Clinical trial NCT01637272: Phase II Study Evaluating Efficacy, Safety and Pharmacokinetics of Pasireotide in Patients With Dumping Syndrome
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Dumping Syndrome
Keywords: Dumping syndrome
SOM230
pasireotide LAR
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-07-11
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Response Rate in Plasma Glucose Level
timeFrame: at Month 3 (M3)
Secondary outcomes:
measure: Response Rate in Plasma Glucose Level
timeFrame: at Month 6 (M6), Month 12 (M12)
measure: Response Rate in Pulse Rate
timeFrame: at baseline, M3, M6, M12
measure: Response Rate in Hematocrit Levels
timeFrame: M3, M6, M12
measure: Insulin Levels During OGTT
timeFrame: M3, M6, M12
measure: Glucagon Levels During OGTT
timeFrame: M3, M6, M12
measure: Glucagon-like Peptide 1 (GLP-1) Levels During OGTT
timeFrame: M3, M6, M12
measure: Gastric Inhibitory Polypeptide (GIP) Levels at During OGTT
timeFrame: M3, M6, M12
measure: Health-related Quality of Live (HRQoL) Short Form- 36 (SF-36) Score(s)
timeFrame: M3, M6, M12
measure: Dumping Severity Score (DSS) at the End of Months 3, 6 and 8
timeFrame: M3, M6, M8
measure: Dumping Score Questionnaire (DSQ) at the End of Months 3, 6 and 12
timeFrame: M3, M6, M12
measure: Patient Global Assessment at the End of Months 3, 6 and 12
timeFrame: M3, M6, M12
measure: Plasma Pharmacokinetic (PK) Parameter of Pasireotide: Cmax, ss (Steady State) and Ctrough, ss, After s.c. Injection
timeFrame: M1 to M3
measure: Plasma Pharmacokinetic (PK) Parameter of Pasireotide: AUC0-3h, ss, After s.c. Injection
timeFrame: M1 to M3
measure: Plasma Pharmacokinetic (PK) Parameter of Pasireotide: Tmax, ss, After s.c. Injection
timeFrame: M1 to M3
measure: Plasma PK Parameter of AUC0-3h, d21, End _inj and AUC0-3h, d28, 3rd_inj Associated With LAR (LAR Core Phase)
timeFrame: M4 to M6
measure: Summary of LAR PK Parameters by Dose
timeFrame: M4 to M6
measure: Pasireotide Concentrations in LAR Phase
timeFrame: M7 to M12
measure: LAR PK Parameter: Ctrough - at Steady State (ss) by Dose
timeFrame: M4 to M12
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Ximed Center for Weight Management Ximed Research
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center SC - SOM230X2203
state: California
city: Rochester
country: United States
facility: Mayo Clinic - Rochester Mayo MN
state: Minnesota
city: Bronx
country: United States
facility: Montefiore Medical Center CLCZ696B2320
state: New York
city: El Paso
country: United States
facility: Texas Tech University Health Science Center
state: Texas
city: Chesapeake
country: United States
facility: Virginia Endocrinology Research SC
state: Virginia
city: Brugge
country: Belgium
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Paris Cedex 13
country: France
facility: Novartis Investigative Site
city: Pessac Cedex
country: France
facility: Novartis Investigative Site
city: Pierre-Benite Cedex
country: France
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Würzburg
country: Germany
facility: Novartis Investigative Site
city: Groningen
country: Netherlands
facility: Novartis Investigative Site
city: Utrecht
country: Netherlands
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: