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

Primary Purpose

Type 2 Diabetes Mellitus

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

exenatide once weekly

Placebo

About this trial

This is an interventional treatment trial for Type 2 Diabetes Mellitus focused on measuring diabetes, exenatide once weekly, Byetta, Amylin, Lilly

Eligibility Criteria

19 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Cohort 1:

Is 19 to 65 years old
Has a body mass index (BMI) of 23 kg/m2 to 35 kg/m2, inclusive, at study start

Cohort 2:

Is 19 to 75 years old
Has been diagnosed with type 2 diabetes mellitus
Has HbA1c of 7.1% to 10.0%, inclusive, at study start
Has a body mass index (BMI) of 25 kg/m2 to 45 kg/m2, inclusive, at study start
Has been treated with diet and exercise alone or with a stable regimen of metformin, a TZD, or a combination of metformin and a TZD, for a minimum of 2 months prior to study start
Either is not treated with or has been on a stable treatment regimen with any of the following medications for a minimum of 2 months prior to study start:
- Hormone replacement therapy (female subjects)
- Oral contraceptives (female subjects)
- Antihypertensive agents
- Lipid-lowering agents
- Thyroid replacement therapy
- Antidepressant agents

Exclusion Criteria:

Cohort 1:

Has a personal history of diabetes mellitus (including impaired glucose tolerance, impaired fasting glucose, or gestational diabetes)
Has received any investigational drug within 30 days (or 5 half-lives of the investigational drug, whichever is greater) prior to study start
Has ever been exposed to exenatide (BYETTA, exenatide once weekly, or any other formulation of exenatide) or any GLP 1 analog

Cohort 2:

Has received any investigational drug within 30 days (or 5 half-lives of the investigational drug, whichever is greater) prior to study start
Has ever been exposed to exenatide (BYETTA, exenatide once weekly, or any other formulation of exenatide) or any GLP 1 analog
Has been treated, is currently being treated, or is expected to require or undergo treatment with any of the following treatment-excluded medications:
- Any DPP-4 inhibitor or sulfonylurea (SU) within 3 months prior to study start
- Alpha glucosidase inhibitor, meglitinide, nateglinide, or pramlintide (SYMLIN®) within 30 days prior to study start
- Insulin within 2 weeks prior to study start or for more than 1 week within 3 months prior to study start
- Systemic corticosteroids by oral, intravenous, or intramuscular route; or potent, inhaled, or intrapulmonary (including ADVAIR®) steroids known to have a high rate of systemic absorption
- Prescription or over-the-counter weight loss medications within 3 months prior to study start

Sites / Locations

Research Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

Cohort 1: Healthy Participants

Cohort 2: Diabetes Participants

Cohort 2: Diabetes Participants Placebo

Arm Description

A single 10-mg dose of exenatide once weekly suspension given to healthy participants via 3 subcutaneous (SC) injections at Day 1.

On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, thiazolidinedione (TZD), or a combination of metformin or TZD were randomized to receive weekly injections of exenatide suspension for 12 weeks.

Outcomes

Primary Outcome Measures

Area Under the Curve (AUC) for Single Dose of 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population

Cohort 1: Blood samples for the assessment of plasma exenatide were collected at time = -15, 60, 90, 120, 180, 240, 360, and 480 minutes relative to study medication injection at time = 0 on Day 1 and the mean is presented below. At all visits following the single injection, a single blood sample was collected for assessment of exenatide concentrations. AUC was measured in picograms * hours per milliliter (pg*hr/mL). Exenatide was measured using a validated enzyme-linked immunosorbent assay (ELISA). AUC calculated using linear trapezoidal method from time x to time y; AUC (0-8h) and (0-tlast) are presented below. Pharmacokinetic (PK) evaluable population consisted of all ITT participants who had at least 4 detectable plasma exenatide measurements [not less than (<) lower limits of quantification (LLOQ)] from Day 1 to Week 12 and had reliable PK data.

Maximum Concentration (Cmax) for Single Dose of 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population

Cohort 1: Blood samples for the assessment of plasma exenatide were collected at time = -15, 60, 90, 120, 180, 240, 360, and 480 minutes relative to study medication injection at time = 0 on Day 1 and the mean is presented below. At all visits following the single injection, a single blood sample was collected for assessment of exenatide concentrations. Cmax was measured in picograms per milliliter (pg/mL). Exenatide concentration was measured using a validated enzyme-linked immunosorbent assay (ELISA). PK evaluable population consisted of all ITT participants who had at least 4 detectable plasma exenatide measurements [not less than (<) lower limits of quantification (LLOQ)] from Day 1 to Week 12 for the evaluation of the PK characteristics of plasma exenatide and had reliable PK data. Cmax (0-8h) and (0-tlast) are presented below.

Time to Maximum Concentration (Tmax) for Single Dose of 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population

Cohort 1: Blood samples for the assessment of plasma exenatide were collected at time(t) = -15, 60, 90, 120, 180, 240, 360, and 480 minutes relative to study medication injection at time = 0 on Day 1 an the mean is presented below. At all visits following the single injection, a single blood sample was collected for assessment of exenatide concentrations. Tmax was measured in hours and Tmax (0-8h) and (0-tlast) are presented below. Exenatide concentration was measured using a validated enzyme-linked immunosorbent assay (ELISA). PK evaluable population consisted of all ITT participants who had at least 4 detectable plasma exenatide measurements [not less than (<) lower limits of quantification (LLOQ)] and had reliable PK data.

Number of Participants With Treatment Emergent Adverse Events (TEAEs), Injection Site TEAEs, Serious Adverse Events (SAEs), Deaths, and Withdrawals Due to AEs in Cohort 1 and Cohort 2 in Intent to Treat (ITT) Population

Treatment emergent (TE)=occurs during or after treatment with study drug. Adverse Event (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. Participants experiencing multiple episodes of a given AE are counted once. Injection site AEs: adverse events that existed prior to Day 1 and worsened after the first administration at Day 1, or occurred after the first administration at Day 1 through Week 12, or after Study Termination if considered by investigator to be clinically significant.

Number of Participants With Concomitant Medications in Cohort 1 and Cohort 2 in ITT Population

Concomitant medications are defined as those medications received on or after the date of the first injection on Day 1, including prior medications that continued past Day 1 and new concomitant medications. Participants may be counted in more than one medication class and no more than once in each class. Categories by Anatomical Therapeutic Chemical (ATC) classification using the World Health Organization (WHO) Drug Dictionary version C1, 01 March 2009. As per protocol, all participants in Cohort 1 could receive up to 2 anti-emetic medications approximately 30 minutes prior to the exenatide.

Mean Change From Baseline to End of Study in Sitting Diastolic and Systolic Blood Pressure in Cohorts 1 and 2 in ITT Population

In Cohort 1, sitting blood pressures were obtained at Screening (Visit 1), Day 1 (Visit 2), Weeks 1-11 (Visits 3-13), Week 12 (Visit 14), and at early termination. Blood pressures (diastolic and systolic) were measured in millimeters of mercury (mmHg). In Cohort 2, sitting blood pressures were obtained at Screening (Visit 1), Day 1 (Visit 2), Weeks 1-10 (Visits 3-12), Week 11 (Visit 15), Week 12 (Visit 16) and at early termination. Baseline was defined as last measurement prior to first injection of study drug.

Mean Change From Baseline to End of Study in Sitting Heart Rate in Cohorts 1 and 2 in ITT Population

In Cohort 1, sitting heart rates were obtained at Screening (Visit 1), Day 1 (Visit 2), Weeks 1-11 (Visits 3-13), Week 12 (Visit 14), and at early termination. Heart rate was measured in beats per minute (bpm). In Cohort 2, sitting heart rates were obtained at Screening (Visit 1), Day 1 (Visit 2), Weeks 1-10 (Visits 3-12), Week 11 (Visit 15), Week 12 (Visit 16) and at early termination. Baseline was defined as last measurement prior to first injection of study drug.

Number of Participants With Hematology and Serum Chemistry Laboratory Values of Potential Clinical Importance in Cohorts 1 and 2 in ITT Population

Abbreviations: Upper Limit of Normal (ULN); milligram per deciliter (mg/dL); units per liter (U/L); micro liters (µL); creatine kinase (CK); gamma-glutamyltransferase (G-GT). Normal ranges = Hematocrit: 40.6-52.3% (male), 35.3-47.0 (female); Platelets 155-361*10^3/µL(male/female); Calcium: 8.6-10.4 mg/dL (male/female); CK: 43-350 U/L (male), 28-207 U/L (female); G-GT: 7-62 U/L (male/female); Glucose 73-105 mg/dL (male/female); Lipase 14-70 U/L (male/female); Uric acid: 3.5-7.8 mg/dL (male), 2.3-5.9 mg/dL (female). Blood samples for laboratories were collected at screening, Day 1, Weeks 4, 8, 12 or early termination. Value for potential clinical importance is presented in each category presented below.

Antibody Titers for Participants With Treatment Emergent Positive Antibodies to Exenatide in Participants Who Received Exenatide in Cohorts 1 and 2

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. Negative titers were assigned a value of 1 in order to calculate geometric mean. Geometric mean of reportable titers, by study week, are presented below.

Area Under the Curve (AUC) for 2 mg Exenatide (Cohort 2) in Participants With Diabetes in the Pharmacokinetic Evaluable Population

Cohort 2: Blood samples for the assessment of plasma exenatide were collected on Day 1, Weeks 2, 4, 6, 8, and 10. At Week 10, blood samples were collected at time = -15, 60, 90, 120, 180, 240, and 360 minutes relative to study medication injection at time = 0. AUC was measured in picograms * hours per milliliter (pg*hr/mL). Exenatide was measured using a validated enzyme-linked immunosorbent assay (ELISA). AUC calculated using linear trapezoidal method from time x to time y; AUC (0-6h) measured at Week 10, AUC (0-168h) steady state measured between Weeks 10 and 11, and AUC (0-tlast) for time interval between Weeks 10 and 12 (approximately336 hours) are presented below. PK evaluable population consisted of all ITT participants who had at least 4 detectable plasma exenatide measurements (not < LLOQ) from Day 1 to Week 12 and had reliable PK data.

Average Exenatide Concentration (Cave) of 2 mg Exenatide (Cohort 2) in Participants With Diabetes in the Pharmacokinetic Evaluable Population

Cohort 2: Blood samples for the assessment of plasma exenatide were collected on Day 1, Weeks 2, 4, 6, 8, and 10. At Week 10, blood samples were collected at time = -15, 60, 90, 120, 180, 240, and 360 minutes relative to study medication injection at time = 0. At all visits following the single injection, a single blood sample was collected for assessment of exenatide concentrations. Cave(0-168h) and Cave(0-tlast) was the time-weighted mean concentration over the sampling period from time x to time y corresponding to AUC (0-168h), and AUC (0-tlast), respectively. Cave was measured in picograms per milliliter (pg/mL). Exenatide concentration was measured using a validated enzyme-linked immunosorbent assay (ELISA). PK evaluable population consisted of all ITT participants who had at least 4 detectable plasma exenatide measurements (not < LLOQ) from Day 1 to Week 12 and had reliable PK data.

Maximum Concentration (Cmax) for 2 mg Exenatide (Cohort 2) in Participants With Diabetes in the Pharmacokinetic Evaluable Population

Cohort 2: Blood samples for the assessment of plasma exenatide were collected on Day 1, Weeks 2, 4, 6, 8, and 10. At Week 10, blood samples were collected at time = -15, 60, 90, 120, 180, 240, and 360 minutes relative to study medication injection at time = 0. Cmax was measured in pg/mL. Exenatide was measured using a validated enzyme-linked immunosorbent assay (ELISA). Cmax summarized at 0-6 h at Week 10, 0-168 h at Weeks 10-11, and 0-tlast at Weeks 10-12. PK evaluable population consisted of all ITT participants who had at least 4 detectable plasma exenatide measurements (not < LLOQ) from Day 1 to Week 12 and had reliable PK data.

Time to Maximum Concentration (Tmax) of 2 mg Exenatide (Cohort 2) in Participants With Diabetes in Pharmacokinetic Evaluable Population

Cohort 2: Blood samples for the assessment of plasma exenatide were collected on Day 1, Weeks 2, 4, 6, 8, and 10. At Week 10, blood samples were collected at time = -15, 60, 90, 120, 180, 240, and 360 minutes relative to study medication injection at time = 0. Tmax was measured in hours (h). Exenatide was measured using a validated ELISA. Tmax summarized at 0-6 h at Week 10, 0-168 h at Weeks 10-11, and 0-tlast at Weeks 10-12. PK evaluable population consisted of all ITT participants who had at least 4 detectable plasma exenatide measurements (not < LLOQ) from Day 1 to Week 12 and had reliable PK data.

Secondary Outcome Measures

AUC (0 Hour to 168 Hour) for 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population

Cohort 1: Blood samples for the assessment of plasma exenatide were collected at time = -15, 60, 90, 120, 180, 240, 360, and 480 minutes relative to study medication injection at time = 0 on Day 1. At all visits following the single injection, a single blood sample was collected for assessment of exenatide concentrations. AUC (0-168 h) data represents average concentration rather than maximum concentration. Exenatide concentration was measured using a validated enzyme-linked immunosorbent assay (ELISA). AUC calculated using linear trapezoidal method from time x to time y and measured in pg*h/mL. PK evaluable population consisted of all ITT participants who had at least 4 detectable plasma exenatide measurements (not < LLOQ) from Day 1 to Week 12 and had reliable PK data.

Average Exenatide Concentration (Cave) of 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population

Cohort 1: Blood samples for the assessment of plasma exenatide were collected at time = -15, 60, 90, 120, 180, 240, 360, and 480 minutes relative to study medication injection at time = 0 on Day 1. At all visits following the single dose, a single blood sample was collected for assessment of exenatide concentrations. Cave(0-168h) was the time-weighted mean concentration over the sampling period from time x to time y corresponding to AUC (0-168h) and was measured in picograms per milliliter (pg/mL). Exenatide concentration was measured using a validated enzyme-linked immunosorbent assay (ELISA). PK evaluable population consisted of all ITT participants who had at least 4 detectable plasma exenatide measurements [not less than (<) lower limits of quantification (LLOQ)] from Day 1 to Week 12 and had reliable PK data.

Least Square Mean Change From Baseline in Hemoglobin A1c (HbA1c) to Week 12 in Participants With Diabetes (Cohort 2) in the ITT Population

HbA1c was measured as a percent of hemoglobin at screening, Day 1, Weeks 4, 8, 12 or early termination. Last observation carried forward (LOCF) was applied to estimate missing values at post baseline timepoints. Baseline=Day 1, last measurement prior to first dose of study drug.

Number of Participants Achieving HbA1c Less Than Equal to (<=) 6.5% and Less Than (<) 7% at Week 12 in Participants With Diabetes (Cohort 2) in the ITT Population

HbA1c was measured as a percent of hemoglobin at screening, Day 1, Weeks 4, 8, 12 or early termination. LOCF was applied to estimate missing values at post baseline timepoints. Baseline=Day 1, last measurement prior to first dose of study drug.

Mean Change From Baseline at Week 12 in Body Weight in Participants With Diabetes (Cohort 2) in the ITT Population

Body weight was measured in kilograms (kg). Baseline was Day 1, last measurement prior to first dose of study drug. Body weight was measured at screening, Day 1, Weeks 4, 8, 12 or early termination and the LOCF approach was applied to estimate missing value at each post baseline timepoint.

Mean Change From Baseline at Week 12 in Fasting Plasma Glucose in Participants With Diabetes (Cohort 2) for the ITT Population

Baseline was the last measurement at the screening visit. Fasting plasma glucose (FPG) was measured at screening, Day 1, Weeks 2, 4, 6, 8, 12, or early termination and reported in milligrams per deciliter (mg/dL).

Full Information

NCT ID

NCT00894322

First Posted

May 5, 2009

Last Updated

September 3, 2015

Sponsor

AstraZeneca

Collaborators

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT00894322

Brief Title

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

Official Title

A Two-Cohort, Single- and Repeat Dose Study to Examine the Pharmacokinetics, Tolerability, and Safety of Ready to Use Exenatide Once Weekly in Healthy Subjects and in Subjects With Type 2 Diabetes Mellitus

Study Type

Interventional

2. Study Status

Record Verification Date

August 2015

Overall Recruitment Status

Completed

Study Start Date

April 2009 (undefined)

Primary Completion Date

August 2009 (Actual)

Study Completion Date

August 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AstraZeneca

Collaborators

Eli Lilly and Company

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This study is designed to evaluate the pharmacokinetics, tolerability, and safety of exenatide once weekly suspension in both healthy subjects and in subjects with type 2 diabetes. The study will also evaluate efficacy in the type 2 diabetes patients. Development of this exenatide once weekly presentation would eliminate the need to reconstitute the product prior to use.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 2 Diabetes Mellitus

Keywords

diabetes, exenatide once weekly, Byetta, Amylin, Lilly

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

Participant

Allocation

Randomized

Enrollment

65 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1: Healthy Participants

Arm Type

Experimental

Arm Description

A single 10-mg dose of exenatide once weekly suspension given to healthy participants via 3 subcutaneous (SC) injections at Day 1.

Arm Title

Cohort 2: Diabetes Participants

Arm Type

Experimental

Arm Description

Arm Title

Cohort 2: Diabetes Participants Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

exenatide once weekly

Intervention Description

subcutaneous injection, 10.0 mg, single injection

Intervention Type

Drug

Intervention Name(s)

exenatide once weekly

Intervention Description

subcutaneous injection, 2.0 mg, once a week for 12 weeks

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

subcutaneous injection, volume equivalent to Cohort 2 experimental intervention, once a week for 12 weeks

Primary Outcome Measure Information:

Title

Area Under the Curve (AUC) for Single Dose of 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population

Description

Time Frame

Day 1, Week 12

Title

Maximum Concentration (Cmax) for Single Dose of 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population

Description

Cohort 1: Blood samples for the assessment of plasma exenatide were collected at time = -15, 60, 90, 120, 180, 240, 360, and 480 minutes relative to study medication injection at time = 0 on Day 1 and the mean is presented below. At all visits following the single injection, a single blood sample was collected for assessment of exenatide concentrations. Cmax was measured in picograms per milliliter (pg/mL). Exenatide concentration was measured using a validated enzyme-linked immunosorbent assay (ELISA). PK evaluable population consisted of all ITT participants who had at least 4 detectable plasma exenatide measurements [not less than (<) lower limits of quantification (LLOQ)] from Day 1 to Week 12 for the evaluation of the PK characteristics of plasma exenatide and had reliable PK data. Cmax (0-8h) and (0-tlast) are presented below.

Time Frame

Day 1, Week 12

Title

Time to Maximum Concentration (Tmax) for Single Dose of 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population

Description

Time Frame

Day 1, Week 12

Title

Description

Time Frame

Day 1 to Week12

Title

Number of Participants With Concomitant Medications in Cohort 1 and Cohort 2 in ITT Population

Description

Time Frame

Day 1 to 12 weeks

Title

Mean Change From Baseline to End of Study in Sitting Diastolic and Systolic Blood Pressure in Cohorts 1 and 2 in ITT Population

Description

Time Frame

Day 1 to Week 12

Title

Mean Change From Baseline to End of Study in Sitting Heart Rate in Cohorts 1 and 2 in ITT Population

Description

Time Frame

Day 1 to Week 12

Title

Number of Participants With Hematology and Serum Chemistry Laboratory Values of Potential Clinical Importance in Cohorts 1 and 2 in ITT Population

Description

Time Frame

Day 1 to Week 12

Title

Antibody Titers for Participants With Treatment Emergent Positive Antibodies to Exenatide in Participants Who Received Exenatide in Cohorts 1 and 2

Description

Time Frame

Day 1 to Week 12

Title

Area Under the Curve (AUC) for 2 mg Exenatide (Cohort 2) in Participants With Diabetes in the Pharmacokinetic Evaluable Population

Description

Time Frame

Week 10-11; Weeks 10 - 12

Title

Average Exenatide Concentration (Cave) of 2 mg Exenatide (Cohort 2) in Participants With Diabetes in the Pharmacokinetic Evaluable Population

Description

Cohort 2: Blood samples for the assessment of plasma exenatide were collected on Day 1, Weeks 2, 4, 6, 8, and 10. At Week 10, blood samples were collected at time = -15, 60, 90, 120, 180, 240, and 360 minutes relative to study medication injection at time = 0. At all visits following the single injection, a single blood sample was collected for assessment of exenatide concentrations. Cave(0-168h) and Cave(0-tlast) was the time-weighted mean concentration over the sampling period from time x to time y corresponding to AUC (0-168h), and AUC (0-tlast), respectively. Cave was measured in picograms per milliliter (pg/mL). Exenatide concentration was measured using a validated enzyme-linked immunosorbent assay (ELISA). PK evaluable population consisted of all ITT participants who had at least 4 detectable plasma exenatide measurements (not < LLOQ) from Day 1 to Week 12 and had reliable PK data.

Time Frame

Week 10 - Week 11; Week 10 - Week 12

Title

Maximum Concentration (Cmax) for 2 mg Exenatide (Cohort 2) in Participants With Diabetes in the Pharmacokinetic Evaluable Population

Description

Cohort 2: Blood samples for the assessment of plasma exenatide were collected on Day 1, Weeks 2, 4, 6, 8, and 10. At Week 10, blood samples were collected at time = -15, 60, 90, 120, 180, 240, and 360 minutes relative to study medication injection at time = 0. Cmax was measured in pg/mL. Exenatide was measured using a validated enzyme-linked immunosorbent assay (ELISA). Cmax summarized at 0-6 h at Week 10, 0-168 h at Weeks 10-11, and 0-tlast at Weeks 10-12. PK evaluable population consisted of all ITT participants who had at least 4 detectable plasma exenatide measurements (not < LLOQ) from Day 1 to Week 12 and had reliable PK data.

Time Frame

Week 10, Weeks 10-11, Weeks 10-12

Title

Time to Maximum Concentration (Tmax) of 2 mg Exenatide (Cohort 2) in Participants With Diabetes in Pharmacokinetic Evaluable Population

Description

Cohort 2: Blood samples for the assessment of plasma exenatide were collected on Day 1, Weeks 2, 4, 6, 8, and 10. At Week 10, blood samples were collected at time = -15, 60, 90, 120, 180, 240, and 360 minutes relative to study medication injection at time = 0. Tmax was measured in hours (h). Exenatide was measured using a validated ELISA. Tmax summarized at 0-6 h at Week 10, 0-168 h at Weeks 10-11, and 0-tlast at Weeks 10-12. PK evaluable population consisted of all ITT participants who had at least 4 detectable plasma exenatide measurements (not < LLOQ) from Day 1 to Week 12 and had reliable PK data.

Time Frame

Week 10, Weeks 10-11, Weeks 10-12

Secondary Outcome Measure Information:

Title

AUC (0 Hour to 168 Hour) for 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population

Description

Cohort 1: Blood samples for the assessment of plasma exenatide were collected at time = -15, 60, 90, 120, 180, 240, 360, and 480 minutes relative to study medication injection at time = 0 on Day 1. At all visits following the single injection, a single blood sample was collected for assessment of exenatide concentrations. AUC (0-168 h) data represents average concentration rather than maximum concentration. Exenatide concentration was measured using a validated enzyme-linked immunosorbent assay (ELISA). AUC calculated using linear trapezoidal method from time x to time y and measured in pg*h/mL. PK evaluable population consisted of all ITT participants who had at least 4 detectable plasma exenatide measurements (not < LLOQ) from Day 1 to Week 12 and had reliable PK data.

Time Frame

Day 1 to Week 1

Title

Average Exenatide Concentration (Cave) of 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population

Description

Cohort 1: Blood samples for the assessment of plasma exenatide were collected at time = -15, 60, 90, 120, 180, 240, 360, and 480 minutes relative to study medication injection at time = 0 on Day 1. At all visits following the single dose, a single blood sample was collected for assessment of exenatide concentrations. Cave(0-168h) was the time-weighted mean concentration over the sampling period from time x to time y corresponding to AUC (0-168h) and was measured in picograms per milliliter (pg/mL). Exenatide concentration was measured using a validated enzyme-linked immunosorbent assay (ELISA). PK evaluable population consisted of all ITT participants who had at least 4 detectable plasma exenatide measurements [not less than (<) lower limits of quantification (LLOQ)] from Day 1 to Week 12 and had reliable PK data.

Time Frame

Day 1 to Week 1

Title

Least Square Mean Change From Baseline in Hemoglobin A1c (HbA1c) to Week 12 in Participants With Diabetes (Cohort 2) in the ITT Population

Description

Time Frame

Day 1 to Week 12

Title

Number of Participants Achieving HbA1c Less Than Equal to (<=) 6.5% and Less Than (<) 7% at Week 12 in Participants With Diabetes (Cohort 2) in the ITT Population

Description

Time Frame

Week 12

Title

Mean Change From Baseline at Week 12 in Body Weight in Participants With Diabetes (Cohort 2) in the ITT Population

Description

Time Frame

Baseline, Week 12

Title

Mean Change From Baseline at Week 12 in Fasting Plasma Glucose in Participants With Diabetes (Cohort 2) for the ITT Population

Description

Time Frame

Baseline, Week 12

10. Eligibility

Sex

All

Minimum Age & Unit of Time

19 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Cohort 1: Is 19 to 65 years old Has a body mass index (BMI) of 23 kg/m2 to 35 kg/m2, inclusive, at study start Cohort 2: Is 19 to 75 years old Has been diagnosed with type 2 diabetes mellitus Has HbA1c of 7.1% to 10.0%, inclusive, at study start Has a body mass index (BMI) of 25 kg/m2 to 45 kg/m2, inclusive, at study start Has been treated with diet and exercise alone or with a stable regimen of metformin, a TZD, or a combination of metformin and a TZD, for a minimum of 2 months prior to study start Either is not treated with or has been on a stable treatment regimen with any of the following medications for a minimum of 2 months prior to study start: Hormone replacement therapy (female subjects) Oral contraceptives (female subjects) Antihypertensive agents Lipid-lowering agents Thyroid replacement therapy Antidepressant agents Exclusion Criteria: Cohort 1: Has a personal history of diabetes mellitus (including impaired glucose tolerance, impaired fasting glucose, or gestational diabetes) Has received any investigational drug within 30 days (or 5 half-lives of the investigational drug, whichever is greater) prior to study start Has ever been exposed to exenatide (BYETTA, exenatide once weekly, or any other formulation of exenatide) or any GLP 1 analog Cohort 2: Has received any investigational drug within 30 days (or 5 half-lives of the investigational drug, whichever is greater) prior to study start Has ever been exposed to exenatide (BYETTA, exenatide once weekly, or any other formulation of exenatide) or any GLP 1 analog Has been treated, is currently being treated, or is expected to require or undergo treatment with any of the following treatment-excluded medications: Any DPP-4 inhibitor or sulfonylurea (SU) within 3 months prior to study start Alpha glucosidase inhibitor, meglitinide, nateglinide, or pramlintide (SYMLIN®) within 30 days prior to study start Insulin within 2 weeks prior to study start or for more than 1 week within 3 months prior to study start Systemic corticosteroids by oral, intravenous, or intramuscular route; or potent, inhaled, or intrapulmonary (including ADVAIR®) steroids known to have a high rate of systemic absorption Prescription or over-the-counter weight loss medications within 3 months prior to study start

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Vice President, Clinical Development

Organizational Affiliation

Amylin Pharmaceuticals, LLC.

Official's Role

Study Director

Facility Information:

Facility Name

Research Site

City

Lincoln

State/Province

Nebraska

Country

United States

12. IPD Sharing Statement

Links:

URL

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=3660&filename=Study_Synopsis.pdf

Description

CSR_Synopsis

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

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