Type 2 Diabetes Mellitus
Conditions
Keywords
patients, glycaemic control on metformin
Brief summary
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
Detailed description
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
Interventions
DRUGAR-C165395XX
Oral dose of AR-C165395XX (tablets)
OTHERPlacebo
Oral dose of placebo for AR-C165395XX (tablets)
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* Provision of informed consent * Male or female of non-childbearing potential (postmenopausal, and/or have undergone hysterectomy and/or bilateral oophorectomy or salpingectomy/tubal ligation) aged ≥18. * Patients with HbA1c ≥7.5 but ≤11% at enrolment visit (Visit 1) * ody mass index \>19 to \<38 kg/m2 * he fasting plasma glucose should be in the range of 3-14 mmol/L (54-252 mg/dL, nclusive) on the morning of Visit 1. * Clinical diagnosis of type 2 diabetes mellitus * Metformin as only anti-diabetic treatment, at least for the last 3 months
Exclusion criteria
* History or sign of any clinically significant disease or disorder which, in the opinion f the investigator, may either put the subject at risk because of participation in the sudy, or influence the results or the subject's ability to participate in the study * Any clinically significant abnormalities in clinical chemistry, haematology or urinalysis results as judged by the investigator * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) laboratory results \>3x upper level of normal range (ULN) Clinical diagnosis of Type 1 diabetes mellitus and/or history of diabetic ketoacidosis or positive Glutamic Acid Decarboxylase Autoantibodies test (GAD antibodies test). * Patients treated with single Insulin therapy within the last 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Endpoint MMTT AUC(0-4h) for Plasma Glucose | Day -1 to Day 3 and Day 6 to Day 9 | MMTT=Mixed Meal Tolerance Test AUC=Area Under Curve |
| 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 | Day -1 to Day 3 and Day 6 to Day 9 | GGI=Glucose and GLP1 infusion AUC=Area Under Curve |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Change From Baseline to Endpoint MMTT AUC(0-4h) for Plasma Insulin | Day -1 to Day 3 and Day 6 to Day 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 |
| Minimum Plasma AZD1981 Concentration at Steady-State, C_ss,Min | Days 2,3,8,9 |
| Change From Baseline MMTT AUC(0-4h) for Plasma Glucagon | Day -1 to Day 3 and Day 6 to Day 9 |
| Change From Baseline to Endpoint MMTT AUC(0-4h) for Plasma C-Peptide | Day -1 to Day 3 and Day 6 to Day 9 |
Countries
United States
Participant flow
Recruitment details
Male or female T2DM patients of non-childbearing potential aged \>=18 with 7.5\<=HbA1c\<=11%, 19\<BMI\<38 kg/m2, fasting plasma glucose in range 3-14 mmol/L and on Metformin as the only anti-diabetic treatment for the last 3 months
Pre-assignment details
30 patients were enrolled in the study. 10 of these were screen failures, leaving 20 patients who started the started the study.
Participants by arm
| Arm | Count |
|---|---|
| AZD1981-Placebo Sequence AZD1981-Placebo | 10 |
| Placebo-AZD1981 Sequence Placebo-AZD1981 | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | AZD1981-Placebo | Placebo-AZD1981 | Total |
|---|---|---|---|
| Age, Continuous | 53.10 Years STANDARD_DEVIATION 9.1 | 54.80 Years STANDARD_DEVIATION 6.8 | 54.00 Years STANDARD_DEVIATION 7.86 |
| Body Mass Index | 31.13 kg/m2 STANDARD_DEVIATION 3.58 | 32.13 kg/m2 STANDARD_DEVIATION 5.37 | 31.63 kg/m2 STANDARD_DEVIATION 4.47 |
| Current Metformin Daily Dose | 1765.00 mg STANDARD_DEVIATION 473.78 | 1895.00 mg STANDARD_DEVIATION 390.48 | 1830.00 mg STANDARD_DEVIATION 427.78 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 6 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 4 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| HbA1c | 9.50 % STANDARD_DEVIATION 1.24 | 9.30 % STANDARD_DEVIATION 0.88 | 9.40 % STANDARD_DEVIATION 1.06 |
| Height | 166.80 cm STANDARD_DEVIATION 10.7 | 164.90 cm STANDARD_DEVIATION 12.59 | 165.80 cm STANDARD_DEVIATION 11.41 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 7 Participants | 16 Participants |
| Sex: Female, Male Female | 2 Participants | 5 Participants | 7 Participants |
| Sex: Female, Male Male | 8 Participants | 5 Participants | 13 Participants |
| T2DM disease duration | 10.30 Years STANDARD_DEVIATION 4.24 | 8.60 Years STANDARD_DEVIATION 5.02 | 9.50 Years STANDARD_DEVIATION 4.61 |
| Weight | 87.28 kg STANDARD_DEVIATION 18.95 | 87.59 kg STANDARD_DEVIATION 20.36 | 87.44 kg STANDARD_DEVIATION 19.14 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 20 | 6 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Change From Baseline to Endpoint GGI AUC(1-2h) for Plasma C-Peptide
GGI=Glucose and GLP1 infusion AUC=Area Under Curve
Time frame: Day -1 to Day 3 and Day 6 to Day 9
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Change From Baseline to Endpoint GGI AUC(1-2h) for Plasma C-Peptide | 1.05 h*pmol/L | Standard Deviation 1.17 |
| Placebo | Change From Baseline to Endpoint GGI AUC(1-2h) for Plasma C-Peptide | 1.06 h*pmol/L | Standard Deviation 1.2 |
p-value: 0.4180% CI: [0.96, 1.03]Mixed Models Analysis
Primary
Change From Baseline to Endpoint MMTT AUC(0-4h) for Plasma Glucose
MMTT=Mixed Meal Tolerance Test AUC=Area Under Curve
Time frame: Day -1 to Day 3 and Day 6 to Day 9
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Change From Baseline to Endpoint MMTT AUC(0-4h) for Plasma Glucose | 0.92 h*nmol/L | Standard Deviation 1.14 |
| Placebo | Change From Baseline to Endpoint MMTT AUC(0-4h) for Plasma Glucose | 0.98 h*nmol/L | Standard Deviation 1.09 |
p-value: 0.0280% CI: [0.9, 0.98]Mixed Models Analysis
Primary
Change From Baseline to Endpoint MMTT C_max for Plasma Glucose
Time frame: Day -1 to Day 3 and Day 6 to Day 9
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Change From Baseline to Endpoint MMTT C_max for Plasma Glucose | 0.93 nmol/L | Standard Deviation 1.12 |
| Placebo | Change From Baseline to Endpoint MMTT C_max for Plasma Glucose | 0.97 nmol/L | Standard Deviation 1.09 |
p-value: 0.0680% CI: [0.92, 0.99]Mixed Models Analysis
Secondary
Apparent Oral Plasma AZD1981 at Steady-State, CL_ss/F
Time frame: Days 2,3,8,9
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Apparent Oral Plasma AZD1981 at Steady-State, CL_ss/F | 21.94 L/h | Standard Deviation 8.19 |
| Placebo | Apparent Oral Plasma AZD1981 at Steady-State, CL_ss/F | NA L/h | — |
Secondary
Change From Baseline MMTT AUC(0-4h) for Plasma Glucagon
Time frame: Day -1 to Day 3 and Day 6 to Day 9
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Change From Baseline MMTT AUC(0-4h) for Plasma Glucagon | 1.02 h*pmol/L | Standard Deviation 1.19 |
| Placebo | Change From Baseline MMTT AUC(0-4h) for Plasma Glucagon | 0.96 h*pmol/L | Standard Deviation 1.25 |
p-value: 0.1880% CI: [0.99, 1.13]Mixed Models Analysis
Secondary
Change From Baseline to Endpoint Fasting Beta-cell Responsiveness
Time frame: Day -1 to Day 3 and Day 6 to Day 9
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Change From Baseline to Endpoint Fasting Beta-cell Responsiveness | 0.01 10^-9*(L/kg)*min | Standard Error 0.01 |
| Placebo | Change From Baseline to Endpoint Fasting Beta-cell Responsiveness | -0.00 10^-9*(L/kg)*min | Standard Error 0.01 |
p-value: 0.4590% CI: [-0.01, 0.03]Mixed Models Analysis
Secondary
Change From Baseline to Endpoint GGI AUC(0-1h) for Plasma C-Peptide
Time frame: Day -1 to Day 3 and Day 6 to Day 9
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Change From Baseline to Endpoint GGI AUC(0-1h) for Plasma C-Peptide | 1.02 h*pmol/L | Standard Deviation 1.16 |
| Placebo | Change From Baseline to Endpoint GGI AUC(0-1h) for Plasma C-Peptide | 1.03 h*pmol/L | Standard Deviation 1.18 |
Secondary
Change From Baseline to Endpoint GGI AUC(0-1h) for Plasma Glucagon
Time frame: Day -1 to Day 3 and Day 6 to Day 9
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Change From Baseline to Endpoint GGI AUC(0-1h) for Plasma Glucagon | 1.01 h*mmol/L | Standard Deviation 1.08 |
| Placebo | Change From Baseline to Endpoint GGI AUC(0-1h) for Plasma Glucagon | 0.97 h*mmol/L | Standard Deviation 1.06 |
Secondary
Change From Baseline to Endpoint GGI AUC(0-1h) for Plasma Insulin
Time frame: Day -1 to Day 3 and Day 6 to Day 9
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Change From Baseline to Endpoint GGI AUC(0-1h) for Plasma Insulin | 1.01 h*mU/L | Standard Deviation 1.19 |
| Placebo | Change From Baseline to Endpoint GGI AUC(0-1h) for Plasma Insulin | 1.07 h*mU/L | Standard Deviation 1.35 |
Secondary
Change From Baseline to Endpoint GGI AUC(0-24h) for Plasma Glucose
Time frame: Day -1 to Day 3 and Day 6 to Day 9
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Change From Baseline to Endpoint GGI AUC(0-24h) for Plasma Glucose | 0.96 h*mmol/L | Standard Deviation 1.09 |
| Placebo | Change From Baseline to Endpoint GGI AUC(0-24h) for Plasma Glucose | 0.97 h*mmol/L | Standard Deviation 1.08 |
Secondary
Change From Baseline to Endpoint GGI AUC(1-2h) for Plasma Glucagon
Time frame: Day -1 to Day 3 and Day 6 to Day 9
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Change From Baseline to Endpoint GGI AUC(1-2h) for Plasma Glucagon | 1.01 h*mmol/L | Standard Deviation 1.06 |
| Placebo | Change From Baseline to Endpoint GGI AUC(1-2h) for Plasma Glucagon | 0.99 h*mmol/L | Standard Deviation 1.06 |
p-value: 0.0680% CI: [1, 1.04]Mixed Models Analysis
Secondary
Change From Baseline to Endpoint GGI AUC(1-2h) for Plasma Insulin
Time frame: Day -1 to Day 3 and Day 6 to Day 9
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Change From Baseline to Endpoint GGI AUC(1-2h) for Plasma Insulin | 1.03 h*mU/L | Standard Deviation 1.25 |
| Placebo | Change From Baseline to Endpoint GGI AUC(1-2h) for Plasma Insulin | 1.04 h*mU/L | Standard Deviation 1.27 |
p-value: 0.3780% CI: [0.91, 1.06]Mixed Models Analysis
Secondary
Change From Baseline to Endpoint MMTT AUC(0-4h) for Plasma C-Peptide
Time frame: Day -1 to Day 3 and Day 6 to Day 9
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Change From Baseline to Endpoint MMTT AUC(0-4h) for Plasma C-Peptide | 1.01 h*pmol/L | Standard Deviation 1.15 |
| Placebo | Change From Baseline to Endpoint MMTT AUC(0-4h) for Plasma C-Peptide | 1.09 h*pmol/L | Standard Deviation 1.14 |
p-value: 0.0480% CI: [0.89, 0.98]Mixed Models Analysis
Secondary
Change From Baseline to Endpoint MMTT AUC(0-4h) for Plasma Insulin
Time frame: Day -1 to Day 3 and Day 6 to Day 9
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Change From Baseline to Endpoint MMTT AUC(0-4h) for Plasma Insulin | 0.99 h*mU/L | Standard Deviation 1.23 |
| Placebo | Change From Baseline to Endpoint MMTT AUC(0-4h) for Plasma Insulin | 1.08 h*mU/L | Standard Deviation 1.16 |
p-value: 0.0680% CI: [0.85, 0.99]Mixed Models Analysis
Secondary
Fasting Insulin at Endpoint
Time frame: Day 3 and Day 9
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Fasting Insulin at Endpoint | 11.70 UIU/ML | Standard Error 1.48 |
| Placebo | Fasting Insulin at Endpoint | 11.40 UIU/ML | Standard Error 1.48 |
Secondary
Maximum Plasma AZD1981 Concentration at Steady-State, C_ss,Max
Time frame: Days 2,3,8,9
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Maximum Plasma AZD1981 Concentration at Steady-State, C_ss,Max | 2507 nmol/L | Geometric Coefficient of Variation 71.09 |
| Placebo | Maximum Plasma AZD1981 Concentration at Steady-State, C_ss,Max | 3662 nmol/L | Geometric Coefficient of Variation 86.9 |
Secondary
Minimum Plasma AZD1981 Concentration at Steady-State, C_ss,Min
Time frame: Days 2,3,8,9
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Minimum Plasma AZD1981 Concentration at Steady-State, C_ss,Min | 202.40 nmol/L | Geometric Coefficient of Variation 39.12 |
| Placebo | Minimum Plasma AZD1981 Concentration at Steady-State, C_ss,Min | 376.20 nmol/L | Geometric Coefficient of Variation 83.28 |
Secondary
Plasma AZD1981 AUC(0-12h)
Time frame: Days 2,3,8,9
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Plasma AZD1981 AUC(0-12h) | 12460 h*nmol/L | Geometric Coefficient of Variation 36.79 |
| Placebo | Plasma AZD1981 AUC(0-12h) | NA h*nmol/L | — |
Secondary
Plasma AZD1981 AUC(0-1h)
Time frame: Days 2,3,8,9
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Plasma AZD1981 AUC(0-1h) | 701.30 h*nmol/L | Geometric Coefficient of Variation 122.3 |
| Placebo | Plasma AZD1981 AUC(0-1h) | 2061 h*nmol/L | Geometric Coefficient of Variation 74.66 |
Secondary
Plasma AZD1981 AUC(0-24h)
Time frame: Days 2,3,8,9
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Plasma AZD1981 AUC(0-24h) | 24930 h*nmol/L | Geometric Coefficient of Variation 36.79 |
| Placebo | Plasma AZD1981 AUC(0-24h) | NA h*nmol/L | — |
Secondary
Plasma AZD1981 AUC(0-2h)
Time frame: Days 2,3,8,9
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Plasma AZD1981 AUC(0-2h) | 2071 h*nmol/L | Geometric Coefficient of Variation 97.56 |
| Placebo | Plasma AZD1981 AUC(0-2h) | 5016 h*nmol/L | Geometric Coefficient of Variation 75.91 |
Secondary
Plasma AZD1981 AUC(0-4h)
Time frame: Days 2,3,8,9
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Plasma AZD1981 AUC(0-4h) | 5793 h*nmol/L | Geometric Coefficient of Variation 53.96 |
| Placebo | Plasma AZD1981 AUC(0-4h) | NA h*nmol/L | — |
Secondary
Plasma AZD1981 AUC(1-2h)
Time frame: Days 2,3,8,9
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Plasma AZD1981 AUC(1-2h) | 1344 h*nmol/L | Geometric Coefficient of Variation 88.76 |
| Placebo | Plasma AZD1981 AUC(1-2h) | 2936 h*nmol/L | Geometric Coefficient of Variation 78.72 |
Secondary
Plasma Paracetamol AUC(0-t)
Time frame: Days 3,9
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Plasma Paracetamol AUC(0-t) | 19730 h*ng/ML | Geometric Coefficient of Variation 46.64 |
| Placebo | Plasma Paracetamol AUC(0-t) | 18850 h*ng/ML | Geometric Coefficient of Variation 26.38 |
Secondary
Plasma Paracetamol Maximum Concentration, C_max
Time frame: Days 3,9
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Plasma Paracetamol Maximum Concentration, C_max | 8074 ng/mL | Geometric Coefficient of Variation 37.32 |
| Placebo | Plasma Paracetamol Maximum Concentration, C_max | 7899 ng/mL | Geometric Coefficient of Variation 30.51 |
Secondary
Time of Maximum Plasma AZD1081 Concentration, t_ss,Max
Time frame: Days 2,3,8,9
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD1981 | Time of Maximum Plasma AZD1081 Concentration, t_ss,Max | 2.00 h |
| Placebo | Time of Maximum Plasma AZD1081 Concentration, t_ss,Max | 1.00 h |
Secondary
Time of Maximum Plasma Paracetamol Concentration, t_max
Time frame: Days 3,9
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD1981 | Time of Maximum Plasma Paracetamol Concentration, t_max | 3.50 h |
| Placebo | Time of Maximum Plasma Paracetamol Concentration, t_max | 3.50 h |