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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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 i

Brief Summary: multi-center, phase II study evaluating efficacy, safety and pharmacokinetics of pasireotide in patients with dumping syndrome

Detailed Summary: 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.
Sponsor: Novartis Pharmaceuticals

Current Primary Outcome: 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: 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


Current Secondary Outcome:

  • 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 Pharmacokinet

    Original Secondary Outcome:

    • 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


    Information By: Novartis

    Dates:
    Date Received: May 9, 2012
    Date Started: January 8, 2013
    Date Completion:
    Last Updated: March 31, 2017
    Last Verified: March 2017