Pasireotide for Low Blood Sugar

(PASIPHY Trial)

Not currently recruiting at 39 trial locations

Overseen By Mario MALDONADO, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: RECORDATI GROUP

Must not be taking: Anticoagulants, QT-prolonging drugs

Disqualifiers: Uncontrolled diabetes, Hypocortisolism, Insulinoma, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if pasireotide can manage low blood sugar in individuals who have undergone weight-loss surgery and continue to experience frequent low blood sugar episodes after meals. Participants will receive varying doses of pasireotide or a placebo to evaluate its effectiveness in reducing symptoms. The trial seeks individuals who had bariatric surgery over six months ago, experience post-meal low blood sugar episodes not controlled by diet, and can self-inject medication. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications for post-bariatric hypoglycemia, such as acarbose, GLP-1 antagonists, and SGLT2 inhibitors, at least 2 to 4 weeks before the screening period. If you are on anticoagulation therapy, a washout period of at least 10 days is needed. Other medications that interfere with glucose metabolism must also be stopped within 5 half-lives of the drug.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that pasireotide has generally been well-tolerated in past studies. No serious side effects occurred at different doses, though some participants experienced temporary increases in blood sugar levels. This indicates that while pasireotide is safe for many, it might affect blood sugar, which is important to consider.

The FDA has already approved pasireotide for other uses, adding confidence in its safety. However, this study will provide more specific information about its safety for people with low blood sugar after weight-loss surgery. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for low blood sugar?

Researchers are excited about pasireotide for low blood sugar because it offers a novel approach compared to standard treatments like diazoxide or octreotide. Unlike these options, pasireotide works by targeting multiple somatostatin receptors, which may lead to more effective control of insulin secretion. Additionally, pasireotide is administered subcutaneously, potentially allowing for more consistent and controlled dosing. This unique combination of a new mechanism of action and delivery method makes pasireotide a promising candidate for managing low blood sugar.

What evidence suggests that Pasireotide might be an effective treatment for low blood sugar?

Research has shown that pasireotide can help manage low blood sugar. In studies, pasireotide prevented low blood sugar in various situations, including in people with insulinoma, a type of tumor that causes low blood sugar. Some individuals experienced quick and significant improvements in their blood sugar levels, with complete resolution of low blood sugar in some cases. Pasireotide has also proven effective and well-tolerated in patients with different conditions, suggesting it may help stabilize blood sugar levels. Overall, these findings suggest that pasireotide could potentially treat low blood sugar. Participants in this trial will receive different dosages of pasireotide or a placebo to further evaluate its effectiveness and safety. ^{6 7 8 9 10}

Who Is on the Research Team?

Arnd H MUELLER, MD

Principal Investigator

Recordati AG

Are You a Good Fit for This Trial?

This trial is for adults over 18 who've had bariatric surgery at least 6 months ago and suffer from low blood sugar after meals but not when fasting. They must be able to self-inject medication after training, have a history of specific symptoms related to low blood sugar, and provide written consent.

Inclusion Criteria

I stopped taking SGLT2 inhibitors at least 4 weeks ago.

I've waited the required time after my last somatostatin treatment to start a new trial.

Patients able to provide and have provided signed written informed consent prior to study participation

Exclusion Criteria

Patients who have a known hypersensitivity to somatostatin receptor analogues

I have been treated with pasireotide before.

Potentially unreliable or vulnerable patients as judged by the investigator

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

3 weeks

Run-in

Participants undergo a 4-week period without any treatment

4 weeks

Blinded Treatment

Participants receive either pasireotide or placebo subcutaneously three times a day for 12 weeks

12 weeks

Extension

Participants openly self-administer pasireotide for 36 weeks, with possible dose adjustments

36 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pasireotide

Trial Overview The study tests Pasireotide Diaspartate in patients with post-bariatric hypoglycemia over a maximum of 59 weeks. It includes a no-treatment run-in period, a blinded treatment phase for 12 weeks, followed by an open-label extension phase for 36 weeks, and ends with a safety follow-up without treatment.

How Is the Trial Designed?

Group I: Pasireotide s.c. 50 mcg Experimental Treatment 1 Intervention

Pasireotide 50 mcg s.c. tid

Group II: Pasireotide 200 mcg Experimental Treatment 1 Intervention

Pasireotide 200 mcg s.c. tid

Group III: Pasireotide 100 mcg Experimental Treatment 1 Intervention

Pasireotide 100 mcg s.c. tid

Group IV: Placebo Placebo Group 1 Intervention

Placebo s.c. tid

Pasireotide is already approved in United States, European Union for the following indications:

Approved in United States as Signifor for:

• Cushing's disease

Approved in European Union as Signifor for:

• Cushing's disease

Who Is Running the Clinical Trial?

RECORDATI GROUP

Lead Sponsor

Trials

13

Recruited

4,500+

Published Research Related to This Trial

Pasireotide is rapidly absorbed in the body, reaching peak plasma concentration within 0.5 hours after a single subcutaneous dose, indicating efficient absorption.

The drug is primarily excreted unchanged, with about 84% of the dose eliminated in its original form, mostly through feces, and no serious adverse events were reported, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of the absorption, metabolism and excretion of [¹⁴C]pasireotide in healthy volunteers using accelerator mass spectrometry. Lin, TH., Hu, K., Flarakos, J., et al.[2014]

In a study involving 45 healthy male volunteers, pasireotide treatment led to significant reductions in insulin secretion during glucose tolerance tests, indicating a mechanism for the hyperglycemia associated with this medication.

The hyperglycemia observed with pasireotide is linked to decreased responses of incretin hormones, rather than changes in insulin sensitivity, suggesting that the drug affects insulin production rather than how the body uses insulin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperglycemia associated with pasireotide: results from a mechanistic study in healthy volunteers. Henry, RR., Ciaraldi, TP., Armstrong, D., et al.[2022]

In a phase II study involving 44 patients with advanced neuroendocrine tumors (NETs), pasireotide effectively controlled symptoms of carcinoid syndrome (diarrhea and flushing) in 27% of patients who were not responding to octreotide LAR.

Pasireotide was generally well tolerated, with the most common side effects being mild to moderate nausea, abdominal pain, weight loss, and hyperglycemia, indicating a favorable safety profile for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pasireotide (SOM230) shows efficacy and tolerability in the treatment of patients with advanced neuroendocrine tumors refractory or resistant to octreotide LAR: results from a phase II study. Kvols, LK., Oberg, KE., O'Dorisio, TM., et al.[2014]

Pasireotide long-acting release (LAR) formulation was well tolerated in patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP NET), with 81% of participants reporting adverse events, primarily mild symptoms like diarrhea and fatigue.

The study achieved steady-state plasma levels of pasireotide after three monthly injections, indicating effective drug delivery and potential for sustained therapeutic effects in patients refractory to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability, pharmacokinetics, and pharmacodynamics of a long-acting release (LAR) formulation of pasireotide (SOM230) in patients with gastroenteropancreatic neuroendocrine tumors: results from a randomized, multicenter, open-label, phase I study. Wolin, EM., Hu, K., Hughes, G., et al.[2022]

Pasireotide is effective in treating Cushing's disease and acromegaly, providing biochemical control and tumor volume reduction, with a similar safety profile to first-generation somatostatin analogues, although it has a higher incidence of hyperglycemia.

This drug may also be beneficial as a second-line therapy for metastatic neuroendocrine tumors and in preventing postoperative complications after pancreatectomy, highlighting its potential versatility in treating various conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pasireotide - Mechanism of Action and Clinical Applications. Sawicka-Gutaj, N., Owecki, M., Ruchala, M.[2018]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25658662/

Pasireotide (SOM230) prevents sulfonylurea-induced ... Pasireotide (SOM230) prevents sulfonylurea-induced hypoglycemia in rats. Exp Clin Endocrinol Diabetes. 2015 Mar;123(3):193-7. doi: 10.1055/s-0034-1398552 ...

2. academic.oup.com academic.oup.com/jcem/article/110/7/e2109/8102131?rss=1

Efficacy and Safety of Pasireotide in Insulinoma-Associated ... Among them, 5 patients (29%) experienced hypoglycemia events years after being diagnosed with insulinoma, while the initial symptoms in the ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7692539/

Pasireotide: A Novel Treatment for Tumor-Induced ... ... pasireotide caused rapid, dramatic improvement in glucose levels (resolving the hypoglycemia completely in the first 2 cases). Two of our cases—pasireotide ...

4. erc.bioscientifica.com erc.bioscientifica.com/view/journals/erc/19/5/657.xml

Pasireotide (SOM230) shows efficacy and tolerability in the ... This paper presents results from a phase II, open-label, multicenter study designed to assess the efficacy and safety of pasireotide in patients with advanced ...

5. withpower.com withpower.com/trial/phase-2-hypoglycemia-9-2023-6e604

Pasireotide for Low Blood Sugar · Info for Participants The study achieved steady-state plasma levels of pasireotide after three monthly injections, indicating effective drug delivery and potential for sustained ...

6. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-effects-of-pasireotide-in-patients-with-low-blood-sugar-after-bariatric-surgery/

Study on the Effects of Pasireotide in Patients with Low ... The purpose of the study is to evaluate how effective and safe Pasireotide Diaspartate is in managing blood sugar levels in patients with PBH.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3346155/

A first-in-man study to evaluate the safety, tolerability, and ... Pasireotide was well tolerated with no serious adverse events observed at any dose. Transient elevations in blood glucose levels were observed 2 ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2012/200677Orig1s000ClinPharmR.pdf

200677Orig1s000 - accessdata.fda.gov Pasireotide effect on glucose is one of safety concerns and PD interaction was assessed in this study. After 7 days of treatment ...

9. mdpi.com mdpi.com/1424-8247/17/12/1631

Real-Life Data on the Safety of Pasireotide in Acromegaly The aim of this study is to evaluate the real-world evidence on adverse drug reactions (ADRs) reported for PAS in the EudraVigilance database.

10. academic.oup.com academic.oup.com/jcem/article/95/6/2781/2598468

Pasireotide (SOM230) Demonstrates Efficacy and Safety in ... Results from this phase II study demonstrate that pasireotide is a promising novel treatment for patients with acromegaly.