A Study to Examine the Efficacy, Safety and Tolerability, and Pharmacokinetics of Exenatide Once Monthly Suspension

HbA1c was measured as a percent (%) of total hemoglobin. The Target values for HbA1c were <7% and ≤ 6.5% at Week 20. Evaluable population was defined as participants who completed study procedures in compliance with the protocol and had adequate exposure to the study drug.

Body weight was measured in kilograms (kg) at Baseline, and during treatment at Weeks 2, 4, 6, 8, 9-11, 12, 13, 14, 15, 16, 17-19, and 20. Baseline was Day 1, or last measurement prior to first dose of study drug. Evaluable population was defined as all participants who completed study procedures in compliance with the protocol and had adequate exposure to the study drug.

Fasting glucose was measured in milligrams per deciliter (mg/dL) at screening, Baseline, and during treatment at Weeks 2, 4, 6, 8, 9-11, 12, 13, 14, 15, 16, 17-19, and 20. Baseline was Day 1, or last measurement prior to first dose of study drug. Evaluable population was defined as all participants who completed study procedures in compliance with the protocol and had adequate exposure to the study drug.

All participants received an initial blood draw prior to the first dose and a single blood sample was collected at all other subsequent visits, for plasma exenatide assessments and the characterization of pharmacokinetic (PK) parameters following multiple monthly doses over the study period. Exenatide was measured using a validated enzyme-linked immunosorbent assay (ELISA). Time weighted average concentration (Cave (2016-2688 h) and Peak to Trough were measured in picograms per milliliter (pg/mL).

Baseline was Day 1, or last measurement prior to first dose of study drug. Vital signs were measured after the participant had rested for approximately 5 minutes and with the participant in a sitting position. Measurement was recorded in millimeters of mercury (mmHg). The blood pressure measurement was repeated after at least 30 seconds and the average of the two readings recorded. ITT population was defined as all participants who received at least one dose of the study drug.

Baseline was Day 1, or last measurement prior to first dose of study drug. Heart rate was measured after the participant had rested for approximately 5 minutes and with the participant in a sitting position. Measurement was recorded in beats per minute (bpm). The measurement was repeated after at least 30 seconds and the average of the two readings recorded. ITT population was defined as all participants who received at least one dose of the study drug.

AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. All participants who received at least one dose of study drug were included in the ITT analysis. Treatment-emergent (TE) adverse events were defined as those with onset at or after initiation of study medication on Day 1 through study termination or early termination.

AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Injection site related adverse events were defined as the adverse events with 'injection site' phrase in preferred term excluding 'injection site nodule'. The following events were Injection Site Reaction AEs: erythema, hematoma, hemorrhage, site pain, site papule, site pruritus, site warmth.

Participants receiving study drug monthly received 5 injections with last injection at Week 16; Participants receiving study drug weekly received 20 injections with last injection at Week 19.

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Serum titers of antibodies to exenatide were evaluated using a validated enzyme-linked immunosorbent assay (Covance Method No. ELISA-0308). Positive antibody to exenatide titer: observed at the indicated visit following a negative or missing titer at baseline, or a positive titer that has increased by at least 3 dilutions at the indicated visit from a detectable baseline. Baseline=Day 1.

Potential clinical importance are the following: Hematocrit values for males less than (<) 36%, females < 30%; hemoglobin for males <12 grams per deciliter (g/dL), females < 10 g/dL; low platelet values <75,000/micro liter (µL), high values greater than (>) 500,000 µL. Laboratory samples were obtained at baseline (Day 1 or if unavailable, last measurement prior to first study drug dose), Weeks 6, 12, 20, and at study termination (Week 24) or early termination. Number of laboratory values of potential clinical importance presented for Weeks 6 - Week 24 or early termination.

Potential clinical importance (PCI): triacylglycerol lipase high values were > 3* upper limit of normal (ULN); creatinine high values in males >1.6 mg/dL, females >1.4 mg/dL; gamma glutamyl transferase (GGT) high value >3* ULN; bilirubin high value > 2 mg/dL; Urate high values > 10 (males), >8 (females) mg/dL; potassium low value < 3 milliequivalents per liter (mEq/L), high value >5.5 mEq/L; calcium low value < 8 mg/dL and high value > 11 mg/dL. Laboratory samples were obtained at baseline (Day 1 or if unavailable, last measurement prior to first study drug dose), Weeks 6, 12, 20, and at study termination (Week 24) or early termination. Number of laboratory values of potential clinical importance (values could be either low or high) are presented for Weeks 6 - Week 24 or early termination. Note: those tests with no values meeting the PCI criteria, ie, 0 values observed across all treatment arms, are not presented.