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

Study Overview
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Brief Summary
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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.

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

Conditions
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Carcinoid Syndrome, Carcinoid, Carcinoid Tumor, Carcinoid Tumor of Ileum, Carcinoid Tumor of Cecum, Carcinoid Syndrome Diarrhea, Carcinoid Intestine Tumor, Carcinoid Tumor of Liver, Carcinoid Tumor of Pancreas

Intervention / Treatment
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* Drug: Randomized: 40 mg Paltusotine
* Drug: Randomized: 80 mg Paltusotine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects ≥18 years of age. Documented carcinoid syndrome requiring medical therapy. 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. Subjects currently treated with lanreotide, octreotide long acting release, or short acting octreotide (subcutaneous or oral) who are currently symptomatically controlled Evaluable documentation of locally advanced or metastatic histopathologically confirmed well-differentiated neuroendocrine tumor (NET). No significant disease progression as assessed by the Investigator within the last 6 months before initiation of study drug dosing. 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. 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. Any malignancy except for eligible NET, basal cell or squamous cell skin carcinoma considered clinically cured, or in situ cervical carcinoma. Diabetes mellitus treated with insulin for less than 6 weeks prior to the study entry

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 40 mg Paltusotine<br> | Drug: Randomized: 40 mg Paltusotine<br>* Two 20 mg tablets QD (Potential post-randomization dose escalation based on efficacy and acceptable tolerability: up to 80 mg)<br>|
| Experimental: 80 mg Paltusotine<br> | Drug: Randomized: 80 mg Paltusotine<br>* Four 20 mg tablets QD (Potential post-randomization dose escalation based on efficacy and acceptable tolerability: up to 120 mg)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events (TEAEs) |  | Baseline 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 at each dose at End of Randomized Treatment Phase (EOR) | Measured at Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CRN00808, Carcinoid syndrome, Neuroendocrine tumor, Paltusotine, Lanreotide, Octreotide, Somatostatin agonist