A long-term trial to learn about the safety of carbetocin as treatment for uncontrollable hunger in people with Prader-Willi Syndrome

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Acadia Pharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

28 Apr 2025 → 19 Dec 2025

Decision date (initial)

2025-03-05

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Acadia Pharmaceuticals Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

To investigate the safety and tolerability of long-term treatment with carbetocin nasal spray for the treatment of hyperphagia in PWS

Secondary objectives 6

1. To investigate the benefit of long-term treatment with carbetocin on hyperphagia in PWS
2. To investigate the benefit of long-term treatment with carbetocin on PWS
3. To investigate the benefit of long-term treatment with carbetocin on anxiousness in PWS
4. To investigate the benefit of long-term treatment with carbetocin on environmental controls
5. To investigate the benefit of long-term treatment with carbetocin on caregiver burden
6. To investigate the benefit of long-term treatment with carbetocin on healthcare utilization

Conditions and MedDRA coding

Hyperphagia related behaviour associated with Prader-Willi Syndrome (PWS)

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Informed consent prior to the conduct of any study procedures is required as follows: a) For subjects who are minors: written informed consent will be obtained from the LAR (or LARs where local regulations require) or from the minor him/herself if deemed able by the Investigator per local regulations. When consent is obtained from the LAR, the subject should provide written or oral assent if deemed able by the Investigator, and according to local regulations. b) For subjects who are of legal age of consent: written informed consent will be obtained from the subject if the subject is not under guardianship and is deemed able by the Investigator. If the subject is under guardianship or deemed not able to provide consent, the subject should provide written or verbal assent if deemed able by the Investigator, and a written informed consent will be obtained from the subject’s LAR(s) according to local regulations. c) The subject’s caregiver provides written consent to participate as an informant in study assessments. The caregiver may or may not be an LAR.
2. Has completed the Week 12/EOT visit of the antecedent study.
3. Met all entry criteria for the antecedent study.
4. May benefit from long-term treatment with open-label carbetocin in the judgment of the Investigator.
5. Lives with a caregiver who understands and is willing and able to adhere to study-related procedures and is willing to participate in all study visits. a) The subject must be under the caregiver’s consistent care and observation during the study when not attending school or day programs. b) The caregiver should be a family member of the subject or someone whose association with the subject is the equivalent of a family relation OR The caregiver is not a family member but has cared for the subject for at least 6 months and plans to continue to care for the subject during this study and spends time with the subject at least 5 days per week. c) The caregiver must have sufficient language skills to complete the assessments in the language of the assessments and be able to utilize electronic media for study visits and questionnaires. Caregivers will be trained to use the electronic media by which assessments are completed and respond in the local language.
6. Caregiver is able to receive study drug shipments, where permitted, and store study drug per instructions during the study.
7. Caregiver is able to snap the intranasal pump device onto the study drug vial.
8. This criterion for female subjects varies depending on the location of the subject’s clinical site due to local regulatory requirements (or requests). a) In the EU: If female, must not be pregnant or breastfeeding. Subjects of childbearing potential should abstain from sexual activity for the duration of the study and for at least 30 days thereafter. If a subject is sexually active or becomes sexually active during the study, she must use a highly effective contraceptive method per Clinical Trials Facilitation and Coordination Group (CTFG) recommendations (Appendix B). The contraceptive method should be used for at least 1 month prior to Baseline, throughout the study, and for at least 30 days thereafter. b) In the UK: If the subject is female, she must not be pregnant or breastfeeding. Subjects of childbearing potential (including subjects who reach menarche during the study) should abstain from sexual activity for the duration of the study and for at least 30 days thereafter. If a subject is sexually active or becomes sexually active during the study, she must use an intrauterine device (IUD) plus barrier method (diaphragm, cap, or sponge with spermicide), OR she must use one of these acceptable methods of contraception and her partner must use a condom for at least 1 month prior to Baseline, throughout the study, and for at least 30 days thereafter. A female is considered of childbearing potential following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. c. In North America: If the subject is female, she must not be pregnant or breastfeeding. Subjects of childbearing potential should abstain from sexual activity for the duration of the study and for at least 30 days thereafter. If a subject is sexually active or becomes sexually active during the study, she must use a non-user-dependent method of contraception (e.g., IUD or implant) or a user-dependent hormonal method of contraception (e.g., injection, oral, transdermal, or intravaginal). The contraceptive method should be used for at least 1 month prior to Baseline, throughout the study, and for at least 30 days thereafter.
9. This criterion for male subjects varies depending on the location of the subject’s clinical site due to local regulatory requirements (or requests). a) In the EU: If male and sexually active, must use a condom (even if vasectomized) from the time of Baseline until 90 days after the last dose of study drug. The male subject’s female partner must use a highly effective contraceptive method per CTFG recommendations (Appendix B). The female partner’s contraceptive method should be used for at least 1 month prior to Baseline, throughout the study, and for at least 30 days thereafter; OR the male subject must not have a female partner of childbearing potential. Male subjects must also agree to not donate sperm from the time of Baseline until 90 days after the last dose of study drug. b. In the UK: If the subject is male and sexually active, he must use a condom (even if vasectomized) from the time of Baseline until 90 days after the last dose of study drug. The male subject’s female partner must use either an IUD or a barrier method (e.g., diaphragm, cap, or sponge with spermicide; a female condom in combination with a male condom is not acceptable); OR the male subject must not have a female partner of childbearing potential. Subjects must also agree not to donate sperm from the time of Baseline until 90 days after the last dose of study drug. c. In North America: If the subject is male and sexually active, he must use a condom (even if vasectomized) from the time of Baseline until 90 days after the last dose of study drug. The male subject’s female partner must use either a non-user dependent method of contraception (e.g., IUD or implant) or a user dependent hormonal method of contraception (e.g., injection, oral, transdermal, or intravaginal). The female partner’s contraceptive method should be used for at least 1 month prior to Baseline, throughout the study, and for at least 30 days thereafter; OR the male subject must not have a female partner of childbearing potential. Subject must also agree not to donate sperm from the time of Baseline until 90 days after the last dose of study drug. b. In the UK: If the subject is male and sexually active, he must use a condom (even if vasectomized) from the time of Baseline until 90 days after the last dose of study drug. The male subject’s female partner must use either an IUD or a barrier method (e.g., diaphragm, cap, or sponge with spermicide; a female condom in combination with a male condom is not acceptable); OR the male subject must not have a female partner of childbearing potential. Subjects must also agree not to donate sperm from the time of Baseline until 90 days after the last dose of study drug. c) In North America: If the subject is male and sexually active, he must use a condom (even if vasectomized) from the time of Baseline until 90 days after the last dose of study drug. The male subject’s female partner must use either a non-user dependent method of contraception (e.g., IUD or implant) or a user dependent hormonal method of contraception (e.g., injection, oral, transdermal, or intravaginal). The female partner’s contraceptive method should be used for at least 1 month prior to Baseline, throughout the study, and for at least 30 days thereafter; OR the male subject must not have a female partner of childbearing potential. Subject must also agree not to donate sperm from the time of Baseline until 90 days after the last dose of study drug.

Exclusion criteria 6

1. Has a history of, or current, cerebrovascular disease, brain trauma, epilepsy, or frequent migraines. A history of febrile seizures is not exclusionary.
2. Has active psychotic symptoms, a history of psychotic symptoms, or a psychotic disorder.
3. Has a history of suicide attempt or inpatient psychiatric hospitalization.
4. Has any of the following: a) QTcF interval of >450 ms at Baseline (before dosing); b) History of a risk factor for torsades de pointes (e.g., heart failure or family history of long QT syndrome); c) History of clinically significant QT prolongation that is deemed to put the subject at increased risk of clinically significant QT prolongation; d) Has any other clinically significant finding on ECG at Baseline (before dosing).
5. Is judged by the Investigator or the Medical Monitor to be inappropriate for the study for any reason.
6. In France only: Is under court protection, not affiliated to a social security system, or a protected adult under French law (Art. L. 1121-6, Art. L. 1121-8, Art. L. 1121-8-1).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Treatment-emergent adverse events (TEAEs)
2. Serious adverse events (SAEs)
3. Withdrawals due to adverse events (AEs)
4. Potentially clinically important changes in other safety assessments
5. Device incidents, or device malfunctions

Secondary endpoints 9

1. Hyperphagia Questionnaire for Clinical Trials (HQ-CT) score – change from Baseline at each visit
2. Clinical Global Impression–Severity (CGI-S) for PWS score – change from Baseline at each visit
3. Percentage of subjects with treatment response based on the HQ-CT (defined as improvement from Baseline ≥8 points) at each visit
4. PWS Anxiousness and Distress Behaviors Questionnaire (PADQ) score – change from Baseline at each visit
5. Clinical Global Impression – Change (CGI-C) for PWS score at each visit
6. CGI-S for hyperphagia in PWS score – change from Baseline at each visit
7. Food Safe Zone score – change from Baseline at each visit
8. Zarit Burden Interview (ZBI) score – change from Baseline at each visit
9. PWS-specific Healthcare Resource Use and Caregiver Burden Questionnaire (PWS-HRUQ) – change from Baseline at each visit

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Acadia Pharmaceuticals Inc.

Sponsor organisation

Acadia Pharmaceuticals Inc.

Address

12830 El Camino Real Suite 400

City

San Diego

Postcode

92130-2976

Country

United States

Scientific contact point

Organisation

Acadia Pharmaceuticals Inc.

Contact name

Alana Salvucci

Public contact point

Organisation

Acadia Pharmaceuticals Inc.

Contact name

Andrew McGinn

Third parties 9

Locations

3 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 60 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications