Dumping Syndrome Patients Clinical Trial
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
multi-center, phase II study evaluating efficacy, safety and pharmacokinetics of pasireotide in patients with dumping syndrome
| Status | Completed |
| Enrollment | 43 |
| Est. completion date | August 2015 |
| Est. primary completion date | August 2015 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
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) |
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Belgium | Novartis Investigative Site | Brugge | |
| Belgium | Novartis Investigative Site | Bruxelles | |
| Belgium | Novartis Investigative Site | Gent | |
| Belgium | Novartis Investigative Site | Leuven | |
| France | Novartis Investigative Site | Paris Cedex 13 | |
| France | Novartis Investigative Site | Pessac Cedex | |
| France | Novartis Investigative Site | Pierre-Benite Cedex | |
| Germany | Novartis Investigative Site | Hamburg | |
| Germany | Novartis Investigative Site | Würzburg | |
| Netherlands | Novartis Investigative Site | Groningen | |
| Netherlands | Novartis Investigative Site | Utrecht | |
| United States | Montefiore Medical Center SC - 3 | Bronx | New York |
| United States | Virginia Endocrinology Research SC | Chesapeake | Virginia |
| United States | Texas Tech University Health Science Center | El Paso | Texas |
| United States | Ximed Center for Weight Management Ximed Research | La Jolla | California |
| United States | Mayo Clinic - Rochester Mayo MN | Rochester | Minnesota |
| United States | Stanford University Medical Center SC - SOM230X2203 | Stanford | California |
| Lead Sponsor | Collaborator |
|---|---|
| Novartis Pharmaceuticals |
United States, Belgium, France, Germany, Netherlands,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Change in response rate in plasma glucose level at the end of subcutaneous (s.c.) dose escalation phase | 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 | baseline, 3 months | No |
| Secondary | Response rate in pulse rate? | 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 | baseline, 3 months, 6 months, 12 months | No |
| Secondary | ?Response rate in hematocrit level? | ?Proportion of patients with change in hematocrit < 3% from pre-OGTT to 30 min during the OGTT | baseline, 3 months, 6 months, 12 months | No |
| Secondary | ?Dumping Score Questionnaire | ?Change in Dumping Score Questionnaire at the end of dose escalation phase, LAR phase, extension phase from baseline | baseline, 3 months, 6 months, 12 months | No |
| Secondary | ?HRQoL SF-36 Score(s) and Patient Global Assessment | ?Change in ?HRQoL SF-36 Score(s) and Patient Global Assessment | baseline, 3 months, 6 months, 12 months | No |
| Secondary | ?Insulin, glucagon, ?Glucagon-like peptide 1 (GLP-1) and ??Gastric Inhibitory Polypeptide (GIP) levels | Changes and percentage changes of insulin, glucagon, ?GLP-1 and GIP | baseline, 3 months, 6 months, 12 months | No |
| Secondary | Incidence of Adverse Events (AEs) | baseline, as necessary during month 3, month 6, month 12 | Yes | |
| Secondary | Laboratory parameters which include Electrocardiogram (ECG), Vital Signs, ?and other safety parameters | baseline, as necessary during month 3, month 6, month 12 | Yes | |
| Secondary | Plasma Pharmacokinetic (PK) parameter AUC0-3h,ss after s.c injection | assess PK of pasireotide at eash s.c. dose level at steady state (ss) | baseline, 90 minutes, 120 minutes, 150minutes, 180 minutes | No |
| Secondary | PK parameter Cmax,ss after s.c injection | assess PK of pasireotide at eash s.c. dose level at steady state | baseline,90 minutes, 120 minutes, 150minutes, 180 minutes | No |
| Secondary | PK parameter Tmax,ss after s.c. injection | assess PK of pasireotide at eash s.c. dose level at steady state | baseline, 90 minutes, 120 minutes, 150minutes, 180 minutes | No |
| Secondary | PK parameter CTrough,ss after s.c. injection | assess PK of pasireotide at eash s.c. dose level at steady state | baseline, 90 minutes, 120 minutes, 150minutes, 180 minutes | No |
| Secondary | PK parameter AUC0-3h, d21 2nd injection associated with LAR administration at steady state | assess PK of pasireotide | baseline, 90 minutes, 120 minutes, 150minutes, 180 minutes | No |
| Secondary | PK parameter Cmax, p2 2nd injection associated with LAR administration at steady state | assess PK of pasireotide | baseline, 90 minutes, 120 minutes, 150 minutes, 180 minutes | No |
| Secondary | PK parameter AUC0-3h, d28 3rd injection associated with third LAR injection at steady state | assess PK of pasireotide | baseline, 90 minutes, 120 minutes, 150minutes, 180 minutes | No |
| Secondary | PK parameter Ctrough d28 associated with each LAR injection at steady state | assess PK of pasireotide (in LAR and extension phase) | baseline, 90 minutes, 120 minutes, 150minutes, 180 minutes | No |
| Secondary | Response rate in plasma glucose level at the end of the long acting release (LAR) phase and dose escalation phase | Response rate = Proportion of patients with no hyperglycemia at 90, 120, 150 and 180 minutes during OGTT | baseline, 3 months, 6 months, 12 months | No |