A Phase 1, Open-label, Multi-Period, Single Sequence Study to Evaluate the Relative Bioavailability, Performance, and Safety of Two Solid Oral Doses (Paltusotine Tablets) in Healthy Volunteers
Crinetics Australia Pty Ltd
14 participants
Jun 1, 2022
Interventional
Conditions
Summary
Paltusotine is an oral somatostain receptor 2 (sst2) agonist being developed for the treatment of acromegaly. This single cohort, 4 period study will evaluate the relative bioavailability of 60 mg paltusotine tablet, test formulation, compared to 60 mg paltusotine tablet, reference formulation, in healthy volunteers. The study will consist of 1 cohort in which participants will receive 1 dose of paltusotine (60 mg total), across 4 periods as follows: Period 1: Participants to receive 1 dose of 3×20 mg tablet, reference formulation, after overnight fast with meal at 4 hours postdose. Period 2: Participants to receive 1 dose of 1×60 mg tablet, test formulation, after overnight fast with meal at 4 hours postdose. Period 3: Participants to receive 1 dose of 1×60 mg tablet, test formulation, after overnight fast with meal at 1 hour postdose. Period 4: Participants to receive 1 dose of 1×60 mg tablet, test formulation, after overnight fast with meal at 4 hours postdose after pre-treatment with lansoprazole (orally disintegrating tablet, 15 mg twice daily) over 4 days. Participants will receive each dose with approximately 240 mL of water, after a 10 hour overnight fast. Participants will then fast for further 4 hours, or 1 hour for Period 3, after dosing. There will be 7 to 9 days between doses, except between Periods 3 and 4 there will be a 7-day washout. There will be up to 14 subjects enrolled in this study.
Eligibility
Inclusion Criteria5
- Male and female subjects 18 to 65 years of age
- BMI 18 to 30 kg/m2
- Females must be non-pregnant and non-lactating, and either surgically sterile, post-menopausal, or must agree to use a highly effective or two clinically acceptable methods of contraception for the duration of the study and for 30 days after the last study visit.
- Male subjects must use a condom and his female partner of childbearing potential must use a highly effective or clinically acceptable form of contraception for the duration of the study and until at least 3 months after the last dose of study drug. Male subjects must also agree to not donate sperm for the duration of the study and until at least 3 months after the last dose of study drug.
- Willing to provide signed informed consent
Exclusion Criteria13
- Prior treatment with paltusotine.
- Any uncontrolled or active major systemic disease.
- History or presence of malignancy except adequately treated basal cell and squamous cell carcinomas of the skin within the past 5 years.
- Active acute or chronic infection.
- Had an unstable psychological disorder less than or equal to 1 year before screening based on the subject’s medical history.
- Had a medically significant illness within 30 days of admission.
- Use of any investigational drug within the past 60 days or 5 half-lives, whichever is longer prior to the first dosing of study drug.
- Use of any prior medication without approval of the Investigator within 14 days prior to admission.
- History of or current alcohol abuse.
- Heavy use of Tobacco and/or nicotine products.
- Taking moderate or strong CYP3A4 inhibitors or inducers.
- Poor CYP2C19 metabolizers, or ultrarapid metabolizers as determined from blood sample collected during Screening.
- Any condition that in the opinion of the investigator would jeopardize the subject's appropriate participation in the study.
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Interventions
The intervention for this study, paltusotine, is an orally bioavailable small molecule somatostatin receptor agonist that lowers growth hormone levels in acromegaly patients. Paltusotine will be supplied as 60 mg paltusotine tablets, test formulation, and 20 mg tablets, reference formulation. The study will consist of 1 cohort in which participants will receive 1 dose of paltusotine (60 mg total), across 4 periods as follows: Period 1: Participants to receive 1 dose of 3×20 mg tablet, reference formulation, after overnight fast with meal at 4 hours postdose. Period 2: Participants to receive 1 dose of 1×60 mg tablet, test formulation, after overnight fast with meal at 4 hours postdose. Period 3: Participants to receive 1 dose of 1×60 mg tablet, test formulation, after overnight fast with meal at 1 hour postdose. Period 4: Participants to receive 1 dose of 1×60 mg tablet, test formulation, after overnight fast with meal at 4 hours postdose after pre-treatment with lansoprazole (orally disintegrating tablet, 15 mg twice daily) over 4 days. The final dose of lansoprazole will be taken at least 60 minutes prior to administration of the test formulation in Period 4. A standard meal will be provided at least 4 hours after study drug administration for Periods 1, 2, and 4, and at least 1 hour after study drug administration for Period 3. The standard meal will provide a total of approximately 500 calories such that 36% of the calories (18 grams) are derived from fat, 14% from protein (16 grams) and 50% from carbohydrates (56 grams). An example test meal is 1 slice of toast (whole meal), 1 butter or margarine packet (as appropriate), 1 condiment packet (as appropriate), 1 cup of cereal/2 Weet-Bix with 250 mL milk, and 1 sugar sachet. Participants will receive each dose with approximately 240 mL of water, after a 10 hour overnight fast. Participants will then fast for further 4 hours, or 1 hour for Period 3, after dosing. There will be 7 to 9 days between doses, except between Periods 3 and 4 there will be a 7-day washout. There will be up to 14 subjects enrolled in this study. Dosing with Paltusotine for all periods will be administered by the study personnel at the research unit, and a mouth check will be conducted following dosing for each participant in all periods. Accountability records will be maintained by the study personnel to ensure compliance. Randomization will not be applicable in this single sequence study. All participants will progress sequentially through Periods 1- 4 in the same order.
Locations(1)
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ACTRN12622000704796