ACTIVE_NOT_RECRUITING

Pasireotide s.c. in Patients With Post-Bariatric Hypoglycaemia

Conditions

Post-Bariatric Hypoglycemia PBH Post Bariatric

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The Total duration of trial participation for each participant with post-bariatric hypoglycemia will be a maximum of 59 weeks, with the following duration of trial periods * 19 weeks for the Core Phase. It is composed of: * a Screening period: a maximum of 3 weeks * a Run-in period (no treatment): 4 weeks * a Blinded Treatment Phase: 12 weeks * 36 weeks Extension Phase = an open-label Treatment period * 4 weeks for the safety follow-up period (without any treatment).

Official Title

A Double-blind Randomized Placebo-controlled Dose-finding Phase II Study to Assess the Efficacy and Safety of Pasireotide s.c. in Patients With Post-Bariatric Hypoglycaemia

Quick Facts

Study Start:2024-01-04

Study Completion:2026-04

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05928390

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.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Male or- non-pregnant female patients ≥ 18 years of age 2. Patients able to provide and have provided signed written informed consent prior to study participation. 3. Patients capable of self-injecting subcutaneously. Specific training to self-inject the study drug will be provided. 4. Post-bariatric surgery more than 6 months prior to screening 5. Patients with a medically documented diagnosis of PBH and documented glucose measurement (less than 70 mg/dl or 3.9 mmol/L) with symptoms of hypoglycaemia, and resolution following administration of rescue carbohydrates 6. Patients must have ≥ 4 post-prandial hypoglycaemia during the 28-day run-in period (in average ≥1 event over a 7-day week) defined as: * Blood glucose less than 54 mg/dL (3.0 mmol/L) as measured by SMBG (level 2) or * Level 3 hypoglycaemic event 7. (The previous inclusion criterion number 7 has been deleted). 8. Patients in whom dietary control has not sufficiently controlled symptoms of PBH. 9. Karnofsky Performance Status ≥ 60 (i.e., requires occasional assistance, but is able to care for most of their personal needs) 10. Patients who received other therapies for PBH (such as acarbose, gama guar, pectin, diazoxide) must have stopped all treatments and such treatments are prohibited for a period of at least 2 weeks or 5 half-life times prior to entering the screening period. 11. GLP-1 antagonists and GLP-1 agonists for patients who have been treated with in the past for the indication of PBH, are prohibited for a period of at least 4 weeks before the start of the screening period. 12. SGLT2 inhibitors (glifozins) for patients who have been treated with in the past for the indication of PBH, are prohibited for a period of at least 4 weeks before the start of the screening period. 13. Patients who have been treated with somatostatin receptor analogues in the past, must have an appropriate interval between the last administration of somatostatin receptor analogues treatment and the start of the run-in period 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) * Pasireotide s.c. for ≥ 72 hours (3 days) * Pasireotide LAR for ≥ 84 days (12 weeks) 1. Bariatric patients who have lap band. 2. Patients with a current diagnosis of uncontrolled Diabetes Mellitus. However, diabetic patients in remission, as defined below, are eligible: * With an HbA1c at screening less than 6.5% * Not taking any medications for hyperglycaemia for at least 3 months prior to screening. * Their qualifying Level 3 hypoglycaemia events (see above) must have occurred at least 1 month after the discontinuation of the glucose lowering agent(s). 3. Patients with hypocortisolism, as defined by serum cortisol levels minor of LLN with presence of clinical signs and symptoms of adrenal insufficiency (e.g., weakness, fatigue, anorexia, nausea, vomiting, hypotension, hyponatremia, or hypoglycaemia) as judged by the Investigators 4. (The previous exclusion criterion number 4 has been deleted). 5. (The previous exclusion criterion number 5 has been deleted). 6. Patients who have a known hypersensitivity to somatostatin receptor analogues. 7. Patients currently using medications that may interfere with glucose metabolism within 5 half-lives of drug. 8. Patients with history of or current insulinoma. 9. Patients who have any severe and/or uncontrolled medical condition 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. * Inadequate end organ function as defined by: * Inadequate bone marrow function: * WBC less than 3.0 x 109/L * Absolute Neutrophil Count (ANC) less than 1.5 x 109/L * Platelets less than100 x 109/L * Hgb less than 11 g/dL * INR ≥ 1.5 * eGFR less than 30 mL/min/1.73m2 * Alkaline phosphatase more than 2.5 x ULN * Serum total bilirubin more than1.5 x ULN * ALT and AST more than 1.5 x ULN 10. History of liver disease, such as cirrhosis or chronic active hepatitis B andC 11. Presence of Hepatitis B surface antigen (HbsAg) and/ or Presence of Hepatitis C antibody test (anti-HCV). Patients with positive HCV Ab must undergo reflex HCV RNA testing, and patients with HCV RNA positivity will be excluded. Patients with positive HCV Ab and negative HCV RNA are eligible. 12. History of, or current alcohol and/or drug misuse/abuse within the past 12 months. A drug/alcohol test will not be required; however, previous medical history will be reviewed. 13. Patients with symptomatic cholelithiasis and/ or acute or chronic pancreatitis. 14. Patients with abnormal coagulation (PT and PTT elevated by 30% above normal limits). 15. 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). 16. Patients who are hypothyroid and not on adequate replacement therapy. 17. Patients who have undergone major surgery/surgical therapy for any cause within 1 month before screening. Patients should have recovered from the surgery and be in good clinical condition before entering the study. 18. Patients requiring gastrostomy tube feedings. 19. 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. 20. 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. 21. Bradycardia and QT-related	* Patients with long QT syndrome or QTcF more than 450 ms for male and QTcF more than 460 ms for female detected at screening. * Patients with uncontrolled or significant cardiac disease, including recent myocardial infarction, unstable angina, congestive heart failure, clinically significant/symptomatic heart rate less than50 bpm, or high-grade AV block, sustained ventricular tachycardia, ventricular fibrillation. * History of syncope or family history of idiopathic sudden death. * Sustained or clinically significant cardiac arrhythmias. * 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. * Hypokalaemia (Potassium less than or = 3.5 mEq/L). * Hypomagnesemia (Magnesium less than 0.7 mmol/L). 22. Participation in any clinical investigation within 4 weeks prior to screening or longer if required by local regulation. (Use of an investigational drug within 1 month prior to screening). 23. Significant acute illness within the two weeks prior to dosing. 24. Female patients who are pregnant, intending to become pregnant or breastfeed during the study. or lactating, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test. 25. Women of childbearing potential (WOCBP) who are unwilling of using highly effective contraception methods. * Combined (estrogen and progesterone containing) (oral, intravaginal, transdermal) hormonal contraception associated with inhibition of ovulation. * Progesterone-only hormonal (oral, injectable, implantable) contraception associated with inhibition of ovulation. * Intrauterine device. * Intrauterine hormone-releasing system. * Bilateral tubal occlusion. * Sexual abstinence defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient. 26. Sexually active males unwilling to use a condom during intercourse while taking the drug and for 4 weeks after pasireotide s.c. last dose. A condom is required to be used also by vasectomized men to prevent delivery of the drug via seminal fluid. 27. Potentially unreliable or vulnerable patients (e.g., person kept in detention) and those judged by the Investigator to be unsuitable for the study.

Inclusion Criteria

Exclusion Criteria

1. Male or- non-pregnant female patients ≥ 18 years of age
2. Patients able to provide and have provided signed written informed consent prior to study participation.
3. Patients capable of self-injecting subcutaneously. Specific training to self-inject the study drug will be provided.
4. Post-bariatric surgery more than 6 months prior to screening
5. Patients with a medically documented diagnosis of PBH and documented glucose measurement (less than 70 mg/dl or 3.9 mmol/L) with symptoms of hypoglycaemia, and resolution following administration of rescue carbohydrates
6. Patients must have ≥ 4 post-prandial hypoglycaemia during the 28-day run-in period (in average ≥1 event over a 7-day week) defined as:
* Blood glucose less than 54 mg/dL (3.0 mmol/L) as measured by SMBG (level 2) or
* Level 3 hypoglycaemic event
7. (The previous inclusion criterion number 7 has been deleted).
8. Patients in whom dietary control has not sufficiently controlled symptoms of PBH.
9. Karnofsky Performance Status ≥ 60 (i.e., requires occasional assistance, but is able to care for most of their personal needs)
10. Patients who received other therapies for PBH (such as acarbose, gama guar, pectin, diazoxide) must have stopped all treatments and such treatments are prohibited for a period of at least 2 weeks or 5 half-life times prior to entering the screening period.
11. GLP-1 antagonists and GLP-1 agonists for patients who have been treated with in the past for the indication of PBH, are prohibited for a period of at least 4 weeks before the start of the screening period.
12. SGLT2 inhibitors (glifozins) for patients who have been treated with in the past for the indication of PBH, are prohibited for a period of at least 4 weeks before the start of the screening period.
13. Patients who have been treated with somatostatin receptor analogues in the past, must have an appropriate interval between the last administration of somatostatin receptor analogues treatment and the start of the run-in period 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)
* Pasireotide s.c. for ≥ 72 hours (3 days)
* Pasireotide LAR for ≥ 84 days (12 weeks)
1. Bariatric patients who have lap band.
2. Patients with a current diagnosis of uncontrolled Diabetes Mellitus. However, diabetic patients in remission, as defined below, are eligible:
* With an HbA1c at screening less than 6.5%
* Not taking any medications for hyperglycaemia for at least 3 months prior to screening.
* Their qualifying Level 3 hypoglycaemia events (see above) must have occurred at least 1 month after the discontinuation of the glucose lowering agent(s).
3. Patients with hypocortisolism, as defined by serum cortisol levels minor of LLN with presence of clinical signs and symptoms of adrenal insufficiency (e.g., weakness, fatigue, anorexia, nausea, vomiting, hypotension, hyponatremia, or hypoglycaemia) as judged by the Investigators
4. (The previous exclusion criterion number 4 has been deleted).
5. (The previous exclusion criterion number 5 has been deleted).
6. Patients who have a known hypersensitivity to somatostatin receptor analogues.
7. Patients currently using medications that may interfere with glucose metabolism within 5 half-lives of drug.
8. Patients with history of or current insulinoma.
9. Patients who have any severe and/or uncontrolled medical condition 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.
* Inadequate end organ function as defined by:
* Inadequate bone marrow function:
* WBC less than 3.0 x 109/L
* Absolute Neutrophil Count (ANC) less than 1.5 x 109/L
* Platelets less than100 x 109/L
* Hgb less than 11 g/dL
* INR ≥ 1.5
* eGFR less than 30 mL/min/1.73m2
* Alkaline phosphatase more than 2.5 x ULN
* Serum total bilirubin more than1.5 x ULN
* ALT and AST more than 1.5 x ULN
10. History of liver disease, such as cirrhosis or chronic active hepatitis B andC
11. Presence of Hepatitis B surface antigen (HbsAg) and/ or Presence of Hepatitis C antibody test (anti-HCV). Patients with positive HCV Ab must undergo reflex HCV RNA testing, and patients with HCV RNA positivity will be excluded. Patients with positive HCV Ab and negative HCV RNA are eligible.
12. History of, or current alcohol and/or drug misuse/abuse within the past 12 months. A drug/alcohol test will not be required; however, previous medical history will be reviewed.
13. Patients with symptomatic cholelithiasis and/ or acute or chronic pancreatitis.
14. Patients with abnormal coagulation (PT and PTT elevated by 30% above normal limits).
15. 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).
16. Patients who are hypothyroid and not on adequate replacement therapy.
17. Patients who have undergone major surgery/surgical therapy for any cause within 1 month before screening. Patients should have recovered from the surgery and be in good clinical condition before entering the study.
18. Patients requiring gastrostomy tube feedings.
19. 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.
20. 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.
21. Bradycardia and QT-related

* Patients with long QT syndrome or QTcF more than 450 ms for male and QTcF more than 460 ms for female detected at screening.
* Patients with uncontrolled or significant cardiac disease, including recent myocardial infarction, unstable angina, congestive heart failure, clinically significant/symptomatic heart rate less than50 bpm, or high-grade AV block, sustained ventricular tachycardia, ventricular fibrillation.
* History of syncope or family history of idiopathic sudden death.
* Sustained or clinically significant cardiac arrhythmias.
* 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.
* Hypokalaemia (Potassium less than or = 3.5 mEq/L).
* Hypomagnesemia (Magnesium less than 0.7 mmol/L).
22. Participation in any clinical investigation within 4 weeks prior to screening or longer if required by local regulation. (Use of an investigational drug within 1 month prior to screening).
23. Significant acute illness within the two weeks prior to dosing.
24. Female patients who are pregnant, intending to become pregnant or breastfeed during the study. or lactating, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
25. Women of childbearing potential (WOCBP) who are unwilling of using highly effective contraception methods.
* Combined (estrogen and progesterone containing) (oral, intravaginal, transdermal) hormonal contraception associated with inhibition of ovulation.
* Progesterone-only hormonal (oral, injectable, implantable) contraception associated with inhibition of ovulation.
* Intrauterine device.
* Intrauterine hormone-releasing system.
* Bilateral tubal occlusion.
* Sexual abstinence defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient.
26. Sexually active males unwilling to use a condom during intercourse while taking the drug and for 4 weeks after pasireotide s.c. last dose. A condom is required to be used also by vasectomized men to prevent delivery of the drug via seminal fluid.
27. Potentially unreliable or vulnerable patients (e.g., person kept in detention) and those judged by the Investigator to be unsuitable for the study.

Contacts and Locations

Principal Investigator

Arnd H MUELLER, MD

STUDY_DIRECTOR

Recordati AG

Study Locations (Sites)

Stanford University School of Medicine, Endocrinology, 800 Welch Road,

Palo Alto, California, 94305

United States

Northwestern University - Feinberg School of Medicine - Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60628

United States

NOLA Care

Metairie, Louisiana, 70006

United States

Velocity Clinical Research - Annapolis

Annapolis, Maryland, 21401

United States

Joslin Diabetes CenterJoslin Diabetes Center, One Joslin Place

Boston, Massachusetts, 02215

United States

Mayo Clinic - Rochester, 200 First Street, SW, 55905

Rochester, Minnesota, 55905

United States

Montefiore Medical Center, 111 E 210th Street,

The Bronx, New York, 10467

United States

Vanderbilt University Medical Center

Nashville, Tennessee, 37204

United States

University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr,

San Antonio, Texas, 78229

United States

University of Wisconsin Health W. E. Clinic END, 451 Junction Rd,

Madison, Wisconsin, 53717

United States

Collaborators and Investigators

Sponsor: RECORDATI GROUP

Arnd H MUELLER, MD, STUDY_DIRECTOR, Recordati AG

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 Registration Dates

Study Start Date2024-01-04

Study Completion Date2026-04

Study Record Updates

Study Start Date2024-01-04

Study Completion Date2026-04

Terms related to this study

Keywords Provided by Researchers

PBH
Post Bariatric

Additional Relevant MeSH Terms

Post-Bariatric Hypoglycemia