Study to Evaluate the Safety, PK, and Dose Response of Paltusotine in Subjects With Carcinoid Syndrome

A Randomized, Parallel Group Study to Evaluate the Safety, Pharmacokinetics, and Dose Response of Paltusotine Treatment in Subjects With Carcinoid Syndrome

The purpose of this study is to evaluate the safety, pharmacokinetics (PK), and exploratory dose response of paltusotine treatment in subjects with carcinoid syndrome. This study consists of a Randomized Treatment Phase followed by an Open-Label Extension (OLE) Phase.

Study Overview

• Status: Completed
• Conditions: Carcinoid Tumor; Carcinoid Syndrome; Carcinoid; Carcinoid Tumor of Ileum; Carcinoid Tumor of Cecum; Carcinoid Syndrome Diarrhea; Carcinoid Intestine Tumor; Carcinoid Tumor of Liver; Carcinoid Tumor of Pancreas
• Intervention / Treatment: Drug: Randomized: 40 mg Paltusotine; Drug: Randomized: 80 mg Paltusotine

Detailed Description

This is a Phase 2, randomized, open-label, parallel-group, multicenter study designed to evaluate the safety, pharmacokinetics, and efficacy of paltusotine treatment in subjects with carcinoid syndrome. The study was conducted in 2 parts: a Randomized Treatment Phase (RTP) which is completed, and an Open-label Extension (OLE) Phase which is still ongoing. The RTP consisted of paltusotine treatment for 8 weeks. Subjects who completed the RTP were eligible to enter the OLE Phase at the recommendation of the Investigator. In the ongoing OLE Phase, paltusotine is being administered for a further 102 weeks. The total duration of paltusotine treatment for the combined RTP and OLE Phase is up to 110 weeks (28 months).

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • CABA, Argentina, C1017AAS
    • Crinetics Study Site
  • CABA, Argentina, C1425BGH
    • Crinetics Study Site
  • Buenos Aires
    • CABA, Buenos Aires, Argentina, C1180 AAX
      • Crinetics Study Site
    • CABA, Buenos Aires, Argentina, C1264AAA
      • Crinetics Study Site
    • CABA, Buenos Aires, Argentina, C1426ANZ
      • Crinetics Study Site
• Brazil
  • Rio de Janeiro, Brazil, 22061-080
    • Crinetics Study Site
  • Ceará
    • Fortaleza, Ceará, Brazil, 60430-275
      • Crinetics Study Site
  • Rio de Janeiro
    • Rio de Janeiro, Rio de Janeiro, Brazil, 20231-092
      • Crinetics Study Site
    • Rio de Janeiro, Rio de Janeiro, Brazil, 22281-100
      • Crinetics Study Site
  • Santa Catarina
    • Criciúma, Santa Catarina, Brazil, 88811508
      • Crinetics Study Site
  • São Paulo
    • São Paulo, São Paulo, Brazil, 01509-010
      • Crinetics Study Site
• Canada
  • Toronto, Canada, M4N 3M5
    • Crinetics Study Site
• Mexico
  • Cuauhtemoc
    • Mexico City, Cuauhtemoc, Mexico, 06100
      • Crinetics Study Site
  • Querétaro
    • Querétaro City, Querétaro, Mexico, 76000
      • Crinetics Study Site
    • Querétaro City, Querétaro, Mexico, 76070
      • Crinetics Study Site
• Peru
  • Lima, Peru, 15036
    • Crinetics Study Site Peru #1
  • Lima, Peru, 15036
    • Crinetics Study Site Peru #2
• Poland
  • Katowice, Poland, 40-514
    • Crinetics Study Site
  • Warsaw, Poland, 02-351
    • Crinetics Study Site
  • Wroclaw, Poland, 53-413
    • Crinetics Study Site
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Crinetics Study Site
    • Los Angeles, California, United States, 90095
      • Crinetics Study Site
    • Newport Beach, California, United States, 92663
      • Crinetics Study Site
    • Stanford, California, United States, 94305
      • Crinetics Study Site
  • Florida
    • Miami, Florida, United States, 33136
      • Crinetics Study Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Crinetics Study Site
  • Kentucky
    • Lexington, Kentucky, United States, 40506
      • Crinetics Study Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Crinetics Study Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Crinetics Study Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Crinetics Study Site
  • New York
    • New York, New York, United States, 10029
      • Crinetics Study Site
    • Stony Brook, New York, United States, 11794
      • Crinetics Study Site
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Crinetics Study Site
    • Columbus, Ohio, United States, 43210
      • Crinetics Study Site
  • Texas
    • Houston, Texas, United States, 77030
      • Crinetics Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female subjects ≥18 years of age. 2. Documented carcinoid syndrome requiring medical therapy.

1. Not currently treated with somatostatin receptor ligands agonists for at least 12 weeks prior to screening and actively symptomatic. This can include treatment-naïve subjects.
2. Subjects currently treated with lanreotide, octreotide long acting release, or short acting octreotide (subcutaneous or oral) who are currently symptomatically controlled
3. Evaluable documentation of locally advanced or metastatic histopathologically confirmed well-differentiated neuroendocrine tumor (NET). Tumors must be Grade 1 (Ki-67 index < 3%, or a mitotic count of < 2 mitoses per 10 high-power fields, if the Ki-67 index is not available) or Grade 2 (Ki-67 index 3-20%, or a mitotic count of 2-20 mitoses per 10 high-power fields, if the Ki-67 index is not available) per the World Health Organization neuroendocrine neoplasm classification (Rindi and Inzani, 2020). Grade 3 tumors are not eligible.
4. No significant disease progression as assessed by the Investigator within the last 6 months before initiation of study drug dosing.

Exclusion Criteria:

1. Diarrhea attributed to any condition(s) other than carcinoid syndrome.
2. Uncontrolled/severe diarrhea associated with significant volume contraction, dehydration, or hypotension.
3. Requires second line treatments (eg, telotristat) for control of carcinoid syndrome symptoms.
4. Treatment with specific NET tumor 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.
5. History of another primary malignancy <3 years prior to the date of first dose, except for adequately treated basal or squamous cell carcinoma of the skin, cancer of the breast or cervix in situ, previously treated or concurrent malignancy determined to be clinically stable and not requiring treatment.
6. Diabetes mellitus treated with insulin for less than 6 weeks prior to the study entry.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 40 mg Paltusotine; Participants received paltusotine 40mg, in tablet form, orally, daily, for 8 weeks.	Drug: Randomized: 40 mg Paltusotine; Two 20 mg tablets QD (Potential post-randomization dose escalation based on efficacy and acceptable tolerability: up to 80 mg)
Experimental: 80 mg Paltusotine; Participants received paltusotine 80mg, in tablet form, orally, daily for 8 weeks.	Drug: Randomized: 80 mg Paltusotine; Four 20 mg tablets QD (Potential post-randomization dose escalation based on efficacy and acceptable tolerability: up to 120 mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety - Incidence of Treatment-emergent Adverse Events (TEAEs)	Incidence of TEAEs, including serious TEAEs and TEAEs leading to discontinuation; change from baseline to the EOR in safety parameters: clinical laboratory tests, physical exam findings, vital signs, 12-lead ECG, and 24-hour continuous cardiac monitoring (only for subjects on 120 mg dose). In addition to all-cause mortality, deaths were categorized by primary cause (e.g., cardiovascular) based on medical adjudication. Events were coded using MedDRA and summarized by treatment group, system organ class, and preferred term. TEAEs were reported per randomized arm. There were 2 randomized arms (40 mg and 80 mg paltusotine, with up-or down-dose titration permitted for symptom control). Results are analyzed based on the initially assigned randomization arm, regardless of the actual dose received.	First dose of investigational medicine to End of Randomized Treatment Phase (8 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK) of Paltusotine	Steady state trough levels by dose and visit for Randomized Treatment Phase (RTP). The "Overall Number of Participants Analyzed" displayed at the top of the PK summary table represents the total number of participants who received each dose at any point during the trial, factoring in dose titrations. PK results are summarized by actual dose taken right before the time of sample collection, rather than by randomized dose. Participants may be included in different dose groups for different visits due to dose titration.	Measured at each visit (pre and post dose) up to Week 8 (i.e., End of Randomized Treatment Phase [EOR])

Collaborators and Investigators

• Sponsor: Crinetics Pharmaceuticals Inc.

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2022
• Primary Completion (Actual): March 7, 2024
• Study Completion (Actual): February 24, 2026

Study Registration Dates

• First Submitted: April 27, 2022
• First Submitted That Met QC Criteria: May 2, 2022
• First Posted (Actual): May 5, 2022

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Octreotide; Lanreotide; Neuroendocrine tumor; Carcinoid syndrome; Paltusotine; CRN00808; Somatostatin agonist
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Chemically-Induced Disorders; Carcinoma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Drug-Related Side Effects and Adverse Reactions; Neuroendocrine Tumors; Carcinoid Tumor; Serotonin Syndrome; Carcinoid Tumors, Intestinal; Health Care Quality, Access, and Evaluation; Investigative Techniques; Epidemiologic Research Design; Epidemiologic Methods; Research Design; Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Public Health; Environment and Public Health; Random Allocation
• Other Study ID Numbers: CRN00808-11

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No