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

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).

Inclusion criteria

• Male or female subjects ≥18 years of age. 2. 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). 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.
• 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.
• 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.
• Diabetes mellitus treated with insulin for less than 6 weeks prior to the study entry.