Brief Summary
multi-center, phase II study evaluating efficacy, safety and pharmacokinetics of pasireotide in patients with dumping syndrome
Brief Title
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Dumping Syndrome
Eligibility Criteria
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).
* 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).
Inclusion Criteria
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.
* 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.
Gender
All
Gender Based
false
Keywords
Dumping syndrome
SOM230
pasireotide LAR
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01637272
Org Class
Industry
Org Full Name
Novartis
Org Study Id
CSOM230X2203
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Multi-center, Intra-patient Dose Escalation Phase II Study to Evaluate the Preliminary Efficacy, Safety and Pharmacokinetics of Pasireotide (SOM230) Subcutaneous (s.c.) Followed by Pasireotide LAR in Patients With Dumping Syndrome
Primary Outcomes
Outcome Description
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
Outcome Measure
Response Rate in Plasma Glucose Level
Outcome Time Frame
at Month 3 (M3)
Secondary Ids
Secondary Id
2012-001534-34
Secondary Outcomes
Outcome Description
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)
Outcome Time Frame
at Month 6 (M6), Month 12 (M12)
Outcome Measure
Response Rate in Plasma Glucose Level
Outcome Description
Pulse rate was defined as percentage of patients with change in pulse rate \>=10 bpm from pre-OGTT to 30 minutes post OGTT.
Outcome Time Frame
at baseline, M3, M6, M12
Outcome Measure
Response Rate in Pulse Rate
Outcome Description
Percentage of patients with change in hematocrit \>= 3% from pre-OGTT to 30 minutes post OGTT.
Outcome Time Frame
M3, M6, M12
Outcome Measure
Response Rate in Hematocrit Levels
Outcome Description
Absolute insulin levels at the end of M3, M6, M12
Outcome Time Frame
M3, M6, M12
Outcome Measure
Insulin Levels During OGTT
Outcome Description
Absolute glucagon levels at the end of Months 3, 6 \& 12
Outcome Time Frame
M3, M6, M12
Outcome Measure
Glucagon Levels During OGTT
Outcome Description
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.
Outcome Time Frame
M3, M6, M12
Outcome Measure
Glucagon-like Peptide 1 (GLP-1) Levels During OGTT
Outcome Description
Absolute Gastric Inhibitory Polypeptide (GIP) levels at the end of Months 3, 6 and 12 at different time points.
Outcome Time Frame
M3, M6, M12
Outcome Measure
Gastric Inhibitory Polypeptide (GIP) Levels at During OGTT
Outcome Description
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.
Outcome Time Frame
M3, M6, M12
Outcome Measure
Health-related Quality of Live (HRQoL) Short Form- 36 (SF-36) Score(s)
Outcome Description
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.
Outcome Time Frame
M3, M6, M8
Outcome Measure
Dumping Severity Score (DSS) at the End of Months 3, 6 and 8
Outcome Description
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.
Outcome Time Frame
M3, M6, M12
Outcome Measure
Dumping Score Questionnaire (DSQ) at the End of Months 3, 6 and 12
Outcome Description
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).
Outcome Time Frame
M3, M6, M12
Outcome Measure
Patient Global Assessment at the End of Months 3, 6 and 12
Outcome Description
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
Outcome Time Frame
M1 to M3
Outcome Measure
Plasma Pharmacokinetic (PK) Parameter of Pasireotide: Cmax, ss (Steady State) and Ctrough, ss, After s.c. Injection
Outcome Description
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.
Outcome Time Frame
M1 to M3
Outcome Measure
Plasma Pharmacokinetic (PK) Parameter of Pasireotide: AUC0-3h, ss, After s.c. Injection
Outcome Description
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.
Outcome Time Frame
M1 to M3
Outcome Measure
Plasma Pharmacokinetic (PK) Parameter of Pasireotide: Tmax, ss, After s.c. Injection
Outcome Time Frame
M4 to M6
Outcome Measure
Plasma PK Parameter of AUC0-3h, d21, End _inj and AUC0-3h, d28, 3rd_inj Associated With LAR (LAR Core Phase)
Outcome Description
Summary of plasma PK parameter Cmax, p2 , 2nd injection and Ctrough, d28 associated with LAR injection (LAR Core phase)
Outcome Time Frame
M4 to M6
Outcome Measure
Summary of LAR PK Parameters by Dose
Outcome Description
Summary of pasireotide concentrations following monthly i.m. injections of pasireotide LAR by incident dose (LAR Pharmacokinetic set)
Outcome Time Frame
M7 to M12
Outcome Measure
Pasireotide Concentrations in LAR Phase
Outcome Description
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.
Outcome Time Frame
M4 to M12
Outcome Measure
LAR PK Parameter: Ctrough - at Steady State (ss) by Dose
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Anirban Gupta
Investigator Email
Investigator Phone