Pasireotide for Low Blood Sugar

(PASIPHY Trial)

Recruiting at 33 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

72 Participants Needed

Trial Summary

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.

How is the drug pasireotide unique for treating low blood sugar?

Pasireotide is unique because it is a multireceptor-targeted somatostatin analog that binds to multiple somatostatin receptor subtypes, which is broader than other similar drugs. This allows it to potentially offer symptom control in conditions where other treatments may not be effective. ^{1 2 3 4 5}

What is the purpose of this trial?

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).

Research Team

Arnd H MUELLER, MD

Principal Investigator

Recordati AG

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Assessment of the absorption, metabolism and excretion of [¹⁴C]pasireotide in healthy volunteers using accelerator mass spectrometry. [2014]

2. United States pubmed.ncbi.nlm.nih.gov

Hyperglycemia associated with pasireotide: results from a mechanistic study in healthy volunteers. [2022]

3. Germany 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. [2022]

4. England 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. [2014]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Pasireotide - Mechanism of Action and Clinical Applications. [2018]