Carbetocin Nasal Spray for Prader-Willi Syndrome

Enrolling by invitation at 31 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: ACADIA Pharmaceuticals Inc.

Disqualifiers: Cerebrovascular disease, Epilepsy, Psychotic disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 36 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a nasal spray treatment called carbetocin for individuals with Prader-Willi Syndrome, a genetic condition affecting growth, metabolism, and development. The main goal is to determine the long-term safety and effectiveness of this treatment. Participants from a related study who might benefit from extended treatment are ideal candidates. To join, individuals must live with a caregiver who can support them and attend study visits. As a Phase 3 trial, this treatment is in the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking therapy.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the study team for guidance.

Is there any evidence suggesting that carbetocin nasal spray is likely to be safe for humans?

A previous study found that carbetocin nasal spray was well tolerated by participants. The 3.2 mg dose, administered three times a day, showed positive effects on reducing overeating and anxious behaviors in people with Prader-Willi syndrome (PWS). This suggests the treatment is generally safe for humans. No major adverse events were reported, indicating that serious side effects were uncommon. As this trial is in a later stage, earlier research has already provided some confidence in its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Prader-Willi Syndrome?

Carbetocin nasal spray is unique because it offers a new way to manage Prader-Willi Syndrome by using a nasal delivery method, which is different from the typical oral or injectable treatments. Researchers are excited about this treatment because carbetocin acts like oxytocin, a hormone that can help regulate appetite and social behaviors, addressing core symptoms of Prader-Willi Syndrome more directly. The nasal spray format could potentially make it easier for patients to use, improving adherence and overall effectiveness.

What evidence suggests that carbetocin nasal spray might be an effective treatment for Prader-Willi Syndrome?

Research shows that carbetocin nasal spray, which participants in this trial will receive, may help treat symptoms of Prader-Willi Syndrome (PWS). Studies have found that a 3.2 mg dose can significantly reduce excessive eating and lower anxiety and distress. Carbetocin is considered superior to oxytocin because it lasts longer in the body and more precisely targets the right areas. These findings suggest that carbetocin could be a helpful treatment for managing PWS symptoms. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with Prader-Willi Syndrome, particularly those who experience hyperphagia or binge eating. Specific eligibility criteria are not provided, but typically participants must meet certain health standards and may need to have a confirmed diagnosis of the condition.

Inclusion Criteria

Has completed the Week12/EOT visit of the antecedent, Study ACP-101-302

Met all entry criteria for the antecedent study

May benefit from long-term treatment with open-label carbetocin in the judgment of the Investigator

Exclusion Criteria

History of suicide attempt or inpatient psychiatric hospitalization

Has a clinically significant abnormality in vital signs at Baseline

Has an average QTcF interval of >450 ms on the Baseline ECG performed before the first dose of carbetocin is given in the present study (i.e., the ECG performed at the EOT visit of the antecedent study)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive carbetocin nasal spray 3.2 mg three times daily (TID) to evaluate long-term safety and tolerability

36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carbetocin

Trial Overview The study is testing the long-term safety and tolerability of a nasal spray containing carbetocin (3.2 mg taken three times daily) in subjects with Prader-Willi Syndrome to see if it can help manage their symptoms.

How Is the Trial Designed?

Group I: Drug: Carbetocin Experimental Treatment 1 Intervention

Carbetocin nasal spray 3.2 mg three times daily (TID)

Who Is Running the Clinical Trial?

ACADIA Pharmaceuticals Inc.

Lead Sponsor

Trials

49

Recruited

11,700+

Founded

1993

Headquarters

San Diego, USA

Known For

Neurological Disorders

Top Products

Nuplazid (pimavanserin), Daybue (trofinetide)

Published Research Related to This Trial

A case study of a 20-year-old female with Prader-Willi syndrome (PWS) showed that the SGLT2 inhibitor empagliflozin significantly improved her glycemic control and reduced body weight after previous treatment with the GLP-1 analog liraglutide.

The findings suggest that SGLT2 inhibitors could be a promising treatment option for managing diabetes in young PWS patients, particularly those with preserved pancreatic insulin secretion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of sodium-glucose cotransporter 2 inhibitor with glucagon-like peptide-1 receptor agonist for the glycemic control of a patient with Prader-Willi syndrome: a case report. Sano, H., Kudo, E., Yamazaki, T., et al.[2020]

In a phase 3 trial involving 130 participants with Prader-Willi syndrome, intranasal carbetocin was found to be well tolerated, with the 3.2 mg dose showing clinically meaningful improvements in hyperphagia and anxiousness compared to placebo.

Although the primary endpoints did not reach statistical significance, the 3.2 mg dose demonstrated nominally significant improvements in hyperphagia, anxiousness, and distress behaviors, with benefits sustained during long-term follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasal Carbetocin Reduces Hyperphagia, Anxiousness, and Distress in Prader-Willi Syndrome: CARE-PWS Phase 3 Trial. Roof, E., Deal, CL., McCandless, SE., et al.[2023]

A review of 14 studies and a case series of 10 adolescents with Prader-Willi syndrome (PWS) indicated that anti-obesity medications (AOMs) can help manage hyperphagia, with 60% of participants showing decreased or stable BMI z-scores after treatment.

No significant side effects were reported in the case series, suggesting that AOMs may be safe for use in youth with PWS, but further research is needed to establish comprehensive treatment guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-Obesity Medication Use in Children and Adolescents with Prader-Willi Syndrome: Case Review and Literature Search. Goldman, VE., Naguib, MN., Vidmar, AP.[2023]

Chronic administration of diazoxide in a mouse model of Prader-Willi syndrome (PWS) significantly reduced body weight and fat mass while improving metabolic parameters like blood glucose levels and endurance capacity.

These results suggest that diazoxide may be an effective treatment for obesity in children with PWS, indicating potential pharmacological targets for managing obesity-related disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic diazoxide treatment decreases fat mass and improves endurance capacity in an obese mouse model of Prader-Willi syndrome. Bischof, JM., Wevrick, R.[2019]

Exenatide, a GLP-1 agonist, was effectively used to manage diabetes in a 19-year-old female with Prader-Willi syndrome, highlighting its potential in this specific population.

The drug demonstrated beneficial effects in reducing weight and suppressing appetite, suggesting it could be a promising treatment strategy for obesity and diabetes associated with Prader-Willi syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating diabetes mellitus in Prader-Willi syndrome with Exenatide. Seetho, IW., Jones, G., Thomson, GA., et al.[2018]

Recombinant human growth hormone (rhGH) treatment in 20 children with Prader-Willi syndrome led to significant catch-up growth, with many reaching adult heights that were markedly taller than historical controls after 10 years.

While rhGH treatment correlated with a reduction in body fat percentage, patients remained severely obese, and their health-related quality of life was still significantly lower than that of the normal population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effects of growth hormone therapy on patients with Prader-Willi syndrome. Sipilä, I., Sintonen, H., Hietanen, H., et al.[2015]

In a randomized, double-blind trial involving 37 adolescents with Prader-Willi syndrome, intranasal carbetocin significantly reduced hyperphagia symptoms compared to placebo, indicating its potential efficacy in managing this condition.

Carbetocin was well tolerated, with a similar incidence of adverse events between the treatment and placebo groups, suggesting it is a safe option for improving behavioral symptoms associated with Prader-Willi syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasal carbetocin reduces hyperphagia in individuals with Prader-Willi syndrome. Dykens, EM., Miller, J., Angulo, M., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36633570/

Intranasal Carbetocin Reduces Hyperphagia, Anxiousness ... Carbetocin was well tolerated, and the 3.2-mg dose was associated with clinically meaningful improvements in hyperphagia and anxiousness and distress behaviors.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10271225/

CARE-PWS Phase 3 Trial Carbetocin was well tolerated, and the 3.2-mg dose was associated with clinically meaningful improvements in hyperphagia and anxiousness and distress behaviors ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06173531

NCT06173531 | Study of Carbetocin Nasal Spray for the ... 12-week, randomized, double-blind, placebo-controlled, parallel-group study of carbetocin nasal spray for the treatment of hyperphagia in Prader-Willi syndrome ...

4. acadia.com acadia.com/en-us/media/news-releases/acadia-pharmaceuticals-initiates-pivotal-phase-3-study

Acadia Pharmaceuticals Initiates Pivotal Phase 3 Study of ... Carbetocin has improved drug qualities relative to oxytocin, including an extended half-life and greater specificity for the oxytocin receptor ...

5. fpwr.org fpwr.org/blog/pws-clinical-trial-webinar-carbetocin

PWS Clinical Trial Webinar: Carbetocin A new study is now enrolling patients ages 7 to 18 years old to determine the safety and efficacy of Carbetocin for the treatment of symptoms related to PWS.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06420297

NCT06420297 | OLE Study of Carbetocin Nasal Spray for ... This is a long-term, OLE study to evaluate long-term safety and tolerability of carbetocin nasal spray (3.2 mg TID) in subjects with PWS.

7. academic.oup.com academic.oup.com/jcem/article/108/7/1696/6986298

Intranasal Carbetocin Reduces Hyperphagia, Anxiousness ... Carbetocin was well tolerated, and the 3.2-mg dose was associated with clinically meaningful improvements in hyperphagia and anxiousness and distress behaviors ...