A Phase 1, Multi-Cohort, Single Dose Study to Assess The Relative Bioavailability, Performance, and Safety of Two Novel Formulations of CRN00808

CRN00808 will be supplied as 10 mg capsules (Reference Formulation) or tablets (Novel Formulation 1 and Novel Formulation 2) for oral administration once daily as described below. Novel formulation 2 will also be supplied as a 20 mg tablet (Cohort 5 only). CRN00808, an investigational drug, is an orally bioavailable small molecule somatostatin receptor 2 (sst2) agonist that lowers growth hormone levels in acromegaly patients. Lansoprazole, a marketed (TGA-approved) proton pump inhibitor, will be supplied as 15 mg tablets for oral administration twice daily (BID) for part of the study as described below. The study will consist of 3 cohorts with 4 periods each, and 2 cohort of 3 periods. Enrolled participants will be assigned to Cohort 1, 2, 3, 4 or 5 and are expected to complete all periods; each period is separated by at least 7 days for Cohort 1, 2 and 3, and at least 10 days for Cohort 4 and 5. Cohort 1 and 2 will be the same except the formulation used: Cohort 1 will receive CRN00808 Novel Formulation 1, and Cohort 2 will receive CRN00808 Novel Formulation 2. Period 1. Subjects will take 15 mg twice daily lansoprazole at least 30 min prior to a meal. Beginning on Day -4, subjects will take the last dose of 15 mg lansoprazole in the morning prior to a single fasting dose of 20 mg CRN00808. Period 2. Fasted subjects will take a single dose of 20 mg CRN00808 Period 3. Fasted subjects will take a single dose of 20 mg CRN00808 with a high-fat, high-calorie meal Period 4. Fasted subjects will take a single dose of CRN00808 at a dose determined from previous pharmacokinetic data. The dose determination will be based on area under the plasma concentration (AUC), maximum plasma concentration (Cmax), and variability comparison of the novel formulation with existing data for the reference formulation (previous clinical experience), provided the selected dose will result in predicted Cmax and AUC that are below the No Observable Adverse Level Cmax and AUC observed in nonclinical toxicity studies. A standard meal will be provided 2 hours after CRN00808 administration for Period 1, 2 and 4 of Cohort 1 and 2. The standard meal will provide a total of approximately 500 calories such that 36% of the calories are derived from fat, 14% from protein, and 50% from carbohydrates. An example meal is 1 slice of toast (wholemeal), 1 butter or margarine, 1 condiment, 1 cup of cereal/ 2 Weet-Bix with 250 mL milk, and 1 sugar sachet. A high-fat, high-calorie meal provided in period 3 of cohort 1 and 2 will provide a total of 800-1000 calories such that 50-60% of the calories are derived from fat, 15-19% from protein and 25-31% from carbohydrates. An example meal is 2 eggs fried in butter, 2 strips of bacon, 2 slices of toast with butter, 4 ounces of hash brown potatoes and 8 ounces of whole milk. Cohort 3 will consist of 4 periods. Period 1 will receive the CRN00808 Reference Formulation. Period 2 through Period 4 will receive CRN00808 Novel Formulation 2. Period 1. Fasted subjects will take a single dose of 20 mg CRN00808 and remain fasting for 2 hours after drug administration Period 2. Fasted subjects will take a single dose of 20 mg CRN00808 and remain fasting for 2 hours after drug administration Period 3. Fasted subjects will take a single dose of 20 mg CRN00808 and remain fasting for 1 hour after drug administration Period 4. Fasted subjects will take a single dose of 20 mg CRN00808 remain fasting for 0.5 hour after drug administration A low-fat meal will be provided after CRN00808 administration for all periods of Cohort 3. The low-fat meal will provide a total of 400-500 calories such that 25% of the calories (11-14 grams) are derived from fat. An example meal is 8 oz of milk, one boiled egg, and one packet flavored instant oatmeal made with water. Cohort 4 will consist of 3 periods. Subjects will receive a single dose of CRN00808 Novel Formulation 2 in each period. Period 1. Fasted subjects will take a single dose of 40 mg CRN00808 and remain fasting for 1 hour after drug administration Period 2. Fasted subjects will take a single dose of 80 mg CRN00808 and remain fasting for 1 hour after drug administration. Period 3. Fasted subjects will take a single dose 80 mg CRN00808 with 4 hours fasting after drug administration. A standard meal will be provided after CRN00808 administration for Cohort 4. The standard meal will provide a total of approximately 500 calories such that 36% of the calories are derived from fat, 14% from protein, and 50% from carbohydrates. An example meal is 1 slice of toast (wholemeal), 1 butter or margarine, 1 condiment, 1 cup of cereal/ 2 Weet-Bix with 250 mL milk, and 1 sugar sachet. Cohort 5 will consist of 3 periods. In each period, a single dose of CRN00808 Novel Formulation 2 (60 mg) will be administered orally (3x20 mg tablets). Period 1. Fasted subjects will take a single dose of 60 mg CRN00808 and remain fasting for 1 hour after drug administration Period 2. Subjects will take 15 mg twice daily lansoprazole at least 30 min prior to a meal, beginning three days prior to CRN00808 administration. Subjects will take the last dose of 15 mg lansoprazole in the morning prior to a single fasting dose of 60 mg CRN00808. Subjects will then remain fasting for 1 hour after drug administration. Period 3. Subjects will receive a single dose of 60 mg CRN00808 within 30 minutes of taking a low-fat meal. For all Cohort 5 periods, subjects will receive their next meal after 4 hours post dosing. A low-fat meal will be provided in Cohort 5. The low-fat meal will provide a total of 400-500 calories such that 25% of the calories (11-14 grams) are derived from fat. An example meal is 8 oz of milk, one boiled egg, and one packet flavored instant oatmeal made with water. For all the periods of each cohort, subjects are expected to stay in the research unit the day before the dosing of each period to ensure the fasting requirement is met. Subjects are required to fast overnight (at least 10 hours; water is permitted until 1 hour before CRN00808 administration) prior to the CRN00808 dosing. All the dosing will be administered by the study personnel at the research unit. An accountability records will be maintained by the study personnel to ensure compliance.