Intra-patient Dose Escalation Study Evaluating Efficacy, Safety and Pharmacokinetics of Pasireotide (SOM230) Subcutaneous (s.c.) Followed by Pasireotide LAR in Patients With Dumping Syndrome

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01637272
First received: May 9, 2012
Last updated: January 10, 2014
Last verified: January 2014
  Purpose

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


Condition Intervention Phase
Dumping Syndrome Patients
Drug: SOM230
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change in response rate in plasma glucose level at the end of subcutaneous (s.c.) dose escalation phase [ Time Frame: baseline, 3 months ] [ Designated as safety issue: No ]
    Response rate is defined as proportion of patients with no hypoglycemia at 90, 120, 150 and 180 minutes during oral glucose tolerance test (OGTT); dose escalation phase = month 3


Secondary Outcome Measures:
  • Response rate in pulse rate [ Time Frame: baseline, 3 months, 6 months, 12 months ] [ Designated as safety issue: No ]
    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 level [ Time Frame: baseline, 3 months, 6 months, 12 months ] [ Designated as safety issue: No ]
    Proportion of patients with change in hematocrit < 3% from pre-OGTT to 30 min during the OGTT

  • Dumping Score Questionnaire [ Time Frame: baseline, 3 months, 6 months, 12 months ] [ Designated as safety issue: No ]
    Change in Dumping Score Questionnaire 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Changes and percentage changes of insulin, glucagon, GLP-1 and GIP

  • Incidence of Adverse Events (AEs) [ Time Frame: baseline, as necessary during month 3, month 6, month 12 ] [ Designated as safety issue: Yes ]
  • Laboratory parameters which include Electrocardiogram (ECG), Vital Signs, and other safety parameters [ Time Frame: baseline, as necessary during month 3, month 6, month 12 ] [ Designated as safety issue: Yes ]
  • Plasma Pharmacokinetic (PK) parameter AUC0-3h,ss after s.c injection [ Time Frame: baseline, 90 minutes, 120 minutes, 150minutes, 180 minutes ] [ Designated as safety issue: No ]
    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,90 minutes, 120 minutes, 150minutes, 180 minutes ] [ Designated as safety issue: No ]
    assess PK of pasireotide at eash s.c. dose level at steady state

  • PK parameter Tmax,ss after s.c. injection [ Time Frame: baseline, 90 minutes, 120 minutes, 150minutes, 180 minutes ] [ Designated as safety issue: No ]
    assess PK of pasireotide at eash s.c. dose level at steady state

  • PK parameter CTrough,ss after s.c. injection [ Time Frame: baseline, 90 minutes, 120 minutes, 150minutes, 180 minutes ] [ Designated as safety issue: No ]
    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, 90 minutes, 120 minutes, 150minutes, 180 minutes ] [ Designated as safety issue: No ]
    assess PK of pasireotide

  • PK parameter Cmax, p2 2nd injection associated with LAR administration at steady state [ Time Frame: baseline, 90 minutes, 120 minutes, 150 minutes, 180 minutes ] [ Designated as safety issue: No ]
    assess PK of pasireotide

  • PK parameter AUC0-3h, d28 3rd injection associated with third LAR injection at steady state [ Time Frame: baseline, 90 minutes, 120 minutes, 150minutes, 180 minutes ] [ Designated as safety issue: No ]
    assess PK of pasireotide

  • PK parameter Ctrough d28 associated with each LAR injection at steady state [ Time Frame: baseline, 90 minutes, 120 minutes, 150minutes, 180 minutes ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Response rate = Proportion of patients with no hyperglycemia at 90, 120, 150 and 180 minutes during OGTT


Estimated Enrollment: 43
Study Start Date: January 2013
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SOM230
subjects with dumping syndrome
Drug: SOM230

Detailed Description:

43 adult patients with dumping syndrome will receive 3 months of pasireotide s.c. during the dose escalation phase (dose can be increased based on the presence of hypoglycemia during OGTT). From Month 3- to Month 6 patients will then switch to pasireotide LAR. The core phase of the study is completed at tghe end of Month 6. Patients will be offered to enter into the 6 month extension phase if they experienced benefit with pasireotide LAR treatment

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:.

  1. Male or female patients ≥ 18 years of age
  2. 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: must be disease free at study entry
    • Gastric cancer surgery: must be stage 0 or I and must be disease free at study entry
  3. 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:

      1. glucose <50mg/dL on a sporadic or scheduled blood analysis -or-
      2. a glucose value <60 mg/dL or ≤ 3.3 mmol/L at 90,120, 150 or 180 min during an OGTT
  4. Patients must have 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
  5. Patients with esophageal cancer must have a negative CT or MRI scan (neck, thoracic, and upper abdominal ) and albumin ≥3.5g/dl at baseline
  6. Patients with gastric cancer must have a negative CT or MRI scan (total abdomen)
  7. Karnofsky Performance Status ≥ 60 (i.e. requires occasional assistance, but is able to care for most of their personal needs)
  8. Patients who received other therapies for dumping syndrome (such as acarbose, gama guar, pectin) must have stopped all treatments and allow 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).
  9. Patients able to provide and have provided signed written informed consent prior to study participation.

Exclusion criteria:

  1. Bariatric patients who have lap band.
  2. Patients with a diagnosis of Diabetes Mellitus.
  3. Patients who have failed treatment with somatostatin analogues for dumping syndrome in the past
  4. Patients who have been treated with somatostatin analogues in the past, must have an appropriate interval between the last administration of somatostatin analogues treatment and the study drug as follows

    • Octreotide s.c. 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
  5. Patients who have a known hypersensitivity to somatostatin analogues.
  6. Patients receiving anti-cancer therapy (chemotherapy and/or radiotherapy)
  7. Patients who have 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 HIV test result (ELISA and Western blot). An HIV test will not be required; however, previous medical history will be reviewed.
    • Non-malignant medical illnesses that are uncontrolled or whose control may be 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
  8. Inadequate end organ function as defined by:

    • Inadequate bone marrow function:
    • WBC < 2.5 x 109/L
    • Absolute Neutrophil Count (ANC) < 1.5 x 109/L
    • Platelets < 100 x 109/L
    • Hb < 9 g/dL
    • INR ≥ 1.3
    • Serum creatinine >2.0 mg/dL
    • Alkaline phosphatase >2.5 x ULN
    • Serum total bilirubin >1.5 x ULN
    • ALT and AST > 2 x ULN
  9. History of liver disease, such as cirrhosis or chronic active hepatitis B and C.
  10. Presence of Hepatitis B surface antigen (HbsAg) and/ orPresence of Hepatitis C antibody test (anti-HCV)
  11. History of, or current alcohol and/or drug misuse/abuse within the past 12 months
  12. Patients with symptomatic cholelithiasis
  13. Patients with abnormal coagulation (PT and PTT elevated by 30% above normal limits).
  14. Patients on continuous anticoagulation therapy. Patients who were on anticoagulant therapy must complete a washout period of at least 10 days and have confirmed normal coagulation parameters before study inclusion (patients receiving aspirin once a day are allowed to be enrolled).
  15. Patients who are hypothyroid and not on adequate replacement therapy
  16. Patients who have undergone major surgery/surgical therapy for any cause within 1 month. Patients should have recovered from the surgery and be in good clinical condition before entering the study.
  17. Patients who have a history of a primary malignancy (or "another" primary malignancy for patients with gastric or esophageal cancer) within the last 1 year, with the exception of locally excised non-melanoma skin cancer, carcinoma in situ of uterine cervix, and excised mucosal gastric cancer or mucosal colon cancer.
  18. Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will be unable to complete the entire study.
  19. Clinically significant abnormal laboratory values considered by the investigator or the medical monitor of the sponsor to be clinically significant or which could have affected the interpretation of the study results.
  20. QT-related exclusion criteria:

    • QTcF at screening > 470 msec
    • History of syncope or family history of idiopathic sudden death
    • Sustained or clinically significant cardiac arrhythmias
    • Risk factors for Torsades de Pointes such as hypokalemia, hypomagnesemia, cardiac failure, clinically significant/symptomatic bradycardia, or high-grade AV block
    • Concomitant disease(s) that could prolong QT such as autonomic neuropathy (caused by diabetes, or Parkinson's disease), HIV, cirrhosis, uncontrolled hypothyroidism or cardiac failure
    • Family history of long QT syndrome
    • Concomitant medications known to prolong the QT interval.
    • Potassium < or = 3.5 mEq/L
    • Magnesium < 0.7 mEq/L
  21. Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulation. (Use of an investigational drug within 1 month prior to dosing)
  22. Significant acute illness within the two weeks prior to dosing.
  23. Female patients who are pregnant or lactating, or are of childbearing potential (defined as all women physiologically capable of becoming pregnant) and not practicing an effective method of contraception/birth control. Sexually active males must use a condom during intercourse while taking the drug and for 2 months after the last dose of study drug and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid. Effective contraception methods include:

    • Use of oral, injected or implanted hormonal methods of contraception or
    • Placement of an intrauterine device (IUD) or intrauterine system (IUS)
    • Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository
    • Total abstinence or patient sterilization (male or female)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01637272

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

Locations
United States, California
Ximed Center for Weight Management Ximed Research Recruiting
La Jolla, California, United States, 92037
Contact: Cynthia Shannon    858-926-2615    cynthia@ximedresearch.com   
Principal Investigator: Sunil Bhoyrul         
United States, Minnesota
Mayo Clinic - Rochester Mayo MN Recruiting
Rochester, Minnesota, United States, 55905
Contact: Isaac Hanson    507-255-8345    Hanson.Isaac@mayo.edu   
Principal Investigator: Adrian Vella         
United States, New York
Montefiore Medical Center SC - 3 Recruiting
Bronx, New York, United States, 10467
Contact: Roger Swayze    646-300-1778    rswayze@montefiore.org   
Principal Investigator: Pratt Vemulapalli         
Weill Cornell Medical College-Cornell University New York Presbyterian Hospital Not yet recruiting
New York, New York, United States, 10021
Contact: Olivera Calukovic    212-746-5069    olivera.calukovic@mssm.edu   
Principal Investigator: Alfons Pomp         
United States, Tennessee
Vanderbilt Ingram Cancer Center SC Withdrawn
Nashville, Tennessee, United States, 37203
United States, Texas
Texas Tech University Health Science Center Recruiting
El Paso, Texas, United States, 79905
Contact: Denise Vasquez    915-545-6626    denise.vasquez@ttuhsc.edu   
Principal Investigator: Richard W. McCallum         
United States, Washington
University of Washington School of Medicine University of Washington Withdrawn
Seattle, Washington, United States, 98195
Belgium
Novartis Investigative Site Recruiting
Brugge, Belgium, 8310
Novartis Investigative Site Recruiting
Bruxelles, Belgium, 1200
Novartis Investigative Site Recruiting
Gent, Belgium, 9000
Novartis Investigative Site Recruiting
Leuven, Belgium, 3000
France
Novartis Investigative Site Recruiting
Paris Cedex 13, France, 75651
Novartis Investigative Site Recruiting
Pierre-Benite Cedex, France, 69495
Germany
Novartis Investigative Site Recruiting
Hamburg, Germany, 20246
Novartis Investigative Site Recruiting
Würzburg, Germany, 97080
Netherlands
Novartis Investigative Site Recruiting
Groningen, Netherlands, 9713 GZ
Novartis Investigative Site Recruiting
Maastricht, Netherlands, 5800
Novartis Investigative Site Not yet recruiting
Utrecht, Netherlands, 3584CX
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01637272     History of Changes
Other Study ID Numbers: CSOM230X2203, 2012-001534-34
Study First Received: May 9, 2012
Last Updated: January 10, 2014
Health Authority: United States: Food and Drug Administration
France: Institutional Ethical Committee
Belgium: Federal Agency for Medicinal Products and Health Products
Germany: Federal Institute for Drugs and Medical Devices
Netherlands: Medicines Evaluation Board (MEB)

Keywords provided by Novartis:
Dumping syndrome

Additional relevant MeSH terms:
Dumping Syndrome
Postgastrectomy Syndromes
Stomach Diseases
Gastrointestinal Diseases
Digestive System Diseases
Postoperative Complications
Pathologic Processes

ClinicalTrials.gov processed this record on July 22, 2014