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

Post-Bariatric Hypoglycemia Clinical Trial

— PASIPHY  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05928390
• Other study ID #: SOM230-RECAG-CL-0576
• Status: Recruiting
• Phase: Phase 2
• Start date: January 4, 2024
• Est. completion date: April 2026

Study information

• Verified date: April 2024
• Source: RECORDATI GROUP
• Contact: Arnd H MUELLER, MD
• Phone: +41 79 857 3664
• Email: mueller.ar[@]recordati.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Recruiting
• Enrollment: 72
• Est. completion date: April 2026
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion 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. 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)

6. 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

7. Historical evidence of previous level 3 hypoglycaemia events at any time

8. Patients who have failed diet recommended by the treating physician for the 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 allow a wash out period of at least 2 weeks prior to entering the run-in period.

11. 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

12. 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

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)

Exclusion Criteria (main ones):

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 <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 previously treated with pasireotide at any time

4. Patients who have a known hypersensitivity to somatostatin receptor analogues.

5. Patients currently using medications that may interfere with glucose metabolism within 5 half-lives of drug.

6. Patients with history of or current insulinoma

7. 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)

8. Patients with symptomatic cholelithiasis and/ or acute or chronic pancreatitis.

9. Patients with abnormal coagulation (PT and PTT elevated by 30% above normal limits).

10. 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).

11. Patients who are hypothyroid and not on adequate replacement therapy.

12. 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.

13. Bradycardia and QT-related exclusion criteria (in the core text of the protocol)

14. 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).

15. Significant acute illness within the two weeks prior to dosing/randomization.

16. 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.

17. Women of childbearing potential (WOCBP) who are unwilling of using highly effective contraception methods (definition in core protocol)

18. Potentially unreliable or vulnerable patients (e.g., person kept in detention) and those judged by the investigator to be unsuitable for the study.

Related Conditions & MeSH terms

• Hypoglycemia
• Post-Bariatric Hypoglycemia

Intervention

Drug:
• Pasireotide Diaspartate
Injectable ampoules

Locations

Country	Name	City	State
Belgium	Universitaire Ziekenhuizen Leuven, Department of Gastroenterology and Hepatology,Herestraat 49	Leuven,
France	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
Italy	Azienda Ospedale - Università Padova, Clinica Medica 3, Via Giustiniani, 2,	Padova
Italy	Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore, L.go Gemelli 8	Rome
Spain	Hospital Clinic Barcelona, Lipid Clinic End, Nutr. Service Hospital Clinic, C. Villarroel, 170,	Barcellona
Spain	Hospital Universitario Vall d'Hebron, Passeig Vall d´Hebron 119-129, Spain	Barcelona
Spain	Hospital Clinico San Carlos, C/ Prof Martin Lagos s/n, Spain	Madrid
United Kingdom	King's College Hospital NHS Foundation Trust, Denmark Hill, SE5 9RS	London,
United States	Joslin Diabetes CenterJoslin Diabetes Center, One Joslin Place	Boston	Massachusetts
United States	Montefiore Medical Center, 111 E 210th Street,	Bronx	New York
United States	Northwestern University - Feinberg School of Medicine - Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Clinical Research Solution: Endocrine and Psychiatry Center, 9539 Huffmeister Rd,	Houston	Texas
United States	Georgia Clinical Research, LLC, 2878 Five Forks Trickum SW, Suite 2A	Lawrenceville	Georgia
United States	University of Wisconsin Health W. E. Clinic END, 451 Junction Rd,	Madison	Wisconsin
United States	Stanford University School of Medicine, Endocrinology, 800 Welch Road,	Palo Alto	California
United States	Mayo Clinic - Rochester, 200 First Street, SW, 55905	Rochester	Minnesota
United States	University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr,	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
RECORDATI GROUP

Countries where clinical trial is conducted

United States,  Belgium,  France,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Level 2 hypoglycaemic events (plasma glucose <54 mg/dL) during a 3-hour MMTT (mixed meal tolerance test)	The response rate defined as the proportion of patients with no level 2 hypoglycaemic events (plasma glucose <54 mg/dL) at 90, 120, 150 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 vs placebo tid respectively	12 weeks