Clinical Trial 23626

• Overview

  Study Title:

  A Randomized, Parallel Group, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Paltusotine in Adults with Carcinoid Syndrome due to Well-Differentiated Neuroendocrine Tumors

  Summary:

  A Phase 3, randomized, double-blinded, placebo-controlled study to evaluate the efficacy and safety of paltusotine treatment vs placebo as well as the long-term safety of paltusotine in adults with carcinoid syndrome due to well-differentiated neuroendocrine tumors. The purpose of this study is to continue the evaluation of the safety, efficacy, and pharmacokinetics (PK) of paltusotine in participants with carcinoid syndrome.

  Objective:

  Primary To assess the efficacy of paltusotine vs placebo in reducing flushing episodes. Secondary To assess the efficacy of paltusotine vs placebo in reducing BMs/day in the mITT Set. To assess the efficacy of paltusotine vs placebo in reducing BMs/day in the subgroup of participants with an average of >3 BMs/day at baseline. To evaluate the effect of paltusotine vs placebo on daily flushing severity. To evaluate the effect of paltusotine vs placebo on BM urgency/day in the subgroup of participants with an average of >1 BM urgency/day at baseline. To evaluate the effect of paltusotine vs placebo on number of days of SA octreotide use. To assess the efficacy of paltusotine vs placebo on the total number of days participants have ≤3 BMs/day in the subgroup of participants who have an average of >3 BMs/day at baseline. To evaluate the effect of paltusotine vs placebo in the use of antidiarrheal medications during the RCP. To evaluate the effect of paltusotine vs placebo in reducing flushing episodes to zero. Exploratory To evaluate the effect of paltusotine vs placebo on the change in flushing responders. To evaluate the effect of paltusotine vs placebo on BM responders among participants with an average of >3 BMs/day at baseline. To evaluate the effect of paltusotine treatment on HRQoL. To evaluate participant-perceived carcinoid symptom severity and change. To evaluate treatment preference. To evaluate the effect of paltusotine treatment on abdominal pain severity. To evaluate the effect of paltusotine treatment on stool consistency. To evaluate the effect of paltusotine treatment on incontinence. To assess the antitumor effect of paltusotine. Safety To evaluate the safety and tolerability of paltusotine vs placebo.

• Treatments

  Therapies:

  SST2 agonist

  Medications:

  Paltusotine (); Paltusotine/Placebo ()

• Inclusion Criteria

  Key Inclusion Criteria:
  • Male or female ≥18 years of age, at the time of Screening.
  • Willing and able to comply with the study procedures as specified in the protocol, including at least 70% compliance with the study diary for the 2-week period.
  • Documented carcinoid syndrome requiring medical therapy. Participants must exhibit symptoms of flushing with or without frequent BMs as follows: 1) For participants who are naïve/not currently treated with somatostatin receptors ligands (SRL), they must exhibit an average of >1 flushing episode/day over a period of 14 days. 2) 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.
  • Evaluable documentation of locally advanced or metastatic histopathologically confirmed well-differentiated neuroendocrine tumor(s) [NETs].
  • No significant disease progression as assessed by the Investigator within the last 6 months before randomization.

• Exclusion Criteria

  Key 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 in the opinion of the Investigator.
  • Treatment with specific NET therapy > Major surgery within 8 weeks before Screening.
  • History of another primary malignancy > Diabetes mellitus treated with insulin for less than 6 weeks prior to the study entry.
  • Poorly controlled diabetes mellitus defined as having a hemoglobin A1c (HbA1c) ≥8.5%
  • Unable to administer short-acting (SA) octreotide (octreotide acetate injection), or prior nonresponse documented with somatostatin agonists.
  • 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 2×upper limit of normal [ULN], and/or total bilirubin (TB) >1.5×ULN. (Participants with previously diagnosed Gilbert's syndrome not accompanied by other hepatobiliary disorders and associated with TB

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