Trial Outcomes & Findings for Study to Assess the Safety and Tolerability After Multiple Oral Doses of AZD1656 in Patients With Type 2 Diabetes Mellitus Treated With Metformin (NCT NCT00817778)
NCT ID: NCT00817778
Last Updated: 2012-11-16
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
27 participants
Primary outcome timeframe
Baseline is pre-dose first day of dosing, end of treatment is the morning following the treatment period
Results posted on
2012-11-16
Participant Flow
Participant milestones
| Measure |
Experimental
AZD1656
|
Placebo Comparator
Placebo
|
|---|---|---|
|
Overall Study
STARTED
|
19
|
8
|
|
Overall Study
COMPLETED
|
16
|
5
|
|
Overall Study
NOT COMPLETED
|
3
|
3
|
Reasons for withdrawal
| Measure |
Experimental
AZD1656
|
Placebo Comparator
Placebo
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
|
Overall Study
Protocol Violation
|
0
|
1
|
|
Overall Study
Study-specific discontinuation criteria
|
0
|
1
|
|
Overall Study
Poor venous access
|
1
|
0
|
Baseline Characteristics
Study to Assess the Safety and Tolerability After Multiple Oral Doses of AZD1656 in Patients With Type 2 Diabetes Mellitus Treated With Metformin
Baseline characteristics by cohort
| Measure |
Experimental
n=19 Participants
AZD1656
|
Placebo Comparator
n=8 Participants
Placebo
|
Total
n=27 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
60.2 years
n=5 Participants
|
60.3 years
n=7 Participants
|
60.2 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline is pre-dose first day of dosing, end of treatment is the morning following the treatment periodOutcome measures
| Measure |
Experimental
n=16 Participants
AZD1656
|
Placebo Comparator
n=5 Participants
Placebo
|
|---|---|---|
|
Systolic Blood Pressure, Change From Baseline to End of Treatment
|
-0.5 mmHg
Standard Deviation 11.48
|
9.2 mmHg
Standard Deviation 10.43
|
PRIMARY outcome
Timeframe: Baseline is pre-dose first day of dosing, end of treatment is the morning following the treatment periodOutcome measures
| Measure |
Experimental
n=16 Participants
AZD1656
|
Placebo Comparator
n=5 Participants
Placebo
|
|---|---|---|
|
Diastolic Blood Pressure, Change From Baseline to End of Treatment
|
-0.2 mmHg
Standard Deviation 6.20
|
2.0 mmHg
Standard Deviation 10.32
|
PRIMARY outcome
Timeframe: Baseline is pre-dose first day of dosing, end of treatment is the morning following the treatment periodOutcome measures
| Measure |
Experimental
n=16 Participants
AZD1656
|
Placebo Comparator
n=5 Participants
Placebo
|
|---|---|---|
|
Pulse, Change From Baseline to End of Treatment
|
2.7 beats/min
Standard Deviation 5.69
|
-1.6 beats/min
Standard Deviation 6.23
|
PRIMARY outcome
Timeframe: Baseline is the day before first dose, end of treatment is last day of treatmentOutcome measures
| Measure |
Experimental
n=16 Participants
AZD1656
|
Placebo Comparator
n=5 Participants
Placebo
|
|---|---|---|
|
Weight, Change From Baseline to End of Treatment
|
0.2 kg
Standard Deviation 1.00
|
0.0 kg
Standard Deviation 3.81
|
PRIMARY outcome
Timeframe: Measured regularly from day before first dose to day after last doseNumber of participants with clinically relevant change of laboratory variables (clinical chemistry, haematology and urinalysis parameters
Outcome measures
| Measure |
Experimental
n=19 Participants
AZD1656
|
Placebo Comparator
n=8 Participants
Placebo
|
|---|---|---|
|
Clinically Relevant Change of Laboratory Variables
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Measured last day of treatmentDose-adjusted to a total daily dose of 100 mg due to titrated doses
Outcome measures
| Measure |
Experimental
n=16 Participants
AZD1656
|
Placebo Comparator
Placebo
|
|---|---|---|
|
Area Under the Plasma Concentration vs Time Curve (AUC0-24) of AZD1656
|
23.17 umol*h/L
Standard Deviation 7.46
|
—
|
SECONDARY outcome
Timeframe: Measured last day of treatmentDose-adjusted to a morning dose of 50 mg due to titrated doses
Outcome measures
| Measure |
Experimental
n=16 Participants
AZD1656
|
Placebo Comparator
Placebo
|
|---|---|---|
|
Maximum Plasma Concentration of AZD1656
|
1.90 umol/L
Standard Deviation 0.99
|
—
|
SECONDARY outcome
Timeframe: Measured last day of treatmentOutcome measures
| Measure |
Experimental
n=16 Participants
AZD1656
|
Placebo Comparator
Placebo
|
|---|---|---|
|
Time to Reach Maximum Plasma Concentration of AZD1656
|
0.625 h
Interval 0.25 to 6.0
|
—
|
SECONDARY outcome
Timeframe: Measured following the afternoon dose last day of treatmentOutcome measures
| Measure |
Experimental
n=10 Participants
AZD1656
|
Placebo Comparator
Placebo
|
|---|---|---|
|
Terminal Elimination Half-life of AZD1656
|
7.07 h
Interval 2.48 to 12.93
|
—
|
SECONDARY outcome
Timeframe: Measured last day of treatmentOutcome measures
| Measure |
Experimental
n=16 Participants
AZD1656
|
Placebo Comparator
Placebo
|
|---|---|---|
|
Apparent Oral Clearance of AZD1656
|
9.02 L/h
Interval 5.39 to 13.94
|
—
|
SECONDARY outcome
Timeframe: Baseline is the day before first dose, end of treatment is last day of treatmentLog ratio (End of treatment/Baseline) has been analysed in a mixed-effect ANOVA model, using treatment as fixed effect 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.
Outcome measures
| Measure |
Experimental
n=16 Participants
AZD1656
|
Placebo Comparator
n=5 Participants
Placebo
|
|---|---|---|
|
P-Glucose (AUC0-24)/24, Change From Baseline to End of Treatment
|
75.85 Relative ratio in percent
Interval 69.82 to 82.39
|
99.42 Relative ratio in percent
Interval 85.05 to 116.23
|
SECONDARY outcome
Timeframe: Baseline is the day before first dose, end of treatment is last day of treatmentLog ratio (End of treatment/Baseline) has been analysed in a mixed-effect ANOVA model, using treatment as fixed effect 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.
Outcome measures
| Measure |
Experimental
n=16 Participants
AZD1656
|
Placebo Comparator
n=5 Participants
Placebo
|
|---|---|---|
|
S-Insulin (AUC0-24)/24, Change From Baseline to End of Treatment
|
103.81 Relative ratio in percent
Interval 90.75 to 118.74
|
86.06 Relative ratio in percent
Interval 67.24 to 110.14
|
SECONDARY outcome
Timeframe: Baseline is the day before first dose, end of treatment is last day of treatmentLog ratio (End of treatment/Baseline) has been analysed in a mixed-effect ANOVA model, using treatment as fixed effect 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.
Outcome measures
| Measure |
Experimental
n=16 Participants
AZD1656
|
Placebo Comparator
n=5 Participants
Placebo
|
|---|---|---|
|
S-C-Peptide (AUC0-24)/24, Change From Baseline to End of Treatment
|
103.60 Relative ratio in percent
Interval 97.1 to 110.54
|
98.01 Relative ratio in percent
Interval 87.1 to 110.29
|
Adverse Events
Experimental
Serious events: 1 serious events
Other events: 15 other events
Deaths: 0 deaths
Placebo Comparator
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Experimental
n=19 participants at risk
AZD1656
|
Placebo Comparator
n=8 participants at risk
Placebo
|
|---|---|---|
|
Cardiac disorders
Rapid Atrial Fibrillation
|
5.3%
1/19
|
0.00%
0/8
|
Other adverse events
| Measure |
Experimental
n=19 participants at risk
AZD1656
|
Placebo Comparator
n=8 participants at risk
Placebo
|
|---|---|---|
|
Cardiac disorders
Supraventricular Tachycardia
|
5.3%
1/19
|
0.00%
0/8
|
|
Ear and labyrinth disorders
Vertigo Positional
|
0.00%
0/19
|
12.5%
1/8
|
|
Eye disorders
Vision Blurred
|
0.00%
0/19
|
12.5%
1/8
|
|
Gastrointestinal disorders
Constipation
|
5.3%
1/19
|
0.00%
0/8
|
|
Gastrointestinal disorders
Diarrhoea
|
5.3%
1/19
|
0.00%
0/8
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/19
|
12.5%
1/8
|
|
Gastrointestinal disorders
Toothache
|
5.3%
1/19
|
0.00%
0/8
|
|
General disorders
Fatigue
|
0.00%
0/19
|
12.5%
1/8
|
|
Infections and infestations
Hordeolum
|
0.00%
0/19
|
12.5%
1/8
|
|
Injury, poisoning and procedural complications
Excoriation
|
0.00%
0/19
|
12.5%
1/8
|
|
Injury, poisoning and procedural complications
Skin Laceration
|
5.3%
1/19
|
0.00%
0/8
|
|
Injury, poisoning and procedural complications
Blood Glucose Decreased
|
47.4%
9/19
|
12.5%
1/8
|
|
Musculoskeletal and connective tissue disorders
Costochondritis
|
0.00%
0/19
|
12.5%
1/8
|
|
Musculoskeletal and connective tissue disorders
Muscle Spasms
|
0.00%
0/19
|
12.5%
1/8
|
|
Nervous system disorders
Dizziness
|
5.3%
1/19
|
25.0%
2/8
|
|
Nervous system disorders
Headache
|
21.1%
4/19
|
25.0%
2/8
|
|
Nervous system disorders
Tremor
|
5.3%
1/19
|
0.00%
0/8
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis Allergic
|
5.3%
1/19
|
0.00%
0/8
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
5.3%
1/19
|
0.00%
0/8
|
|
Skin and subcutaneous tissue disorders
Erythema
|
5.3%
1/19
|
0.00%
0/8
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.3%
1/19
|
0.00%
0/8
|
|
Skin and subcutaneous tissue disorders
Skin Irritation
|
5.3%
1/19
|
0.00%
0/8
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER