PASIREOTIDE DIASPARTATE for Post-bariatric hypoglycaemia

Inclusion criteria

• {"criterion_text":"- 1.\tMale or non-pregnant female patients ≥ 18 years of age."}
• {"criterion_text":"- 10.\tPatients 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 12.\tSGLT2 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."}
• {"criterion_text":"- 13.\tPatients 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 screening period as follows: •\tOctreotide s.c. for ≥ 72 hours (3 days) •\tOctreotide LAR for ≥ 56 days (8 weeks) •\tLanreotide Autogel for ≥ 98 days (14 weeks) •\tLanreotide SR ≥ 28 days (4 weeks) •\tPasireotide s.c. for ≥ 72 hours (3 days) •\tPasireotide LAR for ≥ 84 days (12 weeks)"}
• {"criterion_text":"- 2.\tPatients able to provide and have provided signed written informed consent prior to study participation."}
• {"criterion_text":"- 3.\tPatients capable of self-injecting subcutaneously. Specific training to self-inject the study drug will be provided."}
• {"criterion_text":"- 4.\tPost-bariatric surgery more than 6 months prior to screening."}
• {"criterion_text":"- 5.\tPatients with a medically documented diagnosis of PBH and documented glucose measurement (<70 mg/dl or 3.9 mmol/L) with symptoms of hypoglycaemia, and resolution following administration of rescue carbohydrates."}
• {"criterion_text":"- 6.\tPatients must have ≥ 4 post-prandial hypoglycaemia during the 28-day run-in period (in average ≥1 event over a 7-day week) defined as: •\tBlood glucose <54 mg/dL (3.0 mmol/L) as measured by SMBG (level 2) or •\tLevel 3 hypoglycaemic event"}
• {"criterion_text":"- 7.\t(The previous inclusion criterion number 7 has been deleted)."}
• {"criterion_text":"- 8.\tPatients in whom dietary control has not sufficiently controlled symptoms of PBH."}
• {"criterion_text":"- 9.\tKarnofsky Performance Status ≥ 60 (i.e., requires occasional assistance, but is able to care for most of their personal needs)."}

Exclusion criteria

• {"criterion_text":"- 1.\tBariatric patients who have lap band."}
• {"criterion_text":"- 18.\tPatients requiring gastrostomy tube feedings."}
• {"criterion_text":"- 19.\tPatients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will be unable to complete the entire study."}
• {"criterion_text":"- 2.\tPatients with a current diagnosis of uncontrolled Diabetes Mellitus. However, diabetic patients in remission, as defined below, are eligible: •\tWith an HbA1c at screening <6.5% •\tNot taking any medications for hyperglycaemia for at least 3 months prior to screening. •\tTheir qualifying Level 3 hypoglycaemia events (see above) must have occurred at least 1 month after the discontinuation of the glucose lowering agent(s)."}
• {"criterion_text":"- 20.\tClinically 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"}
• {"criterion_text":"- 21.\tBradycardia and QT-related exclusion criteria: •\tPatients with long QT syndrome or QTcF >450 ms for male and QTcF >460 ms for female detected at screening. •\tPatients with uncontrolled or significant cardiac disease, including recent myocardial infarction, unstable angina, congestive heart failure, clinically significant/symptomatic heart rate < 50 bpm, or high-grade AV block, sustained ventricular tachycardia, ventricular fibrillation. •\tHistory of syncope or family history of idiopathic sudden death. •\tSustained or clinically significant cardiac arrhythmias. •\tConcomitant disease(s) that could prolong QT such as autonomic neuropathy (caused by diabetes, or Parkinson's disease), HIV, cirrhosis, uncontrolled hypothyroidism, or cardiac failure. •\tFamily history of long QT syndrome. •\tConcomitant medications known to prolong the QT interval. •\tHypokalaemia (Potassium < or = 3.5 mEq/L). •\tHypomagnesemia (Magnesium < 0.7 mmol/L)."}
• {"criterion_text":"- 22.\tParticipation 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)."}
• {"criterion_text":"- 23.\tSignificant acute illness within the two weeks prior to dosing."}
• {"criterion_text":"- 24.\tFemale 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."}
• {"criterion_text":"- 25.\tWomen of childbearing potential (WOCBP) who are unwilling of using highly effective contraception methods. Highly effective contraception methods include: •\tCombined (estrogen and progesterone containing) (oral, intravaginal, transdermal) hormonal contraception associated with inhibition of ovulation. •\tProgesterone-only hormonal (oral, injectable, implantable) contraception associated with inhibition of ovulation. •\tIntrauterine device. •\tIntrauterine hormone-releasing system. •\tBilateral tubal occlusion. •\tSexual 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."}
• {"criterion_text":"- 3.\tPatients with hypocortisolism, as defined by serum cortisol levels "}
• {"criterion_text":"- 10.\tHistory of liver disease, such as cirrhosis or chronic active hepatitis B and C."}
• {"criterion_text":"- 4.\t(The previous exclusion criterion number 4 has been deleted)."}
• {"criterion_text":"- 5.\t(The previous exclusion criterion number 5 has been deleted)."}
• {"criterion_text":"- 6.\tPatients who have a known hypersensitivity to somatostatin receptor analogues."}
• {"criterion_text":"- 7.\tPatients currently using medications that may interfere with glucose metabolism within 5 half-lives of drug."}
• {"criterion_text":"- 8.\tPatients with history of or current insulinoma."}
• {"criterion_text":"- 9.\tPatients who have any severe and/or uncontrolled medical condition or other conditions that could affect their participation in the study such as: •\tPatients 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. •\tNon-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with this study treatment. •\tLife-threatening autoimmune and ischemic disorders. •\tInadequate end organ function as defined by: •\tInadequate bone marrow function: •\tWBC < 3.0 x 109/L •\tAbsolute Neutrophil Count (ANC) < 1.5 x 109/L •\tPlatelets < 100 x 109/L •\tHgb < 11 g/dL •\tINR ≥ 1.5 •\teGFR < 30 mL/min/1.73m2 •\tAlkaline phosphatase >2.5 x ULN •\tSerum total bilirubin >1.5 x ULN •\tALT and AST > 1.5 x ULN"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 27. Potentially unreliable or vulnerable patients (e.g., person kept in detention) and those judged by the Investigator to be unsuitable for the study."}
• {"criterion_text":"- 11.\tPresence 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."}
• {"criterion_text":"- 12.\tHistory 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."}
• {"criterion_text":"- 13.\tPatients with symptomatic cholelithiasis and/ or acute or chronic pancreatitis."}
• {"criterion_text":"- 14.\tPatients with abnormal coagulation (PT and PTT elevated by 30% above normal limits)."}
• {"criterion_text":"- 15.\tPatients 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)."}
• {"criterion_text":"- 16.\tPatients who are hypothyroid and not on adequate replacement therapy."}
• {"criterion_text":"- 17.\tPatients 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."}

Primary endpoints

• {"endpoint_text":"- Change in the blood glucose levels, as measured by the peak to nadir glucose AUC, during the MMTT at baseline to the MMTT at 12 weeks of treatment with pasireotide s.c. 50 µg, or 100 µg or 200 µg tid vs placebo tid.","definition_or_measurement_approach":"Measured as peak-to-nadir glucose area under the curve (AUC) during a mixed meal tolerance test (MMTT) comparing baseline MMTT to MMTT at 12 weeks; treatment arms: pasireotide s.c. 50 µg, 100 µg or 200 µg three times daily (tid) versus placebo tid."}

Secondary endpoints

• {"endpoint_text":"- Secondary and exploratory – For the Core phase Key secondary endpoint: 1.\tChange from baseline in the rate of the composite (and individual components) of clinically significant hypoglycaemic events as measured as the frequency of level 2 hypoglycaemic events (glucose level <54 mg/dL or 3.0 mmol/L) measured by SMBG OR the frequency of level 3 hypoglycaemic (requiring external assistance) events/4-weeks at 12 weeks of treatment with pasireotide s.c. 50 µg, or 100 µg or 200 µg tid vs placebo tid.","definition_or_measurement_approach":"Frequency of level 2 hypoglycaemic events (plasma glucose <54 mg/dL) measured by SMBG OR frequency of level 3 events (requiring external assistance) per 4-week period at 12 weeks."}
• {"endpoint_text":"- Secondary endpoints: 1.\tChange in the nadir and peak of blood glucose levels, during the MMTT at baseline to the MMTT at 12 weeks of treatment with pasireotide s.c. 50 µg, or 100 µg or 200 µg tid vs placebo tid","definition_or_measurement_approach":"Change in nadir and peak glucose values measured during MMTT from baseline to week 12."}
• {"endpoint_text":"- 2.\tChange from baseline in the proportion of patients with no level 2 hypoglycaemic events (plasma glucose <54 mg/dL or 3.0 mmol/L) at 60, 90, 105, 120, 135, 150, 165 and 180 min during a 3-hour MMTT after 12 weeks of treatment with pasireotide s.c. 50 µg, or 100 µg or 200 µg tid or vs placebo tid respectively","definition_or_measurement_approach":"Proportion of patients without level 2 hypoglycaemia at specified time points (60–180 min) during a 3-hour MMTT at week 12."}
• {"endpoint_text":"- 3.\tChanges in HRQoL (SF-36 score, Hypoglycaemia Fear Survey-II, Dumping Score Questionnaire and Patient Global Assessment) from baseline to week 12 of treatment with pasireotide s.c. 50, or 100 or 200 µg tid or placebo tid","definition_or_measurement_approach":"HRQoL assessed by SF-36, Hypoglycaemia Fear Survey-II, Dumping Score Questionnaire and Patient Global Assessment at baseline and week 12."}
• {"endpoint_text":"- 4.\tIncidence of AEs, laboratory, and ECG findings at pasireotide s.c. 50 µg, or 100 µg or 200 µg tid or placebo tid. Changes from baseline in laboratory values, ECG readings, gallbladder imaging and in vital signs","definition_or_measurement_approach":"Safety assessed by adverse events, labs, ECGs, gallbladder imaging, and vital sign changes versus baseline during treatment."}
• {"endpoint_text":"- Exploratory endpoints: 1.\tChange from baseline in the rate of the composite (and individual components) of clinically significant hypoglycaemic events as measured as the frequency of level 2 hypoglycaemic events (glucose level <54 mg/dL or 3.0 mmol/L) measured by SMBG OR the frequency of level 3 hypoglycaemic (requiring external assistance) events/4-weeks at 4 and 8 weeks of treatment with pasireotide s.c. 50 µg, or 100 µg or 200 µg tid vs placebo tid","definition_or_measurement_approach":"Frequency of level 2 events (SMBG) or level 3 events per 4-week period at weeks 4 and 8."}
• {"endpoint_text":"- 2.\tChange from baseline in the rate of level 2 hypoglycaemic events (glucose level <54 mg/dL or 3.0 mmol/L for at least 15 minutes) including the overall, diurnal and nocturnal events measured by CGM at 4, 8 and 12 weeks of treatment with pasireotide s.c. 50 µg, or 100 µg or 200 µg tid vs placebo tid","definition_or_measurement_approach":"Rate of level 2 events measured by continuous glucose monitoring (CGM), overall/diurnal/nocturnal at weeks 4, 8, 12."}
• {"endpoint_text":"- 3.\tChange from baseline in duration of Level 2 hypoglycaemic events (glucose level <54 mg/dL or 3.0 mmol/L for at least 15 minutes), including the overall, diurnal and nocturnal events by CGM at 4, 8, and 12 weeks of treatment with pasireotide s.c. 50, or 100 or 200 µg tid or placebo tid","definition_or_measurement_approach":"Duration of level 2 events by CGM (overall/diurnal/nocturnal) at weeks 4, 8, 12."}
• {"endpoint_text":"- 4.\tChange from baseline in percent time with Level 2 hypoglycaemic events (glucose level <54 mg/dL or 3.0 mmol/L for at least 15 min) including the overall, diurnal and nocturnal events by CGM at 4, 8, and 12 weeks of treatment with pasireotide s.c. 50, or 100 or 200 µg tid or placebo tid","definition_or_measurement_approach":"Percent time below 54 mg/dL by CGM (overall/diurnal/nocturnal) at weeks 4, 8, 12."}
• {"endpoint_text":"- 5.\tAbsolute and percent changes in insulin, glucagon and GLP-1 secretion from baseline during the MMTT after 12 weeks of treatment with pasireotide s.c. 50 µg, or 100 µg or 200 µg tid or placebo tid","definition_or_measurement_approach":"Absolute and percent changes in insulin, glucagon, GLP-1 measured during MMTT at week 12; analytes quantified (PK/biomarker analyses)."}
• {"endpoint_text":"- 6.\tChange from baseline in the frequency of use of rescue therapy and/or rescue carbohydrates at home to manage Level 2 or Level 3 hypoglycaemic events at 4, 8, and 12 weeks of treatment with pasireotide s.c. 50 µg, or 100 µg or 200 µg tid vs placebo tid","definition_or_measurement_approach":"Frequency of rescue therapy/rescue carbohydrate use at home reported at weeks 4, 8, 12."}
• {"endpoint_text":"- 7.\tProportion of participants with change in pulse rate <10 bpm during the MMTT after 12 weeks of treatment with pasireotide s.c. 50 µg, or 100 µg or 200 µg tid or placebo tid","definition_or_measurement_approach":"Proportion of participants with <10 bpm change in pulse rate during MMTT at week 12."}
• {"endpoint_text":"- 8.\tProportion of participants with change in haematocrit <3% during the MMTT after 12 weeks of treatment with pasireotide s.c. 50 µg, or 100 µg or 200 µg tid or placebo tid","definition_or_measurement_approach":"Proportion with <3% change in haematocrit during MMTT at week 12."}
• {"endpoint_text":"- Secondary and Exploratory endpoints For the Extension Phase. Secondary For the Extension phase 1.\tIncidence of AEs, laboratory, and ECG findings with pasireotide s.c. tid. Changes from baseline in laboratory values, ECG readings, gallbladder imaging and in vital signs during the whole extension period","definition_or_measurement_approach":"Safety endpoints during extension (incidence of AEs, labs, ECG, gallbladder imaging, vitals) over extension period."}
• {"endpoint_text":"- Exploratory For the Extension phase 1.\tChange in the blood glucose levels, as measured by the peak to nadir glucose AUC, during the MMTT at baseline to the MMTT at 24 weeks of treatment with pasireotide s.c. tid.","definition_or_measurement_approach":"Peak-to-nadir glucose AUC change during MMTT from baseline to week 24 in extension."}
• {"endpoint_text":"- 2.\tChange from baseline in the rate of the composite (and individual components) of clinically significant hypoglycaemic events as measured as the frequency level 2 hypoglycaemic events (glucose level <54 mg/dL or 3.0 mmol/L) measured by SMBG or Level 3 hypoglycaemic events (requiring external assistance) at weeks 16, 20, 24, 32, 40 and 48 of treatment with pasireotide s.c. tid","definition_or_measurement_approach":"Frequency of level 2 (SMBG) or level 3 events at specified weeks during extension."}
• {"endpoint_text":"- 3.\tChange in the nadir and the peak of blood glucose levels, during the MMTT at baseline to the MMTT at 24 weeks of treatment with pasireotide s.c. tid","definition_or_measurement_approach":"Change in nadir and peak glucose during MMTT baseline to week 24 in extension."}
• {"endpoint_text":"- 4.\tChange from baseline in the proportion of patients with no level 2 hypoglycaemic events (plasma glucose <54 mg/dL or 3.0 mmol/L) at 60, 90, 105, 120, 135, 150, 165 and 180 min during a 3-hour MMTT after 24 weeks of treatment with pasireotide s.c. tid","definition_or_measurement_approach":"Proportion without level 2 events at specified MMTT time points at week 24."}
• {"endpoint_text":"- 5.\tChanges in HRQoL (SF-36 score, Dumping Score Questionnaire, Hypoglycaemia Fear Survey-II and Patient Global Assessment) from baseline with pasireotide s.c. tid at weeks 24 and 48 of treatment","definition_or_measurement_approach":"HRQoL measures (SF-36, DSQ, HFS-II, PGA) at weeks 24 and 48 in extension."}
• {"endpoint_text":"- 6.\tChange from baseline in the rate of level 2 hypoglycaemic events (blood glucose <54 mg/dL or 3.0 mmol/L for at least 15 minutes) including the overall, diurnal and nocturnal events by CGM with pasireotide s.c. tid at weeks 16, 20, 24, 32, 40 and 48 of treatment","definition_or_measurement_approach":"Rate of level 2 events by CGM (overall/diurnal/nocturnal) at specified weeks during extension."}
• {"endpoint_text":"- 7.\tChange from baseline in duration of Level 2 hypoglycaemic events (glucose level <54 mg/dL or 3.0 mmol/L for at least 15 minutes) including the overall, diurnal and nocturnal events by CGM with pasireotide s.c. tid at weeks 16, 20, 24, 32, 40 and 48 of treatment","definition_or_measurement_approach":"Duration of level 2 events by CGM at specified weeks in extension."}
• {"endpoint_text":"- 8.\tChange from baseline in percent time with Level 2 hypoglycaemic events (glucose level <54 mg/dL or 3.0 mmol/L for at least 15 minutes) including the overall, diurnal and nocturnal events by CGM with pasireotide s.c. tid at weeks 16, 20, 24, 32, 40 and 48 of treatment","definition_or_measurement_approach":"Percent time below threshold by CGM at specified weeks in extension."}
• {"endpoint_text":"- 9.\tAbsolute and percent changes in insulin, glucagon and GLP-1 secretion from baseline during the MMTT after 24 weeks of treatment with pasireotide s.c. tid","definition_or_measurement_approach":"Absolute and percent changes of insulin, glucagon, GLP-1 during MMTT at week 24."}
• {"endpoint_text":"- 10.\tChange from baseline in the frequency of use of rescue therapy and/or rescue carbohydrates at home to manage Level 2 or Level 3 hypoglycaemic events during treatment with pasireotide s.c. tid at weeks 16, 20, 24, 32, 40 and 48 of treatment","definition_or_measurement_approach":"Frequency of rescue therapy/carbohydrate use at home reported at specified weeks in extension."}
• {"endpoint_text":"- 11.\tProportion of participants with change in pulse rate <10 bpm during the MMTT at 24 weeks of treatment with pasireotide s.c. tid","definition_or_measurement_approach":"Proportion with <10 bpm change in pulse during MMTT at week 24."}
• {"endpoint_text":"- 12.\tProportion of participants with change in haematocrit <3% during the MMTT 24 weeks of treatment with pasireotide s.c. tid","definition_or_measurement_approach":"Proportion with <3% haematocrit change during MMTT at week 24."}

Methods

• Digital Advertising package (multiple languages) — digital adverts described in document titles (English/French/German/Dutch); targeted at potential participants (patient-facing).
• Website package (multiple languages) — materials for study website to inform participants; country/language-specific packages provided (English/French/Dutch/German).
• Pre-screener package (multiple languages) — materials to pre-screen potential participants prior to site contact.
• Participant Journey / Recruitment material (Participant Journey documents) — stepwise recruitment and participant information material (country-specific versions: Belgium, France, Italy, Spain).
• Patient Brochure Trifold (EN/FR/NL) — printed patient-facing brochure.
• Advocacy and social media kit (EN/FR/DE/NL) — materials for advocacy engagement and social media outreach.
• Dear Doctor Letter — clinician-targeted recruitment contact materials.
• K1 Recruitment arrangements documents per country (Belgium/France/Italy/Spain) describing local recruitment arrangements.

Belgium

Earliest CTIS Part Ii Submission Date

05-04-2024

Latest Decision Or Authorization Date

26-08-2025

Processing Time Days

508

Number Of Sites

1

Number Of Participants

4

France

Earliest CTIS Part Ii Submission Date

08-03-2024

Latest Decision Or Authorization Date

28-08-2025

Processing Time Days

539

Number Of Sites

3

Number Of Participants

8

Italy

Earliest CTIS Part Ii Submission Date

05-04-2024

Latest Decision Or Authorization Date

26-08-2025

Processing Time Days

508

Number Of Sites

4

Number Of Participants

8

Spain

Earliest CTIS Part Ii Submission Date

05-04-2024

Latest Decision Or Authorization Date

28-08-2025

Processing Time Days

510

Number Of Sites

7

Number Of Participants

10

Primary sponsor

Full Name

Recordati AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

Medpace Finland Oy

Responsibilities

Operational and study management roles (sponsorDuties codes: 1,10,12,2,4,5,6,7 as listed in source)

Name

Medpace Imaging Core Lab

Responsibilities

ECG Analysis/Review

Name

MEDPACE LABORATORIES

Responsibilities

Clinical hematology, chemistry, biomarker analyses

Name

Medpace Reference Laboratories LLC

Responsibilities

Biomarker analyses

Third parties

• {"country":"Germany","full_name":"Nuvisan GmbH","duties_or_roles":"PK and immunogenicity tests","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Precision Digital Health Inc.","duties_or_roles":"SUMMA Platform – SUMMA Mobile, SUMMA Site Portal, Site and Participant Materials, Training, Device coordination and procurement, Site Support for SUMMA Mobile and SUMMA Site Portal, Data Exports","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medpace Imaging Core Lab","duties_or_roles":"ECG Analysis/Review","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Belgium","full_name":"MEDPACE LABORATORIES","duties_or_roles":"Clinical hematology, chemistry, biomarker analyses","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Medpace Reference Laboratories LLC","duties_or_roles":"Biomarker analyses","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Finland","full_name":"Medpace Finland Oy","duties_or_roles":"Multiple sponsor responsibilities (codes provided in source: 1,10,12,2,4,5,6,7)","organisation_type":"Pharmaceutical company"}