Type 2 Diabetes Mellitus
Conditions
Brief summary
The purpose of this study is to determine if MSDC-0160 is effective in the treatment of Type 2 diabetes.
Interventions
DRUGPlacebo
Once daily, oral
DRUGPioglitazone
Once daily, oral
DRUGMSDC-0160 90 mg
Once daily, oral
DRUGMSDC-0160 220 mg
Once daily, oral
Sponsors
Metabolic Solutions Development Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Type 2 Diabetes naive or on metformin * Male and female (postmenopausal or surgically sterilized), 18 to 70 years of age.
Exclusion criteria
* Use of diabetes medications other than metformin. * History of heart failure or previous myocardial infarction. * Blood pressure great than 160/100 mmHg.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Averaged Postprandial Glucose in Response to a MMT Test | 28 days | Change from baseline of averaged postprandial glucose (mmol/L) in response to a Mixed-meal tolerance (MMT) test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Averaged Insulin Levels in Response to a Mixed-meal Tolerance Test | After four weeks of active therapy | Change from baseline in averaged post prandial insulin levels in response to a mixed-meal tolerance test. |
| Change From Baseline in FFAs | After 28 days of active therapy | Change from baseline in Free Fatty Acids (FFAs)following 28 days of active therapy, as part of a lipid profile assessment |
| Change From Baseline in Triglycerides | 28 days | Change compared to baseline in triglycerides following 28 days of active therapy, as part of a lipid profile assessment |
| Change From Baseline in HDL | 28 days | Change from baseline in HDL following 28 days of active therapy, as part of a lipid profile assessment |
Countries
United States
Participant flow
Recruitment details
The study was conducted in the United States by 10 investigators between 26 Sep 2008 and 02 Feb 2009.
Pre-assignment details
This was a Ph 2A, double-blind, randomized, comparator- & placebo-controlled study of Mitoglitazone in otherwise healthy adult patients with type 2 diabetes. The study consisted of a maximum 21-day screening period, a 2 week, single-blind, placebo lead-in period, a 4 week, double-blind treatment period and a 1 week posttreatment follow-up period.
Participants by arm
| Arm | Count |
|---|---|
| MSDC-0160 90 mg MSDC-0160 90 mg once daily | 22 |
| MSDC-0160 220 mg MSDC-0160 220 mg once daily | 21 |
| Pioglitazone Pioglitazone 45 mg once daily | 21 |
| Placebo Microcrystaline cellulose once daily | 22 |
| Total | 86 |
Baseline characteristics
| Characteristic | MSDC-0160 90 mg | MSDC-0160 220 mg | Pioglitazone | Placebo | Total |
|---|---|---|---|---|---|
| Age Continuous | 56.3 years STANDARD_DEVIATION 8.2 | 53.7 years STANDARD_DEVIATION 9.22 | 57.7 years STANDARD_DEVIATION 6.38 | 54.5 years STANDARD_DEVIATION 8.79 | 55.5 years STANDARD_DEVIATION 8.15 |
| Region of Enrollment United States | 22 participants | 21 participants | 21 participants | 22 participants | 86 participants |
| Sex: Female, Male Female | 10 Participants | 9 Participants | 14 Participants | 13 Participants | 46 Participants |
| Sex: Female, Male Male | 12 Participants | 12 Participants | 7 Participants | 9 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 22 | 3 / 22 | 2 / 21 | 2 / 21 |
| serious Total, serious adverse events | 0 / 22 | 0 / 22 | 0 / 21 | 0 / 21 |
Outcome results
Primary
Change From Baseline in Averaged Postprandial Glucose in Response to a MMT Test
Change from baseline of averaged postprandial glucose (mmol/L) in response to a Mixed-meal tolerance (MMT) test.
Time frame: 28 days
Population: All patients who were compliant during the treatment period and who had a Day 8 and Day 43 averaged mixed-meal tolerance test and laboratory assessments. Compliance during the treatment period was determined by the sponsor through a manual review of pill counts, including a review of comments from the study sites.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Mitoglitazone 90 mg | Change From Baseline in Averaged Postprandial Glucose in Response to a MMT Test | 0.16 mmol/L | Standard Error 0.349 |
| Mitoglitazone 220 mg | Change From Baseline in Averaged Postprandial Glucose in Response to a MMT Test | -0.44 mmol/L | Standard Error 0.358 |
| Pioglitazone 45 mg | Change From Baseline in Averaged Postprandial Glucose in Response to a MMT Test | -1.10 mmol/L | Standard Error 0.39 |
| Placebo | Change From Baseline in Averaged Postprandial Glucose in Response to a MMT Test | 0.51 mmol/L | Standard Error 0.34 |
Secondary
Change From Baseline in Averaged Insulin Levels in Response to a Mixed-meal Tolerance Test
Change from baseline in averaged post prandial insulin levels in response to a mixed-meal tolerance test.
Time frame: After four weeks of active therapy
Population: All patients who were compliant during the treatment period and who had a Day 8 and Day 43 averaged mixed-meal tolerance (MMT) test and laboratory assessments. Compliance during the treatment period was determined by the sponsor through a manual review of pill counts, including a review of comments from the study sites.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Mitoglitazone 90 mg | Change From Baseline in Averaged Insulin Levels in Response to a Mixed-meal Tolerance Test | 0.74 uIU/mL | Standard Error 4.664 |
| Mitoglitazone 220 mg | Change From Baseline in Averaged Insulin Levels in Response to a Mixed-meal Tolerance Test | -9.77 uIU/mL | Standard Error 4.785 |
| Pioglitazone 45 mg | Change From Baseline in Averaged Insulin Levels in Response to a Mixed-meal Tolerance Test | -12.24 uIU/mL | Standard Error 5.215 |
| Placebo | Change From Baseline in Averaged Insulin Levels in Response to a Mixed-meal Tolerance Test | -1.60 uIU/mL | Standard Error 4.552 |
Secondary
Change From Baseline in FFAs
Change from baseline in Free Fatty Acids (FFAs)following 28 days of active therapy, as part of a lipid profile assessment
Time frame: After 28 days of active therapy
Population: All patients who were compliant during the treatment period and who had a Day 8 and Day 43 averaged mixed-meal tolerance (MMT) test and laboratory assessments. Compliance during the treatment period was determined by the sponsor through a manual review of pill counts, including a review of comments from the study sites.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Mitoglitazone 90 mg | Change From Baseline in FFAs | -0.05 mmol/L | Standard Error 0.051 |
| Mitoglitazone 220 mg | Change From Baseline in FFAs | -0.15 mmol/L | Standard Error 0.052 |
| Pioglitazone 45 mg | Change From Baseline in FFAs | -0.19 mmol/L | Standard Error 0.057 |
| Placebo | Change From Baseline in FFAs | -0.01 mmol/L | Standard Error 0.05 |
Secondary
Change From Baseline in HDL
Change from baseline in HDL following 28 days of active therapy, as part of a lipid profile assessment
Time frame: 28 days
Population: All patients who were compliant during the treatment period and who had a Day 8 and Day 43 averaged mixed-meal tolerance (MMT) test and laboratory assessments. Compliance during the treatment period was determined by the sponsor through a manual review of pill counts, including a review of comments from the study sites.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Mitoglitazone 90 mg | Change From Baseline in HDL | 0.00 mmol/L | Standard Error 0.034 |
| Mitoglitazone 220 mg | Change From Baseline in HDL | 0.11 mmol/L | Standard Error 0.034 |
| Pioglitazone 45 mg | Change From Baseline in HDL | 0.09 mmol/L | Standard Error 0.038 |
| Placebo | Change From Baseline in HDL | -0.03 mmol/L | Standard Error 0.033 |
Secondary
Change From Baseline in Triglycerides
Change compared to baseline in triglycerides following 28 days of active therapy, as part of a lipid profile assessment
Time frame: 28 days
Population: All patients who were compliant during the treatment period and who had a Day 8 and Day 43 averaged mixed-meal tolerance (MMT) test and laboratory assessments. Compliance during the treatment period was determined by the sponsor through a manual review of pill counts, including a review of comments from the study sites.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Mitoglitazone 90 mg | Change From Baseline in Triglycerides | 0.12 mmol/L | Standard Error 0.16 |
| Mitoglitazone 220 mg | Change From Baseline in Triglycerides | -0.21 mmol/L | Standard Error 0.164 |
| Pioglitazone 45 mg | Change From Baseline in Triglycerides | -0.49 mmol/L | Standard Error 0.179 |
| Placebo | Change From Baseline in Triglycerides | 0.15 mmol/L | Standard Error 0.156 |
Post Hoc
Change From Baseline in FPG
Change from baseline in fasting plasma glucose (FPG) following 28 days of active therapy
Time frame: 28 days
Population: All patients who were compliant during the treatment period and who had Day 8 and Day 43 fasting plasma glucose values. Compliance during the treatment period was determined by the sponsor through a manual review of pill counts, including a review of comments from the study sites.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Mitoglitazone 90 mg | Change From Baseline in FPG | -0.20 mmol/L | Standard Error 0.263 |
| Mitoglitazone 220 mg | Change From Baseline in FPG | -0.97 mmol/L | Standard Error 0.27 |
| Pioglitazone 45 mg | Change From Baseline in FPG | -1.38 mmol/L | Standard Error 0.294 |
| Placebo | Change From Baseline in FPG | -0.04 mmol/L | Standard Error 0.257 |
Post Hoc
Change From Baseline in Insulin
Change from Baseline in insulin levels following 28 days of active therapy
Time frame: 28 days
Population: All patients who were compliant during the treatment period and who had a Day 8 and Day 43 pre-dose laboratory assessments. Compliance during the treatment period was determined by the sponsor through a manual review of pill counts, including a review of comments from the study sites.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Mitoglitazone 90 mg | Change From Baseline in Insulin | -5.01 uIU/mL | Standard Error 1.82 |
| Mitoglitazone 220 mg | Change From Baseline in Insulin | -2.91 uIU/mL | Standard Error 1.867 |
| Pioglitazone 45 mg | Change From Baseline in Insulin | -6.58 uIU/mL | Standard Error 2.034 |
| Placebo | Change From Baseline in Insulin | -0.70 uIU/mL | Standard Error 1.776 |