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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 Metformin
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AZD1656 | Experimental | 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 |
|
| Placebo | Placebo Comparator | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZD1656 | Drug | Subjects will be treated with tolerable dose twice daily for another 24 days. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Number of participants with clinically relevant change of laboratory variables (clinical chemistry, haematology and urinalysis parameters | Measured regularly from day before first dose to day after last dose |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Measured last day of treatment |
| Maximum Plasma Concentration of AZD1656 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Klas Malmberg, MD, PhD, Prof | AstraZeneca R&D Mölndal | Study Director |
| Emanuel P DeNoia, M.D | Healthcare Discoveries LLC Icon Development Solutions | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | San Antonio | Texas | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Experimental | AZD1656 |
| FG001 | Placebo Comparator | Placebo |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Experimental | AZD1656 |
| BG001 | Placebo Comparator | Placebo |
| BG002 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Systolic Blood Pressure, Change From Baseline to End of Treatment | Posted | Mean | Standard Deviation | mmHg | Baseline is pre-dose first day of dosing, end of treatment is the morning following the treatment period |
|
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Experimental | AZD1656 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Rapid Atrial Fibrillation | Cardiac disorders | MedDRA 12.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Supraventricular Tachycardia | Cardiac disorders | MedDRA 10.0 | Systematic Assessment |
The primary objective of the study was to assess safety and tolerability and hence the study was not sized based on statistical considerations. The most import outcome, "no safety or tolerability concerns were identified", is not a numerical variable
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Gerard Lynch | AstraZeneca | aztrial_results_posting@astrazeneca.com |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C576407 | AZD1656 |
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| Placebo |
| Drug |
Subjects will be treated with tolerable dose twice daily for another 24 days. |
|
Dose-adjusted to a morning dose of 50 mg due to titrated doses
| Measured last day of treatment |
| Time to Reach Maximum Plasma Concentration of AZD1656 | Measured last day of treatment |
| Terminal Elimination Half-life of AZD1656 | Measured following the afternoon dose last day of treatment |
| Apparent Oral Clearance of AZD1656 | Measured last day of treatment |
| P-Glucose (AUC0-24)/24, Change From Baseline to End of Treatment | Log ratio (End of treatment/Baseline) has been analysed in a mixed-effect ANOVA model, using treatment as fixed effect 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. | Baseline is the day before first dose, end of treatment is last day of treatment |
| S-Insulin (AUC0-24)/24, Change From Baseline to End of Treatment | Log ratio (End of treatment/Baseline) has been analysed in a mixed-effect ANOVA model, using treatment as fixed effect 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. | Baseline is the day before first dose, end of treatment is last day of treatment |
| S-C-Peptide (AUC0-24)/24, Change From Baseline to End of Treatment | Log ratio (End of treatment/Baseline) has been analysed in a mixed-effect ANOVA model, using treatment as fixed effect 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. | Baseline is the day before first dose, end of treatment is last day of treatment |
| Protocol Violation |
|
| Study-specific discontinuation criteria |
|
| Poor venous access |
|
| Total |
Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
| Primary | Diastolic Blood Pressure, Change From Baseline to End of Treatment | Posted | Mean | Standard Deviation | mmHg | Baseline is pre-dose first day of dosing, end of treatment is the morning following the treatment period |
|
|
|
| Primary | Pulse, Change From Baseline to End of Treatment | Posted | Mean | Standard Deviation | beats/min | Baseline is pre-dose first day of dosing, end of treatment is the morning following the treatment period |
|
|
|
| Primary | Weight, Change From Baseline to End of Treatment | Posted | Mean | Standard Deviation | kg | Baseline is the day before first dose, end of treatment is last day of treatment |
|
|
|
| Primary | Clinically Relevant Change of Laboratory Variables | Number of participants with clinically relevant change of laboratory variables (clinical chemistry, haematology and urinalysis parameters | Posted | Number | Participants | Measured regularly from day before first dose to day after last dose |
|
|
|
| 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 | Posted | Geometric Mean | Standard Deviation | umol*h/L | Measured last day of treatment |
|
|
|
| Secondary | Maximum Plasma Concentration of AZD1656 | Dose-adjusted to a morning dose of 50 mg due to titrated doses | Posted | Geometric Mean | Standard Deviation | umol/L | Measured last day of treatment |
|
|
|
| Secondary | Time to Reach Maximum Plasma Concentration of AZD1656 | Posted | Median | Full Range | h | Measured last day of treatment |
|
|
|
| Secondary | Terminal Elimination Half-life of AZD1656 | Posted | Geometric Mean | Full Range | h | Measured following the afternoon dose last day of treatment |
|
|
|
| Secondary | Apparent Oral Clearance of AZD1656 | Posted | Geometric Mean | Full Range | L/h | Measured last day of treatment |
|
|
|
| Secondary | P-Glucose (AUC0-24)/24, Change From Baseline to End of Treatment | Log ratio (End of treatment/Baseline) has been analysed in a mixed-effect ANOVA model, using treatment as fixed effect 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. | Posted | Least Squares Mean | 95% Confidence Interval | Relative ratio in percent | Baseline is the day before first dose, end of treatment is last day of treatment |
|
|
|
| Secondary | S-Insulin (AUC0-24)/24, Change From Baseline to End of Treatment | Log ratio (End of treatment/Baseline) has been analysed in a mixed-effect ANOVA model, using treatment as fixed effect 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. | Posted | Least Squares Mean | 95% Confidence Interval | Relative ratio in percent | Baseline is the day before first dose, end of treatment is last day of treatment |
|
|
|
| Secondary | S-C-Peptide (AUC0-24)/24, Change From Baseline to End of Treatment | Log ratio (End of treatment/Baseline) has been analysed in a mixed-effect ANOVA model, using treatment as fixed effect 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. | Posted | Least Squares Mean | 95% Confidence Interval | Relative ratio in percent | Baseline is the day before first dose, end of treatment is last day of treatment |
|
|
|
| 1 |
| 19 |
| 15 |
| 19 |
| EG001 | Placebo Comparator | Placebo | 0 | 8 | 7 | 8 |
| Vertigo Positional | Ear and labyrinth disorders | MedDRA 10.0 | Systematic Assessment |
|
| Vision Blurred | Eye disorders | MedDRA 10.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 10.0 | Systematic Assessment |
|
| Hordeolum | Infections and infestations | MedDRA 10.0 | Systematic Assessment |
|
| Excoriation | Injury, poisoning and procedural complications | MedDRA 10.0 | Systematic Assessment |
|
| Skin Laceration | Injury, poisoning and procedural complications | MedDRA 10.0 | Systematic Assessment |
|
| Blood Glucose Decreased | Injury, poisoning and procedural complications | MedDRA 10.0 | Systematic Assessment |
|
| Costochondritis | Musculoskeletal and connective tissue disorders | MedDRA 10.0 | Systematic Assessment |
|
| Muscle Spasms | Musculoskeletal and connective tissue disorders | MedDRA 10.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 10.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 10.0 | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA 10.0 | Systematic Assessment |
|
| Rhinitis Allergic | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 10.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 10.0 | Systematic Assessment |
|
| Skin Irritation | Skin and subcutaneous tissue disorders | MedDRA 10.0 | Systematic Assessment |
|
| Supraventricular Tachycardia | Cardiac disorders | MedDRA 12.0 | Systematic Assessment |
|
CONTRACT RESEARCH ORGANIZATION AGREEMENT by and between ASTRAZENECA AB and the CRO. CRO agrees that AstraZeneca shall have the exclusive right to publish the results of the Study, including all Work Product, and that such results may not be published or otherwise disseminated by CRO without the prior written approval of AstraZeneca.
| D004700 | Endocrine System Diseases |