Trial Outcomes & Findings for The PK and PD of Dapagliflozin Therapy in Combination With Insulin in Japanese Subjects With T1DM (NCT NCT02582840)

NCT ID: NCT02582840

Last Updated: 2019-01-18

Results Overview

Serial blood samples for determination of study drug were collected predose Day 1, Day 7 (60 minutes prior to dose), Day 7 (0, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose).

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 42 participants
• Primary outcome timeframe: Day 1-7
• Results posted on: 2019-01-18

Participant Flow

26 October 2015 to 04 June 2016, Japan, patients with type 1 diabetes mellitus.

Of 62 patients who signed informed consent, 42 eligible patients randomized and completed the 7-day treatment period (Part A) of the study.

Participant milestones

Measure	Placebo + Insulin Placebo administered orally once daily in the morning.	Dapagliflozin 5mg + Insulin Dapagliflozin 5 mg administered orally once daily in the morning.	Dapagliflozin 10 mg + Insulin Dapagliflozin 10 mg administered orally once daily in the morning.
Overall Study STARTED	14	14	14
Overall Study COMPLETED	14	14	14
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

The PK and PD of Dapagliflozin Therapy in Combination With Insulin in Japanese Subjects With T1DM

Baseline characteristics by cohort

Measure	Placebo + Insulin n=14 Participants Placebo administered orally once daily in the morning.	Dapagliflozin 5mg + Insulin n=14 Participants Dapagliflozin 5 mg administered orally once daily in the morning.	Dapagliflozin 10 mg + Insulin n=14 Participants Dapagliflozin 10 mg administered orally once daily in the morning.	Total n=42 Participants Total of all reporting groups
Age, Continuous	42.6 years STANDARD_DEVIATION 10.62 • n=5 Participants	37.0 years STANDARD_DEVIATION 10.05 • n=7 Participants	37.1 years STANDARD_DEVIATION 10.21 • n=5 Participants	38.9 years STANDARD_DEVIATION 10.38 • n=4 Participants
Age, Customized <45 Years	10 Participants n=5 Participants	10 Participants n=7 Participants	10 Participants n=5 Participants	30 Participants n=4 Participants
Age, Customized >=45 Years	4 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	12 Participants n=4 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants	24 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	8 Participants n=7 Participants	7 Participants n=5 Participants	18 Participants n=4 Participants
Race/Ethnicity, Customized Asian	14 Participants n=5 Participants	14 Participants n=7 Participants	14 Participants n=5 Participants	42 Participants n=4 Participants
Region of Enrollment Japan	14 Participants n=5 Participants	14 Participants n=7 Participants	14 Participants n=5 Participants	42 Participants n=4 Participants
Duration of Type 1 Diabetes	16.89 years STANDARD_DEVIATION 10.530 • n=5 Participants	15.94 years STANDARD_DEVIATION 9.235 • n=7 Participants	14.69 years STANDARD_DEVIATION 12.368 • n=5 Participants	15.84 years STANDARD_DEVIATION 10.561 • n=4 Participants
Hemoglobin A1c (HbA1c)%	8.13 percent of hemoglobin STANDARD_DEVIATION 0.835 • n=5 Participants	7.91 percent of hemoglobin STANDARD_DEVIATION 0.610 • n=7 Participants	7.89 percent of hemoglobin STANDARD_DEVIATION 0.553 • n=5 Participants	7.98 percent of hemoglobin STANDARD_DEVIATION 0.669 • n=4 Participants
Fasting Plasma Glucose (FPG)	134.00 mg/dL STANDARD_DEVIATION 63.898 • n=5 Participants	142.93 mg/dL STANDARD_DEVIATION 49.930 • n=7 Participants	133.36 mg/dL STANDARD_DEVIATION 42.239 • n=5 Participants	136.76 mg/dL STANDARD_DEVIATION 51.675 • n=4 Participants
C-Peptide < 0.1 ng/mL	12 Participants 0.083 • n=5 Participants	13 Participants 0.107 • n=7 Participants	11 Participants 0.036 • n=5 Participants	0.12 Participants 0.079 • n=4 Participants
C-Peptide >= 0.1 ng/mL	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants

PRIMARY outcome

Timeframe: Day 1-7

Population: Pharmacokinetic set - Part A (PK-A): The PK set consisted of all randomized subjects who had at least one dose of randomized study medication for Part A and had an evaluable plasma concentration data of dapagliflozin and/or its major metabolite dapagliflozin 3-O-glucuronide.

Serial blood samples for determination of study drug were collected predose Day 1, Day 7 (60 minutes prior to dose), Day 7 (0, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose).

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=10 Participants Dapagliflozin 5 mg administered orally once daily in the morning.	Dapagliflozin 10mg + Insulin n=10 Participants Dapagliflozin 10 mg administered orally once daily in the morning.	Dapagliflozin 10mg + Insulin Dapagliflozin 10 mg administered orally once daily in the morning.
Dapagliflozin Maximum Observed Plasma Concentration (Cmax) of 7 Days Repeated Doses of Dapagliflozin - Pharmacokinetic (PK) Set	69.31 ng/mL Geometric Coefficient of Variation 26.42	162.09 ng/mL Geometric Coefficient of Variation 26.03	—

PRIMARY outcome

Timeframe: Day 1-7

Population: Pharmacokinetic set - Part A (PK-A): The PK set consisted of all randomized subjects who had at least one dose of randomized study medication for Part A and had an evaluable plasma concentration data of dapagliflozin and/or its major metabolite dapagliflozin 3-O-glucuronide.

Serial blood samples for determination of study drug were collected predose Day 1, Day 7 (60 minutes prior to dose), Day 7 (0, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose).

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=10 Participants Dapagliflozin 5 mg administered orally once daily in the morning.	Dapagliflozin 10mg + Insulin n=10 Participants Dapagliflozin 10 mg administered orally once daily in the morning.	Dapagliflozin 10mg + Insulin Dapagliflozin 10 mg administered orally once daily in the morning.
Dapagliflozin Minimum Observed Plasma Concentration (Cmin) of 7 Days Repeated Doses of Dapagliflozin - Pharmacokinetic (PK) Set	3.40 ng/mL Geometric Coefficient of Variation 80.14	5.71 ng/mL Geometric Coefficient of Variation 52.36	—

PRIMARY outcome

Timeframe: Day 1-7

Population: Pharmacokinetic set - Part A (PK-A): The PK set consisted of all randomized subjects who had at least one dose of randomized study medication for Part A and had an evaluable plasma concentration data of dapagliflozin and/or its major metabolite dapagliflozin 3-O-glucuronide.

Serial blood samples for determination of study drug were collected predose Day 1, Day 7 (60 minutes prior to dose), Day 7 (0, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose).

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=10 Participants Dapagliflozin 5 mg administered orally once daily in the morning.	Dapagliflozin 10mg + Insulin n=10 Participants Dapagliflozin 10 mg administered orally once daily in the morning.	Dapagliflozin 10mg + Insulin Dapagliflozin 10 mg administered orally once daily in the morning.
Dapagliflozin Time of Maximum Observed Plasma Concentration (Tmax) of 7 Days Repeated Doses of Dapagliflozin - Pharmacokinetic (PK) Set	2.00 hours Full Range 52.36 • Interval 1.0 to 3.0	2.00 hours Interval 1.0 to 3.0	—

PRIMARY outcome

Timeframe: Day 1-7

Population: Pharmacokinetic set - Part A (PK-A): The PK set consisted of all randomized subjects who had at least one dose of randomized study medication for Part A and had an evaluable plasma concentration data of dapagliflozin and/or its major metabolite dapagliflozin 3-O-glucuronide.

Serial blood samples for determination of study drug were collected predose Day 1, Day 7 (60 minutes prior to dose), Day 7 (0, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose).

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=10 Participants Dapagliflozin 5 mg administered orally once daily in the morning.	Dapagliflozin 10mg + Insulin n=10 Participants Dapagliflozin 10 mg administered orally once daily in the morning.	Dapagliflozin 10mg + Insulin Dapagliflozin 10 mg administered orally once daily in the morning.
Dapagliflozin Area Under the Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration AUC(0-T) of 7 Days Repeated Doses of Dapagliflozin - Pharmacokinetic (PK) Set	322.72 ng*h/mL Geometric Coefficient of Variation 44.69 • Interval 1.0 to 3.0	670.01 ng*h/mL Geometric Coefficient of Variation 36.92	—

PRIMARY outcome

Timeframe: Day 1-7

Population: Pharmacokinetic set - Part A (PK-A): The PK set consisted of all randomized subjects who had at least one dose of randomized study medication for Part A and had an evaluable plasma concentration data of dapagliflozin and/or its major metabolite dapagliflozin 3-O-glucuronide.

Serial blood samples for determination of study drug were collected predose Day 1, Day 7 (60 minutes prior to dose), Day 7 (0, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose).

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=10 Participants Dapagliflozin 5 mg administered orally once daily in the morning.	Dapagliflozin 10mg + Insulin n=10 Participants Dapagliflozin 10 mg administered orally once daily in the morning.	Dapagliflozin 10mg + Insulin Dapagliflozin 10 mg administered orally once daily in the morning.
Dapagliflozin 3-O-Glucuronide Maximum Observed Plasma Concentration (Cmax) of 7 Days Repeated Doses of Dapagliflozin - Pharmacokinetic (PK) Set	61.88 ng/mL Geometric Coefficient of Variation 31.95	136.62 ng/mL Geometric Coefficient of Variation 31.96	—

PRIMARY outcome

Timeframe: Day 1-7

Population: Pharmacokinetic set - Part A (PK-A): The PK set consisted of all randomized subjects who had at least one dose of randomized study medication for Part A and had an evaluable plasma concentration data of dapagliflozin and/or its major metabolite dapagliflozin 3-O-glucuronide.

Serial blood samples for determination of study drug were collected predose Day 1, Day 7 (60 minutes prior to dose), Day 7 (0, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose).

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=10 Participants Dapagliflozin 5 mg administered orally once daily in the morning.	Dapagliflozin 10mg + Insulin n=10 Participants Dapagliflozin 10 mg administered orally once daily in the morning.	Dapagliflozin 10mg + Insulin Dapagliflozin 10 mg administered orally once daily in the morning.
Dapagliflozin 3-O-Glucuronide Minimum Observed Plasma Concentration (Cmin) of 7 Days Repeated Doses of Dapagliflozin - Pharmacokinetic (PK) Set	3.89 ng/mL Geometric Coefficient of Variation 56.43	6.25 ng/mL Geometric Coefficient of Variation 35.45	—

PRIMARY outcome

Timeframe: Day 1-7

Population: Pharmacokinetic set - Part A (PK-A): The PK set consisted of all randomized subjects who had at least one dose of randomized study medication for Part A and had an evaluable plasma concentration data of dapagliflozin and/or its major metabolite dapagliflozin 3-O-glucuronide.

Serial blood samples for determination of study drug were collected predose Day 1, Day 7 (60 minutes prior to dose), Day 7 (0, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose).

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=10 Participants Dapagliflozin 5 mg administered orally once daily in the morning.	Dapagliflozin 10mg + Insulin n=10 Participants Dapagliflozin 10 mg administered orally once daily in the morning.	Dapagliflozin 10mg + Insulin Dapagliflozin 10 mg administered orally once daily in the morning.
Dapagliflozin 3-O-Glucuronide Time of Maximum Observed Plasma Concentration (Tmax) of 7 Days Repeated Doses of Dapagliflozin - Pharmacokinetic (PK) Set	2.00 hours Full Range 52.36 • Interval 1.0 to 4.0	2.00 hours Interval 1.0 to 3.0	—

PRIMARY outcome

Timeframe: Day 1-7

Population: Pharmacokinetic set - Part A (PK-A): The PK set consisted of all randomized subjects who had at least one dose of randomized study medication for Part A and had an evaluable plasma concentration data of dapagliflozin and/or its major metabolite dapagliflozin 3-O-glucuronide.

Serial blood samples for determination of study drug were collected predose Day 1, Day 7 (60 minutes prior to dose), Day 7 (0, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose).

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=10 Participants Dapagliflozin 5 mg administered orally once daily in the morning.	Dapagliflozin 10mg + Insulin n=10 Participants Dapagliflozin 10 mg administered orally once daily in the morning.	Dapagliflozin 10mg + Insulin Dapagliflozin 10 mg administered orally once daily in the morning.
Dapagliflozin 3-O-Glucuronide Area Under the Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration AUC(0-T) of 7 Days Repeated Doses of Dapagliflozin - Pharmacokinetic (PK) Set	345.87 ng*h/mL Geometric Coefficient of Variation 29.32 • Interval 1.0 to 3.0	675.50 ng*h/mL Geometric Coefficient of Variation 23.66	—

PRIMARY outcome

Timeframe: Day 1-7

Population: Pharmacokinetic set - Part A (PK-A): The PK set consisted of all randomized subjects who had at least one dose of randomized study medication for Part A and had an evaluable plasma concentration data of dapagliflozin and/or its major metabolite dapagliflozin 3-O-glucuronide.

Serial blood samples for determination of study drug were collected predose Day 1, Day 7 (60 minutes prior to dose), Day 7 (0, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose).

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=10 Participants Dapagliflozin 5 mg administered orally once daily in the morning.	Dapagliflozin 10mg + Insulin n=10 Participants Dapagliflozin 10 mg administered orally once daily in the morning.	Dapagliflozin 10mg + Insulin Dapagliflozin 10 mg administered orally once daily in the morning.
Dapagliflozin Ratio of Metabolite to Parent AUC of 7 Days Repeated Doses of Dapagliflozin - Pharmacokinetic (PK) Set	0.75 ratio Geometric Coefficient of Variation 44.26 • Interval 1.0 to 3.0	0.70 ratio Geometric Coefficient of Variation 30.40	—

PRIMARY outcome

Timeframe: Baseline (the last available assessment prior to the first dose of study medication), Day 7

Population: Pharmacodynamic set Part A (PD-A): The PD set consisted of all randomized subjects who received at least one dose of randomized study medication for Part A, and who had a non missing baseline value and at least one post-baseline value for at least one pharmacodynamic variable.

The 24-hour period is defined based on the morning void, from the first morning void to the one of the next day.

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=14 Participants Dapagliflozin 5 mg administered orally once daily in the morning.	Dapagliflozin 10mg + Insulin n=14 Participants Dapagliflozin 10 mg administered orally once daily in the morning.	Dapagliflozin 10mg + Insulin n=14 Participants Dapagliflozin 10 mg administered orally once daily in the morning.
24-hour Urinary Glucose (g/24h) Mean Change From Baseline on Day 7 - Pharmacodynamic (PD) Set	-6.16 g/24-hour Standard Deviation 30.337 • Interval 1.0 to 3.0	96.55 g/24-hour Standard Deviation 30.083	101.28 g/24-hour Standard Deviation 20.129

SECONDARY outcome

Timeframe: Baseline (the last available assessment on or prior to the first dose of study medication), Day 7

Population: Pharmacodynamic set Part A (PD-A): The PD set consisted of all randomized subjects who received at least one dose of randomized study medication for Part A, and who had a non missing baseline value and at least one post-baseline value for at least one pharmacodynamic variable.

Total daily insulin dose is defined as the sum of all insulin doses (basal+bolus+premixed) for each day. Mean percent change from baseline was calculated using the geometric mean back-transformed from the results calculated under the logarithm transformation.

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=14 Participants Dapagliflozin 5 mg administered orally once daily in the morning.	Dapagliflozin 10mg + Insulin n=14 Participants Dapagliflozin 10 mg administered orally once daily in the morning.	Dapagliflozin 10mg + Insulin n=14 Participants Dapagliflozin 10 mg administered orally once daily in the morning.
Total Daily Insulin (IU) Percent Change From Baseline to Day 7 - Pharmacodynamic (PD) Set	-4.97 percent chagne Standard Error 5.280 • Interval 1.0 to 3.0	-36.86 percent chagne Standard Error 3.324	-39.13 percent chagne Standard Error 2.675

SECONDARY outcome

Timeframe: Baseline (the last available assessment on or prior to the first dose of study medication), Day 7

Population: Pharmacodynamic set Part A (PD-A): The PD set consisted of all randomized subjects who received at least one dose of randomized study medication for Part A, and who had a non missing baseline value and at least one post-baseline value for at least one pharmacodynamic variable.

Mean percent change from baseline was calculated using the geometric mean back-transformed from the results calculated under the logarithm transformation.

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=14 Participants Dapagliflozin 5 mg administered orally once daily in the morning.	Dapagliflozin 10mg + Insulin n=14 Participants Dapagliflozin 10 mg administered orally once daily in the morning.	Dapagliflozin 10mg + Insulin n=14 Participants Dapagliflozin 10 mg administered orally once daily in the morning.
Daily Basal Insulin (IU) Percent Change From Baseline to Day 7 - Pharmacodynamic (PD) Set	-16.75 percent change Standard Error 7.215 • Interval 1.0 to 3.0	-36.74 percent change Standard Error 5.671	-39.63 percent change Standard Error 3.466

SECONDARY outcome

Timeframe: Baseline (the last available assessment on or prior to the first dose of study medication), Day 7

Population: Pharmacodynamic set Part A (PD-A): The PD set consisted of all randomized subjects who received at least one dose of randomized study medication for Part A, and who had a non missing baseline value and at least one post-baseline value for at least one pharmacodynamic variable.

Mean percent change from baseline was calculated using the geometric mean back-transformed from the results calculated under the logarithm transformation.

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=14 Participants Dapagliflozin 5 mg administered orally once daily in the morning.	Dapagliflozin 10mg + Insulin n=14 Participants Dapagliflozin 10 mg administered orally once daily in the morning.	Dapagliflozin 10mg + Insulin n=14 Participants Dapagliflozin 10 mg administered orally once daily in the morning.
Daily Bolus Insulin (IU) Percent Change From Baseline to Day 7 - Pharmacodynamic (PD) Set	4.56 percent change Standard Error 5.905 • Interval 1.0 to 3.0	-36.06 percent change Standard Error 4.238	-39.89 percent change Standard Error 3.367

SECONDARY outcome

Timeframe: Baseline (the last available assessment on or prior to the first dose of study medication), Day 7

Population: Pharmacodynamic set Part A (PD-A): The PD set consisted of all randomized subjects who received at least one dose of randomized study medication for Part A, and who had a non missing baseline value and at least one post-baseline value for at least one pharmacodynamic variable.

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=14 Participants Dapagliflozin 5 mg administered orally once daily in the morning.	Dapagliflozin 10mg + Insulin n=14 Participants Dapagliflozin 10 mg administered orally once daily in the morning.	Dapagliflozin 10mg + Insulin n=14 Participants Dapagliflozin 10 mg administered orally once daily in the morning.
Fasting Plasma Glucose (FPG) (mg/dL) Change From Baseline to Day 7 - Pharmacodynamic (PD) Set	11.0 mg/dL Standard Deviation 41.31 • Interval 1.0 to 3.0	-10.4 mg/dL Standard Deviation 62.10	-13.1 mg/dL Standard Deviation 44.69

SECONDARY outcome

Timeframe: Baseline (the last available assessment on or prior to the first dose of study medication), Day 7

Population: Pharmacodynamic set Part A (PD-A): The PD set consisted of all randomized subjects who received at least one dose of randomized study medication for Part A, and who had a non missing baseline value and at least one post-baseline value for at least one pharmacodynamic variable.

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=14 Participants Dapagliflozin 5 mg administered orally once daily in the morning.	Dapagliflozin 10mg + Insulin n=14 Participants Dapagliflozin 10 mg administered orally once daily in the morning.	Dapagliflozin 10mg + Insulin n=14 Participants Dapagliflozin 10 mg administered orally once daily in the morning.
Seated Systolic Blood Pressure (mmHG) Change From Baseline to Day 7 - Pharmacodynamic (PD) Set	-3.1 mmHG Standard Deviation 7.81 • Interval 1.0 to 3.0	-2.1 mmHG Standard Deviation 7.71	1.5 mmHG Standard Deviation 10.66

Adverse Events

Placebo + Insulin

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Dapagliflozin 5mg + Insulin

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Dapagliflozin 10 mg + Insulin

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Placebo + Insulin n=14 participants at risk Placebo administered orally once daily in the morning.	Dapagliflozin 5mg + Insulin n=14 participants at risk Dapagliflozin 5 mg administered orally once daily in the morning.	Dapagliflozin 10 mg + Insulin n=14 participants at risk Dapagliflozin 10 mg administered orally once daily in the morning.
General disorders THIRST	0.00% 0/14 • Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days.	7.1% 1/14 • Number of events 1 • Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days.	28.6% 4/14 • Number of events 4 • Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days.
General disorders MALAISE	0.00% 0/14 • Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days.	0.00% 0/14 • Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days.	7.1% 1/14 • Number of events 1 • Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days.
Infections and infestations MUMPS	0.00% 0/14 • Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days.	0.00% 0/14 • Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days.	7.1% 1/14 • Number of events 1 • Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days.
Infections and infestations SINUSITIS	0.00% 0/14 • Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days.	0.00% 0/14 • Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days.	7.1% 1/14 • Number of events 1 • Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days.
Infections and infestations INFLUENZA	7.1% 1/14 • Number of events 1 • Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days.	0.00% 0/14 • Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days.	0.00% 0/14 • Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days.
Investigations URINE OUTPUT INCREASED	0.00% 0/14 • Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days.	0.00% 0/14 • Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days.	14.3% 2/14 • Number of events 2 • Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days.
Metabolism and nutrition disorders DECREASED APPETITE	0.00% 0/14 • Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days.	0.00% 0/14 • Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days.	7.1% 1/14 • Number of events 1 • Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days.
Renal and urinary disorders POLLAKIURIA	0.00% 0/14 • Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days.	14.3% 2/14 • Number of events 2 • Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days.	14.3% 2/14 • Number of events 2 • Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days.

Additional Information

Yu Shimizuishi

AstraZeneca K.K.

Phone: 81 6 7711 4669

Email: Yu.Shimizuishi@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER