Type 2 Diabetes Mellitus
Conditions
Keywords
Diabetes, T2DM
Brief summary
The purpose of this study is to examine the effect of AZD6793 on the Pharmacokinetics and Pharmacodynamics of Metformin in Participants with Type 2 Diabetes Mellitus.
Detailed description
This is a double-blind, placebo-controlled, 2-period cross-over study conducted at a single study centre to assess the pharmacokinetics and pharmacodynamics (ie, glucose lowering effect) of metformin in participants with T2DM when metformin is administered alone and in combination with multiple doses of AZD6793. This study will consist of 2 treatment periods separated by a washout period of 7 to 14 days. Approximately 28 eligible participants will be randomized to study intervention such that 24 evaluable participants complete the study (12 participants in each treatment sequence).
Interventions
DRUGAZD6793
Participants will receive oral doses of metformin with an interval of 12 hours between doses. The morning doses of metformin will be administered together with AZD6793 (Treatment A).
DRUGAZD6793 Placebo
Participants will receive oral doses of metformin with an interval of 12 hours between doses. The morning doses of metformin will be administered together with AZD6793 placebo (Treatment B).
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Investigators, site staff, sponsor and their representatives will remain blinded to each participant's assigned study intervention throughout the course of the study. In order to maintain this blind, an otherwise uninvolved 3rd party will be responsible for the reconstitution and dispensation of all study intervention and will endeavor to ensure that there are no differences in time taken to dispense following randomization.
Intervention model description
Potential participants will be screened to assess their eligibility to enter the study up to 21 days prior to the start of the 14-day outpatient run-in period. Eligible participants will return to the study site for an outpatient visit on Day -14 and enter a 14-day outpatient run-in period. During this period they will receive metformin twice a day. Upon completion of the metformin run-in period, eligible participants will be admitted to the study site on Day -1 of Period 1 and randomized on Day 1 of Period 1 in a 1:1 ratio to one of two treatment sequences, AB or BA. AB being the test compound with metformin first and then metformin alone. BA being metformin alone first and then metformin with the test compound following their respective washout periods. After completion of Day 8 of Period 2, participants will receive a follow-up phone call about 5 days after their discharge.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Physician-diagnosis of T2DM * On a stable dose of metformin 2000 mg per day for at least 3 months prior to screening. * stable glycaemic control indicated by no change in treatment for diabetes within 3 months prior to screening * HbA1c (Hemoglobin A1c) ≤ 8.5% at screening * Body Mass Index (BMI) within the range 18.5 to 35 kg/m2 , inclusive, at screening.
Exclusion criteria
* Physician diagnosis of type 1 diabetes. * History of any clinically important disease or disorder. * History or presence of chronic Gastrointestinal, hepatic, renal, or pancreatic disease * History of Human immunodeficiency viruses (HIV) infection or a positive HIV test. * History of prior episode(s) of lactic acidosis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean glucose levels | Day 7 | Mean glucose levels on Day 7 of each treatment period as assessed by Continuous Glucose Monitoring (CGM) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CGM Metric (Time in range) | Day 7 of each treatment period | The percentage of time (or hours/day) that blood glucose levels remain within a target |
| CGM Metric (Time in tight range) | Day 7 of each treatment period | A metric measuring the percentage of time blood glucose remains between a pre-defined range. |
| CGM Metric (time below range) | Day 7 of each treatment period | A metric representing the percentage of time and minutes per day spent with blood glucose below a certain range. |
| CGM Metric (time above range) | Day 7 of each treatment period | A metric representing the percentage of time and minutes per day spent with blood glucose above a certain range. |
| CGM Metric (AUC(0-24)) | Day 7 of each treatment period | area under the concentration-time curve from time 0 to 24 hours postdose |
| CGM Measure (Plasma fasting glucose) | Day 7 of each treatment period | A measure of glucose levels when a participant is in a fasting state. |
| CGM Measure (AUC(0-4) after each meal) | Day 7 of each treatment period | area under the concentration-time curve from time 0 to 4 hours postdose after each meal |
| CGM Measure (Total glucose AUC(0-24)) | Day 7 of each treatment period | area under the concentration-time curve from time 0 to 24 hours postdose |
| Metformin Plasma PK (AUC(0-12)) | Day 7 of each treatment period | area under the concentration-time curve from time 0 to 12 hours postdose |
| Metformin Plasma PK (Cmax) | Day 7 of each treatment period | maximum observed concentration |
| Metformin Plasma PK (tmax) | Day 7 of each treatment period | time to reach maximum observed plasma concentration |
| Metformin Plasma PK (t1/2λz) | Day 7 of each treatment period | Terminal elimination half-life |
| Metformin Plasma PK (CL/F) | Day 7 of each treatment period | apparent total body clearance |
| Metformin Plasma PK (Vz/F) | Day 7 of each treatment period | apparent volume of distribution during the terminal phase. |
| Metformin Plasma PK (R AUC(0-12)) | Day 7 of each treatment period | Ratio of test to reference based on AUC(0-12) |
| Metformin Plasma PK (R Cmax) | Day 7 of each treatment period | Ratio of test to reference based on Cmax |
| Metformin Urine PK (Ae(0-12)) | Day 7 of each treatment period | cumulative amount excreted into the urine from time 0 to 12 hours postdose |
| Metformin Urine PK (fe(0-12)) | Day 7 of each treatment period | Percentage of dose excreted unchanged in urine from time zero to 12 hours post-dose |
| Metformin Urine PK (CLR) | Day 7 of each treatment period | renal clearance from plasma |
| AZD6793 plasma PK (AUC(0-24)) | Days 1 through 7 of each treatment period | area under the concentration-time curve from time 0 to 24 hours postdose |
| AZD6793 plasma PK (Cmax) | Days 1 through 7 of each treatment period | maximum observed concentration |
| AZD6793 plasma PK (tmax) | Days 1 through 7 of each treatment period | time to reach maximum observed plasma concentration |
| AZD6793 plasma PK (t1/2λz) | Days 1 through 7 of each treatment period | Terminal elimination half-life |
| AZD6793 plasma PK (Ctrough) | Days 1 through 7 of each treatment period | concentration observed immediately prior to dosing |
| AZD6793 plasma PK (Rac AUC(0-24)) | Days 1 through 7 of each treatment period | accumulation ratio based on AUC(0-24) |
| AZD6793 plasma PK (Rac Cmax) | Days 1 through 7 of each treatment period | Accumulation ration based on Cmax |
Countries
Germany
Outcome results
None listed