Pasireotide s.c. in Patients With Post-Bariatric Hypoglycaemia
- Registration Number
- NCT05928390
- Lead Sponsor
- RECORDATI GROUP
- Brief Summary
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).
- Detailed Description
Subjects with post-bariatric hypoglycemia will be screened for participation in this trial. Eligible patients will complete the rest of the Core phase by entering a run-in period of 4 weeks without any treatment.
At the end of the run-in period, participants will be randomized to receive in a blinded manner either pasireotide 50 µg or pasireotide 100 µg or pasireotide 200 µg or Placebo subcutaneously three times a day (prior to each meal).
Participants will blindly self-administer their treatment for a total of 12 weeks when the primary endpoint will be assessed.
All participants completing the core phase will be offered to enter the extension phase. Participants will openly self-administer pasireotide 50 µg or pasireotide 100 µg or pasireotide 200 µg subcutaneously three times a day for a total of 36 weeks of treatment. There will be no more placebo during this extension phase of treatment.
Dose changes/adjustments will be possible only during the extension phase and the decision to change the dose of pasireotide will be left to the investigator's judgment.
All participants will come for a safety visit after discontinuation or completion of treatment.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 72
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Male or- non-pregnant female patients ≥ 18 years of age
-
Patients able to provide and have provided signed written informed consent prior to study participation.
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Patients capable of self-injecting subcutaneously. Specific training to self-inject the study drug will be provided.
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Post-bariatric surgery more than 6 months prior to screening
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Patient with a documented diagnosis of Post-Bariatric Hypoglycaemia (PBH) defined as having:
- postprandial neuroglycopenia occurring >1 hour after meals
- no hypoglycaemia in fasting conditions
- documented history of hypoglycaemia based on
- glucose value <50mg/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 (Oral Glucose Tolerance Test) - OR-
- glucose value <54 mg/dL at 60, 90, 120 or 180 min during a 3-hour MMTT (Mixed Meal Tolerance Test)
-
Patients must have at least one glucose level < 54 mg/dL at 30, 90, 120, 150 or 180 min during the 3-hour MMTT at screening
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Historical evidence of previous level 3 hypoglycaemia events at any time
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Patients who have failed diet recommended by the treating physician for the PBH
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Karnofsky Performance Status ≥ 60 (i.e., requires occasional assistance, but is able to care for most of their personal needs)
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Patients who received other therapies for PBH (such as acarbose, gama guar, pectin, diazoxide) must have stopped all treatments and allow a wash out period of at least 2 weeks prior to entering the run-in period.
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Patients who have been treated with Glucagon Like Peptide-1 (GLP-1) antagonists in the past must have a wash-out period of at least 4 weeks before the start of the run-in period
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Patients who have been treated with Sodium-Glucose Transport Protein 2 (SGLT2) inhibitors (glifozins) in the past must have a wash-out period of at least 4 weeks before the start of the run-in period
-
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)
Exclusion Criteria (main ones):
-
Bariatric patients who have lap band.
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Patients with a current diagnosis of uncontrolled Diabetes Mellitus. However, diabetic patients in remission, as defined below, are eligible:
- With an HbA1c at screening <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).
-
Patients previously treated with pasireotide at any time
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Patients who have a known hypersensitivity to somatostatin receptor analogues.
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Patients currently using medications that may interfere with glucose metabolism within 5 half-lives of drug.
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Patients with history of or current insulinoma
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Patients who have any severe and/or uncontrolled medical condition or other conditions that could affect their participation in the study (defined in the core text of the protocol)
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Patients with symptomatic cholelithiasis and/ or acute or chronic pancreatitis.
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Patients with abnormal coagulation (PT and PTT elevated by 30% above normal limits).
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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).
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Patients who are hypothyroid and not on adequate replacement therapy.
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Patients who have undergone major surgery/surgical therapy for any cause within 1 month. Patients should have recovered from the surgery and be in good clinical condition before entering the study.
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Bradycardia and QT-related exclusion criteria (in the core text of the protocol)
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Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulation. (Use of an investigational drug within 1 month prior to dosing).
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Significant acute illness within the two weeks prior to dosing/randomization.
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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.
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Women of childbearing potential (WOCBP) who are unwilling of using highly effective contraception methods (definition in core protocol)
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Potentially unreliable or vulnerable patients (e.g., person kept in detention) and those judged by the investigator to be unsuitable for the study.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pasireotide s.c. 50 mcg Pasireotide Diaspartate Pasireotide 50 mcg s.c. tid Pasireotide 100 mcg Pasireotide Diaspartate Pasireotide 100 mcg s.c. tid Pasireotide 200 mcg Pasireotide Diaspartate Pasireotide 200 mcg s.c. tid Placebo Pasireotide Diaspartate Placebo s.c. tid
- Primary Outcome Measures
Name Time Method Evaluation of the efficacy of pasireotide s.c. on blood glucose concentration during an MMTT in patients with PBH after 12 weeks of treatment. 12 weeks Change in the blood glucose levels is 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.
- Secondary Outcome Measures
Name Time Method Efficacy of pasireotide s.c. on the rate of level 2 hypoglycaemic event measured by SMBG 4, 8 and 12 weeks Change from baseline in the rate of level 2 hypoglycaemic events (glucose level \<54 mg/dL or 3.0 mmol/L)
Efficacy of pasireotide s.c. on level 2 hypoglycaemic events after MMTT 12 weeks The response rate defined as the proportion of patients with no level 2 hypoglycaemic events (glucose level \<54 mg/dL or 3.0 mmol/L) during a 3-hour MMTT
Efficacy of pasireotide s.c. on the rate of level 3 hypoglycaemic events 4, 8 and 12 weeks Change from baseline in the rate of Level 3 hypoglycaemic events (requiring external assistance)
Efficacy of pasireotide s.c. on the rate of level 2 hypoglycaemic events by CGM 4, 8 and 12 weeks Change 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)
Effect of pasireotide s.c. on the duration of level 2 hypoglycaemic events by CGM 16, 20, 24, 32, 40 and 48 weeks Change from baseline in duration of Level 2 hypoglycaemic events (plasma glucose \<54 mg/dL or 3.0 mmol/L for at least 15 minutes)
Effect of pasireotide s.c. on the percent time with Level 2 hypoglycaemia by CGM 4,8 and 12 weeks Change from baseline in percent time (total hours of CGM readings below 54 mg/dL divided by total CGM wear time) with Level 2 hypoglycaemic events (glucose level \<54 mg/dL or 3.0 mmol/L)
Use of rescue therapy and/or rescue carbohydrates required for the treatment of level 2 hypoglycaemic events 16, 20, 24, 32, 40 and 48 weeks Change from baseline in the frequency of use of rescue therapy and/or rescue carbohydrates at home (glucose level \<54 mg/dL or 3.0 mmol/L)
Use of rescue therapy and/or rescue carbohydrates required for the treatment of level 3 hypoglycaemic events 16, 20, 24, 32, 40 and 48 weeks Change from baseline in the frequency of use of rescue therapy and/or rescue carbohydrates at home to manage Level 3 hypoglycaemic events (requiring external assistance)
Efficacy of pasireotide s.c. on the pulse rate during the MMTT 24 weeks Proportion of participants with change in pulse rate \<10 bpm during the MMTT
Efficacy of pasireotide s.c. on haematocrit during the MMTT 24 weeks Proportion of participants with change in haematocrit \<3%
Effect of pasireotide s.c. on the changes of glucagon 24 weeks Change in glucagon from baseline during the MMTT
Effect of pasireotide s.c. on the changes of insulin 24 weeks Change in insulin from baseline during the MMTT
Effect of pasireotide s.c. on the changes of GLP-1 secretion 24 weeks Change in GLP-1 secretion from baseline during the MMTT
Safety profile of pasireotide 12 weeks Incidence of AEs, laboratory, and ECG findings
Efficacy of pasireotide s.c. on rate of level 2 hypoglycaemic events by CGM 16, 20, 24, 32, 40 and 48 weeks Change from baseline in the rate of level 2 hypoglycaemic events (plasma glucose \<54 mg/dL or 3.0 mmol/L for at least 15 minutes)
Efficacy of pasireotide s.c. on rate of level 2 hypoglycaemic events by SMBG 16,20,24,32,40 and 48 weeks Change from baseline in the rate of level 2 hypoglycaemia events (plasma glucose \<54 mg/dL or 3.0 mmol/L)
Efficacy of pasireotide s.c. on rate of level 3 hypoglycaemic events 16,20,24,32,40 and 48 weeks Change from baseline in the rate of level 3 hypoglycaemia events (requiring external assistance)
Effect of pasireotide s.c. on the percent time with Level 2 hypoglycaemic events by CGM 16, 20, 24, 32, 40 and 48 weeks Change from baseline in percent time (total hours of CGM readings below 54 mg/dL divided by total CGM wear time) with Level 2 hypoglycaemic events (glucose level \<54 mg/dL or 3.0 mmol/L)
Safety profile of pasireotide s.c. 48 weeks Incidence of AEs, laboratory, and ECG findings
Effect of pasireotide s.c. on HRQoL in SF-36 health survey 12, 24 and 48 weeks Changes in Health-Related Quality of Life (HRQoL) assessment from baseline. SF-36 survey assesses health-related limitations in eight dimensions: physical functioning (PF), role limitations due to physical functioning (RP), bodily pain (BP), general health perceptions (GH), vitality (VT), social functioning (SF), role limitations due to emotional problems (RE), and mental health (MH). Two summary scores, the Physical Component Summary (PCS) and the Mental Component Summary (MCS), can be calculated from the eight-dimension scores (scale scores). In the SF-36 health survey a higher score indicates a better state
Trial Locations
- Locations (31)
Stanford University School of Medicine, Endocrinology, 800 Welch Road,
🇺🇸Palo Alto, California, United States
Georgia Clinical Research, LLC, 2878 Five Forks Trickum SW, Suite 2A
🇺🇸Lawrenceville, Georgia, United States
Northwestern University - Feinberg School of Medicine - Ann & Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
NOLA Care
🇺🇸Metairie, Louisiana, United States
Velocity Clinical Research - Annapolis
🇺🇸Annapolis, Maryland, United States
Joslin Diabetes CenterJoslin Diabetes Center, One Joslin Place
🇺🇸Boston, Massachusetts, United States
University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr,
🇺🇸San Antonio, Texas, United States
IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant Orsola
🇮🇹Bologna, Italy
Azienda Ospedale - Università Padova, Clinica Medica 3, Via Giustiniani, 2,
🇮🇹Padova, Italy
Hospital Universitario Vall d'Hebron, Passeig Vall d´Hebron 119-129, Spain
🇪🇸Barcelona, Spain
Mayo Clinic - Rochester, 200 First Street, SW, 55905
🇺🇸Rochester, Minnesota, United States
Montefiore Medical Center, 111 E 210th Street,
🇺🇸Bronx, New York, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
HCL Centre Hospitalier Lyon Sud
🇫🇷Pierre-Benite Cedex, France
Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore, L.go Gemelli 8
🇮🇹Rome, Italy
Hospital Clinic Barcelona, Lipid Clinic End, Nutr. Service Hospital Clinic, C. Villarroel, 170,
🇪🇸Barcellona, Spain
Hospital Universitari de Girona Dr. Josep Trueta
🇪🇸Girona, Spain
King's College Hospital NHS Foundation Trust, Denmark Hill, SE5 9RS
🇬🇧London,, United Kingdom
Clinical Research Solution: Endocrine and Psychiatry Center, 9539 Huffmeister Rd,
🇺🇸Houston, Texas, United States
University of Wisconsin Health W. E. Clinic END, 451 Junction Rd,
🇺🇸Madison, Wisconsin, United States
Universitaire Ziekenhuizen Leuven, Department of Gastroenterology and Hepatology,Herestraat 49
🇧🇪Leuven,, Belgium
AP-HP Hopital Europeen Georges Pompidou, 20, rue Leblanc,
🇫🇷Paris, France
Hopital Rangueil, Attachée de Recherche Clinique, Centre Investigation Clinique, CHU, Cedex 9, France
🇫🇷Toulouse, France
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
🇮🇹Palermo, Italy
Hospital Germans Trias i Pujol
🇪🇸Barcelona, Spain
Hospital Universitario Reina Sofia
🇪🇸Córdoba, Spain
Hospital Clinico San Carlos, C/ Prof Martin Lagos s/n, Spain
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
North Bristol NHS Trust
🇬🇧Bristol, United Kingdom
Hammersmith Hospital
🇬🇧London, United Kingdom
Guy's Hospital
🇬🇧London, United Kingdom