Carcinoid Syndrome Efficacy Study Featuring an Oral Daily Paltusotine Regimen

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Crinetics Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

26 Sep 2025 → ongoing

Decision date (initial)

2025-11-14

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Therapy, Safety

To assess the efficacy of paltusotine vs placebo in reducing flushing episodes

Secondary objectives 1

1. Key Secondary: To assess the efficacy of paltusotine vs placebo in reducing BMs/day.

Conditions and MedDRA coding

Carcinoid syndrome

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 1. Willing and able to provide written informed consent prior to any study-related procedures.
2. 2. Willing and able to comply with the study procedures as specified in the protocol, including at least 70% compliance with the Carcinoid Syndrome Symptom Diary for the 2-week period prior to the S2 Visit and prior to the Day 1 Visit.
3. 3. Male or female ≥18 years of age, at the time of Screening.
4. 4. 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 SRLs, they must exhibit an average of >1 flushing episode/day over a period of 14 days and have a screening plasma 5-HIAA or serotonin result ≥2×ULN.  For participants who will wash out from SRL treatment, they must 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.
5. 5. Evaluable documentation of locally advanced or metastatic histopathologically confirmed well-differentiated NET(s). Tumors must be Grade 1 or Grade 2 (Ki-67 index ≤20%, or a mitotic count of ≤20 mitoses per 10 high-power fields if the Ki-67 index is not available) per the World Health Organization neuroendocrine neoplasm classification. Participants with Grade 3 tumors are not eligible.
6. 6. No significant disease progression as assessed by the Investigator within the last 6 months before randomization into the RCP. Note: A CT or MRI scan will be performed during the Screening Period and should be compared with previous pretrial imaging to assess disease stability for established participants on SRL maintenance therapy, while clinical symptoms and/or biomarker assessments should be used to assess disease stability for newly diagnosed participants naïve to SRLs.
7. 7. Historical documentation of positive somatostatin receptor tumor status by PET or somatostatin receptor scintigraphy. Note: If participant does not have historical documentation, this can be done during the Screening Period.
8. 8. Participants who are currently treated with octreotide/lanreotide and who agree to wash out of treatment must have historical instance of an elevated 5-HIAA or serotonin level, using either a urine or blood sample.
9. 9. Female participants who engage in heterosexual intercourse must:  Be of nonchildbearing potential, defined as either surgically sterile (ie, hysterectomy, bilateral salpingectomy, or bilateral oophorectomy), OR  Be postmenopausal with at least 1 year of amenorrhea. In participants with less than 1 year of amenorrhea, confirmation is required with 2 FSH measurements. A documented, historical test result measured prior to Screening may be used as 1 of the 2 measurements. The FSH value should be ≥30 IU/L to confirm menopausal status, OR  Agree to use a highly effective method of contraception from the beginning of the Screening Period until at least 2 weeks after the last dose of study drug. Contraceptive use by men and women also should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Periodic abstinence (ie, calendar, ovulation, symptothermal, and postovulation methods) and withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method (LAM) are not acceptable methods of contraception. Female condom and male condom should not be used together.
10. 10. Male participants must agree to use a condom when sexually active with a female partner of childbearing potential from Screening until at least 2 weeks after the last dose of study drug (or be surgically sterile [ie, vasectomy with a confirmed absence of sperm in ejaculate] or agree to remain abstinent on a long-term and persistent basis). Male participants should also agree to not donate sperm for the duration of the study and until at least 2 weeks after the last dose of study drug.

Exclusion criteria 14

1. 1. Diarrhea attributed to any condition(s) other than carcinoid syndrome.
2. 2. Uncontrolled/severe diarrhea associated with significant volume contraction, dehydration, or hypotension.
3. 3. Requires second line treatments (eg, telotristat) for control of carcinoid syndrome symptoms in the opinion of the Investigator.
4. 4. Treatment with specific NET therapy <4 weeks before Screening (such as everolimus or sunitinib) or hepatic embolization, radiotherapy, PRRT, and/or tumor debulking <12 weeks before Screening.
5. 5. Major surgery within 8 weeks before Screening.
6. 6. History of another primary malignancy <3 years prior to the date of randomization in the RCP unless at least 1 of the following criteria are met:  Adequately treated basal or squamous cell carcinoma of the skin.  Cancer of the breast or cervix in situ.  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.
7. 7. Diabetes mellitus treated with insulin for less than 6 weeks prior to the study entry.
8. 8. Poorly controlled diabetes mellitus defined as having a HbA1c ≥8.5% (ie, ≥69.5 mmol/mol) or estimated HbA1c based on fructosamine if HbA1c is not evaluable (eg, due to hemoglobinopathy).
9. 9. History of unstable angina or acute myocardial infarction within the 12 weeks preceding the Screening Period or other clinically significant cardiac disease (including clinically significant carcinoid heart disease) at the time of Screening as judged by the Investigator.
10. 10. Unable to administer SA octreotide (octreotide acetate injection), or prior nonresponse documented with somatostatin agonists.
11. 11. Known allergy or hypersensitivity to any of the test materials or related compounds.
12. 12. Any clinically significant and active infection such as those requiring systemic treatment within 14 days before randomization.
13. 13. 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 <30 mL/min/1.73 m2, cirrhosis, baseline AST and/or ALT >2×ULN, and/or TB >1.5×ULN. (Participants with previously diagnosed Gilbert’s syndrome not accompanied by other hepatobiliary disorders and associated with TB <3.5 mg/dL [<51.3 µmol/L] will be permitted.)
14. 14. Current alcohol or drug abuse, or within the last year, is not permitted.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Treatment group difference of change from baseline to Week 12 in flushing episodes/day averaged over the 14 days prior to Week 12.

Secondary endpoints 1

1. Key Secondary: Treatment group difference of change from baseline to Week 12 in BMs/day averaged over the 14 days.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Crinetics Pharmaceuticals Inc.

Sponsor organisation

Crinetics Pharmaceuticals Inc.

Address

6055 Lusk Boulevard

City

San Diego

Postcode

92121-2700

Country

United States

Scientific contact point

Organisation

Crinetics Pharmaceuticals Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Crinetics Pharmaceuticals Inc.

Contact name

Clinical Medical Lead

Locations

8 EU/EEA countries · 45 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 89 files

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

Application history

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