Trial Outcomes & Findings for Safety and Tolerability After Four Weeks of Treatment With AZD1656 in Patients With Type 2 Diabetes (NCT NCT00856908)
NCT ID: NCT00856908
Last Updated: 2012-12-06
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
20 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
2012-12-06
Participant Flow
Participant milestones
| Measure |
Experimental
AZD1656 dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
Placebo Comparator
placebo Dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
|---|---|---|
|
Overall Study
STARTED
|
15
|
5
|
|
Overall Study
COMPLETED
|
14
|
5
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Experimental
AZD1656 dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
Placebo Comparator
placebo Dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
Baseline Characteristics
Safety and Tolerability After Four Weeks of Treatment With AZD1656 in Patients With Type 2 Diabetes
Baseline characteristics by cohort
| Measure |
Experimental
n=15 Participants
AZD1656 dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
Placebo Comparator
n=5 Participants
placebo Dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
52.6 years
n=5 Participants
|
57.2 years
n=7 Participants
|
53.8 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
8 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=14 Participants
AZD1656 dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
Placebo Comparator
n=5 Participants
placebo Dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
|---|---|---|
|
Systolic Blood Pressure, Change From Baseline to End of Treatment
|
0.4 mmHg
Standard Deviation 8.5
|
5.0 mmHg
Standard Deviation 6.4
|
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=14 Participants
AZD1656 dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
Placebo Comparator
n=5 Participants
placebo Dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
|---|---|---|
|
Diastolic Blood Pressure, Change From Baseline to End of Treatment
|
3.4 mmHg
Standard Deviation 7.6
|
0.6 mmHg
Standard Deviation 2.9
|
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=14 Participants
AZD1656 dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
Placebo Comparator
n=5 Participants
placebo Dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
|---|---|---|
|
Pulse, Change From Baseline to End of Treatment
|
0.7 beats/min
Standard Deviation 4.4
|
-5.4 beats/min
Standard Deviation 4.0
|
PRIMARY outcome
Timeframe: Baseline is the day before first dose, end of treatment is last day of treatmentOutcome measures
| Measure |
Experimental
n=14 Participants
AZD1656 dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
Placebo Comparator
n=5 Participants
placebo Dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
|---|---|---|
|
Weight, Change From Baseline to End of Treatment
|
-0.54 kg
Standard Deviation 1.65
|
-1.32 kg
Standard Deviation 1.18
|
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=15 Participants
AZD1656 dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
Placebo Comparator
n=5 Participants
placebo Dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
|---|---|---|
|
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=14 Participants
AZD1656 dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
Placebo Comparator
placebo Dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
|---|---|---|
|
Area Under the Plasma Concentration vs Time Curve (AUC0-24) of AZD1656
|
23.49 umol*h/L
Interval 18.73 to 29.45
|
—
|
SECONDARY outcome
Timeframe: Measured following the morning dose last day of treatmentDose-adjusted to a morning dose of 50 mg due to titrated doses
Outcome measures
| Measure |
Experimental
n=14 Participants
AZD1656 dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
Placebo Comparator
placebo Dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
|---|---|---|
|
Maximum Plasma Concentration of AZD1656
|
2.415 umol/L
Interval 1.992 to 2.928
|
—
|
SECONDARY outcome
Timeframe: Measured last day of treatmentOutcome measures
| Measure |
Experimental
n=14 Participants
AZD1656 dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
Placebo Comparator
placebo Dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
|---|---|---|
|
Time to Reach Maximum Plasma Concentration of AZD1656
|
0.500 h
Interval 0.25 to 2.5
|
—
|
SECONDARY outcome
Timeframe: Measured following the evening dose last day of treatmentOutcome measures
| Measure |
Experimental
n=13 Participants
AZD1656 dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
Placebo Comparator
placebo Dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
|---|---|---|
|
Terminal Elimination Half-life of AZD1656
|
5.239 h
Interval 3.1 to 10.1
|
—
|
SECONDARY outcome
Timeframe: Measured last day of treatmentOutcome measures
| Measure |
Experimental
n=14 Participants
AZD1656 dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
Placebo Comparator
placebo Dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
|---|---|---|
|
Apparent Oral Clearance of AZD1656
|
9.382 L/h
Interval 4.92 to 16.2
|
—
|
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 an ANCOVA model, using treatment as fixed factor 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. Changes in percent have been obtained by subtraction by 100.
Outcome measures
| Measure |
Experimental
n=14 Participants
AZD1656 dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
Placebo Comparator
n=5 Participants
placebo Dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
|---|---|---|
|
P-Glucose (AUC0-24)/24, Change From Baseline to End of Treatment
|
-7 relative change in percent
Interval -19.0 to 6.2
|
4 relative change in percent
Interval -18.0 to 33.0
|
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 an ANCOVA model, using treatment as fixed factor 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. Changes in percent have been obtained by subtraction by 100
Outcome measures
| Measure |
Experimental
n=14 Participants
AZD1656 dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
Placebo Comparator
n=5 Participants
placebo Dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
|---|---|---|
|
S-Insulin (AUC0-24)/24, Change From Baseline to End of Treatment
|
-2 relative change in percent
Interval -15.0 to 12.0
|
-29 relative change in percent
Interval -45.0 to -9.3
|
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 an ANCOVA model, using treatment as fixed factor 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. Changes in percent have been obtained by subtraction by 100.
Outcome measures
| Measure |
Experimental
n=14 Participants
AZD1656 dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
Placebo Comparator
n=5 Participants
placebo Dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
|---|---|---|
|
S-C-Peptide (AUC0-24)/24, Change From Baseline to End of Treatment
|
-4 relative change in percent
Interval -18.0 to 13.0
|
-3 relative change in percent
Interval -26.0 to 28.0
|
Adverse Events
Experimental
Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths
Placebo Comparator
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Experimental
n=15 participants at risk
AZD1656 dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
Placebo Comparator
n=5 participants at risk
placebo Dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
6.7%
1/15
|
0.00%
0/5
|
|
Gastrointestinal disorders
Diarrhoea
|
20.0%
3/15
|
40.0%
2/5
|
|
Gastrointestinal disorders
Constipation
|
6.7%
1/15
|
0.00%
0/5
|
|
Gastrointestinal disorders
Nausea
|
6.7%
1/15
|
20.0%
1/5
|
|
General disorders
Non-Cardiac Chest Pain
|
6.7%
1/15
|
0.00%
0/5
|
|
General disorders
Pain
|
0.00%
0/15
|
20.0%
1/5
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
0.00%
0/15
|
20.0%
1/5
|
|
Infections and infestations
Urinary Tract Infection
|
13.3%
2/15
|
20.0%
1/5
|
|
Injury, poisoning and procedural complications
Application Site Reaction
|
13.3%
2/15
|
0.00%
0/5
|
|
Injury, poisoning and procedural complications
Catheter Site Pain
|
13.3%
2/15
|
0.00%
0/5
|
|
Investigations
Blood Glucose Decreased
|
13.3%
2/15
|
0.00%
0/5
|
|
Metabolism and nutrition disorders
Iron Deficiency Anaemia
|
0.00%
0/15
|
20.0%
1/5
|
|
Metabolism and nutrition disorders
Oedema Peripheral
|
6.7%
1/15
|
0.00%
0/5
|
|
Musculoskeletal and connective tissue disorders
Limb Discomfort
|
6.7%
1/15
|
0.00%
0/5
|
|
Musculoskeletal and connective tissue disorders
Pain In Extremity
|
26.7%
4/15
|
0.00%
0/5
|
|
Nervous system disorders
Headache
|
66.7%
10/15
|
20.0%
1/5
|
|
Nervous system disorders
Restless Legs Syndrome
|
6.7%
1/15
|
0.00%
0/5
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
|
6.7%
1/15
|
0.00%
0/5
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
6.7%
1/15
|
0.00%
0/5
|
|
Vascular disorders
Ecchymosis
|
6.7%
1/15
|
0.00%
0/5
|
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