A Randomized, Parallel Group Study to Evaluate the Safety, Pharmacokinetics, and Dose Response of Paltusotine Treatment in Subjects with Carcinoid Syndrome.
- Conditions
- E340 Carcinoid syndromeCarcinoid syndromeE340
- Registration Number
- PER-049-22
- Lead Sponsor
- Crinetics Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Without startig enrollment
- Sex
- All
- Target Recruitment
- 0
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 is in line with the preferr
Any malignancy except for eligible NET, basal cell or squamous cell skin carcinoma considered clinically cured, or in situ cervical carcinoma.
Life expectancy <12 months from Screening.
Major surgery within 8 weeks before Screening.
Diabetes mellitus treated with insulin for less than 6 weeks prior to the study entry, or with change in total daily insulin dose by >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 systemic e
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method