 5.37 |
| SOM230 - 3 Months (sc) | Dumping Score Questionnaire (DSQ) at the End of Months 3, 6 and 12 | Early symptoms (n=15, 20, 23) | 9.6 scores on a scale | Standard Deviation 10.27 |
| SOM230 - 3 Months (sc) | Dumping Score Questionnaire (DSQ) at the End of Months 3, 6 and 12 | Overall score (n=15, 20, 23) | 14.5 scores on a scale | Standard Deviation 15.26 |
| SOM230 - 12 Months (Ext) | Dumping Score Questionnaire (DSQ) at the End of Months 3, 6 and 12 | Late symptoms (n=15, 20, 23) | 5.6 scores on a scale | Standard Deviation 6.57 |
| SOM230 - 12 Months (Ext) | Dumping Score Questionnaire (DSQ) at the End of Months 3, 6 and 12 | Early symptoms (n=15, 20, 23) | 9.2 scores on a scale | Standard Deviation 10.05 |
| SOM230 - 12 Months (Ext) | Dumping Score Questionnaire (DSQ) at the End of Months 3, 6 and 12 | Overall score (n=15, 20, 23) | 14.8 scores on a scale | Standard Deviation 14.65 |
| SOM230 - 12 Months (Ext) | Dumping Score Questionnaire (DSQ) at the End of Months 3, 6 and 12 | Early symptoms (n=15, 20, 23) | 10.7 scores on a scale | Standard Deviation 10.94 |
| SOM230 - 12 Months (Ext) | Dumping Score Questionnaire (DSQ) at the End of Months 3, 6 and 12 | Overall score (n=15, 20, 23) | 16.3 scores on a scale | Standard Deviation 16.23 |
| SOM230 - 12 Months (Ext) | Dumping Score Questionnaire (DSQ) at the End of Months 3, 6 and 12 | Late symptoms (n=15, 20, 23) | 5.7 scores on a scale | Standard Deviation 5.93 |
Secondary
Dumping Severity Score (DSS) at the End of Months 3, 6 and 8
Absolute Dumping Severity Score (DSS) scores at end of M3, M6 & M8. At study start patients were assessed using DSS (older version of DSQ); however after the implementation of protocol amendment 2, all patients were expected to use DSQ. No results available for M12 as last patient that answered the DSS was at M8. DSS = disease-specific patient (Pt.) reported outcome (PRO) questionnaire uses a 4-point Likert scale (0, absent; 1, mild; 2, relevant; 3, severe; 4) to ask Pt. to evaluate intensity of early dumping symptoms (within 30 minutes (\<30 minutes) after food ingestion). The questionnaire also evaluates 65 late dumping symptoms (more than 1.5 hours (\>90 minutes) after food ingestion). Early & late dumping score calculated by adding the scores of the respective questions. Cumulative dumping score is obtained by adding early & late scores. DSS Range (min (absent) - max (severe)): Early dumping: 0-24; Late Dumping: 0-18; Cumulative: 0-42. Lower scores represent a better outcome.
Time frame: M3, M6, M8
Population: The sc full analysis set (sc FAS) consisted of all patients who received at least one dose of pasireotide sc during core sc phase. The LAR full analysis set (LAR FAS) consisted of all patients who received at least one dose of pasireotide LAR during core LAR phase.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOM230 - 3 Months (sc) | Dumping Severity Score (DSS) at the End of Months 3, 6 and 8 | Late symptoms (n=20, 9, 2) | 6.7 scores on a scale | Standard Deviation 5.42 |
| SOM230 - 3 Months (sc) | Dumping Severity Score (DSS) at the End of Months 3, 6 and 8 | Early symptoms (n=20, 9, 2) | 7.1 scores on a scale | Standard Deviation 6.38 |
| SOM230 - 3 Months (sc) | Dumping Severity Score (DSS) at the End of Months 3, 6 and 8 | Overall score (n=20, 9, 2) | 13.7 scores on a scale | Standard Deviation 11.11 |
| SOM230 - 12 Months (Ext) | Dumping Severity Score (DSS) at the End of Months 3, 6 and 8 | Late symptoms (n=20, 9, 2) | 6.4 scores on a scale | Standard Deviation 5.27 |
| SOM230 - 12 Months (Ext) | Dumping Severity Score (DSS) at the End of Months 3, 6 and 8 | Early symptoms (n=20, 9, 2) | 6.8 scores on a scale | Standard Deviation 6.46 |
| SOM230 - 12 Months (Ext) | Dumping Severity Score (DSS) at the End of Months 3, 6 and 8 | Overall score (n=20, 9, 2) | 13.2 scores on a scale | Standard Deviation 10.65 |
| SOM230 - 12 Months (Ext) | Dumping Severity Score (DSS) at the End of Months 3, 6 and 8 | Early symptoms (n=20, 9, 2) | 9.0 scores on a scale | Standard Deviation 8.49 |
| SOM230 - 12 Months (Ext) | Dumping Severity Score (DSS) at the End of Months 3, 6 and 8 | Overall score (n=20, 9, 2) | 15.0 scores on a scale | Standard Deviation 12.73 |
| SOM230 - 12 Months (Ext) | Dumping Severity Score (DSS) at the End of Months 3, 6 and 8 | Late symptoms (n=20, 9, 2) | 6.0 scores on a scale | Standard Deviation 4.24 |
Secondary
Gastric Inhibitory Polypeptide (GIP) Levels at During OGTT
Absolute Gastric Inhibitory Polypeptide (GIP) levels at the end of Months 3, 6 and 12 at different time points.
Time frame: M3, M6, M12
Population: The sc full analysis set (sc FAS) consisted of all patients who received at least one dose of pasireotide sc during core sc phase.~The LAR full analysis set (LAR FAS) consisted of all patients who received at least one dose of pasireotide LAR during core LAR phase.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOM230 - 3 Months (sc) | Gastric Inhibitory Polypeptide (GIP) Levels at During OGTT | 30 Minutes (n=32, 29, 22) | 15.704 pmol/L | Standard Deviation 10.6395 |
| SOM230 - 3 Months (sc) | Gastric Inhibitory Polypeptide (GIP) Levels at During OGTT | 120 Minutes (n=31, 29, 22) | 2.089 pmol/L | Standard Deviation 1.4681 |
| SOM230 - 3 Months (sc) | Gastric Inhibitory Polypeptide (GIP) Levels at During OGTT | 90 Minutes(n=31, 29, 22) | 4.141 pmol/L | Standard Deviation 2.8978 |
| SOM230 - 3 Months (sc) | Gastric Inhibitory Polypeptide (GIP) Levels at During OGTT | Pre-OGTT (n=31, 29, 23) | 2.608 pmol/L | Standard Deviation 1.7441 |
| SOM230 - 3 Months (sc) | Gastric Inhibitory Polypeptide (GIP) Levels at During OGTT | 180 Minutes (n=31, 29, 22) | 1.260 pmol/L | Standard Deviation 1.2218 |
| SOM230 - 3 Months (sc) | Gastric Inhibitory Polypeptide (GIP) Levels at During OGTT | 150 Minutes (n=30, 29, 22) | 1.376 pmol/L | Standard Deviation 1.2049 |
| SOM230 - 3 Months (sc) | Gastric Inhibitory Polypeptide (GIP) Levels at During OGTT | 60 Minutes (n= 32, 30, 22) | 9.471 pmol/L | Standard Deviation 6.1861 |
| SOM230 - 12 Months (Ext) | Gastric Inhibitory Polypeptide (GIP) Levels at During OGTT | 90 Minutes(n=31, 29, 22) | 6.5 pmol/L | Standard Deviation 7.32 |
| SOM230 - 12 Months (Ext) | Gastric Inhibitory Polypeptide (GIP) Levels at During OGTT | Pre-OGTT (n=31, 29, 23) | 1.5 pmol/L | Standard Deviation 1 |
| SOM230 - 12 Months (Ext) | Gastric Inhibitory Polypeptide (GIP) Levels at During OGTT | 30 Minutes (n=32, 29, 22) | 30.3 pmol/L | Standard Deviation 19.73 |
| SOM230 - 12 Months (Ext) | Gastric Inhibitory Polypeptide (GIP) Levels at During OGTT | 60 Minutes (n= 32, 30, 22) | 14.3 pmol/L | Standard Deviation 13.37 |
| SOM230 - 12 Months (Ext) | Gastric Inhibitory Polypeptide (GIP) Levels at During OGTT | 120 Minutes (n=31, 29, 22) | 2.4 pmol/L | Standard Deviation 1.73 |
| SOM230 - 12 Months (Ext) | Gastric Inhibitory Polypeptide (GIP) Levels at During OGTT | 150 Minutes (n=30, 29, 22) | 2.1 pmol/L | Standard Deviation 3.22 |
| SOM230 - 12 Months (Ext) | Gastric Inhibitory Polypeptide (GIP) Levels at During OGTT | 180 Minutes (n=31, 29, 22) | 3.8 pmol/L | Standard Deviation 12.77 |
| SOM230 - 12 Months (Ext) | Gastric Inhibitory Polypeptide (GIP) Levels at During OGTT | 120 Minutes (n=31, 29, 22) | 3.0 pmol/L | Standard Deviation 2.81 |
| SOM230 - 12 Months (Ext) | Gastric Inhibitory Polypeptide (GIP) Levels at During OGTT | 30 Minutes (n=32, 29, 22) | 24.8 pmol/L | Standard Deviation 18.88 |
| SOM230 - 12 Months (Ext) | Gastric Inhibitory Polypeptide (GIP) Levels at During OGTT | 180 Minutes (n=31, 29, 22) | 2.5 pmol/L | Standard Deviation 3.72 |
| SOM230 - 12 Months (Ext) | Gastric Inhibitory Polypeptide (GIP) Levels at During OGTT | 150 Minutes (n=30, 29, 22) | 1.9 pmol/L | Standard Deviation 1.44 |
| SOM230 - 12 Months (Ext) | Gastric Inhibitory Polypeptide (GIP) Levels at During OGTT | 90 Minutes(n=31, 29, 22) | 5.2 pmol/L | Standard Deviation 5.18 |
| SOM230 - 12 Months (Ext) | Gastric Inhibitory Polypeptide (GIP) Levels at During OGTT | 60 Minutes (n= 32, 30, 22) | 11.6 pmol/L | Standard Deviation 9.05 |
| SOM230 - 12 Months (Ext) | Gastric Inhibitory Polypeptide (GIP) Levels at During OGTT | Pre-OGTT (n=31, 29, 23) | 1.7 pmol/L | Standard Deviation 1.51 |
Secondary
Glucagon Levels During OGTT
Absolute glucagon levels at the end of Months 3, 6 & 12
Time frame: M3, M6, M12
Population: The sc full analysis set (sc FAS) consisted of all patients who received at least one dose of pasireotide sc during core sc phase. The LAR full analysis set (LAR FAS) consisted of all patients who received at least one dose of pasireotide LAR during core LAR phase.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOM230 - 3 Months (sc) | Glucagon Levels During OGTT | 180 Minutes (n= 32, 29, 22) | 20.16 pmol/L | Standard Deviation 7.097 |
| SOM230 - 3 Months (sc) | Glucagon Levels During OGTT | 150 Minutes (n= 32 28, 22) | 19.94 pmol/L | Standard Deviation 7.169 |
| SOM230 - 3 Months (sc) | Glucagon Levels During OGTT | 90 Minutes (n= 32, 29, 22) | 20.07 pmol/L | Standard Deviation 7.898 |
| SOM230 - 3 Months (sc) | Glucagon Levels During OGTT | 60 Minutes (n= 33, 28, 22) | 20.80 pmol/L | Standard Deviation 7.33 |
| SOM230 - 3 Months (sc) | Glucagon Levels During OGTT | Pre-OGTT (n= 31, 30, 23) | 20.70 pmol/L | Standard Deviation 6.162 |
| SOM230 - 3 Months (sc) | Glucagon Levels During OGTT | 120 Minutes (n= 32, 29, 22) | 19.73 pmol/L | Standard Deviation 7.369 |
| SOM230 - 3 Months (sc) | Glucagon Levels During OGTT | 30 Minutes (n= 33, 29, 22) | 20.64 pmol/L | Standard Deviation 7.037 |
| SOM230 - 12 Months (Ext) | Glucagon Levels During OGTT | 120 Minutes (n= 32, 29, 22) | 23.1 pmol/L | Standard Deviation 5.4 |
| SOM230 - 12 Months (Ext) | Glucagon Levels During OGTT | 150 Minutes (n= 32 28, 22) | 23.7 pmol/L | Standard Deviation 6.67 |
| SOM230 - 12 Months (Ext) | Glucagon Levels During OGTT | 30 Minutes (n= 33, 29, 22) | 25.8 pmol/L | Standard Deviation 6.57 |
| SOM230 - 12 Months (Ext) | Glucagon Levels During OGTT | 180 Minutes (n= 32, 29, 22) | 22.7 pmol/L | Standard Deviation 5.45 |
| SOM230 - 12 Months (Ext) | Glucagon Levels During OGTT | 60 Minutes (n= 33, 28, 22) | 23.7 pmol/L | Standard Deviation 5.76 |
| SOM230 - 12 Months (Ext) | Glucagon Levels During OGTT | Pre-OGTT (n= 31, 30, 23) | 22.6 pmol/L | Standard Deviation 5.85 |
| SOM230 - 12 Months (Ext) | Glucagon Levels During OGTT | 90 Minutes (n= 32, 29, 22) | 22.7 pmol/L | Standard Deviation 5.16 |
| SOM230 - 12 Months (Ext) | Glucagon Levels During OGTT | 180 Minutes (n= 32, 29, 22) | 22.3 pmol/L | Standard Deviation 6.58 |
| SOM230 - 12 Months (Ext) | Glucagon Levels During OGTT | Pre-OGTT (n= 31, 30, 23) | 21.4 pmol/L | Standard Deviation 6.82 |
| SOM230 - 12 Months (Ext) | Glucagon Levels During OGTT | 60 Minutes (n= 33, 28, 22) | 22.9 pmol/L | Standard Deviation 7.07 |
| SOM230 - 12 Months (Ext) | Glucagon Levels During OGTT | 90 Minutes (n= 32, 29, 22) | 21.5 pmol/L | Standard Deviation 7.69 |
| SOM230 - 12 Months (Ext) | Glucagon Levels During OGTT | 120 Minutes (n= 32, 29, 22) | 22.0 pmol/L | Standard Deviation 7.31 |
| SOM230 - 12 Months (Ext) | Glucagon Levels During OGTT | 150 Minutes (n= 32 28, 22) | 21.8 pmol/L | Standard Deviation 7.27 |
| SOM230 - 12 Months (Ext) | Glucagon Levels During OGTT | 30 Minutes (n= 33, 29, 22) | 23.8 pmol/L | Standard Deviation 6.97 |
Secondary
Glucagon-like Peptide 1 (GLP-1) Levels During OGTT
Absolute Glucagon-like peptide 1 (GLP-1) levels at the end of at the end of Months 3, 6 and 12 at different time points.
Time frame: M3, M6, M12
Population: The sc full analysis set (sc FAS) consisted of all patients who received at least one dose of pasireotide sc during core sc phase. The LAR full analysis set (LAR FAS) consisted of all patients who received at least one dose of pasireotide LAR during core LAR phase.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOM230 - 3 Months (sc) | Glucagon-like Peptide 1 (GLP-1) Levels During OGTT | 30 Minutes(n=32, 29, 22) | 12.811 pmol/L | Standard Deviation 6.6194 |
| SOM230 - 3 Months (sc) | Glucagon-like Peptide 1 (GLP-1) Levels During OGTT | 120 Minutes (n=31, 29, 22) | 5.003 pmol/L | Standard Deviation 4.1183 |
| SOM230 - 3 Months (sc) | Glucagon-like Peptide 1 (GLP-1) Levels During OGTT | 90 Minutes (n=31, 29, 22) | 6.986 pmol/L | Standard Deviation 4.9729 |
| SOM230 - 3 Months (sc) | Glucagon-like Peptide 1 (GLP-1) Levels During OGTT | Pre-OGTT (n=31, 29, 23) | 3.021 pmol/L | Standard Deviation 2.1936 |
| SOM230 - 3 Months (sc) | Glucagon-like Peptide 1 (GLP-1) Levels During OGTT | 180 Minutes (n=31, 29, 22) | 2.974 pmol/L | Standard Deviation 1.9902 |
| SOM230 - 3 Months (sc) | Glucagon-like Peptide 1 (GLP-1) Levels During OGTT | 150 Minutes(n=31, 29, 22) | 3.565 pmol/L | Standard Deviation 2.3879 |
| SOM230 - 3 Months (sc) | Glucagon-like Peptide 1 (GLP-1) Levels During OGTT | 60 Minutes (n= 32, 30, 22) | 11.208 pmol/L | Standard Deviation 11.1218 |
| SOM230 - 12 Months (Ext) | Glucagon-like Peptide 1 (GLP-1) Levels During OGTT | 90 Minutes (n=31, 29, 22) | 8.2 pmol/L | Standard Deviation 4.96 |
| SOM230 - 12 Months (Ext) | Glucagon-like Peptide 1 (GLP-1) Levels During OGTT | Pre-OGTT (n=31, 29, 23) | 2.1 pmol/L | Standard Deviation 1.37 |
| SOM230 - 12 Months (Ext) | Glucagon-like Peptide 1 (GLP-1) Levels During OGTT | 30 Minutes(n=32, 29, 22) | 21.0 pmol/L | Standard Deviation 18.01 |
| SOM230 - 12 Months (Ext) | Glucagon-like Peptide 1 (GLP-1) Levels During OGTT | 60 Minutes (n= 32, 30, 22) | 14.6 pmol/L | Standard Deviation 18.44 |
| SOM230 - 12 Months (Ext) | Glucagon-like Peptide 1 (GLP-1) Levels During OGTT | 120 Minutes (n=31, 29, 22) | 5.2 pmol/L | Standard Deviation 3.94 |
| SOM230 - 12 Months (Ext) | Glucagon-like Peptide 1 (GLP-1) Levels During OGTT | 150 Minutes(n=31, 29, 22) | 4.2 pmol/L | Standard Deviation 4.2 |
| SOM230 - 12 Months (Ext) | Glucagon-like Peptide 1 (GLP-1) Levels During OGTT | 180 Minutes (n=31, 29, 22) | 3.3 pmol/L | Standard Deviation 3.49 |
| SOM230 - 12 Months (Ext) | Glucagon-like Peptide 1 (GLP-1) Levels During OGTT | 120 Minutes (n=31, 29, 22) | 5.0 pmol/L | Standard Deviation 2.98 |
| SOM230 - 12 Months (Ext) | Glucagon-like Peptide 1 (GLP-1) Levels During OGTT | 30 Minutes(n=32, 29, 22) | 17.4 pmol/L | Standard Deviation 17.64 |
| SOM230 - 12 Months (Ext) | Glucagon-like Peptide 1 (GLP-1) Levels During OGTT | 180 Minutes (n=31, 29, 22) | 3.2 pmol/L | Standard Deviation 2.44 |
| SOM230 - 12 Months (Ext) | Glucagon-like Peptide 1 (GLP-1) Levels During OGTT | 150 Minutes(n=31, 29, 22) | 3.7 pmol/L | Standard Deviation 2.46 |
| SOM230 - 12 Months (Ext) | Glucagon-like Peptide 1 (GLP-1) Levels During OGTT | 90 Minutes (n=31, 29, 22) | 7.2 pmol/L | Standard Deviation 3.71 |
| SOM230 - 12 Months (Ext) | Glucagon-like Peptide 1 (GLP-1) Levels During OGTT | 60 Minutes (n= 32, 30, 22) | 12.6 pmol/L | Standard Deviation 8.76 |
| SOM230 - 12 Months (Ext) | Glucagon-like Peptide 1 (GLP-1) Levels During OGTT | Pre-OGTT (n=31, 29, 23) | 1.6 pmol/L | Standard Deviation 1.26 |
Secondary
Health-related Quality of Live (HRQoL) Short Form- 36 (SF-36) Score(s)
Absolute HRQoL SF-36 Scores at end of the Months 3, 6 and 12 from s.c. baseline. SF-36, a 36-Item Short Form Health Survey (SF-36) is a set of generic, coherent, and easily administered quality-of-life measures. These measures rely upon patient self-reporting. Items are scored so that a high score defines a more favorable health state. In addition, each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively.
Time frame: M3, M6, M12
Population: The sc full analysis set (sc FAS) consisted of all patients who received at least one dose of pasireotide sc during core sc phase. The LAR full analysis set (LAR FAS) consisted of all patients who received at least one dose of pasireotide LAR during core LAR phase.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOM230 - 3 Months (sc) | Health-related Quality of Live (HRQoL) Short Form- 36 (SF-36) Score(s) | Mental Component Summary (n=35, 29, 23) | 44.093 scores on a scale | Standard Deviation 12.2144 |
| SOM230 - 3 Months (sc) | Health-related Quality of Live (HRQoL) Short Form- 36 (SF-36) Score(s) | Physical Component Summary (n=35, 29, 23) | 44.801 scores on a scale | Standard Deviation 8.3378 |
| SOM230 - 12 Months (Ext) | Health-related Quality of Live (HRQoL) Short Form- 36 (SF-36) Score(s) | Physical Component Summary (n=35, 29, 23) | 45.306 scores on a scale | Standard Deviation 9.5622 |
| SOM230 - 12 Months (Ext) | Health-related Quality of Live (HRQoL) Short Form- 36 (SF-36) Score(s) | Mental Component Summary (n=35, 29, 23) | 44.838 scores on a scale | Standard Deviation 11.6573 |
| SOM230 - 12 Months (Ext) | Health-related Quality of Live (HRQoL) Short Form- 36 (SF-36) Score(s) | Physical Component Summary (n=35, 29, 23) | 46.505 scores on a scale | Standard Deviation 8.5105 |
| SOM230 - 12 Months (Ext) | Health-related Quality of Live (HRQoL) Short Form- 36 (SF-36) Score(s) | Mental Component Summary (n=35, 29, 23) | 47.021 scores on a scale | Standard Deviation 11.5053 |
Secondary
Insulin Levels During OGTT
Absolute insulin levels at the end of M3, M6, M12
Time frame: M3, M6, M12
Population: The sc full analysis set (sc FAS) consisted of all patients who received at least one dose of pasireotide sc during core sc phase. The LAR full analysis set (LAR FAS) consisted of all patients who received at least one dose of pasireotide LAR during core LAR phase.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOM230 - 3 Months (sc) | Insulin Levels During OGTT | 30 Minutes (n=30, 29, 23) | 196.3 pmol/L | Standard Deviation 253.1 |
| SOM230 - 3 Months (sc) | Insulin Levels During OGTT | 120 Minutes(n=32, 30, 22) | 183.7 pmol/L | Standard Deviation 209.9 |
| SOM230 - 3 Months (sc) | Insulin Levels During OGTT | 90 Minutes (n=31, 30, 22) | 309.1 pmol/L | Standard Deviation 263.92 |
| SOM230 - 3 Months (sc) | Insulin Levels During OGTT | Pre-OGTT (n= 31, 29, 21) | 37.0 pmol/L | Standard Deviation 24.55 |
| SOM230 - 3 Months (sc) | Insulin Levels During OGTT | 180 Minutes (n=32, 29, 22) | 58.5 pmol/L | Standard Deviation 52.65 |
| SOM230 - 3 Months (sc) | Insulin Levels During OGTT | 150 Minutes(n=33, 30, 22) | 103.2 pmol/L | Standard Deviation 166.67 |
| SOM230 - 3 Months (sc) | Insulin Levels During OGTT | 60 Minutes (n= 31, 30, 22) | 367.5 pmol/L | Standard Deviation 354.73 |
| SOM230 - 12 Months (Ext) | Insulin Levels During OGTT | 90 Minutes (n=31, 30, 22) | 420.4 pmol/L | Standard Deviation 544.78 |
| SOM230 - 12 Months (Ext) | Insulin Levels During OGTT | Pre-OGTT (n= 31, 29, 21) | 34.7 pmol/L | Standard Deviation 19.73 |
| SOM230 - 12 Months (Ext) | Insulin Levels During OGTT | 30 Minutes (n=30, 29, 23) | 499.8 pmol/L | Standard Deviation 276.8 |
| SOM230 - 12 Months (Ext) | Insulin Levels During OGTT | 60 Minutes (n= 31, 30, 22) | 573.2 pmol/L | Standard Deviation 428.46 |
| SOM230 - 12 Months (Ext) | Insulin Levels During OGTT | 120 Minutes(n=32, 30, 22) | 205.7 pmol/L | Standard Deviation 514.45 |
| SOM230 - 12 Months (Ext) | Insulin Levels During OGTT | 150 Minutes(n=33, 30, 22) | 102.8 pmol/L | Standard Deviation 228.92 |
| SOM230 - 12 Months (Ext) | Insulin Levels During OGTT | 180 Minutes (n=32, 29, 22) | 69.1 pmol/L | Standard Deviation 154.11 |
| SOM230 - 12 Months (Ext) | Insulin Levels During OGTT | 120 Minutes(n=32, 30, 22) | 195.1 pmol/L | Standard Deviation 247.43 |
| SOM230 - 12 Months (Ext) | Insulin Levels During OGTT | 30 Minutes (n=30, 29, 23) | 294.1 pmol/L | Standard Deviation 177.25 |
| SOM230 - 12 Months (Ext) | Insulin Levels During OGTT | 180 Minutes (n=32, 29, 22) | 52.0 pmol/L | Standard Deviation 58.81 |
| SOM230 - 12 Months (Ext) | Insulin Levels During OGTT | 150 Minutes(n=33, 30, 22) | 76.0 pmol/L | Standard Deviation 106.05 |
| SOM230 - 12 Months (Ext) | Insulin Levels During OGTT | 90 Minutes (n=31, 30, 22) | 472.0 pmol/L | Standard Deviation 438.82 |
| SOM230 - 12 Months (Ext) | Insulin Levels During OGTT | 60 Minutes (n= 31, 30, 22) | 602.1 pmol/L | Standard Deviation 381.6 |
| SOM230 - 12 Months (Ext) | Insulin Levels During OGTT | Pre-OGTT (n= 31, 29, 21) | 29.0 pmol/L | Standard Deviation 14.43 |
Secondary
LAR PK Parameter: Ctrough - at Steady State (ss) by Dose
In the LAR treatment phase, monthly injections of pasireotide LAR 10, 20, 30 and 40 mg were given to participants and trough concentration at steady state (Ctrough,ss) were obtained but due to only 1 participant in the 40mg arm, standard deviation could not be calculated.
Time frame: M4 to M12
Population: The LAR PK analysis set consisted of all patients who received at least one of the scheduled full monthly im LAR injections and had evaluable PK data (concentration) in the LAR phase of the study (Visit 9 through end of LAR phase visit).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SOM230 - 3 Months (sc) | LAR PK Parameter: Ctrough - at Steady State (ss) by Dose | 3.34 ng/mL | Standard Deviation 1.52 |
| SOM230 - 12 Months (Ext) | LAR PK Parameter: Ctrough - at Steady State (ss) by Dose | 3.76 ng/mL | Standard Deviation 1.48 |
| SOM230 - 12 Months (Ext) | LAR PK Parameter: Ctrough - at Steady State (ss) by Dose | 8.19 ng/mL | Standard Deviation 3.22 |
| SOM sc 200 ug t.i.d. | LAR PK Parameter: Ctrough - at Steady State (ss) by Dose | 4.63 ng/mL | — |
Secondary
Pasireotide Concentrations in LAR Phase
Summary of pasireotide concentrations following monthly i.m. injections of pasireotide LAR by incident dose (LAR Pharmacokinetic set)
Time frame: M7 to M12
Population: The LAR PK analysis set consisted of all patients who received at least one of the scheduled full monthly im LAR injections and had evaluable PK data (concentration) in the LAR phase of the study (Visit 9 through end of LAR phase visit).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOM230 - 3 Months (sc) | Pasireotide Concentrations in LAR Phase | M7 - 0hr (pre-dose) (n = 4, 11, 11, 0, 0) | 2.25 ng/mL | Standard Deviation 1.56 |
| SOM230 - 3 Months (sc) | Pasireotide Concentrations in LAR Phase | M8 - 0hr (pre-dose) (n = 5, 7, 11, 0, 0) | 2.91 ng/mL | Standard Deviation 2.42 |
| SOM230 - 3 Months (sc) | Pasireotide Concentrations in LAR Phase | M9 - 0hr (pre-dose) (n = 5, 6, 9, 6, 0) | 2.97 ng/mL | Standard Deviation 1.68 |
| SOM230 - 3 Months (sc) | Pasireotide Concentrations in LAR Phase | M10 - 0hr (pre-dose) (n = 5, 6, 8, 5, 0) | 3.53 ng/mL | Standard Deviation 1.75 |
| SOM230 - 3 Months (sc) | Pasireotide Concentrations in LAR Phase | M11 - 0hr (pre-dose) (n = 5, 4, 8, 4, 3) | 3.45 ng/mL | Standard Deviation 1.98 |
| SOM230 - 3 Months (sc) | Pasireotide Concentrations in LAR Phase | M12 - 0hr (pre-dose) (n = 5, 3, 8, 4, 3) | 3.27 ng/mL | Standard Deviation 2.02 |
| SOM230 - 12 Months (Ext) | Pasireotide Concentrations in LAR Phase | M11 - 0hr (pre-dose) (n = 5, 4, 8, 4, 3) | 3.48 ng/mL | Standard Deviation 0.772 |
| SOM230 - 12 Months (Ext) | Pasireotide Concentrations in LAR Phase | M12 - 0hr (pre-dose) (n = 5, 3, 8, 4, 3) | 4.63 ng/mL | Standard Deviation 1.04 |
| SOM230 - 12 Months (Ext) | Pasireotide Concentrations in LAR Phase | M7 - 0hr (pre-dose) (n = 4, 11, 11, 0, 0) | 4.3 ng/mL | Standard Deviation 2.19 |
| SOM230 - 12 Months (Ext) | Pasireotide Concentrations in LAR Phase | M9 - 0hr (pre-dose) (n = 5, 6, 9, 6, 0) | 4.01 ng/mL | Standard Deviation 2.27 |
| SOM230 - 12 Months (Ext) | Pasireotide Concentrations in LAR Phase | M10 - 0hr (pre-dose) (n = 5, 6, 8, 5, 0) | 5.48 ng/mL | Standard Deviation 3.62 |
| SOM230 - 12 Months (Ext) | Pasireotide Concentrations in LAR Phase | M8 - 0hr (pre-dose) (n = 5, 7, 11, 0, 0) | 3.77 ng/mL | Standard Deviation 1.57 |
| SOM230 - 12 Months (Ext) | Pasireotide Concentrations in LAR Phase | M10 - 0hr (pre-dose) (n = 5, 6, 8, 5, 0) | 8.38 ng/mL | Standard Deviation 2.81 |
| SOM230 - 12 Months (Ext) | Pasireotide Concentrations in LAR Phase | M11 - 0hr (pre-dose) (n = 5, 4, 8, 4, 3) | 7.99 ng/mL | Standard Deviation 3.54 |
| SOM230 - 12 Months (Ext) | Pasireotide Concentrations in LAR Phase | M7 - 0hr (pre-dose) (n = 4, 11, 11, 0, 0) | 7.76 ng/mL | Standard Deviation 4.31 |
| SOM230 - 12 Months (Ext) | Pasireotide Concentrations in LAR Phase | M9 - 0hr (pre-dose) (n = 5, 6, 9, 6, 0) | 6.38 ng/mL | Standard Deviation 3.15 |
| SOM230 - 12 Months (Ext) | Pasireotide Concentrations in LAR Phase | M8 - 0hr (pre-dose) (n = 5, 7, 11, 0, 0) | 6.5 ng/mL | Standard Deviation 2.91 |
| SOM230 - 12 Months (Ext) | Pasireotide Concentrations in LAR Phase | M12 - 0hr (pre-dose) (n = 5, 3, 8, 4, 3) | 10.3 ng/mL | Standard Deviation 6.05 |
| SOM sc 200 ug t.i.d. | Pasireotide Concentrations in LAR Phase | M10 - 0hr (pre-dose) (n = 5, 6, 8, 5, 0) | 11.8 ng/mL | Standard Deviation 8.26 |
| SOM sc 200 ug t.i.d. | Pasireotide Concentrations in LAR Phase | M8 - 0hr (pre-dose) (n = 5, 7, 11, 0, 0) | NA ng/mL | — |
| SOM sc 200 ug t.i.d. | Pasireotide Concentrations in LAR Phase | M9 - 0hr (pre-dose) (n = 5, 6, 9, 6, 0) | 7.53 ng/mL | Standard Deviation 4.45 |
| SOM sc 200 ug t.i.d. | Pasireotide Concentrations in LAR Phase | M12 - 0hr (pre-dose) (n = 5, 3, 8, 4, 3) | 6.55 ng/mL | Standard Deviation 2.05 |
| SOM sc 200 ug t.i.d. | Pasireotide Concentrations in LAR Phase | M11 - 0hr (pre-dose) (n = 5, 4, 8, 4, 3) | 6.53 ng/mL | Standard Deviation 1.83 |
| SOM sc 200 ug t.i.d. | Pasireotide Concentrations in LAR Phase | M7 - 0hr (pre-dose) (n = 4, 11, 11, 0, 0) | NA ng/mL | — |
| SOM LAR 60mg | Pasireotide Concentrations in LAR Phase | M11 - 0hr (pre-dose) (n = 5, 4, 8, 4, 3) | 17.9 ng/mL | Standard Deviation 7.15 |
| SOM LAR 60mg | Pasireotide Concentrations in LAR Phase | M9 - 0hr (pre-dose) (n = 5, 6, 9, 6, 0) | NA ng/mL | — |
| SOM LAR 60mg | Pasireotide Concentrations in LAR Phase | M8 - 0hr (pre-dose) (n = 5, 7, 11, 0, 0) | NA ng/mL | — |
| SOM LAR 60mg | Pasireotide Concentrations in LAR Phase | M12 - 0hr (pre-dose) (n = 5, 3, 8, 4, 3) | 18.1 ng/mL | Standard Deviation 13.8 |
| SOM LAR 60mg | Pasireotide Concentrations in LAR Phase | M10 - 0hr (pre-dose) (n = 5, 6, 8, 5, 0) | NA ng/mL | — |
| SOM LAR 60mg | Pasireotide Concentrations in LAR Phase | M7 - 0hr (pre-dose) (n = 4, 11, 11, 0, 0) | NA ng/mL | — |
Secondary
Patient Global Assessment at the End of Months 3, 6 and 12
Treatment with pasireotide LAR (both early and late dumping scores), was assessed by patient global assessment. Patient Global Assessment served as an additional approach to symptom based measurement by DSQ. It incorporated a patient global assessment question: Considering all the ways that your disease affects you, rate how you are feeling during the last 7 days compared with your situation before starting the study .Patients Global Assessment was measured utilizing a 7 point scale (from 1=a lot worse to 7= a lot better).
Time frame: M3, M6, M12
Population: The sc full analysis set (sc FAS) consisted of all patients who received at least one dose of pasireotide sc during core sc phase. The LAR full analysis set (LAR FAS) consisted of all patients who received at least one dose of pasireotide LAR during core LAR phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SOM230 - 3 Months (sc) | Patient Global Assessment at the End of Months 3, 6 and 12 | 5.1 scores on a scale | Standard Deviation 1.19 |
| SOM230 - 12 Months (Ext) | Patient Global Assessment at the End of Months 3, 6 and 12 | 5.1 scores on a scale | Standard Deviation 1.27 |
| SOM230 - 12 Months (Ext) | Patient Global Assessment at the End of Months 3, 6 and 12 | 5.9 scores on a scale | Standard Deviation 0.95 |
Secondary
Plasma Pharmacokinetic (PK) Parameter of Pasireotide: AUC0-3h, ss, After s.c. Injection
A pre-dose PK blood sample was collected before the morning pasireotide s.c. dose of 50 μg, 100 ug, 150 ug and 200 ug. OGTT was performed right after the morning s.c. dose (Time point zero); additional PK blood samples were collected at the same time points as the OGTT evaluation at 30, 60, 90, 120, 150 and 180 minutes.
Time frame: M1 to M3
Population: The sc PK analysis set consisted of all patients who received at least one of the scheduled full daily sc dose (3 injections) and had evaluable PK data (concentration) in the sc dose escalation phase of the study (Visit 2 through Visit 8).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SOM230 - 3 Months (sc) | Plasma Pharmacokinetic (PK) Parameter of Pasireotide: AUC0-3h, ss, After s.c. Injection | 3.04 hr*ng/mL | Standard Deviation 1.13 |
| SOM230 - 12 Months (Ext) | Plasma Pharmacokinetic (PK) Parameter of Pasireotide: AUC0-3h, ss, After s.c. Injection | 6.53 hr*ng/mL | Standard Deviation 3.45 |
| SOM230 - 12 Months (Ext) | Plasma Pharmacokinetic (PK) Parameter of Pasireotide: AUC0-3h, ss, After s.c. Injection | 8.84 hr*ng/mL | Standard Deviation 3.89 |
| SOM sc 200 ug t.i.d. | Plasma Pharmacokinetic (PK) Parameter of Pasireotide: AUC0-3h, ss, After s.c. Injection | 11.5 hr*ng/mL | Standard Deviation 6.23 |
Secondary
Plasma Pharmacokinetic (PK) Parameter of Pasireotide: Cmax, ss (Steady State) and Ctrough, ss, After s.c. Injection
A pre-dose PK blood sample was collected before the morning pasireotide s.c. dose of 50 μg, 100 ug, 150 ug and 200 ug. OGTT was performed right after the morning s.c. dose (Time point zero); additional PK blood samples were collected at the same time points as the OGTT evaluation at 30, 60, 90, 120, 150 and 180 minutes. 'n' = number of subjects with non-missing values
Time frame: M1 to M3
Population: The sc PK analysis set consisted of all patients who received at least one of the scheduled full daily sc dose (3 injections) and had evaluable PK data (concentration) in the sc dose escalation phase of the study (Visit 2 through Visit 8).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOM230 - 3 Months (sc) | Plasma Pharmacokinetic (PK) Parameter of Pasireotide: Cmax, ss (Steady State) and Ctrough, ss, After s.c. Injection | Cmax, ss (n=35, 28, 18, 10) | 1.49 ng/mL | Standard Deviation 0.613 |
| SOM230 - 3 Months (sc) | Plasma Pharmacokinetic (PK) Parameter of Pasireotide: Cmax, ss (Steady State) and Ctrough, ss, After s.c. Injection | Ctrough, ss (n=37, 30, 22, 12) | 0.574 ng/mL | Standard Deviation 0.436 |
| SOM230 - 12 Months (Ext) | Plasma Pharmacokinetic (PK) Parameter of Pasireotide: Cmax, ss (Steady State) and Ctrough, ss, After s.c. Injection | Ctrough, ss (n=37, 30, 22, 12) | 1.11 ng/mL | Standard Deviation 0.909 |
| SOM230 - 12 Months (Ext) | Plasma Pharmacokinetic (PK) Parameter of Pasireotide: Cmax, ss (Steady State) and Ctrough, ss, After s.c. Injection | Cmax, ss (n=35, 28, 18, 10) | 3.31 ng/mL | Standard Deviation 1.78 |
| SOM230 - 12 Months (Ext) | Plasma Pharmacokinetic (PK) Parameter of Pasireotide: Cmax, ss (Steady State) and Ctrough, ss, After s.c. Injection | Cmax, ss (n=35, 28, 18, 10) | 4.56 ng/mL | Standard Deviation 2.22 |
| SOM230 - 12 Months (Ext) | Plasma Pharmacokinetic (PK) Parameter of Pasireotide: Cmax, ss (Steady State) and Ctrough, ss, After s.c. Injection | Ctrough, ss (n=37, 30, 22, 12) | 1.5 ng/mL | Standard Deviation 0.798 |
| SOM sc 200 ug t.i.d. | Plasma Pharmacokinetic (PK) Parameter of Pasireotide: Cmax, ss (Steady State) and Ctrough, ss, After s.c. Injection | Cmax, ss (n=35, 28, 18, 10) | 5.62 ng/mL | Standard Deviation 3.18 |
| SOM sc 200 ug t.i.d. | Plasma Pharmacokinetic (PK) Parameter of Pasireotide: Cmax, ss (Steady State) and Ctrough, ss, After s.c. Injection | Ctrough, ss (n=37, 30, 22, 12) | 2.03 ng/mL | Standard Deviation 1.54 |
Secondary
Plasma Pharmacokinetic (PK) Parameter of Pasireotide: Tmax, ss, After s.c. Injection
A pre-dose PK blood sample was collected before the morning pasireotide s.c. dose of 50 μg, 100 ug, 150 ug and 200 ug. OGTT was performed right after the morning s.c. dose (Time point zero); additional PK blood samples were collected at the same time points as the OGTT evaluation at 30, 60, 90, 120, 150 and 180 minutes.
Time frame: M1 to M3
Population: The sc PK analysis set consisted of all patients who received at least one of the scheduled full daily sc dose (3 injections) and had evaluable PK data (concentration) in the sc dose escalation phase of the study (Visit 2 through Visit 8).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SOM230 - 3 Months (sc) | Plasma Pharmacokinetic (PK) Parameter of Pasireotide: Tmax, ss, After s.c. Injection | 0.583 hr |
| SOM230 - 12 Months (Ext) | Plasma Pharmacokinetic (PK) Parameter of Pasireotide: Tmax, ss, After s.c. Injection | 0.6 hr |
| SOM230 - 12 Months (Ext) | Plasma Pharmacokinetic (PK) Parameter of Pasireotide: Tmax, ss, After s.c. Injection | 0.583 hr |
| SOM sc 200 ug t.i.d. | Plasma Pharmacokinetic (PK) Parameter of Pasireotide: Tmax, ss, After s.c. Injection | 0.633 hr |
Secondary
Plasma PK Parameter of AUC0-3h, d21, End _inj and AUC0-3h, d28, 3rd_inj Associated With LAR (LAR Core Phase)
Time frame: M4 to M6
Population: The LAR PK analysis set consisted of all patients who received at least one of the scheduled full monthly im LAR injections and had evaluable PK data (concentration) in the LAR phase of the study (Visit 9 through end of LAR phase visit).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOM230 - 3 Months (sc) | Plasma PK Parameter of AUC0-3h, d21, End _inj and AUC0-3h, d28, 3rd_inj Associated With LAR (LAR Core Phase) | AUC0-3h,d28, 3rd_injection (n = 9, 16) | 5.97 hr*ng/mL | Standard Deviation 2.41 |
| SOM230 - 3 Months (sc) | Plasma PK Parameter of AUC0-3h, d21, End _inj and AUC0-3h, d28, 3rd_inj Associated With LAR (LAR Core Phase) | AUC0-3h,d21, 2nd injection (n = 12, 14) | 6.92 hr*ng/mL | Standard Deviation 4.12 |
| SOM230 - 12 Months (Ext) | Plasma PK Parameter of AUC0-3h, d21, End _inj and AUC0-3h, d28, 3rd_inj Associated With LAR (LAR Core Phase) | AUC0-3h,d21, 2nd injection (n = 12, 14) | 14.9 hr*ng/mL | Standard Deviation 6.71 |
| SOM230 - 12 Months (Ext) | Plasma PK Parameter of AUC0-3h, d21, End _inj and AUC0-3h, d28, 3rd_inj Associated With LAR (LAR Core Phase) | AUC0-3h,d28, 3rd_injection (n = 9, 16) | 9.3 hr*ng/mL | Standard Deviation 4.11 |
Secondary
Response Rate in Hematocrit Levels
Percentage of patients with change in hematocrit \>= 3% from pre-OGTT to 30 minutes post OGTT.
Time frame: M3, M6, M12
Population: The sc full analysis set (sc FAS) consisted of all patients who received at least one dose of pasireotide sc during core sc phase. The LAR full analysis set (LAR FAS) consisted of all patients who received at least one dose of pasireotide LAR during core LAR phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SOM230 - 3 Months (sc) | Response Rate in Hematocrit Levels | hematocrit >= 3% at baseline | 27.9 Percentage of participants |
| SOM230 - 3 Months (sc) | Response Rate in Hematocrit Levels | hematocrit >= 3% at post baseline | 16.3 Percentage of participants |
| SOM230 - 12 Months (Ext) | Response Rate in Hematocrit Levels | hematocrit >= 3% at baseline | 21.2 Percentage of participants |
| SOM230 - 12 Months (Ext) | Response Rate in Hematocrit Levels | hematocrit >= 3% at post baseline | 27.3 Percentage of participants |
| SOM230 - 12 Months (Ext) | Response Rate in Hematocrit Levels | hematocrit >= 3% at baseline | 21.2 Percentage of participants |
| SOM230 - 12 Months (Ext) | Response Rate in Hematocrit Levels | hematocrit >= 3% at post baseline | 24.2 Percentage of participants |
Secondary
Response Rate in Plasma Glucose Level
Response rate is defined as percentage of patients with no glucose values \< 60 mg/dL at 90,120, 150 and 180 min during the Oral Glucose Tolerance Test (OGTT) at the end of 6 months (end of LAR/Core phase) and at the end of 12 months (extension phase)
Time frame: at Month 6 (M6), Month 12 (M12)
Population: The LAR full analysis set (LAR FAS) consisted of all patients who received at least one dose of pasireotide LAR during core LAR phase.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOM230 - 3 Months (sc) | Response Rate in Plasma Glucose Level | 36.4 percentage of participants |
| SOM230 - 12 Months (Ext) | Response Rate in Plasma Glucose Level | 39.4 percentage of participants |
Secondary
Response Rate in Pulse Rate
Pulse rate was defined as percentage of patients with change in pulse rate \>=10 bpm from pre-OGTT to 30 minutes post OGTT.
Time frame: at baseline, M3, M6, M12
Population: The sc full analysis set (sc FAS) consisted of all patients who received at least one dose of pasireotide sc during core sc phase. The LAR full analysis set (LAR FAS) consisted of all patients who received at least one dose of pasireotide LAR during core LAR phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SOM230 - 3 Months (sc) | Response Rate in Pulse Rate | rate ≥ 10 bpm at baseline | 60.5 Percentage of participants |
| SOM230 - 3 Months (sc) | Response Rate in Pulse Rate | rate ≥ 10 bpm at post-baseline | 18.6 Percentage of participants |
| SOM230 - 12 Months (Ext) | Response Rate in Pulse Rate | rate ≥ 10 bpm at baseline | 24.2 Percentage of participants |
| SOM230 - 12 Months (Ext) | Response Rate in Pulse Rate | rate ≥ 10 bpm at post-baseline | 36.4 Percentage of participants |
| SOM230 - 12 Months (Ext) | Response Rate in Pulse Rate | rate ≥ 10 bpm at baseline | 24.2 Percentage of participants |
| SOM230 - 12 Months (Ext) | Response Rate in Pulse Rate | rate ≥ 10 bpm at post-baseline | 27.3 Percentage of participants |
Secondary
Summary of LAR PK Parameters by Dose
Summary of plasma PK parameter Cmax, p2 , 2nd injection and Ctrough, d28 associated with LAR injection (LAR Core phase)
Time frame: M4 to M6
Population: The LAR PK analysis set consisted of all patients who received at least one of the scheduled full monthly im LAR injections and had evaluable PK data (concentration) in the LAR phase of the study (Visit 9 through end of LAR phase visit).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOM230 - 3 Months (sc) | Summary of LAR PK Parameters by Dose | Cmax, p2, 2nd_inj (n = 10, 13) | 3.2 ng/mL | Standard Deviation 1.55 |
| SOM230 - 3 Months (sc) | Summary of LAR PK Parameters by Dose | Ctrough (n= 14, 19) | 2.29 ng/mL | Standard Deviation 1.05 |
| SOM230 - 12 Months (Ext) | Summary of LAR PK Parameters by Dose | Cmax, p2, 2nd_inj (n = 10, 13) | 6.2 ng/mL | Standard Deviation 2.6 |
| SOM230 - 12 Months (Ext) | Summary of LAR PK Parameters by Dose | Ctrough (n= 14, 19) | 3.33 ng/mL | Standard Deviation 1.34 |