A Phase 1, Open Label, Randomized, Two-Period, Crossover Study to Evaluate the Relative Bioavailability of Two Paltusotine Tablet Strengths in Healthy Volunteers

INTERVENTION: 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 20 mg and 30 mg tablets. The study will consist of 1 cohort in which participants will receive 1 dose of 2 x 30mg and 1 dose of 3 x 20mg of paltusotine (60mg total), across 2 periods in a randomised format as follows: Period 1: 6 Participants to receive 1 dose of 2 x 30mg tablets, 6 Participants to receive 1 dose of 3 x 20mg tablets. Period 2: Participants to receive the other dose to what was received in Period 1. Participants will receive each dose with approximately 240ml of water, after a 10 hour overnight fast. Participants will then fast for further 4 hours after dosing. There will be 10 to 14 days between doses. There will be up to 12 subjects enrolled in this study, with at least 4 male and 4 females. CONDITION: Acromegaly; ; Acromegaly Metabolic and Endocrine ‐ Other endocrine disorders PRIMARY OUTCOME: Relative bioavailability of paltusotine tablets at the same dose (60 mg) using tablets of two different strengths; three 20 mg tablets and two 30 mg tablets, as assessed by Pharmacokinetic blood plasma concentration. [Pharmacokinetic blood plasma sampling is to occur at the following timepoints: ; Periods 1 and 2: within 30 min pre dose, 15 min, 30 min, 45 min, 1 hr, 1.25 hrs, 1.5 hrs, 2.0 hrs, 3.0 hrs, 4.0 hrs, 6.0 hrs, 8.0 hrs, 10 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs, 96 hrs and 144hrs post dose. ] SECONDARY OUTCOME: Average bioequivalence (ABE) paltusotine tablets at the same dose (60 mg) using tablets of two different strengths; three 20 mg tablets and two 30 mg tablets, as assessed by Pharmacokinetic blood plasma concentration. [Pharmacokinetic blood plasma sampling is to occur at the following timepoints: ; Periods 1 and 2: within 30 min pre dose, 15 min, 30 min, 45 min, 1 hr, 1.25 hrs, 1.5 hrs, 2.0 hrs, 3.0 hrs, 4.0 hrs, 6.0 hrs, 8.0 hrs, 10 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs, 96 hrs and 144hrs post dose. ] Safety and tolerability of paltusotine as assessed by Physical Examinations, 12 Lead ECG, Vital Sign measurements, Safety Laboratory tests, and adverse event assessments.[Physical Examinations will be performed at the following timepoints: ; Screening, Day ‐1 (period 1 and 2), and Day 7 (period 2 only) ; 12 Lead ECG will be performed in triplicate at the following timepoints: ; Screening, Period 1 and 2 at Day ‐1, Day 1 1 hr and 3 hrs post dose, Day 2 24hrs post dose, and Day 7 (period 2 only) ; Vital signs, including Blood Pressure (via digital blood pressure monitor), Temperature (via digital tympanic thermometer) and Respiratory rate (manual count), at the following timepoints: Screening, Period 1 and 2 at Day ‐1, Day 1 1 hr and 3 hrs post dose, Day 2 24hrs post dose, and Day 7 (period 2 only) ; Safety Laboratory tests, including Serum Chemistry, Haematology and urinalysis, will be performed as the following timepoints: ; Screening, Period 1 and 2 at Day ‐1, prior to breakfast on Day 2, and prior to breakfast on Day 7 (Period 2 only). ; Adverse events will be recorded from the time that a subject signs consent until the final follow up visit. Site staff will question subjects on their health when conducting other assessments throughout the trial. Adverse events will be assessed by study investigators. Adverse events known to be associated with somatostatin receptor agonists include abdominal pain, diarrhea, and nausea ; ; ; ; ] INCLUSION CRITERIA: ‐ 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 not donate ova and to use a highly effective or two clinically acceptable methods of contraception ‐ male subjects must use a condom and his female partner of childbearing potential must use a highly effective or clinically acceptable form of contraception. 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