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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 Insulin
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | 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 |
|
| 2 | 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 | Tolerable dose given twice daily |
| |
| Placebo |
| 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 |
| Marcus Hompesch, MD | Profil Institut for Clinical Research Inc. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Chula Vista | California | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | Placebo Comparator |
| 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 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 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal Pain Upper | Gastrointestinal disorders | MedDRA 12.0 | 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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| Drug |
Tolerable dose given twice daily |
|
Dose-adjusted to a morning dose of 50 mg due to titrated doses
| Measured following the morning dose 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 evening 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 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. | 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 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 | 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 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. | Baseline is the day before first dose, end of treatment is last day of treatment |
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
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Units | Counts |
|---|---|
| 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 | 95% Confidence Interval | 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 | 95% Confidence Interval | umol/L | Measured following the morning dose 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 | Mean | Full Range | h | Measured following the evening dose last day of treatment |
|
|
|
| Secondary | Apparent Oral Clearance of AZD1656 | Posted | 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 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. | Posted | Least Squares Mean | 95% Confidence Interval | relative change 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 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 | Posted | Least Squares Mean | 95% Confidence Interval | relative change 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 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. | Posted | Least Squares Mean | 95% Confidence Interval | relative change in percent | Baseline is the day before first dose, end of treatment is last day of treatment |
|
|
|
| 0 |
| 15 |
| 13 |
| 15 |
| EG001 | 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 | 0 | 5 | 3 | 5 |
| Diarrhoea | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Non-Cardiac Chest Pain | General disorders | MedDRA (12.0) | Systematic Assessment |
|
| Pain | General disorders | MedDRA (12.0) | Systematic Assessment |
|
| Upper Respiratory Tract Infection | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
|
| Urinary Tract Infection | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
|
| Application Site Reaction | Injury, poisoning and procedural complications | MedDRA (12.0) | Systematic Assessment |
|
| Catheter Site Pain | Injury, poisoning and procedural complications | MedDRA (12.0) | Systematic Assessment |
|
| Blood Glucose Decreased | Investigations | MedDRA (12.0) | Systematic Assessment |
|
| Iron Deficiency Anaemia | Metabolism and nutrition disorders | MedDRA (12.0) | Systematic Assessment |
|
| Oedema Peripheral | Metabolism and nutrition disorders | MedDRA (12.0) | Systematic Assessment |
|
| Limb Discomfort | Musculoskeletal and connective tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Pain In Extremity | Musculoskeletal and connective tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Restless Legs Syndrome | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Ecchymosis | Vascular 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 |