Study to investigate the safety and efficacy of high dose of Symbicort® SMART in Japanese patients

Study identifier:D589LC00003

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A comparison of tolerability of 10 inhalations of Symbicort® Turbuhaler® 160/4.5 μg and 10 inhalations of terbutaline Turbuhaler® 0.4 mg on top of Symbicort® Turbuhaler® 160/4.5 μg 1 inhalation bid, randomized, double-blind, cross over, phase III study in Japanese adults asthma patients

Medical condition

asthma

Phase

Phase 3

Healthy volunteers

Study drug

Symbicort Turbuhaler, Terbutaline Turbuhaler

Sex

All

Actual Enrollment

Study type

Interventional

Age

16 Years - 65 Years

Date

Study Start Date: 01 Jan 2009

Primary Completion Date: 01 Jul 2009

Study Completion Date: 01 Jul 2009

Study design

Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Aug 2012 by AstraZeneca Pharmaceuticals

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Tokyo, Japan

Location

Research Site

Ibaragi, Japan

Arms	Assigned Interventions
Experimental: First Symbicort, then Terbutaline Symbicort Turbuhaler 160/4.5μg for 3 days First , then Terbutaline Turbuhaler 0.4 mg for 3 days	Drug: Symbicort Turbuhaler 160/4.5μg for 3 days Drug: Terbutaline Turbuhaler 0.4 mg for 3 days
Experimental: First Turbuhaler, then Symbicort Terbutaline Turbuhaler 0.4 mg for 3 days First, then Symbicort Turbuhaler 160/4.5μg for 3 days,	Drug: Symbicort Turbuhaler 160/4.5μg for 3 days Drug: Terbutaline Turbuhaler 0.4 mg for 3 days

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Patients recruited from 2 hospitals in Japan between January 2009 and July 2009. 28 patients enrolled; 25 patients randomized, 3 patients were not randomized (1 due to incorrect enrollment and 2 due to adverse event)

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Symbicort First, then Terbutaline	Symbicort Turbuhaler 160/4.5μg for 3 days First , then Terbutaline Turbuhaler 0.4 mg for 3 days
Terbutaline First, then Symbicort	Terbutaline Turbuhaler 0.4 mg for 3 days First, then Symbicort Turbuhaler 160/4.5μg for 3 days,

Participant Flow for 3 periods

Period 1: First Intervention

	Symbicort First, then Terbutaline	Terbutaline First, then Symbicort
STARTED	13	12
COMPLETED	13	12
NOT COMPLETED	0	0

Period 2: Washout period of 7 - 14 days

	Symbicort First, then Terbutaline	Terbutaline First, then Symbicort
STARTED	13	12
COMPLETED	11	12
NOT COMPLETED	2	0
Adverse Event	2	0

Period 3: Second Intervention

	Symbicort First, then Terbutaline	Terbutaline First, then Symbicort
STARTED	11	12
COMPLETED	11	12
NOT COMPLETED	0	0

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
All study participants

Baseline Measures

	All study participants
Number of Participants [units: Participants]	25
Age Continuous [units: years] Mean ± Standard Deviation	44.3 ± 14.8
Gender, Male/Female [units: Participants]
Female	15
Male	10

Outcome Measures

1. Primary Outcome Measure: Adverse events [ Time Frame: 3 days ]

Measure Type	Primary
Measure Name	Adverse events
Measure Description	Total number of adverse events
Time Frame	3 days
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Symbicort	Symbicort Turbuhaler 160/4.5μg
Terbutaline	Terbutaline Turbuhaler 0.4 mg

Measured Values

	Symbicort	Terbutaline
Number of Participants Analyzed [units:participants]	25	23
Adverse events [units: adverse events]	14	24

No statistical analysis provided for Adverse events

2. Primary Outcome Measure: Serum potassium - Average concentration from trapezoidal Area Under the Curve (AUC) [ Time Frame: up to 740 min after start dosing for each treatment day ]

Measure Type	Primary
Measure Name	Serum potassium - Average concentration from trapezoidal Area Under the Curve (AUC)
Measure Description	The mean AUC value was calculated as AUC (calculated using the trapezoidal method) divided by the length of the sampling period.
Time Frame	up to 740 min after start dosing for each treatment day
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Symbicort	Symbicort Turbuhaler 160/4.5μg
Terbutaline	Terbutaline Turbuhaler 0.4 mg

Measured Values

	Symbicort	Terbutaline
Number of Participants Analyzed [units:participants]	25	23
Serum potassium - Average concentration from trapezoidal Area Under the Curve (AUC) [units: mEq/L] Mean (Standard Deviation)	4.01 (0.25)	3.88 (0.26)

No statistical analysis provided for Serum potassium - Average concentration from trapezoidal Area Under the Curve (AUC)

3. Primary Outcome Measure: Blood glucose - Average concentration from trapezoidal Area Under the Curve (AUC) [ Time Frame: up to 140 min after start dosing for each treatment day ]

Measure Type	Primary
Measure Name	Blood glucose - Average concentration from trapezoidal Area Under the Curve (AUC)
Measure Description	The mean AUC value was calculated as AUC (calculated using the trapezoidal method) divided by the length of the sampling period.
Time Frame	up to 140 min after start dosing for each treatment day
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Symbicort	Symbicort Turbuhaler 160/4.5μg
Terbutaline	Terbutaline Turbuhaler 0.4 mg

Measured Values

	Symbicort	Terbutaline
Number of Participants Analyzed [units:participants]	25	23
Blood glucose - Average concentration from trapezoidal Area Under the Curve (AUC) [units: mg/dLiters] Mean (Standard Deviation)	121.1 (20.3)	129.5 (22.0)

No statistical analysis provided for Blood glucose - Average concentration from trapezoidal Area Under the Curve (AUC)

4. Primary Outcome Measure: Electrocardiogram (ECG)- Average Trapezoidal Area Under the Curve (AUC) [ Time Frame: up to 740 min after start dosing for each treatment day ]

Measure Type	Primary
Measure Name	Electrocardiogram (ECG)- Average Trapezoidal Area Under the Curve (AUC)
Measure Description	The mean AUC of QTcF (ECG interval measured from the beginning of the Q wave to the end of the T wave, corrected for heart rate using Fridericia’s formula)was calculated as AUC (calculated using the trapezoidal method) divided by the length of the sampling period.
Time Frame	up to 740 min after start dosing for each treatment day
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Symbicort	Symbicort Turbuhaler 160/4.5μg
Terbutaline	Terbutaline Turbuhaler 0.4 mg

Measured Values

	Symbicort	Terbutaline
Number of Participants Analyzed [units:participants]	25	23
Electrocardiogram (ECG)- Average Trapezoidal Area Under the Curve (AUC) [units: ms] Mean (Standard Deviation)	411.71 (15.07)	414.33 (14.04)

No statistical analysis provided for Electrocardiogram (ECG)- Average Trapezoidal Area Under the Curve (AUC)

5. Primary Outcome Measure: Vital sign (blood pressure)- Average Trapezoidal Area Under the Curve (AUC) [ Time Frame: up to 740 min after start dosing for each treatment day ]

Measure Type	Primary
Measure Name	Vital sign (blood pressure)- Average Trapezoidal Area Under the Curve (AUC)
Measure Description	The mean AUC value was calculated as AUC (calculated using the trapezoidal method) divided by the length of the sampling period.
Time Frame	up to 740 min after start dosing for each treatment day
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Symbicort	Symbicort Turbuhaler 160/4.5μg
Terbutaline	Terbutaline Turbuhaler 0.4 mg

Measured Values

	Symbicort	Terbutaline
Number of Participants Analyzed [units:participants]	25	23
Vital sign (blood pressure)- Average Trapezoidal Area Under the Curve (AUC) [units: mmHg] Mean (Standard Deviation)	115.3 (6.3)	114.9 (8.0)

No statistical analysis provided for Vital sign (blood pressure)- Average Trapezoidal Area Under the Curve (AUC)

6. Primary Outcome Measure: Vital sign (pulse rate)- Average Trapezoidal Area Under the Curve (AUC) [ Time Frame: up to 740 min after start dosing for each treatment day ]

Measure Type	Primary
Measure Name	Vital sign (pulse rate)- Average Trapezoidal Area Under the Curve (AUC)
Measure Description	The mean AUC value was calculated as AUC (calculated using the trapezoidal method) divided by the length of the sampling period.
Time Frame	up to 740 min after start dosing for each treatment day
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Symbicort	Symbicort Turbuhaler 160/4.5μg
Terbutaline	Terbutaline Turbuhaler 0.4 mg

Measured Values

	Symbicort	Terbutaline
Number of Participants Analyzed [units:participants]	25	23
Vital sign (pulse rate)- Average Trapezoidal Area Under the Curve (AUC) [units: beats/min] Mean (Standard Deviation)	70.0 (6.6)	74.1 (7.5)

No statistical analysis provided for Vital sign (pulse rate)- Average Trapezoidal Area Under the Curve (AUC)

Serious Adverse Events

Time Frame	No text entered.
Additional Description	Of 25 patients in safety analysis set, 2 patients did not receive terbutaline due to adverse events lead to discontinuation. Therefore, data from 25 patients for Symbicort and 23 patients for terbutaline were used for the safety evaluation.

Reporting Groups

	Description
Symbicort	Symbicort Turbuhaler 160/4.5μg for 3 days
Terbutaline	Terbutaline Turbuhaler 0.4 mg for 3 days

Serious Adverse Events

	Symbicort	Terbutaline
Total, serious adverse events
# participants affected / at risk	0/25 (0.00%)	0/23 (0.00%)

Other Adverse Events

Time Frame	No text entered.
Additional Description	Of 25 patients in safety analysis set, 2 patients did not receive terbutaline due to adverse events lead to discontinuation. Therefore, data from 25 patients for Symbicort and 23 patients for terbutaline were used for the safety evaluation.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Symbicort	Symbicort Turbuhaler 160/4.5μg for 3 days
Terbutaline	Terbutaline Turbuhaler 0.4 mg for 3 days