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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT01637272
• Date of registration: 09/05/2012
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals
• Public title: Phase II Study Evaluating Efficacy, Safety and Pharmacokinetics of Pasireotide in Patients With Dumping Syndrome
• Scientific 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
• Date of first enrolment: January 8, 2013
• Target sample size: 43
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01637272
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Belgium, France, Germany, Netherlands, United States

Contacts

• Name: Novartis Pharmaceuticals
• Affiliation: Novartis Pharmaceuticals

Key inclusion & exclusion 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).



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Dumping Syndrome

Intervention(s)

Drug: SOM230

Primary Outcome(s)

Response Rate in Plasma Glucose Level [Time Frame: at Month 3 (M3)]

Secondary Outcome(s)

??Glucagon-like Peptide 1 (GLP-1) Levels During OGTT [Time Frame: M3, M6, M12]

Summary of LAR PK Parameters by Dose [Time Frame: M4 to M6]

?Dumping Score Questionnaire (DSQ) at the End of Months 3, 6 and 12 [Time Frame: M3, M6, M12]

??Gastric Inhibitory Polypeptide (GIP) Levels at During OGTT [Time Frame: M3, M6, M12]

?Health-related Quality of Live (HRQoL) Short Form- 36 (SF-36) Score(s) [Time Frame: M3, M6, M12]

?Insulin Levels During OGTT [Time Frame: M3, M6, M12]

Plasma Pharmacokinetic (PK) Parameter of Pasireotide: Tmax, ss, After s.c. Injection [Time Frame: M1 to M3]

LAR PK Parameter: Ctrough - at Steady State (ss) by Dose [Time Frame: M4 to M12]

Plasma Pharmacokinetic (PK) Parameter of Pasireotide: AUC0-3h, ss, After s.c. Injection [Time Frame: M1 to M3]

Patient Global Assessment at the End of Months 3, 6 and 12 [Time Frame: 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]

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]

Response Rate in Plasma Glucose Level [Time Frame: at Month 6 (M6), Month 12 (M12)]

Response Rate in Pulse Rate [Time Frame: at baseline, M3, M6, M12]

?Glucagon Levels During OGTT [Time Frame: M3, M6, M12]

?Dumping Severity Score (DSS) at the End of Months 3, 6 and 8 [Time Frame: M3, M6, M8]

?Response Rate in Hematocrit Levels [Time Frame: M3, M6, M12]

Pasireotide Concentrations in LAR Phase [Time Frame: M7 to M12]

Secondary ID(s)

2012-001534-34

CSOM230X2203

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 10/05/2017
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01637272