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CompletedNCT00817778Updated Nov 16, 2012Results posted

Study to Assess the Safety and Tolerability After Multiple Oral Doses of AZD1656 in Patients With Type 2 Diabetes Mellitus Treated With Metformin

A Phase 2 interventional study of AZD1656 and Placebo in Type 2 Diabetes, sponsored by AstraZeneca. Completed at 1 site in United States. Open to participants aged 30 Years to 75 Years. Per ClinicalTrials.gov, last updated 2012-11-16.

Sponsored by AstraZeneca · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
27
Allocation
Randomized
Ages
30 Years to 75 Years
Sex
All
01

Study summary

The purpose of this study is to assess the 1 month safety and tolerability after multiple oral doses of AZD1656 in patients with Type 2 Diabetes Mellitus Treated with Metformin

02

Conditions studied

  • Type 2 Diabetes

Keywords

  • Type II Diabetes
03

In context

Diabetes Mellitus

10,925 studies on the registry are indexed under Diabetes Mellitus; 1,318 are open to participants now.

This study's enrollment of 27 is below the median of 80 across 8,367 interventional studies indexed under Diabetes Mellitus.

Browse Diabetes Mellitus studies →

Lead sponsor

AstraZeneca is the lead sponsor of 3,429 studies on the registry; 270 are open to participants now.

Of its 357 completed or terminated interventional studies of FDA-regulated products, 173 (48%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
30 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Male or women of non-childbearing potential (postmenopausal, and/or have undergone hysterectomy and/or bilateral oophorectomy or salpingectomy/ tubal ligation)
  • Ongoing treatment with metformin on a stable dose of ≥ 1500 mg/day for at least 8 weeks prior to randomisation
  • HbA1c ≤ 10% at enrolment (HbA1c value according to international Diabetes Control and Complications Trial [DCCT] standard)

Exclusion criteria

Exclusion Criteria:

  • History of ischemic heart disease, symptomatic heart failure, stroke, transitory ischemic attack or symptomatic peripheral vascular disease
  • Clinically significant abnormalities in ECG, clinical chemistry, haematology, or urine analysis results. Positive test for Hepatitis B surface antigen or antibodies to human immunodeficiency virus (HIV) or antibodies to Hepatitis C virus
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Participant)
Enrollment
27 participants (actual)

Study arms

  • 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

    Drug: AZD1656

  • 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

    Drug: Placebo

Interventions

  • DrugAZD1656

    Subjects will be treated with tolerable dose twice daily for another 24 days.

  • DrugPlacebo

    Subjects will be treated with tolerable dose twice daily for another 24 days.

06

What researchers measure

Primary outcomes

  1. Systolic Blood Pressure, Change From Baseline to End of Treatment

    Time frame: Baseline is pre-dose first day of dosing, end of treatment is the morning following the treatment period

  2. Diastolic Blood Pressure, Change From Baseline to End of Treatment

    Time frame: Baseline is pre-dose first day of dosing, end of treatment is the morning following the treatment period

  3. Pulse, Change From Baseline to End of Treatment

    Time frame: Baseline is pre-dose first day of dosing, end of treatment is the morning following the treatment period

  4. Weight, Change From Baseline to End of Treatment

    Time frame: Baseline is the day before first dose, end of treatment is last day of treatment

  5. Clinically Relevant Change of Laboratory Variables

    Number of participants with clinically relevant change of laboratory variables (clinical chemistry, haematology and urinalysis parameters

    Time frame: Measured regularly from day before first dose to day after last dose

Secondary outcomes

  1. Area Under the Plasma Concentration vs Time Curve (AUC0-24) of AZD1656

    Dose-adjusted to a total daily dose of 100 mg due to titrated doses

    Time frame: Measured last day of treatment

  2. Maximum Plasma Concentration of AZD1656

    Dose-adjusted to a morning dose of 50 mg due to titrated doses

    Time frame: Measured last day of treatment

  3. Time to Reach Maximum Plasma Concentration of AZD1656

    Time frame: Measured last day of treatment

  4. Terminal Elimination Half-life of AZD1656

    Time frame: Measured following the afternoon dose last day of treatment

  5. Apparent Oral Clearance of AZD1656

    Time frame: Measured last day of treatment

  6. P-Glucose (AUC0-24)/24, Change From Baseline to End of Treatment

    Log 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.

    Time frame: Baseline is the day before first dose, end of treatment is last day of treatment

  7. S-Insulin (AUC0-24)/24, Change From Baseline to End of Treatment

    Log 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.

    Time frame: Baseline is the day before first dose, end of treatment is last day of treatment

  8. S-C-Peptide (AUC0-24)/24, Change From Baseline to End of Treatment

    Log 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.

    Time frame: Baseline is the day before first dose, end of treatment is last day of treatment

07

Results

Posted Nov 16, 2012
Limitations and caveats
The primary objective of the study was to assess safety and tolerability and hence the study was not sized based on statistical considerations. The most import outcome, "no safety or tolerability concerns were identified", is not a numerical variable

Participant flow

Participant flow — Overall Study
MilestoneExperimentalPlacebo Comparator
Started198
Completed165
Not completed33
Withdrew: Adverse event10
Withdrew: Withdrawal by subject11
Withdrew: Protocol violation01
Withdrew: Study-specific discontinuation criteria01
Withdrew: Poor venous access10

Outcome measures

PrimarySystolic Blood Pressure, Change From Baseline to End of Treatment
Time frame:
Baseline is pre-dose first day of dosing, end of treatment is the morning following the treatment period
Reported as:
Mean · mmHg
Systolic Blood Pressure, Change From Baseline to End of Treatment
mmHgExperimentalPlacebo Comparator
Systolic Blood Pressure, Change From Baseline to End of Treatment-0.5 ± 11.489.2 ± 10.43
PrimaryDiastolic Blood Pressure, Change From Baseline to End of Treatment
Time frame:
Baseline is pre-dose first day of dosing, end of treatment is the morning following the treatment period
Reported as:
Mean · mmHg
Diastolic Blood Pressure, Change From Baseline to End of Treatment
mmHgExperimentalPlacebo Comparator
Diastolic Blood Pressure, Change From Baseline to End of Treatment-0.2 ± 6.202.0 ± 10.32
PrimaryPulse, Change From Baseline to End of Treatment
Time frame:
Baseline is pre-dose first day of dosing, end of treatment is the morning following the treatment period
Reported as:
Mean · beats/min
Pulse, Change From Baseline to End of Treatment
beats/minExperimentalPlacebo Comparator
Pulse, Change From Baseline to End of Treatment2.7 ± 5.69-1.6 ± 6.23
PrimaryWeight, Change From Baseline to End of Treatment
Time frame:
Baseline is the day before first dose, end of treatment is last day of treatment
Reported as:
Mean · kg
Weight, Change From Baseline to End of Treatment
kgExperimentalPlacebo Comparator
Weight, Change From Baseline to End of Treatment0.2 ± 1.000.0 ± 3.81
PrimaryClinically Relevant Change of Laboratory Variables

Number of participants with clinically relevant change of laboratory variables (clinical chemistry, haematology and urinalysis parameters

Time frame:
Measured regularly from day before first dose to day after last dose
Reported as:
Number · Participants
Clinically Relevant Change of Laboratory Variables
ParticipantsExperimentalPlacebo Comparator
Clinically Relevant Change of Laboratory Variables00
SecondaryArea Under the Plasma Concentration vs Time Curve (AUC0-24) of AZD1656

Dose-adjusted to a total daily dose of 100 mg due to titrated doses

Time frame:
Measured last day of treatment
Reported as:
Geometric mean · umol*h/L
Area Under the Plasma Concentration vs Time Curve (AUC0-24) of AZD1656
umol*h/LExperimental
Area Under the Plasma Concentration vs Time Curve (AUC0-24) of AZD165623.17 ± 7.46
SecondaryMaximum Plasma Concentration of AZD1656

Dose-adjusted to a morning dose of 50 mg due to titrated doses

Time frame:
Measured last day of treatment
Reported as:
Geometric mean · umol/L
Maximum Plasma Concentration of AZD1656
umol/LExperimental
Maximum Plasma Concentration of AZD16561.90 ± 0.99
SecondaryTime to Reach Maximum Plasma Concentration of AZD1656
Time frame:
Measured last day of treatment
Reported as:
Median · h
Time to Reach Maximum Plasma Concentration of AZD1656
hExperimental
Time to Reach Maximum Plasma Concentration of AZD16560.625 (0.25 to 6.00)
SecondaryTerminal Elimination Half-life of AZD1656
Time frame:
Measured following the afternoon dose last day of treatment
Reported as:
Geometric mean · h
Terminal Elimination Half-life of AZD1656
hExperimental
Terminal Elimination Half-life of AZD16567.07 (2.48 to 12.93)
SecondaryApparent Oral Clearance of AZD1656
Time frame:
Measured last day of treatment
Reported as:
Geometric mean · L/h
Apparent Oral Clearance of AZD1656
L/hExperimental
Apparent Oral Clearance of AZD16569.02 (5.39 to 13.94)
SecondaryP-Glucose (AUC0-24)/24, Change From Baseline to End of Treatment

Log 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.

Time frame:
Baseline is the day before first dose, end of treatment is last day of treatment
Reported as:
Least squares mean · Relative ratio in percent
P-Glucose (AUC0-24)/24, Change From Baseline to End of Treatment
Relative ratio in percentExperimentalPlacebo Comparator
P-Glucose (AUC0-24)/24, Change From Baseline to End of Treatment75.85 (69.82 to 82.39)99.42 (85.05 to 116.23)
SecondaryS-Insulin (AUC0-24)/24, Change From Baseline to End of Treatment

Log 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.

Time frame:
Baseline is the day before first dose, end of treatment is last day of treatment
Reported as:
Least squares mean · Relative ratio in percent
S-Insulin (AUC0-24)/24, Change From Baseline to End of Treatment
Relative ratio in percentExperimentalPlacebo Comparator
S-Insulin (AUC0-24)/24, Change From Baseline to End of Treatment103.81 (90.75 to 118.74)86.06 (67.24 to 110.14)
SecondaryS-C-Peptide (AUC0-24)/24, Change From Baseline to End of Treatment

Log 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.

Time frame:
Baseline is the day before first dose, end of treatment is last day of treatment
Reported as:
Least squares mean · Relative ratio in percent
S-C-Peptide (AUC0-24)/24, Change From Baseline to End of Treatment
Relative ratio in percentExperimentalPlacebo Comparator
S-C-Peptide (AUC0-24)/24, Change From Baseline to End of Treatment103.60 (97.10 to 110.54)98.01 (87.10 to 110.29)

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Experimental—1/19 (5.3%)15/19 (78.9%)
Placebo Comparator—0/8 (0%)7/8 (87.5%)
Most frequent serious events
Most frequent serious events
EventExperimentalPlacebo Comparator
Rapid Atrial FibrillationCardiac disorders1/190/8
Most frequent other events
Showing 10 of 23
Most frequent other events
EventExperimentalPlacebo Comparator
Blood Glucose DecreasedInjury, poisoning and procedural complications9/191/8
DizzinessNervous system disorders1/192/8
HeadacheNervous system disorders4/192/8
Vertigo PositionalEar and labyrinth disorders0/191/8
Vision BlurredEye disorders0/191/8
NauseaGastrointestinal disorders0/191/8
FatigueGeneral disorders0/191/8
HordeolumInfections and infestations0/191/8
ExcoriationInjury, poisoning and procedural complications0/191/8
CostochondritisMusculoskeletal and connective tissue disorders0/191/8

Baseline characteristics

Age Continuous
Age Continuous(years)ExperimentalPlacebo ComparatorTotal
Mean60.2 (39 to 72)60.3 (34 to 74)60.2 (34 to 74)
Sex: Female, Male
Sex: Female, Male(Participants)ExperimentalPlacebo ComparatorTotal
Female6511
Male13316
08

Study locations

1 site
  • Research Site
    San Antonio, Texas, United States
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 16, 2012, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00817778
Lead sponsor
AstraZeneca
Responsible party
Sponsor
First posted
Jan 6, 2009
Start date
Jan 2009
Primary completion
Jul 2009
Completion
Jul 2009
Results posted
Nov 16, 2012
Last update
Nov 16, 2012

Study contacts

Klas Malmberg, MD, PhD, Prof
study director · AstraZeneca R&D Mölndal
Emanuel P DeNoia, M.D
principal investigator · Healthcare Discoveries LLC Icon Development Solutions

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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