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NCT07087054PHASE3Recruiting

Carcinoid Syndrome Efficacy Study Featuring an Oral Daily Paltusotine Regimen

Crinetics Pharmaceuticals Inc.

Start Date

11/19/2025

Completion Date

1/1/2030

Summary

A Phase 3, randomized, double-blinded, placebo-controlled study to evaluate the efficacy and safety of paltusotine treatment vs placebo as well as the long-term safety of paltusotine in adults with carcinoid syndrome due to well-differentiated neuroendocrine tumors. The purpose of this study is to continue the evaluation of the safety, efficacy, and pharmacokinetics (PK) of paltusotine in participants with carcinoid syndrome.

Detailed Description

This is a global, randomized, parallel-group, placebo-controlled study to evaluate the efficacy and safety of paltusotine in adults with carcinoid syndrome. The study includes a screening period of up to 11 weeks, a double-blinded randomized control period of 16 weeks, an open label extension period of 104 weeks, and a follow-up period of 4 weeks.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: * Male or female ≥18 years of age, at the time of Screening. * Willing and able to comply with the study procedures as specified in the protocol, including at least 70% compliance with the study diary for the 2-week period. * Documented carcinoid syndrome requiring medical therapy. Participants must exhibit symptoms of flushing with or without frequent BMs as follows: * For participants who are naïve/not currently treated with somatostatin receptors ligands (SRL), they must exhibit an average of \>1 flushing episode/day over a period of 14 days * For participants who will wash out from SRL treatment, they must be symptomatically controlled and exhibit an increase in daily average flushing episodes and an average of \>1 flushing episode/day over a period of 14 days during the Washout Period. * Evaluable documentation of locally advanced or metastatic histopathologically confirmed well-differentiated neuroendocrine tumor(s) \[NETs\]. * No significant disease progression as assessed by the Investigator within the last 6 months before randomization. Exclusion Criteria: * Diarrhea attributed to any condition(s) other than carcinoid syndrome. * Uncontrolled/severe diarrhea associated with significant volume contraction, dehydration, or hypotension. * Requires second line treatments (eg, telotristat) for control of carcinoid syndrome symptoms in the opinion of the Investigator. * Treatment with specific NET therapy \<4 weeks before Screening (such as everolimus or sunitinib) or hepatic embolization, radiotherapy, peptide receptor radionuclide therapy (PRRT), and/or tumor debulking \<12 weeks before Screening. * Major surgery within 8 weeks before Screening. * History of another primary malignancy \<3 years prior to the date of randomization, except for adequately treated basal or squamous cell carcinoma of the skin, cancer of the breast has been completely locally excised and carcinoma in situ of the cervix has also been resected, previously treated malignancy, if all treatment for that malignancy was completed at least 3 years prior to first dose of study treatment, and no current evidence of disease, concurrent malignancy determined to be clinically stable and not requiring treatment. * Diabetes mellitus treated with insulin for less than 6 weeks prior to the study entry. * Poorly controlled diabetes mellitus defined as having a hemoglobin A1c (HbA1c) ≥8.5% * Unable to administer short-acting (SA) octreotide (octreotide acetate injection), or prior nonresponse documented with somatostatin agonists. * Clinically significant concomitant disease or indicator of disease that is not a result of the primary disease under study, including but not limited to cardiovascular disease, estimated glomerular filtration rate 2×upper limit of normal \[ULN\], and/or total bilirubin (TB) \>1.5×ULN. (Participants with previously diagnosed Gilbert's syndrome not accompanied by other hepatobiliary disorders and associated with TB * Alcohol or drug abuse is not permitted at any time during the study * Diagnosed with symptomatic cholelithiasis

Interventions

DRUG

Paltusotine

DRUG

Placebo

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Conditions

Carcinoid SyndromeCarcinoidCarcinoid TumorCarcinoid Tumor of IleumCarcinoid Tumor of CecumCarcinoid Tumor of LiverCarcinoid Tumor of PancreasCarcinoid Syndrome DiarrheaCarcinoid Intestine Tumor

Locations

Banner MD Anderson Cancer Center

Gilbert, Arizona 85234

United States

Hoag Memorial Hospital Presbyterian

Newport Beach, California 92663

United States

Yale University - New Haven Hospital - Yale Cancer Center

New Haven, Connecticut 06510

United States

University of Miami

Miami, Florida 33136

United States

Moffitt Cancer Center

Tampa, Florida 33612

United States

Winshop Cancer Institute - Emory University

Atlanta, Georgia 30322

United States

University of Iowa Health Care

Iowa City, Iowa 52242

United States

University of Kentucky Medical Center

Lexington, Kentucky 40536

United States

Louisiana State University Health Sciences

Metairie, Louisiana 70006

United States

Henry Ford Cancer - Detroit

Detroit, Michigan 48202

United States

Mayo Clinic

Rochester, Minnesota 55905

United States

Icahn School of Medicine at Mount Sinai

New York, New York 10029

United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio 44106

United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania 19104

United States

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah 84112

United States

University of Virginia Comprehensive Cancer Center

Charlottesville, Virginia 22903

United States

Medical College of Wisconcin

Milwaukee, Wisconsin 53222

United States

Hospital de Gastroenterologia Dr. Carlos Bonorino Udaondo

Buenos Aires, 1264

Argentina

Sanatorio Guemes

Buenos Aires, C1180AAX

Argentina

Centro de Endocrinologia y Diabetes Dr. A. Gutman ICM - Investigaciones

Buenos Aires, C1425BGH

Argentina

Instituto Médico Especializado Alexander Fleming

Buenos Aires, C1426ANZ

Argentina

Instituto Médico de la Fundación Estudios Clínicos

Santa Fe, 2000

Argentina

AC Camargo Cancer Center

São Paulo, Brazil 01509-010

Brazil

Fundacao PIO XII - Hospital de Amor Barretos

Barretos, 14784-400

Brazil

Sociedade Literaria e Caritativa Santos Agostinho - Hospital Sao José

Criciúma, 88811-000

Brazil

Nucleo de Pesquisa e Desenvolvimento de Medicamentos (MPDM)

Fortaleza, 60430-275

Brazil

Associacao Hospitalar Moinhos de Vento

Porto Alegre, 90560-032

Brazil

Instituto Nacional de Cancer (INCA)

Rio de Janeiro, 20230-130

Brazil

Clinical Universidad Catolica del Maule, Ltda

Maule, Chile 3460000

Chile

Centro de Oncologia de Precision

Santiago, Chile 7560908

Chile

CECIM-Centro de Estudios Cliicos e Investigaciones Medicas

Santiago, 8320000

Chile

Hospital Universitario San Ignacio

Bogotá, DC 110231

Colombia

Instituto Nacional de Cancerologia

Bogotá, DC 110411

Colombia

CHRU Tours - Hopital Trousseau

Chambray-lès-Tours, 37170

France

Hopital Beaujun - APHP

Clichy, 92110

France

APHM- Hopital de la Timone

Marseille, 13005

France

Centre Hospitalier Universitaire Nantes

Nantes, 44093

France

Centre Antoine Lacassagne

Nice, 06100

France

CHU Bordeaux - Hopital Haut-Leveque

Pessac, 33600

France

Centro de Oncolégica VIVA

Mexico City, 06760

Mexico

Hospital Universitari Vall d'Hebron

Barcelona, 08035

Spain

Hospital Universitario Ramon y Cajal

Madrid, 28034

Spain

Hospital Universitario 12 de Octubre

Madrid, 28041

Spain

King's College Hospital

London, UK SE59RS

United Kingdom

Oxford University Hospitals NHS Foundation Trust

Oxford, UK OX37LE

United Kingdom

Queen Elizabeth Hospital Brimingham

Birmingham, B15 2TH

United Kingdom

University Hospital of Wales

Cardiff, CF144XW

United Kingdom

The Beatson WOS Cancer Centre

Glasgow, G120YN

United Kingdom

Royal Free Hospital

London, NW3 2QG

United Kingdom

NIHR Clinical Research Facility, Royal Hallamshire Hospital

Sheffield, S102JF

United Kingdom

University Hospital Southampton NHS Foundation Trust

Southampton, SO166YD

United Kingdom