Carcinoid Syndrome MedDRA version: 20.0 Level: PT Classification code 10007270 Term: Carcinoid syndrome System Organ Class: 10014698 - Endocrine disorders
Conditions
Interventions
Product Name: Paltusotine
Pharmaceutical Form: Tablet
INN or Proposed INN: Paltusotine
Current Sponsor code: CRN00808
Other descriptive name: Paltusotine
Concentration unit: mg milligram(s)
Concentrat
Sponsors
Crinetics Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Willing and able to provide written informed consent prior to any study related procedures. 2. 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. 3.Male or female subjects =18 years of age, at the time of Screening. 4.Documented carcinoid syndrome requiring medical therapy. Eligible subjects fall into one of the following categories: •Not currently treated with SRL agonists for at least 12 weeks prior to screening, 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). This can include treatment-naïve subjects. •Subjects currently treated with lanreotide, octreotide LAR, or short acting octreotide (subcutaneous or oral) who are currently symptomatically controlled (average <4 BM/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. These subjects must have at least one historical instance of an elevated 5-HIAA or serotonin level. 5. 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. Grade 3 tumors are not eligible. 6. No significant disease progression as assessed by the Investigator within the last 6 months before initiation of study drug dosing. 7. Historical documentation of positive SSTR tumor status by PET or somatostatin receptor scintigraphy 8. Plasma 5-HIAA =2× ULN during Screening for subjects not currently treated with any SRL therapy who are not washing out of SRLs. 9.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. •Acceptable highly effective methods of contraception include: - Combined estrogen-progestin oral hormonal contraception associated with consistent inhibition of ovulation - Desogestrel-based progestin only contraception associated with consistent inhibition of ovulation; this includes oral, injectable, and implantable methods - Intravaginal and transdermal hormone delivery methods - Intrauterine device (with or without hormone elution) - Bilateral tubal occlusion or ligation (must be documented) - Vasectomized partner (must be documented) or - Sexual abstinence (only when it is the usual and preferred lifestyle of the subject) In addition to these methods of contraception, the male partner should use a condom from the beginning of Screening to the last study visit. 10. 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 is in line with the preferred and usual lifestyle]. Male subjects should also agree to not donate s
Exclusion criteria
Exclusion criteria: 1.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 not currently treated with any SRL therapy. 2.Uncontrolled/severe diarrhea associated with significant volume contraction, dehydration, or hypotension. 3.Requires second line treatments (eg, telotristat) for control of carcinoid syndrome symptoms in the opinion of the Investigator. 4.Treatment with specific NET tumor therapy 480 msec (or QTcF >500 msec in the presence of complete bundle branch block) or PR interval >240 msec during Screening based on a central reading of an ave
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Safety: To evaluate the safety and tolerability of paltusotine at 40, 80, and 120 mg QD doses Pharmacokinetics: To assess the PK of 40, 80, and 120 mg paltusotine ;Secondary Objective: Not Applicable - please refer to Protocol for list of Exploratory Efficacy objectives;Primary end point(s): Safety: 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) Pharmacokinetics: Steady state trough levels at each dose at EOR ;Timepoint(s) of evaluation of this end point: Safety: from Baseline to the EOR Pharmacokinetics: EOR | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Not Applicable - please refer to Protocol for timepoints for evaluation of Exploratory Efficacy endpoints;Secondary end point(s): Not Applicable - please refer to Protocol for list of Exploratory Efficacy endpoints | — |
Countries
Argentina, Brazil, Canada, Mexico, Peru, Poland, United States
Contacts
Public ContactCrinetics Clinical Trials
Crinetics Pharmaceuticals, Inc.
Outcome results
None listed