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

March 31, 2017 updated by: Novartis Pharmaceuticals

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
43

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brugge, Belgium, 8310
        • Novartis Investigative Site
      • Bruxelles, Belgium, 1200
        • Novartis Investigative Site
      • Gent, Belgium, 9000
        • Novartis Investigative Site
      • Leuven, Belgium, 3000
        • Novartis Investigative Site
  • France
      • Paris Cedex 13, France, 75651
        • Novartis Investigative Site
      • Pessac Cedex, France, 33604
        • Novartis Investigative Site
      • Pierre-Benite Cedex, France, 69495
        • Novartis Investigative Site
  • Germany
      • Hamburg, Germany, 20246
        • Novartis Investigative Site
      • Würzburg, Germany, 97080
        • Novartis Investigative Site
  • Netherlands
      • Groningen, Netherlands, 9713 GZ
        • Novartis Investigative Site
      • Utrecht, Netherlands, 3584CX
        • Novartis Investigative Site
  • United States
    • California
      • La Jolla, California, United States, 92037
        • Ximed Center for Weight Management Ximed Research
      • Stanford, California, United States, 94304
        • Stanford University Medical Center SC - SOM230X2203
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic - Rochester Mayo MN
    • New York
      • Bronx, New York, United States, 10467
        • Montefiore Medical Center CLCZ696B2320
    • Texas
      • El Paso, Texas, United States, 79905
        • Texas Tech University Health Science Center
    • Virginia
      • Chesapeake, Virginia, United States, 23321
        • Virginia Endocrinology Research SC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: SOM230
Subjects with dumping syndrome treated with pasireotide
Drug: SOM230
Pasireotide (SOM230) sc injection was provided as solution for injection in individual 1-point-cut 1 mL ampule, containing nominally 200 μg of pasireotide (as free base). Doses: 50, 100, 150 and 200 μg. Pasireotide im LAR depot injection was provided as micro particles powder in vials containing nominally 10, 20, 40 & 60 mg of pasireotide (as free base) & solvent for suspension for injection in ampules for the reconstitution of the LAR micro particles. Doses: 10, 20, 30, 40 or 60 mg
Other Names:
  • pasireotide

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
at Month 3 (M3)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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)
at Month 6 (M6), Month 12 (M12)
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.
at baseline, M3, M6, M12
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.
M3, M6, M12
Insulin Levels During OGTT
Time Frame: M3, M6, M12
Absolute insulin levels at the end of M3, M6, M12
M3, M6, M12
Glucagon Levels During OGTT
Time Frame: M3, M6, M12
Absolute glucagon levels at the end of Months 3, 6 & 12
M3, M6, M12
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.
M3, M6, M12
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.
M3, M6, M12
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.
M3, M6, M12
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.
M3, M6, M8
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.
M3, M6, M12
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).
M3, M6, M12
Plasma Pharmacokinetic (PK) Parameter of Pasireotide: Cmax, ss (Steady State) and Ctrough, ss, After s.c. Injection
Time Frame: M1 to M3
A pre-dose PK blood sample was collected before the morning pasireotide s.c. dose of 50 μg, 100 ug, 150 ug and 200 ug. OGTT was performed right after the morning s.c. dose (Time point zero); additional PK blood samples were collected at the same time points as the OGTT evaluation at 30, 60, 90, 120, 150 and 180 minutes. 'n' = number of subjects with non-missing values
M1 to M3
Plasma Pharmacokinetic (PK) Parameter of Pasireotide: AUC0-3h, ss, After s.c. Injection
Time Frame: M1 to M3
A pre-dose PK blood sample was collected before the morning pasireotide s.c. dose of 50 μg, 100 ug, 150 ug and 200 ug. OGTT was performed right after the morning s.c. dose (Time point zero); additional PK blood samples were collected at the same time points as the OGTT evaluation at 30, 60, 90, 120, 150 and 180 minutes.
M1 to M3
Plasma Pharmacokinetic (PK) Parameter of Pasireotide: Tmax, ss, After s.c. Injection
Time Frame: M1 to M3
A pre-dose PK blood sample was collected before the morning pasireotide s.c. dose of 50 μg, 100 ug, 150 ug and 200 ug. OGTT was performed right after the morning s.c. dose (Time point zero); additional PK blood samples were collected at the same time points as the OGTT evaluation at 30, 60, 90, 120, 150 and 180 minutes.
M1 to M3
Plasma PK Parameter of AUC0-3h, d21, End _inj and AUC0-3h, d28, 3rd_inj Associated With LAR (LAR Core Phase)
Time Frame: M4 to M6
M4 to M6
Summary of LAR PK Parameters by Dose
Time Frame: M4 to M6
Summary of plasma PK parameter Cmax, p2 , 2nd injection and Ctrough, d28 associated with LAR injection (LAR Core phase)
M4 to M6
Pasireotide Concentrations in LAR Phase
Time Frame: M7 to M12
Summary of pasireotide concentrations following monthly i.m. injections of pasireotide LAR by incident dose (LAR Pharmacokinetic set)
M7 to M12
LAR PK Parameter: Ctrough - at Steady State (ss) by Dose
Time Frame: M4 to M12
In the LAR treatment phase, monthly injections of pasireotide LAR 10, 20, 30 and 40 mg were given to participants and trough concentration at steady state (Ctrough,ss) were obtained but due to only 1 participant in the 40mg arm, standard deviation could not be calculated.
M4 to M12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 8, 2013

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 7, 2015

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 7, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 9, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 10, 2012

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 11, 2012

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 10, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 31, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CSOM230X2203
  • 2012-001534-34 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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