Type II Diabetes
Conditions
Keywords
Type II Diabetes
Brief summary
The purpose of this study is to assess the 1 month safety and tolerability after multiple oral doses of AZD1656 in patients with Type 2 Diabetes Mellitus Treated with Insulin
Interventions
DRUGAZD1656
Tolerable dose given twice daily
DRUGPlacebo
Tolerable dose given twice daily
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
30 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* type II diabetes patients, female with non child-bearing potential * Subjects with T2DM diagnosis for at least one year, treated with insulin alone or insulin in combination with other anti-diabetic drugs. Subjects must have been treated with insulin the last 3 months prior to enrolment (screening) * HbA1c \<11% at enrolment (screening) (HbA1c value according to international Diabetes Control and Complications Trial \[DCCT\] standard). * FPG in the range of 7.0 to 13.0 mmol/L (126 to 234 mg/dL)
Exclusion criteria
* History of ischemic heart disease, symptomatic heart failure, stroke, transitory ischemic attack or symptomatic peripheral vascular disease * Use of glitazones, warfarin, amiodarone within 3 months prior to enrolment (screening) and use of potent CYP450 inhibitors, eg, ketoconazole and macrolide antibiotics within 14 days before randomisation. * Any clinically significant abnormality identified on physical examination, laboratory tests or ECG, which in the judgment of the investigator would compromise the patients' safety or successful participation in the clinical study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Systolic Blood Pressure, Change From Baseline to End of Treatment | Baseline is pre-dose first day of dosing, end of treatment is the morning following the treatment period | — |
| Diastolic Blood Pressure, Change From Baseline to End of Treatment | Baseline is pre-dose first day of dosing, end of treatment is the morning following the treatment period | — |
| Pulse, Change From Baseline to End of Treatment | Baseline is pre-dose first day of dosing, end of treatment is the morning following the treatment period | — |
| Weight, Change From Baseline to End of Treatment | Baseline is the day before first dose, end of treatment is last day of treatment | — |
| Clinically Relevant Change of Laboratory Variables | Measured regularly from day before first dose to day after last dose | Number of participants with clinically relevant change of laboratory variables (clinical chemistry, haematology and urinalysis parameters |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| P-Glucose (AUC0-24)/24, Change From Baseline to End of Treatment | Baseline is the day before first dose, end of treatment is last day of treatment | Log ratio (End of treatment/Baseline) has been analysed in an ANCOVA model, using treatment as fixed factor and log(Baseline) as covariate. Resulting estimates have been back-transformed from the log-scale and then multiplied by 100 to obtain the relative ratio (end of treatment/placebo) in percent. Changes in percent have been obtained by subtraction by 100. |
| Area Under the Plasma Concentration vs Time Curve (AUC0-24) of AZD1656 | Measured last day of treatment | Dose-adjusted to a total daily dose of 100 mg due to titrated doses |
| S-C-Peptide (AUC0-24)/24, Change From Baseline to End of Treatment | Baseline is the day before first dose, end of treatment is last day of treatment | Log ratio (End of treatment/Baseline) has been analysed in an ANCOVA model, using treatment as fixed factor and log(Baseline) as covariate. Resulting estimates have been back-transformed from the log-scale and then multiplied by 100 to obtain the relative ratio (end of treatment/placebo) in percent. Changes in percent have been obtained by subtraction by 100. |
| S-Insulin (AUC0-24)/24, Change From Baseline to End of Treatment | Baseline is the day before first dose, end of treatment is last day of treatment | Log ratio (End of treatment/Baseline) has been analysed in an ANCOVA model, using treatment as fixed factor and log(Baseline) as covariate. Resulting estimates have been back-transformed from the log-scale and then multiplied by 100 to obtain the relative ratio (end of treatment/placebo) in percent. Changes in percent have been obtained by subtraction by 100 |
| Maximum Plasma Concentration of AZD1656 | Measured following the morning dose last day of treatment | Dose-adjusted to a morning dose of 50 mg due to titrated doses |
| Time to Reach Maximum Plasma Concentration of AZD1656 | Measured last day of treatment | — |
| Terminal Elimination Half-life of AZD1656 | Measured following the evening dose last day of treatment | — |
| Apparent Oral Clearance of AZD1656 | Measured last day of treatment | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Experimental AZD1656 dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days | 15 |
| Placebo Comparator placebo Dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days | 5 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Experimental | Placebo Comparator | Total |
|---|---|---|---|
| Age Continuous | 52.6 years | 57.2 years | 53.8 years |
| Sex: Female, Male Female | 9 Participants | 3 Participants | 12 Participants |
| Sex: Female, Male Male | 6 Participants | 2 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 15 | 3 / 5 |
| serious Total, serious adverse events | 0 / 15 | 0 / 5 |
Outcome results
Primary
Clinically Relevant Change of Laboratory Variables
Number of participants with clinically relevant change of laboratory variables (clinical chemistry, haematology and urinalysis parameters
Time frame: Measured regularly from day before first dose to day after last dose
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental | Clinically Relevant Change of Laboratory Variables | 0 Participants |
| Placebo Comparator | Clinically Relevant Change of Laboratory Variables | 0 Participants |
Primary
Diastolic Blood Pressure, Change From Baseline to End of Treatment
Time frame: Baseline is pre-dose first day of dosing, end of treatment is the morning following the treatment period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental | Diastolic Blood Pressure, Change From Baseline to End of Treatment | 3.4 mmHg | Standard Deviation 7.6 |
| Placebo Comparator | Diastolic Blood Pressure, Change From Baseline to End of Treatment | 0.6 mmHg | Standard Deviation 2.9 |
Primary
Pulse, Change From Baseline to End of Treatment
Time frame: Baseline is pre-dose first day of dosing, end of treatment is the morning following the treatment period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental | Pulse, Change From Baseline to End of Treatment | 0.7 beats/min | Standard Deviation 4.4 |
| Placebo Comparator | Pulse, Change From Baseline to End of Treatment | -5.4 beats/min | Standard Deviation 4 |
Primary
Systolic Blood Pressure, Change From Baseline to End of Treatment
Time frame: Baseline is pre-dose first day of dosing, end of treatment is the morning following the treatment period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental | Systolic Blood Pressure, Change From Baseline to End of Treatment | 0.4 mmHg | Standard Deviation 8.5 |
| Placebo Comparator | Systolic Blood Pressure, Change From Baseline to End of Treatment | 5.0 mmHg | Standard Deviation 6.4 |
Primary
Weight, Change From Baseline to End of Treatment
Time frame: Baseline is the day before first dose, end of treatment is last day of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental | Weight, Change From Baseline to End of Treatment | -0.54 kg | Standard Deviation 1.65 |
| Placebo Comparator | Weight, Change From Baseline to End of Treatment | -1.32 kg | Standard Deviation 1.18 |
Secondary
Apparent Oral Clearance of AZD1656
Time frame: Measured last day of treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Experimental | Apparent Oral Clearance of AZD1656 | 9.382 L/h |
Secondary
Area Under the Plasma Concentration vs Time Curve (AUC0-24) of AZD1656
Dose-adjusted to a total daily dose of 100 mg due to titrated doses
Time frame: Measured last day of treatment
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Experimental | Area Under the Plasma Concentration vs Time Curve (AUC0-24) of AZD1656 | 23.49 umol*h/L |
Secondary
Maximum Plasma Concentration of AZD1656
Dose-adjusted to a morning dose of 50 mg due to titrated doses
Time frame: Measured following the morning dose last day of treatment
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Experimental | Maximum Plasma Concentration of AZD1656 | 2.415 umol/L |
Secondary
P-Glucose (AUC0-24)/24, Change From Baseline to End of Treatment
Log ratio (End of treatment/Baseline) has been analysed in an ANCOVA model, using treatment as fixed factor and log(Baseline) as covariate. Resulting estimates have been back-transformed from the log-scale and then multiplied by 100 to obtain the relative ratio (end of treatment/placebo) in percent. Changes in percent have been obtained by subtraction by 100.
Time frame: Baseline is the day before first dose, end of treatment is last day of treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Experimental | P-Glucose (AUC0-24)/24, Change From Baseline to End of Treatment | -7 relative change in percent |
| Placebo Comparator | P-Glucose (AUC0-24)/24, Change From Baseline to End of Treatment | 4 relative change in percent |
Secondary
S-C-Peptide (AUC0-24)/24, Change From Baseline to End of Treatment
Log ratio (End of treatment/Baseline) has been analysed in an ANCOVA model, using treatment as fixed factor and log(Baseline) as covariate. Resulting estimates have been back-transformed from the log-scale and then multiplied by 100 to obtain the relative ratio (end of treatment/placebo) in percent. Changes in percent have been obtained by subtraction by 100.
Time frame: Baseline is the day before first dose, end of treatment is last day of treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Experimental | S-C-Peptide (AUC0-24)/24, Change From Baseline to End of Treatment | -4 relative change in percent |
| Placebo Comparator | S-C-Peptide (AUC0-24)/24, Change From Baseline to End of Treatment | -3 relative change in percent |
Secondary
S-Insulin (AUC0-24)/24, Change From Baseline to End of Treatment
Log ratio (End of treatment/Baseline) has been analysed in an ANCOVA model, using treatment as fixed factor and log(Baseline) as covariate. Resulting estimates have been back-transformed from the log-scale and then multiplied by 100 to obtain the relative ratio (end of treatment/placebo) in percent. Changes in percent have been obtained by subtraction by 100
Time frame: Baseline is the day before first dose, end of treatment is last day of treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Experimental | S-Insulin (AUC0-24)/24, Change From Baseline to End of Treatment | -2 relative change in percent |
| Placebo Comparator | S-Insulin (AUC0-24)/24, Change From Baseline to End of Treatment | -29 relative change in percent |
Secondary
Terminal Elimination Half-life of AZD1656
Time frame: Measured following the evening dose last day of treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Experimental | Terminal Elimination Half-life of AZD1656 | 5.239 h |
Secondary
Time to Reach Maximum Plasma Concentration of AZD1656
Time frame: Measured last day of treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental | Time to Reach Maximum Plasma Concentration of AZD1656 | 0.500 h |