Trial Outcomes & Findings for Study to Evaluate the Safety, PK, and Dose Response of Paltusotine in Subjects With Carcinoid Syndrome (NCT NCT05361668)

Last Updated: 2025-10-31

Results Overview

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.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

36 participants

Primary outcome timeframe

First dose of investigational medicine to End of Randomized Treatment Phase (8 weeks)

Results posted on

2025-10-31

Participant Flow

In general, results are reported based on the dose assigned at randomization, regardless of the actual dose received.

Participant milestones

Participant milestones
Measure	40 mg Paltusotine Randomized: 40 mg paltusotine: Two 20 mg tablets QD (Potential post-randomization dose escalation based on efficacy and acceptable tolerability: up to 80 mg)	80 mg Paltusotine Randomized: 80 mg paltusotine: Four 20 mg tablets QD (Potential post-randomization dose escalation based on efficacy and acceptable tolerability: up to 120 mg)
Overall Study STARTED	18	18
Overall Study Adverse Event	1	1
Overall Study Physician Decision	0	3
Overall Study Withdrawal by Subject	0	1
Overall Study COMPLETED	17	13
Overall Study NOT COMPLETED	1	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	40 mg Paltusotine n=18 Participants Randomized: 40 mg paltusotine: Two 20 mg tablets QD (Potential post-randomization dose escalation based on efficacy and acceptable tolerability: up to 80 mg)	80 mg Paltusotine n=18 Participants Randomized: 80 mg paltusotine: Four 20 mg tablets QD (Potential post-randomization dose escalation based on efficacy and acceptable tolerability: up to 120 mg)	Total n=36 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=5 Participants	9 Participants n=7 Participants	20 Participants n=5 Participants
Age, Categorical >=65 years	7 Participants n=5 Participants	9 Participants n=7 Participants	16 Participants n=5 Participants
Age, Continuous	58.6 years n=5 Participants	62.9 years n=7 Participants	60.8 years n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	11 Participants n=7 Participants	19 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	7 Participants n=7 Participants	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants	9 Participants n=7 Participants	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment Europe	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment United States	9 participants n=5 Participants	10 participants n=7 Participants	19 participants n=5 Participants
Region of Enrollment South America	8 participants n=5 Participants	7 participants n=7 Participants	15 participants n=5 Participants
Body Mass Index (BMI)	29.057 kg/m^2 STANDARD_DEVIATION 4.3181 • n=5 Participants	28.609 kg/m^2 STANDARD_DEVIATION 10.8261 • n=7 Participants	28.833 kg/m^2 STANDARD_DEVIATION 17.58 • n=5 Participants
Symptomatic Entry Criteria Met - n (%) Bowel Movement Criteria Only	6 Participants n=5 Participants	8 Participants n=7 Participants	14 Participants n=5 Participants
Symptomatic Entry Criteria Met - n (%) Flushing Criteria Only	4 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants
Symptomatic Entry Criteria Met - n (%) Bowel Movement and Flushing Criteria	8 Participants n=5 Participants	3 Participants n=7 Participants	11 Participants n=5 Participants
Baseline Mean Daily Bowel Movements (/day)	3.881 BMs per day STANDARD_DEVIATION 2.0398 • n=5 Participants	3.343 BMs per day STANDARD_DEVIATION 1.3705 • n=7 Participants	3.612 BMs per day STANDARD_DEVIATION 1.7343 • n=5 Participants
Baseline Mean Daily Flushing Criteria Episode (/day)	2.325 FE per day STANDARD_DEVIATION 1.3219 • n=5 Participants	2.413 FE per day STANDARD_DEVIATION 2.3313 • n=7 Participants	2.369 FE per day STANDARD_DEVIATION 1.8683 • n=5 Participants
Duration Since Carcinoid Syndrome Diagnosis (Months)	102.566 months STANDARD_DEVIATION 82.0788 • n=5 Participants	54.459 months STANDARD_DEVIATION 37.1727 • n=7 Participants	78.513 months STANDARD_DEVIATION 67.3684 • n=5 Participants
Screening Group, n (%) Not Currently on SRLs or Naïve to SRLs	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Screening Group, n (%) Currently Treated with Lanreotide, Octreotide LAR, or Short-acting Octreotide	13 Participants n=5 Participants	14 Participants n=7 Participants	27 Participants n=5 Participants
Tumor Confirmation Method, n (%) MRI	9 Participants n=5 Participants	5 Participants n=7 Participants	14 Participants n=5 Participants
Tumor Confirmation Method, n (%) CT Scan	9 Participants n=5 Participants	13 Participants n=7 Participants	22 Participants n=5 Participants

PRIMARY outcome

Timeframe: First dose of investigational medicine to End of Randomized Treatment Phase (8 weeks)

Population: Safety Analysis Set included all randomized participants receiving ≥1 dose. TEAEs (reported per randomized arm) are defined as AEs from first to last dose date (end of RTP, or early term), plus 28 days (Safety follow up). Dose changes at Weeks 2 or 4 were allowed for symptom control (increase) or poor tolerability (decrease). Results are provided by randomized arms (40 mg and 80 mg paltusotine).

Outcome measures

Outcome measures
Measure	40 mg Paltusotine n=18 Participants Randomized: 40 mg paltusotine: Two 20 mg tablets QD (Potential post-randomization dose escalation based on efficacy and acceptable tolerability: up to 80 mg)	80 mg Paltusotine n=18 Participants Randomized: 80 mg paltusotine: Four 20 mg tablets QD (Potential post-randomization dose escalation based on efficacy and acceptable tolerability: up to 120 mg)	120 mg Paltusotine 120 mg paltusotine: Six 20 mg tablets QD
Safety - Incidence of Treatment-emergent Adverse Events (TEAEs) Treatment-Emergent Adverse Events (TEAE)	16 participants	15 participants	—
Safety - Incidence of Treatment-emergent Adverse Events (TEAEs) TEAE Related to CS Symptoms	10 participants	9 participants	—
Safety - Incidence of Treatment-emergent Adverse Events (TEAEs) Highest Severity of TEAE: Severe TEAE	3 participants	1 participants	—
Safety - Incidence of Treatment-emergent Adverse Events (TEAEs) Highest Severity of TEAE: Mild TEAE	7 participants	7 participants	—
Safety - Incidence of Treatment-emergent Adverse Events (TEAEs) Serious TEAE	2 participants	2 participants	—
Safety - Incidence of Treatment-emergent Adverse Events (TEAEs) Treatment Related TEAE	10 participants	13 participants	—
Safety - Incidence of Treatment-emergent Adverse Events (TEAEs) Treatment Related Serious TEAE	0 participants	0 participants	—
Safety - Incidence of Treatment-emergent Adverse Events (TEAEs) TEAE Leading to Study Discontinuation	1 participants	1 participants	—
Safety - Incidence of Treatment-emergent Adverse Events (TEAEs) TEAE Leading to Actions Taken with Study Treatment: Dose Increased	3 participants	1 participants	—
Safety - Incidence of Treatment-emergent Adverse Events (TEAEs) TEAE Leading to Actions Taken with Study Treatment: Dose Decreased	0 participants	2 participants	—
Safety - Incidence of Treatment-emergent Adverse Events (TEAEs) Actions Taken with Study Treatment: Drug Withdrawn	0 participants	1 participants	—
Safety - Incidence of Treatment-emergent Adverse Events (TEAEs) Actions Taken with Study Treatment: Drug Interrupted	3 participants	2 participants	—
Safety - Incidence of Treatment-emergent Adverse Events (TEAEs) Actions Taken with Study Treatment: Dose Not Changed	16 participants	15 participants	—
Safety - Incidence of Treatment-emergent Adverse Events (TEAEs) Actions Taken with Study Treatment: Not Applicable	2 participants	4 participants	—
Safety - Incidence of Treatment-emergent Adverse Events (TEAEs) Highest Severity of TEAE: Moderate TEAE	6 participants	7 participants	—

SECONDARY outcome

Timeframe: Measured at each visit (pre and post dose) up to Week 8 (i.e., End of Randomized Treatment Phase [EOR])

Population: The PK Analysis Set included all randomized participants with ≥1 paltusotine dose and ≥1 plasma measurement. Post-dose samples were taken 1-3 hrs after dosing, and steady-state troughs were assessed pre and post dose, through Week 8. Primary PK summaries were based on the RTP. Dose adjustments at Weeks 2 or 4 were allowed for symptom control (dose increase) or tolerability (dose decrease).

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.

Outcome measures

Outcome measures
Measure	40 mg Paltusotine n=20 Participants Randomized: 40 mg paltusotine: Two 20 mg tablets QD (Potential post-randomization dose escalation based on efficacy and acceptable tolerability: up to 80 mg)	80 mg Paltusotine n=24 Participants Randomized: 80 mg paltusotine: Four 20 mg tablets QD (Potential post-randomization dose escalation based on efficacy and acceptable tolerability: up to 120 mg)	120 mg Paltusotine n=3 Participants 120 mg paltusotine: Six 20 mg tablets QD
Pharmacokinetics (PK) of Paltusotine WEEK 1 (POST-DOSE)	188 ng/mL Geometric Coefficient of Variation 80.8	360 ng/mL Geometric Coefficient of Variation 103.3	—
Pharmacokinetics (PK) of Paltusotine WEEK 2 (PRE-DOSE)	61.4 ng/mL Geometric Coefficient of Variation 153.5	193 ng/mL Geometric Coefficient of Variation 83.5	—
Pharmacokinetics (PK) of Paltusotine WEEK 2 (POST-DOSE)	217 ng/mL Geometric Coefficient of Variation 90.5	473 ng/mL Geometric Coefficient of Variation 78.7	1240 ng/mL Geometric Coefficient of Variation 0.0
Pharmacokinetics (PK) of Paltusotine WEEK 4 (PRE-DOSE)	68.2 ng/mL Geometric Coefficient of Variation 179.1	158 ng/mL Geometric Coefficient of Variation 74.7	218 ng/mL Geometric Coefficient of Variation 0.0
Pharmacokinetics (PK) of Paltusotine WEEK 4 (POST-DOSE)	209 ng/mL Geometric Coefficient of Variation 202.1	462 ng/mL Geometric Coefficient of Variation 82.7	545 ng/mL Geometric Coefficient of Variation 184.5
Pharmacokinetics (PK) of Paltusotine WEEK 6 (PRE-DOSE)	57.8 ng/mL Geometric Coefficient of Variation 188.8	155 ng/mL Geometric Coefficient of Variation 63.1	146 ng/mL Geometric Coefficient of Variation 58.4
Pharmacokinetics (PK) of Paltusotine WEEK 6 (POST-DOSE)	261 ng/mL Geometric Coefficient of Variation 108.6	532 ng/mL Geometric Coefficient of Variation 89.4	474 ng/mL Geometric Coefficient of Variation 79.0
Pharmacokinetics (PK) of Paltusotine WEEK 8 - EOR (PRE-DOSE)	63.3 ng/mL Geometric Coefficient of Variation 122.1	165 ng/mL Geometric Coefficient of Variation 44.5	201 ng/mL Geometric Coefficient of Variation 69.1

Adverse Events

40 mg Paltusotine

Serious events: 2 serious events

Other events: 16 other events

Deaths: 0 deaths

80 mg Paltusotine

Serious events: 2 serious events

Other events: 15 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	40 mg Paltusotine n=18 participants at risk Randomized: 40 mg paltusotine: Two 20 mg tablets QD (Potential post-randomization dose escalation based on efficacy and acceptable tolerability: up to 80 mg)	80 mg Paltusotine n=18 participants at risk Randomized: 80 mg paltusotine: Four 20 mg tablets QD (Potential post-randomization dose escalation based on efficacy and acceptable tolerability: up to 120 mg)
Cardiac disorders Cardiac failure	0.00% 0/18 • Adverse event data were collected over the 8 weeks of the RTP phase, and an EOS Visit was to occur to collect the safety data and other assessments, 28 days after last dose of study drug and was required for subjects who completed the study or early terminated. TEAE data were summarized from first dose date until last dose date (end of RTP or early term) plus 28 days (Safety follow up). AE results were reported based on the dose assigned at randomization (40 mg and 80 mg paltusotine), regardless of the actual dose received at the time of AE reporting. Dose changes at Weeks 2 or 4 were allowed for symptom control (increase) or poor tolerability (decrease).	5.6% 1/18 • Adverse event data were collected over the 8 weeks of the RTP phase, and an EOS Visit was to occur to collect the safety data and other assessments, 28 days after last dose of study drug and was required for subjects who completed the study or early terminated. TEAE data were summarized from first dose date until last dose date (end of RTP or early term) plus 28 days (Safety follow up). AE results were reported based on the dose assigned at randomization (40 mg and 80 mg paltusotine), regardless of the actual dose received at the time of AE reporting. Dose changes at Weeks 2 or 4 were allowed for symptom control (increase) or poor tolerability (decrease).
Metabolism and nutrition disorders Dehydration	0.00% 0/18 • Adverse event data were collected over the 8 weeks of the RTP phase, and an EOS Visit was to occur to collect the safety data and other assessments, 28 days after last dose of study drug and was required for subjects who completed the study or early terminated. TEAE data were summarized from first dose date until last dose date (end of RTP or early term) plus 28 days (Safety follow up). AE results were reported based on the dose assigned at randomization (40 mg and 80 mg paltusotine), regardless of the actual dose received at the time of AE reporting. Dose changes at Weeks 2 or 4 were allowed for symptom control (increase) or poor tolerability (decrease).	5.6% 1/18 • Adverse event data were collected over the 8 weeks of the RTP phase, and an EOS Visit was to occur to collect the safety data and other assessments, 28 days after last dose of study drug and was required for subjects who completed the study or early terminated. TEAE data were summarized from first dose date until last dose date (end of RTP or early term) plus 28 days (Safety follow up). AE results were reported based on the dose assigned at randomization (40 mg and 80 mg paltusotine), regardless of the actual dose received at the time of AE reporting. Dose changes at Weeks 2 or 4 were allowed for symptom control (increase) or poor tolerability (decrease).
Gastrointestinal disorders Large intestinal obstruction	0.00% 0/18 • Adverse event data were collected over the 8 weeks of the RTP phase, and an EOS Visit was to occur to collect the safety data and other assessments, 28 days after last dose of study drug and was required for subjects who completed the study or early terminated. TEAE data were summarized from first dose date until last dose date (end of RTP or early term) plus 28 days (Safety follow up). AE results were reported based on the dose assigned at randomization (40 mg and 80 mg paltusotine), regardless of the actual dose received at the time of AE reporting. Dose changes at Weeks 2 or 4 were allowed for symptom control (increase) or poor tolerability (decrease).	5.6% 1/18 • Adverse event data were collected over the 8 weeks of the RTP phase, and an EOS Visit was to occur to collect the safety data and other assessments, 28 days after last dose of study drug and was required for subjects who completed the study or early terminated. TEAE data were summarized from first dose date until last dose date (end of RTP or early term) plus 28 days (Safety follow up). AE results were reported based on the dose assigned at randomization (40 mg and 80 mg paltusotine), regardless of the actual dose received at the time of AE reporting. Dose changes at Weeks 2 or 4 were allowed for symptom control (increase) or poor tolerability (decrease).
Nervous system disorders Encephalopathy	5.6% 1/18 • Adverse event data were collected over the 8 weeks of the RTP phase, and an EOS Visit was to occur to collect the safety data and other assessments, 28 days after last dose of study drug and was required for subjects who completed the study or early terminated. TEAE data were summarized from first dose date until last dose date (end of RTP or early term) plus 28 days (Safety follow up). AE results were reported based on the dose assigned at randomization (40 mg and 80 mg paltusotine), regardless of the actual dose received at the time of AE reporting. Dose changes at Weeks 2 or 4 were allowed for symptom control (increase) or poor tolerability (decrease).	0.00% 0/18 • Adverse event data were collected over the 8 weeks of the RTP phase, and an EOS Visit was to occur to collect the safety data and other assessments, 28 days after last dose of study drug and was required for subjects who completed the study or early terminated. TEAE data were summarized from first dose date until last dose date (end of RTP or early term) plus 28 days (Safety follow up). AE results were reported based on the dose assigned at randomization (40 mg and 80 mg paltusotine), regardless of the actual dose received at the time of AE reporting. Dose changes at Weeks 2 or 4 were allowed for symptom control (increase) or poor tolerability (decrease).
Renal and urinary disorders Infections and infestations	5.6% 1/18 • Adverse event data were collected over the 8 weeks of the RTP phase, and an EOS Visit was to occur to collect the safety data and other assessments, 28 days after last dose of study drug and was required for subjects who completed the study or early terminated. TEAE data were summarized from first dose date until last dose date (end of RTP or early term) plus 28 days (Safety follow up). AE results were reported based on the dose assigned at randomization (40 mg and 80 mg paltusotine), regardless of the actual dose received at the time of AE reporting. Dose changes at Weeks 2 or 4 were allowed for symptom control (increase) or poor tolerability (decrease).	0.00% 0/18 • Adverse event data were collected over the 8 weeks of the RTP phase, and an EOS Visit was to occur to collect the safety data and other assessments, 28 days after last dose of study drug and was required for subjects who completed the study or early terminated. TEAE data were summarized from first dose date until last dose date (end of RTP or early term) plus 28 days (Safety follow up). AE results were reported based on the dose assigned at randomization (40 mg and 80 mg paltusotine), regardless of the actual dose received at the time of AE reporting. Dose changes at Weeks 2 or 4 were allowed for symptom control (increase) or poor tolerability (decrease).

Other adverse events

Additional Information

Study Director

Crinetics Pharmaceuticals, Inc.

Phone: (858) 450-6464

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place