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A study to assess the Pharmacodynamics of oral AR-C165395XX after Administration of Repeated Doses for 3 days in Subjects with Type 2 Diabetes Mellitus
A Single Centre, Double-blind, Randomised, Placebo-controlled, Cross-over Phase I Study to Assess the Pharmacodynamics of oral AR-C165395XX after Administration of Repeated Doses for 3 days in Subjects with Type 2 Diabetes Mellitus
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AR-C165395XX + placebo | Experimental | 1st period AR-C165395XX 2nd period placebo |
|
| Placebo + AR-C165395XX | Placebo Comparator | 1st period Placebo for AR-C165395XX 2nd period AR-C165395XX |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AR-C165395XX | Drug | Oral dose of AR-C165395XX (tablets) |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to Endpoint MMTT AUC(0-4h) for Plasma Glucose | MMTT=Mixed Meal Tolerance Test AUC=Area Under Curve | Day -1 to Day 3 and Day 6 to Day 9 |
| Change From Baseline to Endpoint MMTT C_max for Plasma Glucose | Day -1 to Day 3 and Day 6 to Day 9 | |
| Change From Baseline to Endpoint GGI AUC(1-2h) for Plasma C-Peptide | GGI=Glucose and GLP1 infusion AUC=Area Under Curve | Day -1 to Day 3 and Day 6 to Day 9 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to Endpoint MMTT AUC(0-4h) for Plasma Insulin | Day -1 to Day 3 and Day 6 to Day 9 | |
| Change From Baseline MMTT AUC(0-4h) for Plasma Glucagon | Day -1 to Day 3 and Day 6 to Day 9 |
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Inclusion Criteria
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Liliana Uribe-Bruce, MD, MCI | Profil Institute for Clinical Research, Inc. | Principal Investigator |
| Stanko Skrtic, MD, PhD | AstraZeneca R&D Mölndal | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Chula Vista | California | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30557325 | Derived | Skrtic S, Tyrberg B, Broberg M, Ericsson H, Schnecke V, Kjaer M, Hompesch M, Andersson EM, Ryberg E, Aivazidis A, Wennberg Huldt C, Lofgren L, Morrow L, Parkinson J, Ryden-Bergsten T, Watkins E, Sorhede Winzell M. Exploring the insulin secretory properties of the PGD2-GPR44/DP2 axis in vitro and in a randomized phase-1 trial of type 2 diabetes patients. PLoS One. 2018 Dec 17;13(12):e0208998. doi: 10.1371/journal.pone.0208998. eCollection 2018. |
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30 patients were enrolled in the study. 10 of these were screen failures, leaving 20 patients who started the started the study.
Male or female T2DM patients of non-childbearing potential aged >=18 with 7.5<=HbA1c<=11%, 19\
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| ID | Title | Description |
|---|---|---|
| FG000 | AZD1981-Placebo | Sequence AZD1981-Placebo |
| FG001 | Placebo-AZD1981 | Sequence Placebo-AZD1981 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | AZD1981-Placebo | Sequence AZD1981-Placebo |
| BG001 | Placebo-AZD1981 | Sequence Placebo-AZD1981 |
| 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 | Change From Baseline to Endpoint MMTT AUC(0-4h) for Plasma Glucose | MMTT=Mixed Meal Tolerance Test AUC=Area Under Curve | One value per subject and treatment. AZD1981 value calculated at Day -1 to Day 3 if subject in sequence AZ1981-Placebo or at Day 6 to Day 9 if subject in sequence Placebo-AZD1981. Placebo value calculated at Day -1 to Day 3 if subject in sequence Placebo-AZD1981 and at Day 6 to Day 9 if subject in sequence AZD1981-Placebo. | Posted | Geometric Mean | Standard Deviation | h*nmol/L | Day -1 to Day 3 and Day 6 to Day 9 |
|
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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 | AZD1981 | AZD1981, oral tablet |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Stanko Skrtic, MD, PhD | AstraZeneca | ClinicalTrialTransparency@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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| Placebo |
| Other |
Oral dose of placebo for AR-C165395XX (tablets) |
|
| Change From Baseline to Endpoint MMTT AUC(0-4h) for Plasma C-Peptide | Day -1 to Day 3 and Day 6 to Day 9 |
| Change From Baseline to Endpoint GGI AUC(0-1h) for Plasma Insulin | Day -1 to Day 3 and Day 6 to Day 9 |
| Change From Baseline to Endpoint GGI AUC(1-2h) for Plasma Insulin | Day -1 to Day 3 and Day 6 to Day 9 |
| Change From Baseline to Endpoint GGI AUC(0-1h) for Plasma Glucagon | Day -1 to Day 3 and Day 6 to Day 9 |
| Change From Baseline to Endpoint GGI AUC(1-2h) for Plasma Glucagon | Day -1 to Day 3 and Day 6 to Day 9 |
| Change From Baseline to Endpoint Fasting Beta-cell Responsiveness | Day -1 to Day 3 and Day 6 to Day 9 |
| Fasting Insulin at Endpoint | Day 3 and Day 9 |
| Maximum Plasma AZD1981 Concentration at Steady-State, C_ss,Max | Days 2,3,8,9 |
| Time of Maximum Plasma AZD1081 Concentration, t_ss,Max | Days 2,3,8,9 |
| Plasma AZD1981 AUC(0-1h) | Days 2,3,8,9 |
| Plasma AZD1981 AUC(0-2h) | Days 2,3,8,9 |
| Minimum Plasma AZD1981 Concentration at Steady-State, C_ss,Min | Days 2,3,8,9 |
| Plasma AZD1981 AUC(1-2h) | Days 2,3,8,9 |
| Plasma Paracetamol Maximum Concentration, C_max | Days 3,9 |
| Time of Maximum Plasma Paracetamol Concentration, t_max | Days 3,9 |
| Plasma Paracetamol AUC(0-t) | Days 3,9 |
| Change From Baseline to Endpoint GGI AUC(0-1h) for Plasma C-Peptide | Day -1 to Day 3 and Day 6 to Day 9 |
| Change From Baseline to Endpoint GGI AUC(0-24h) for Plasma Glucose | Day -1 to Day 3 and Day 6 to Day 9 |
| Plasma AZD1981 AUC(0-4h) | Days 2,3,8,9 |
| Plasma AZD1981 AUC(0-12h) | Days 2,3,8,9 |
| Plasma AZD1981 AUC(0-24h) | Days 2,3,8,9 |
| Apparent Oral Plasma AZD1981 at Steady-State, CL_ss/F | Days 2,3,8,9 |
| BG002 |
| Total |
Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Weight | Mean | Standard Deviation | kg |
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| Height | Mean | Standard Deviation | cm |
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| Body Mass Index | Mean | Standard Deviation | kg/m2 |
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| T2DM disease duration | Mean | Standard Deviation | Years |
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| Current Metformin Daily Dose | Mean | Standard Deviation | mg |
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| HbA1c | Percentage of glycosylated hemoglobin, DCCT | Mean | Standard Deviation | % |
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| Primary | Change From Baseline to Endpoint MMTT C_max for Plasma Glucose | One value per subject and treatment. AZD1981 value calculated at Day -1 to Day 3 if subject in sequence AZ1981-Placebo or at Day 6 to Day 9 if subject in sequence Placebo-AZD1981. Placebo value calculated at Day -1 to Day 3 if subject in sequence Placebo-AZD1981 and at Day 6 to Day 9 if subject in sequence AZD1981-Placebo. | Posted | Geometric Mean | Standard Deviation | nmol/L | Day -1 to Day 3 and Day 6 to Day 9 |
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| Primary | Change From Baseline to Endpoint GGI AUC(1-2h) for Plasma C-Peptide | GGI=Glucose and GLP1 infusion AUC=Area Under Curve | One value per subject and treatment. AZD1981 value calculated at Day -1 to Day 3 if subject in sequence AZ1981-Placebo or at Day 6 to Day 9 if subject in sequence Placebo-AZD1981. Placebo value calculated at Day -1 to Day 3 if subject in sequence Placebo-AZD1981 and at Day 6 to Day 9 if subject in sequence AZD1981-Placebo. | Posted | Geometric Mean | Standard Deviation | h*pmol/L | Day -1 to Day 3 and Day 6 to Day 9 |
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| Secondary | Change From Baseline to Endpoint MMTT AUC(0-4h) for Plasma Insulin | One value per subject and treatment. AZD1981 value calculated at Day -1 to Day 3 if subject in sequence AZ1981-Placebo or at Day 6 to Day 9 if subject in sequence Placebo-AZD1981. Placebo value calculated at Day -1 to Day 3 if subject in sequence Placebo-AZD1981 and at Day 6 to Day 9 if subject in sequence AZD1981-Placebo. | Posted | Geometric Mean | Standard Deviation | h*mU/L | Day -1 to Day 3 and Day 6 to Day 9 |
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| Secondary | Change From Baseline MMTT AUC(0-4h) for Plasma Glucagon | One value per subject and treatment. AZD1981 value calculated at Day -1 to Day 3 if subject in sequence AZ1981-Placebo or at Day 6 to Day 9 if subject in sequence Placebo-AZD1981. Placebo value calculated at Day -1 to Day 3 if subject in sequence Placebo-AZD1981 and at Day 6 to Day 9 if subject in sequence AZD1981-Placebo. | Posted | Geometric Mean | Standard Deviation | h*pmol/L | Day -1 to Day 3 and Day 6 to Day 9 |
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| Secondary | Change From Baseline to Endpoint MMTT AUC(0-4h) for Plasma C-Peptide | One value per subject and treatment. AZD1981 value calculated at Day -1 to Day 3 if subject in sequence AZ1981-Placebo or at Day 6 to Day 9 if subject in sequence Placebo-AZD1981. Placebo value calculated at Day -1 to Day 3 if subject in sequence Placebo-AZD1981 and at Day 6 to Day 9 if subject in sequence AZD1981-Placebo. | Posted | Geometric Mean | Standard Deviation | h*pmol/L | Day -1 to Day 3 and Day 6 to Day 9 |
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| Secondary | Change From Baseline to Endpoint GGI AUC(0-1h) for Plasma Insulin | One value per subject and treatment. AZD1981 value calculated at Day -1 to Day 3 if subject in sequence AZ1981-Placebo or at Day 6 to Day 9 if subject in sequence Placebo-AZD1981. Placebo value calculated at Day -1 to Day 3 if subject in sequence Placebo-AZD1981 and at Day 6 to Day 9 if subject in sequence AZD1981-Placebo. | Posted | Geometric Mean | Standard Deviation | h*mU/L | Day -1 to Day 3 and Day 6 to Day 9 |
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| Secondary | Change From Baseline to Endpoint GGI AUC(1-2h) for Plasma Insulin | One value per subject and treatment. AZD1981 value calculated at Day -1 to Day 3 if subject in sequence AZ1981-Placebo or at Day 6 to Day 9 if subject in sequence Placebo-AZD1981. Placebo value calculated at Day -1 to Day 3 if subject in sequence Placebo-AZD1981 and at Day 6 to Day 9 if subject in sequence AZD1981-Placebo. | Posted | Geometric Mean | Standard Deviation | h*mU/L | Day -1 to Day 3 and Day 6 to Day 9 |
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| Secondary | Change From Baseline to Endpoint GGI AUC(0-1h) for Plasma Glucagon | One value per subject and treatment. AZD1981 value calculated at Day -1 to Day 3 if subject in sequence AZ1981-Placebo or at Day 6 to Day 9 if subject in sequence Placebo-AZD1981. Placebo value calculated at Day -1 to Day 3 if subject in sequence Placebo-AZD1981 and at Day 6 to Day 9 if subject in sequence AZD1981-Placebo. | Posted | Geometric Mean | Standard Deviation | h*mmol/L | Day -1 to Day 3 and Day 6 to Day 9 |
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| Secondary | Change From Baseline to Endpoint GGI AUC(1-2h) for Plasma Glucagon | One value per subject and treatment. AZD1981 value calculated at Day -1 to Day 3 if subject in sequence AZ1981-Placebo or at Day 6 to Day 9 if subject in sequence Placebo-AZD1981. Placebo value calculated at Day -1 to Day 3 if subject in sequence Placebo-AZD1981 and at Day 6 to Day 9 if subject in sequence AZD1981-Placebo. | Posted | Geometric Mean | Standard Deviation | h*mmol/L | Day -1 to Day 3 and Day 6 to Day 9 |
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| Secondary | Change From Baseline to Endpoint Fasting Beta-cell Responsiveness | One value per subject and treatment. AZD1981 value calculated at Day -1 to Day 3 if subject in sequence AZ1981-Placebo or at Day 6 to Day 9 if subject in sequence Placebo-AZD1981. Placebo value calculated at Day -1 to Day 3 if subject in sequence Placebo-AZD1981 and at Day 6 to Day 9 if subject in sequence AZD1981-Placebo. | Posted | Least Squares Mean | Standard Error | 10^-9*(L/kg)*min | Day -1 to Day 3 and Day 6 to Day 9 |
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| Secondary | Fasting Insulin at Endpoint | One value per subject and treatment. AZD1981 value calculated at Day 3 if subject in sequence AZD1981-Placebo or at Day 9 if subject in sequence Placebo-AZD1981. Placebo value calculated at Day 3 if subject in sequence Placebo-AZD1981 or at Day 9 if subject in sequence AZD1981-Placebo. | Posted | Least Squares Mean | Standard Error | UIU/ML | Day 3 and Day 9 |
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| Secondary | Maximum Plasma AZD1981 Concentration at Steady-State, C_ss,Max | One value per subject and method (MMTT/GGI). Value calculated on days 2 and 3 if subject in sequence AZD1981-Placebo or on days 8 and 9 if subject in sequence Placebo-AZD1981. | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol/L | Days 2,3,8,9 |
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| Secondary | Time of Maximum Plasma AZD1081 Concentration, t_ss,Max | One value per subject and method (MMTT/GGI). Value calculated on days 2 and 3 if subject in sequence AZD1981-Placebo or on days 8 and 9 if subject in sequence Placebo-AZD1981. | Posted | Median | Full Range | h | Days 2,3,8,9 |
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| Secondary | Plasma AZD1981 AUC(0-1h) | One value per subject and method (MMTT/GGI). Value calculated on days 2 and 3 if subject in sequence AZD1981-Placebo or on days 8 and 9 if subject in sequence Placebo-AZD1981. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*nmol/L | Days 2,3,8,9 |
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| Secondary | Plasma AZD1981 AUC(0-2h) | One value per subject and method (MMTT/GGI). Value calculated on days 2 and 3 if subject in sequence AZD1981-Placebo or on days 8 and 9 if subject in sequence Placebo-AZD1981. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*nmol/L | Days 2,3,8,9 |
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| Secondary | Minimum Plasma AZD1981 Concentration at Steady-State, C_ss,Min | One value per subject and method (MMTT/GGI). Value calculated on days 2 and 3 if subject in sequence AZD1981-Placebo or on days 8 and 9 if subject in sequence Placebo-AZD1981. | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol/L | Days 2,3,8,9 |
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| Secondary | Plasma AZD1981 AUC(1-2h) | One value per subject and method (MMTT/GGI). Value calculated on days 2 and 3 if subject in sequence AZD1981-Placebo or on days 8 and 9 if subject in sequence Placebo-AZD1981. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*nmol/L | Days 2,3,8,9 |
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| Secondary | Plasma Paracetamol Maximum Concentration, C_max | One value per subject and treatment. AZD1981 value calculated at Day 3 if subject in sequence AZD1981-Placebo or at Day 9 if subject in sequence Placebo-AZD1981. Placebo value calculated at Day 3 if subject in sequence Placebo-AZD1981 or at Day 9 if subject in sequence AZD1981-Placebo. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Days 3,9 |
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| Secondary | Time of Maximum Plasma Paracetamol Concentration, t_max | One value per subject and treatment. AZD1981 value calculated at Day 3 if subject in sequence AZD1981-Placebo or at Day 9 if subject in sequence Placebo-AZD1981. Placebo value calculated at Day 3 if subject in sequence Placebo-AZD1981 or at Day 9 if subject in sequence AZD1981-Placebo. | Posted | Median | Full Range | h | Days 3,9 |
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| Secondary | Plasma Paracetamol AUC(0-t) | One value per subject and treatment. AZD1981 value calculated at Day 3 if subject in sequence AZD1981-Placebo or at Day 9 if subject in sequence Placebo-AZD1981. Placebo value calculated at Day 3 if subject in sequence Placebo-AZD1981 or at Day 9 if subject in sequence AZD1981-Placebo. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/ML | Days 3,9 |
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| Secondary | Change From Baseline to Endpoint GGI AUC(0-1h) for Plasma C-Peptide | One value per subject and treatment. AZD1981 value calculated at Day -1 to Day 3 if subject in sequence AZ1981-Placebo or at Day 6 to Day 9 if subject in sequence Placebo-AZD1981. Placebo value calculated at Day -1 to Day 3 if subject in sequence Placebo-AZD1981 and at Day 6 to Day 9 if subject in sequence AZD1981-Placebo. | Posted | Geometric Mean | Standard Deviation | h*pmol/L | Day -1 to Day 3 and Day 6 to Day 9 |
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| Secondary | Change From Baseline to Endpoint GGI AUC(0-24h) for Plasma Glucose | One value per subject and treatment. AZD1981 value calculated at Day -1 to Day 3 if subject in sequence AZ1981-Placebo or at Day 6 to Day 9 if subject in sequence Placebo-AZD1981. Placebo value calculated at Day -1 to Day 3 if subject in sequence Placebo-AZD1981 and at Day 6 to Day 9 if subject in sequence AZD1981-Placebo. | Posted | Geometric Mean | Standard Deviation | h*mmol/L | Day -1 to Day 3 and Day 6 to Day 9 |
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| Secondary | Plasma AZD1981 AUC(0-4h) | One value per subject and method (MMTT/GGI). Value calculated on days 2 and 3 if subject in sequence AZD1981-Placebo or on days 8 and 9 if subject in sequence Placebo-AZD1981. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*nmol/L | Days 2,3,8,9 |
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| Secondary | Plasma AZD1981 AUC(0-12h) | One value per subject and method (MMTT/GGI). Value calculated on days 2 and 3 if subject in sequence AZD1981-Placebo or on days 8 and 9 if subject in sequence Placebo-AZD1981. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*nmol/L | Days 2,3,8,9 |
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| Secondary | Plasma AZD1981 AUC(0-24h) | One value per subject and method (MMTT/GGI). Value calculated on days 2 and 3 if subject in sequence AZD1981-Placebo or on days 8 and 9 if subject in sequence Placebo-AZD1981. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*nmol/L | Days 2,3,8,9 |
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| Secondary | Apparent Oral Plasma AZD1981 at Steady-State, CL_ss/F | One value per subject and method (MMTT/GGI). Value calculated on days 2 and 3 if subject in sequence AZD1981-Placebo or on days 8 and 9 if subject in sequence Placebo-AZD1981. | Posted | Mean | Standard Deviation | L/h | Days 2,3,8,9 |
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| 0 |
| 20 |
| 5 |
| 20 |
| EG001 | Placebo | Placebo, oral tablet | 0 | 20 | 6 | 20 |
| Diarrhoea | Gastrointestinal disorders | Systematic Assessment |
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| Abdominal distension | Gastrointestinal disorders | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
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| Frequent bowel movements | Gastrointestinal disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | Systematic Assessment |
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| Vessel puncture site haemorrhage | General disorders | Systematic Assessment |
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| Local swelling | General disorders | Systematic Assessment |
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| Vessel puncture site reaction | General disorders | Systematic Assessment |
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| Insomnia | Psychiatric disorders | Systematic Assessment |
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| Dermatitis contact | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| D004700 | Endocrine System Diseases |