Study to Assess Safety and Efficacy of sc Pasireotide in Patients With Dumping Syndrome (CSOM230BBE01T)

Exploratory Randomized, Placebo-controlled Study to Assess Safety and Efficacy of sc Pasireotide in Patients With Dumping Syndrome

Dumping Syndrome consists of (1) a too rapid gastric emptying, (2) an inappropriate release of GI hormones (as a reaction to the hyperosmolar contents in the duodenum) and (3) an hyperinsulinemic response to a too rapid absorption of glucose. Because it is not well known which somatostatin receptor(s) (sst1-5) influence(s) Dumping Syndrome most, the goal of this trial is to evaluate :

• the effect of pasireotide (sst1, 2, 3, 5 agonist) on the control of gastric emptying.
• the effect of pasireotide (sst1, 2, 3, 5 agonist) on the release of GI hormones (during OGTT).
• the effect of pasireotide (sst1, 2, 3, 5 agonist) on the hyperinsulimic response (during OGTT).
• the efficacy of pasireotide (sst1, 2, 3, 5 agonist) for control of objective parameters of Dumping Syndrome (hematocrit (Hct), pulse rate and occurrence of hypoglycemia after an Oral Glucose Tolerance Test (OGTT) with 75g of glucose)
• the efficacy of pasireotide (sst1, 2, 3, 5 agonist) for control of overall symptoms as measured by the combined Dumping Syndrome score
• the efficacy of pasireotide (sst1, 2, 3, 5 agonist) for control of symptoms as measured by (a) early and (b) late phase dumping symptom score separately
• the efficacy of pasireotide (sst1, 2, 3, 5 agonist) for control of quality of life (QoL SF-36)

Study Overview

• Status: Completed
• Conditions: Postoperative Dumping Syndrome
• Intervention / Treatment: Drug: Pasireotide; Drug: Placebo

Detailed Description

This will be a single centre, randomized, double-blind, controlled cross-over study during 35 days.

After a 4 weeks screening period, patients who fulfill the entrance criteria will be randomly assigned on a 1:1 basis to either the pasireotide treatment arm or to the placebo treatment arm. They will be treated with pasireotide sc or placebo sc for 2 weeks. After 2 weeks, patients will be switched to the other treatment arm after a 7 days wash out period. This phase is double-blind: both the patient and investigator will be blinded to treatment assignment.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • University Hospitals Leuven

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female patients aged between 18 and 80 years.
• Patients with diagnosis of Dumping Syndrome:

• Having symptoms of Dumping Syndrome (sum of combined Dumping Syndrome score ≥10) AND

  • either (a) having had a documented episode of postprandial hypoglycemia in the medical history
  • or either (b) demonstrating a hypoglycemia (<60mg/dl) or hematocrite increase of > 3% or a pulse increase of 10 bpm after an oral glucose tolerance test with 75 g of glucose.
• Patients for whom written informed consent to participate in the study has been obtained. Patients will need to provide their informed consent prior to starting any medication washout period

Exclusion Criteria:

• Patients who have undergone major surgery/surgical therapy for any cause within 1 month
• Patients with symptomatic cholecystolithiasis in the medical history unless a cholecystectomy is performed (ultrasound abdomen maximum 6 months old).
• Patients who have failed treatment with somatostatin analogues in the past (specifically patients who have been treated with octreotide s.c. for more than 2 days or with a long acting somatostatin analogue for more than 8 weeks).
• Patients who have been treated with somatostatin analogues during the last 12 weeks before inclusion.
• Patients who have a known hypersensitivity to somatostatin analogues.
• Patients with the diagnosis of Diabetes Mellitus
• Patients with important co-morbidity (cardiac, pulmonary, renal , hepatic diseases)
• Patients with abnormal coagulation (PT and PTT elevated by 30% above normal limits)
• Patients receiving anticoagulants that affect PT or PTT
• Female patients who are pregnant or lactating, or are of childbearing potential and not practicing a medically acceptable method of birth control. Female patients must use barrier contraception in addition to condoms. If oral contraception is used, the patient must have been practicing this method for at least three months prior to the enrollment and must agree to continue the oral contraceptive throughout the course of the study, and for three months after the study has ended. Male patients who are sexually active are required to use condoms during the study and for 3 months afterwards.
• History of immunocompromise, including a positive HIV test result (ELISA and Western blot). A HIV test will not be required; however, previous medical history will be reviewed
• Patients who have participated in any clinical investigation with an investigational drug within 1 month prior to dosing
• Patients with additional active malignant disease within the last five years (with the exception of basal cell carcinoma or carcinoma in situ of the cervix)
• Patients with the presence of active or suspected acute or chronic uncontrolled infection
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Pasireotide; pasireotide 300 microgram s.c. t.i.d.	Drug: Pasireotide; somatostatin analogue pasireotide; Other Names: SOM230
PLACEBO_COMPARATOR: Placebo; saline s.c. t.i.d.	Drug: Placebo; placebo s.c.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary efficacy endpoint: symptoms related to Dumping Syndrome Severity Score	The dumping score is the sum of the early and late dumping symptoms. Early dumping starts immediately after a meal, within 1 hour (< 1 hour). Late dumping starts later than 1 hour after a meal (≥ 1 hour). In case a symptom starts immediately after a meal and lasts longer than 1 hour, the score for early AND late dumping should be ticked. Dumping Score None Mild Moderate Severe Early Dumping 0 1 2 3 Sweating 0 1 2 3 Flushes 0 1 2 3 Dizziness 0 1 2 3 Palpitations 0 1 2 3 Abdominal pain 0 1 2 3 Diarrhea 0 1 2 3 Bloating 0 1 2 3 Nausea 0 1 2 3 None Mild Moderate Severe Late Dumping 0 1 2 3 Sweating 0 1 2 3 Palpitations 0 1 2 3 Hunger 0 1 2 3 Drowsiness to unconsciousness 0 1 2 3 Trembling 0 1 2 3 Irritability 0 1 2 3	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect on hypoglycemia	• The secondary efficacy variables include the proportion of patients with reduced hypoglycemic events	2 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Control of Hct rise	Proportion of patients with hematocrit rise during OGTT	2 weeks
Control of pulse rate rise	Proportion of patients with pulse rate rise during OGTT	2 weeks

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (ACTUAL): January 1, 2010
• Study Completion (ACTUAL): January 1, 2010

Study Registration Dates

• First Submitted: July 1, 2013
• First Submitted That Met QC Criteria: July 4, 2013
• First Posted (ESTIMATE): July 10, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): July 10, 2013
• Last Update Submitted That Met QC Criteria: July 4, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: hypoglycemia; OGTT; dumping syndrome
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Postoperative Complications; Disease; Gastrointestinal Diseases; Stomach Diseases; Postgastrectomy Syndromes; Syndrome; Dumping Syndrome; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pasireotide
• Other Study ID Numbers: CSOM230BBE01T; 2008-000700-84 (EUDRACT_NUMBER)