E340 Carcinoid syndrome Carcinoid syndrome
Conditions
Interventions
1- Drug: Randomized: 40 mg Paltusotine
Two 20 mg tablets QD (Potential post-randomization dose escalation based on efficacy and acceptable tolerability: up to 80 mg) -
2- Drug:
Sponsors
Crinetics Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Willing and able to comply with the study procedures as specified in the protocol, including at least 70% compliance with electronic symptom diary for the 2-week period prior to the S2 visit and prior to the Day 1 visit. Male or female subjects =18 years of age, at the time of Screening. Willing and able to provide written informed consent prior to any study-related procedures. Documented carcinoid syndrome requiring medical therapy including at least one historical instance of an elevated 5-HIAA level. Eligible subjects fall into one of the following categories: ? Naïve to SRLs and actively symptomatic (average of =4 BM/day or >2 flushing episodes per day in at least 2 days over a period of 2 weeks) ? Subjects currently treated with lanreotide, octreotide LAR, or short-acting octreotide (subcutaneous or oral) who are currently symptomatically controlled (average <4 BM/day with =5 BMs on any single day and average =2 flushing episodes/day over a 2-week period) and willing to wash out of their medication. The subject must demonstrate symptomatic worsening after washout. Evaluable documentation of locally advanced or metastatic histopathologically confirmed well-differentiated NET. 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 (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. Historical documentation of positive SSTR tumor status by PET or somatostatin receptor scintigraphy.* Plasma 5-HIAA =2× ULN during Screening for naïve subjects not washing out of SRLs. Females 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, OR must agree to use a highly effective method of contraception from the beginning of Screening to the last study visit. If the subject is male, the subject should agree to use a condom when sexually active with a female partner of childbearing potential from Screening until at least 30 days after the last dose of study drug or be surgically sterile [ie, vasectomy with documentation]; or remain abstinent [when this i
Exclusion criteria
Exclusion criteria: Any malignancy except for eligible NET, basal cell or squamous cell skin carcinoma considered clinically cured, or in situ cervical carcinoma. Life expectancy 15% within 6 weeks prior to Screening. Diarrhea attributed to any condition(s) other than carcinoid syndrome (including but not limited to fat malabsorption, bile acid malabsorption, short bowel syndrome, pancreatic exocrine insufficiency, infections, VIPoma, Zollinger-Ellison syndrome). Exception to this are subjects with prior cholecystectomy or small bowel resections, provided diarrhea is controlled prior to washout or if naïve to SRLs. 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 tumor-directed therapy <4 weeks before Screening or hepatic embolization, radiotherapy, peptide receptor radionuclide therapy (PRRT), and/or tumor debulking <12 weeks before Screening. Karnofsky performance status <60%. History of unstable angina or acute myocardial infarction within the 12 weeks preceding the Screening Visit or other clinically significant cardiac disease (including clinically significant carcinoid heart disease) at the time of Screening as judged by the Investigator. Known history of, or current alcohol or drug abuse, within the last year. Concomitant mental condition rendering him/her unable to understand the nature, scope, and possible consequences of the study, and/or evidence of poor Compliance with medical instructions. Current use of medications that are strong inducers of cytochrome P450 3A4 (CYP3A4) (including but not limited to carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John’s wort) within 2 weeks prior to Screening because they may reduce sy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of TEAEs NAME OF THE RESULT: 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) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: 12 weeks ;Steady state NAME OF THE RESULT: Steady state through levels at each dose at EOR PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: 12 weeks ;Incidence of TEAEs NAME OF THE RESULT: Open-label extension (OLE) phase Incidence of TEAEs, including serious TEAEs and TEAEs leading to discontinuation; change from EOR to EOT in safety parameters: clinical laboratory tests, physical exam findings, vital signs, and 12-lead ECG PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: 50 weeks ;Steady state NAME OF THE RESULT: Open-label extension (OLE) phase Steady state trough levels at each dose at EOT PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: 50 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of TEAEs NAME OF THE RESULT: 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) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: 12 weeks ;Steady state NAME OF THE RESULT: Steady state through levels at each dose at EOR PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: 12 weeks ;Change in mean daily BM episodes NAME OF THE RESULT: Change in mean daily urgency episodes (defined as BMs that make subjects rush to the bathroom): From the Baseline Period of Screening to the last week of the Randomized Treatment Phase PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: 12 weeks ;Incidence of TEAEs NAME OF THE RESULT: Open-label extension (OLE) phase Incidence of TEAEs, including serious TEAEs and TEAEs leading to discontinuation; change from EOR to EOT in safety parameters: clinical laboratory tests, physical exam findings, vital signs, and 12-lead ECG PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: 50 weeks ;Steady state NAME OF THE RESULT: Open-label extension (OLE) phase Steady state trough levels at each dose at EOT PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE | — |
Countries
Argentina, Austria, Belgium, Brazil, Bulgaria, France, Germany, Hungary, Israel, Italy, Peru, Poland, Russian Federation, Serbia, Spain, United Kindgdom, United States
Contacts
Public ContactALFREDO LIZARDO SAN MARTIN
RESOLUTION LATIN AMERICA PERU SOCIEDAD ANONIMA - RESOLUTION LATIN AMERICA PERU S.A.
Outcome results
None listed