Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Dapagliflozin Extended Release Capsules in Healthy Volunteers.

The intervention is LYN-045, an extended release (ER) oral capsule containing dapagliflozin 35 mg. The rationale for the development of this ER formulation is to reduce the frequency of dosing orally administered dapagliflozin once weekly or less and thereby improving the management of type 2 diabetes. The study will consist of three cohorts, with each cohort receiving a different formulation of LYN-045. In Cohort 1, 8 participants will receive the base formulation - LYN-045-B. Each participant will receive: On day 1, a single dose of immediate release (IR) dapagliflozin (FORXIGA®) 10 mg oral tablet that will be administered to facilitate characterisation of the dapagliflozin pharmacokinetics. On day 4, the LYN-045-B will be administered as single dose ER oral capsule containing 35 mg dapagliflozin. On both days (1 and 4), the single oral dose of the IR dapagliflozin tablet or LYN-045-B ER oral capsule will be administered and directly observed by a trained nurse (at a minimum) in an inpatient unit. Eligible healthy volunteers enrolled into the study should expect to participate in the study for up to 4 weeks, from the time of enrolment through the last study visit. In Cohort 2, 16 participants will be dosed with the stiffer core formulation – LYN-045-SC – 8 with a stabilising ring and 8 without. On day 1, the LYN-045-SC will be administered as single dose ER oral capsule containing 35 mg dapagliflozin. The single oral dose of LYN-045-SC ER oral capsule will be administered and directly observed by a trained nurse (at a minimum) in an inpatient unit. Eligible healthy volunteers enrolled into the study should expect to participate in the study for up to 4 weeks, from the time of enrolment through the last study visit. In Cohort 3, 10 participants will be dosed with the flexible arm formulation – LYN-045-FA – once with a stabilising ring and once without (two total doses). Each participant in Cohort 3 will receive: On day -4, a single dose of immediate release (IR) dapagliflozin (FORXIGA®) 10 mg oral tablet that will be administered to facilitate characterisation of the dapagliflozin pharmacokinetics. On Day 1, the LYN-045-FA with or without the stabilising ring will be administered as single dose ER oral capsule containing 35 mg dapagliflozin. After confirmation of gastric emptying, on Day 10 a single oral dose of LYN-045-FA ER oral capsule will be administered. Participants will receive the formulation (with/without ring) not received on Day 1. All administration of LYN-045-FA will be directly observed by a trained nurse (at a minimum) in an inpatient unit. Eligible healthy volunteers enrolled into the study should expect to participate in the study for up to 4 weeks, from the time of enrolment through the last study visit. In Cohort 4, 16 participants will be dosed with the disintegrating matrix formulations – 1 dose of LYN-045-DM – with a short disintegrating matrix (SDM) and one dose with a Long disintegrating matrix (LDM). On day -2 and Day -1, a single dose of immediate release (IR) dapagliflozin (FORXIGA®) 10 mg oral tablet will be administered to facilitate characterisation of the dapagliflozin pharmacokinetics. On day 1, the LYN-045-SDM will be administered as single dose oral capsule containing 35 mg dapagliflozin. On day 10, the LYN-045-LDM will be administered as single dose oral capsule containing 35 mg dapagliflozin. The oral doses of the LYN-045-DM oral capsules will be administered and directly observed by a trained nurse (at a minimum) in an inpatient unit. Eligible healthy volunteers enrolled into the study should expect to participate in the study for up to 4 weeks, from the time of enrolment through the last study visit. In Cohort 5, 20 participants will be dosed with disintegrating matrix formulations LYN-045-DMR – 10 volunteers will receive 1 dose of LYN-045-DMR1, and 10 further volunteers will receive one dose of LYN-045-DMR2. On Day 1 a single dose of LYN-045-DMR will be administered as single dose oral capsule containing 35 mg dapagliflozin. The oral dose of the LYN-045-DMR oral capsule will be administered and directly observed by a trained nurse (at a minimum) in an inpatient unit. Eligible healthy volunteers enrolled into the study should expect to participate in the study for up to 3 weeks, from the time of enrolment through the last study visit.