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Trial record 2 of 7 for:    "Postgastrectomy Syndrome" | "Hormones, Hormone Substitutes, and Hormone Antagonists"

Phase II Study Evaluating Efficacy, Safety and Pharmacokinetics of Pasireotide in Patients With Dumping Syndrome

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ClinicalTrials.gov Identifier: NCT01637272
Recruitment Status : Completed
First Posted : July 11, 2012
Results First Posted : May 10, 2017
Last Update Posted : May 10, 2017
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE May 9, 2012
First Posted Date  ICMJE July 11, 2012
Results First Submitted Date  ICMJE July 29, 2016
Results First Posted Date  ICMJE May 10, 2017
Last Update Posted Date May 10, 2017
Actual Study Start Date  ICMJE January 8, 2013
Actual Primary Completion Date August 7, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 31, 2017)
Response Rate in Plasma Glucose Level [ Time Frame: 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
Original Primary Outcome Measures  ICMJE
 (submitted: July 10, 2012)
Change in response rate in plasma glucose level at the end of subcutaneous (s.c.) dose escalation phase [ Time Frame: baseline, 3 months ]
Response rate is defined as proportion of patients with no hypoglycemia at 120, 150 and 180 minutes during oral glucose tolerance test (OGTT); dose escalation phase = month 3
Change History Complete list of historical versions of study NCT01637272 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 31, 2017)
  • Response Rate in Plasma Glucose Level [ Time Frame: 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)
  • Response Rate in Pulse Rate [ Time Frame: 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 [ Time Frame: M3, M6, M12 ]
    Percentage of patients with change in hematocrit >= 3% from pre-OGTT to 30 minutes post OGTT.
  • Insulin Levels During OGTT [ Time Frame: M3, M6, M12 ]
    Absolute insulin levels at the end of M3, M6, M12
  • Glucagon Levels During OGTT [ Time Frame: M3, M6, M12 ]
    Absolute glucagon levels at the end of Months 3, 6 & 12
  • Glucagon-like Peptide 1 (GLP-1) Levels During OGTT [ Time Frame: 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 [ Time Frame: M3, M6, M12 ]
    Absolute Gastric Inhibitory Polypeptide (GIP) levels at the end of Months 3, 6 and 12 at different time points.
  • Health-related Quality of Live (HRQoL) Short Form- 36 (SF-36) Score(s) [ Time Frame: 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 [ Time Frame: 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.
  • Dumping Score Questionnaire (DSQ) at the End of Months 3, 6 and 12 [ Time Frame: 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.
  • Patient Global Assessment at the End of Months 3, 6 and 12 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: M4 to M6 ]
  • Summary of LAR PK Parameters by Dose [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 10, 2012)
  • Response Rate in Pulse Rate [ Time Frame: baseline, 3 months, 6 months, 12 months ]
    Response rate = Proportion of patients with change in pulse rate < 10 bpm from pre-OGTT to 30 min during OGTT; dose escalation phase = month 3, LAR phase = month 6, extension phase = month 12
  • Response Rate in Hematocrit Levels [ Time Frame: baseline, 3 months, 6 months, 12 months ]
    Proportion of patients with change in hematocrit < 3% from pre-OGTT to 30 min during the OGTT
  • Dumping Severity Score . [ Time Frame: baseline, 3 months, 6 months, 12 months ]
    Change in Dumping Severity Score at the end of dose escalation phase, LAR phase, extension phase from baseline
  • HRQoL SF-36 Score(s) and Patient Global Assessment [ Time Frame: baseline, 3 months, 6 months, 12 months ]
    Change in HRQoL SF-36 Score(s) and Patient Global Assessment
  • Insulin, glucagon, Glucagon-like peptide 1 (GLP-1) and Gastric Inhibitory Polypeptide (GIP) levels [ Time Frame: baseline, 3 months, 6 months, 12 months ]
    Changes and percentage changes of iInsulin, glucagon, GLP-1 and GIP
  • Incidence of Adverse Events (AEs) [ Time Frame: baseline, as necessary during month 3, month 6, month 12 ]
  • Laboratory parameters which include Electrocardiogram (ECG), Vital Signs, and other safety parameters [ Time Frame: baseline, as necessary during month 3, month 6, month 12 ]
  • Plasma Pharmacokinetic (PK) parameter AUC0-3h,ss after s.c injection [ Time Frame: baseline, 120 minutes, 150minutes, 180 minutes ]
    assess PK of pasireotide at eash s.c. dose level at steady state (ss)
  • PK parameter Cmax,ss after s.c injection [ Time Frame: baseline, 120 minutes, 150minutes, 180 minutes ]
    assess PK of pasireotide at eash s.c. dose level at steady state
  • PK parameter Tmax,ss after s.c. injection [ Time Frame: baseline, 120 minutes, 150minutes, 180 minutes ]
    assess PK of pasireotide at eash s.c. dose level at steady state
  • PK parameter CTrough,ss after s.c. injection [ Time Frame: baseline, 120 minutes, 150minutes, 180 minutes ]
    assess PK of pasireotide at eash s.c. dose level at steady state
  • PK parameter AUC0-3h, d21 2nd injection associated with LAR administration at steady state [ Time Frame: baseline, 120 minutes, 150minutes, 180 minutes ]
    assess PK of pasireotide
  • PK parameter Cmax, p2 2nd injection associated with LAR administration at steady state [ Time Frame: baseline, 120 minutes, 150 minutes, 180 minutes ]
    assess PK of pasireotide
  • PK parameter AUC0-3h, d28 3rd injection associated with third LAR injection at steady state [ Time Frame: baseline, 120 minutes, 150minutes, 180 minutes ]
    assess PK of pasireotide
  • PK parameter Ctrough d28 associated with each LAR injection at steady state [ Time Frame: baseline, 120 minutes, 150minutes, 180 minutes ]
    assess PK of pasireotide (in LAR and extension phase)
  • Response rate in plasma glucose level at the end of the long acting release (LAR) phase and dose escalation phase [ Time Frame: baseline, 3 months, 6 months, 12 months ]
    Response rate = Proportion of patients with no hyperglycemia at 120, 150 and 180 minutes during OGTT
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase II Study Evaluating Efficacy, Safety and Pharmacokinetics of Pasireotide in Patients With Dumping Syndrome
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Dumping Syndrome
Intervention  ICMJE Drug: SOM230
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
Other Name: pasireotide
Study Arms  ICMJE Experimental: SOM230
Subjects with dumping syndrome treated with pasireotide
Intervention: Drug: SOM230
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 10, 2012)
43
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 7, 2015
Actual Primary Completion Date August 7, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   France,   Germany,   Netherlands,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01637272
Other Study ID Numbers  ICMJE CSOM230X2203
2012-001534-34 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP