Type 2 Diabetes Mellitus
Conditions
Brief summary
The current study investigates Welchol as monotherapy to improve glycemic control in subjects with Type 2 Diabetes Mellitus not adequately controlled with diet and exercise alone. The study will evaluate if Welchol monotherapy for Type 2 Diabetes Mellitus will be safe, well tolerated and efficacious.
Interventions
DRUGWelchol
Welchol 625mg tablets
DRUGPlacebo
placebo
Sponsors
Daiichi Sankyo
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female subjects \>= 18 years of age; * Women of childbearing potential (WOCBP) must be using an adequate method of contraception as detailed in the protocol. * Diagnosis of Type 2 Diabetes Mellitus; * HbA1C \>= 7.5% and =\< 9.5 % at screening; * Fasting C-peptide \>0.5 ng/mL at screening; * Drug naïve (no prior treatment with OAD) or having received no pharmacologic therapy for diabetes for the 3 month period prior to screening; * Clinically stable in regards to medical conditions other than type 2 diabetes; * Concomitant medications must be at stable doses for at least 30 days prior to enrollment, and are not anticipated to need adjustment during the study period; and * Fasting glucose =\< 240 mg/dL at randomization
Exclusion criteria
* A history of type 1 diabetes and/or a history of ketoacidosis; * History of bowel obstruction; * History of hypertriglyceridemia-induced pancreatitis; * Fasting serum triglyceride concentrations \>500 mg/dL; * History of dysphagia, swallowing disorders, gastroparesis, other gastrointestinal (GI) motility disorders, or major GI surgery; * History of insulin use of \>= 2 weeks duration in the previous 3 months or a total of \> 2 months of insulin therapy at any time prior to screening; * Two or more fasting self-monitored blood glucose (SMBG) levels \>240 mg/dL during the placebo lead-in period. * Previous treatment with a bile acid sequestrant, including Welchol within the 3 months prior to screening; * Body mass index (BMI) \>40 kg/m2; * Weight loss \> 3% in prior 3 months; and * LDL \<60 mg/dL.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Hemoglobin A1c | 24 week | change in HbA1c from baseline to Week 24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| % Subjects With a Decrease in HbA1c of >= 0.7 Percentage Units | 24 weeks | to determine the percentage of participants who experience a reduction in HbA1c of at least 0.7 percentage units at 24 weeks from baseline. |
| % Subjects Achieving an HbA1C Goal of <7.0 | 24 weeks | % Subjects achieving an HbA1C goal of \<7.0 at 24 weeks |
| % Subjects With a Decrease in FPG >=30 mg/dL | from baseline to 24 weeks | % Subjects with a decrease in Fasting Plasma Glucose \>=30 mg/dL from baseline to 24 weeks |
| Changes in Total Cholesterol [TC] | from baseline to 24 weeks | To assess the effects of Welchol on changes in total cholesterol \[TC\] |
| Changes in Low Density Lipoprotein Cholesterol [LDL-C] | from baseline to 24 weeks | To assess the effects of Welchol on changes in low density lipoprotein cholesterol \[LDL-C\] |
| Change in Fasting Plasma Glucose | from baseline to 24 weeks | to determine changes in Glycemic control after 24 weeks on therapy |
| Changes in Non-HDL-C | from baseline to 24 weeks | To assess the effects of Welchol on changes in non-HDL-C |
| Changes in Triglycerides [TG] | from baseline to 24 weeks | To assess the effects of Welchol on changes in triglycerides \[TG\] |
| Changes in Apolipoprotein A-I (apoA-I) | from baseline to 24 weeks | To assess the effects of Welchol on changes in apolipoprotein A-I (apoA-I) |
| Changes in Apolipoprotein B (apoB) | from baseline to 24 weeks | To assess the effects of Welchol on changes in apolipoprotein B (apoB) |
| Change in Postprandial Plasma Glucose, 2 Hours After a Meal Tolerance Test | from baseline to 24 weeks | To assess the change from baseline on postprandial plasma glucose, 2 hours after a meal tolerance test |
| Changes in High Density Lipoprotein Cholesterol [HDL-C] | from baseline to 24 weeks | To assess the effects of Welchol on changes in high density lipoprotein cholesterol \[HDL-C\] |
Countries
United States
Participant flow
Recruitment details
From January 2009 through July 2011, subjects were recruited from medical clinics, private practice and research clinics.
Pre-assignment details
There was a 2-week placebo lead-in prior to randomization to treatment arm. Participants were excluded if two or more fasting blood glucose readings \>240 mg/dL occurred during lead-in. Subjects were excluded if there had been oral antidiabetic, significant insulin, or bile acid sequestrant therapy in the 3 months prior to screening.
Participants by arm
| Arm | Count |
|---|---|
| Welchol Welchol 625mg tablets
Welchol : Welchol 625mg tablets | 176 |
| Placebo placebo
Placebo : placebo | 181 |
| Total | 357 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 8 |
| Overall Study | hyperglycemia that met protocol-specifie | 0 | 4 |
| Overall Study | Lack of Efficacy | 3 | 0 |
| Overall Study | Lost to Follow-up | 10 | 14 |
| Overall Study | Other | 11 | 7 |
| Overall Study | Protocol Violation | 3 | 0 |
| Overall Study | Withdrawal by Subject | 13 | 22 |
Baseline characteristics
| Characteristic | Welchol | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 14 Participants | 25 Participants |
| Age, Categorical Between 18 and 65 years | 165 Participants | 167 Participants | 332 Participants |
| Age, Continuous | 52.6 years STANDARD_DEVIATION 10.25 | 51.8 years STANDARD_DEVIATION 10.52 | 52.2 years STANDARD_DEVIATION 10.38 |
| baseline body mass index category <30 kg/m*2 | 68 participants | 66 participants | 134 participants |
| baseline body mass index category >= 30 kg/m*2 | 108 participants | 115 participants | 223 participants |
| Body mass index | 32.0 kg/m*2 STANDARD_DEVIATION 6.5 | 31.8 kg/m*2 STANDARD_DEVIATION 4.94 | 31.9 kg/m*2 STANDARD_DEVIATION 5.75 |
| Duration of type 2 diabetes | 4.3 years STANDARD_DEVIATION 4.69 | 3.9 years STANDARD_DEVIATION 4.39 | 4.1 years STANDARD_DEVIATION 4.54 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 86 Participants | 80 Participants | 166 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 90 Participants | 101 Participants | 191 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 12 Participants | 11 Participants | 23 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 8 Participants | 20 Participants |
| Race (NIH/OMB) Black or African American | 27 Participants | 29 Participants | 56 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) White | 122 Participants | 131 Participants | 253 Participants |
| Region of Enrollment United States | 176 participants | 181 participants | 357 participants |
| Sex: Female, Male Female | 82 Participants | 92 Participants | 174 Participants |
| Sex: Female, Male Male | 94 Participants | 89 Participants | 183 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 91 / 175 | 77 / 171 |
| serious Total, serious adverse events | 7 / 175 | 3 / 171 |
Outcome results
Primary
Percent Change in Hemoglobin A1c
change in HbA1c from baseline to Week 24
Time frame: 24 week
Population: Intent to Treat, Last Observation Carried Forward (LOCF) Some participants may not have had lab results for this specific analysis and therefore excluded.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Welchol | Percent Change in Hemoglobin A1c | -0.41 percentage change of hemoglobin A1c | Standard Error 0.091 |
| Placebo | Percent Change in Hemoglobin A1c | -0.14 percentage change of hemoglobin A1c | Standard Error 0.091 |
Comparison: least squares mean; 80% power to detect a 0.3% changep-value: 0.0369ANCOVA
Secondary
Change in Fasting Plasma Glucose
to determine changes in Glycemic control after 24 weeks on therapy
Time frame: from baseline to 24 weeks
Population: Some participants may not have had lab results for this specific analysis and therefore excluded.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Welchol | Change in Fasting Plasma Glucose | -4.6 mg/dL | Standard Error 3.45 |
| Placebo | Change in Fasting Plasma Glucose | 5.7 mg/dL | Standard Error 3.51 |
p-value: 0.0373ANCOVA
Secondary
Change in Postprandial Plasma Glucose, 2 Hours After a Meal Tolerance Test
To assess the change from baseline on postprandial plasma glucose, 2 hours after a meal tolerance test
Time frame: from baseline to 24 weeks
Population: Some participants may not have had lab results for this specific analysis and therefore excluded.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Welchol | Change in Postprandial Plasma Glucose, 2 Hours After a Meal Tolerance Test | -9.3 mg/dL | Standard Error 5.72 |
| Placebo | Change in Postprandial Plasma Glucose, 2 Hours After a Meal Tolerance Test | -1.5 mg/dL | Standard Error 5.86 |
Secondary
Changes in Apolipoprotein A-I (apoA-I)
To assess the effects of Welchol on changes in apolipoprotein A-I (apoA-I)
Time frame: from baseline to 24 weeks
Population: Some participants may not have had lab results for this specific analysis and therefore excluded.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Welchol | Changes in Apolipoprotein A-I (apoA-I) | 3.2 mg/dL | Standard Error 0.8 |
| Placebo | Changes in Apolipoprotein A-I (apoA-I) | 0.9 mg/dL | Standard Error 0.81 |
Secondary
Changes in Apolipoprotein B (apoB)
To assess the effects of Welchol on changes in apolipoprotein B (apoB)
Time frame: from baseline to 24 weeks
Population: Some participants may not have had lab results for this specific analysis and therefore excluded.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Welchol | Changes in Apolipoprotein B (apoB) | -5.6 mg/dL | Standard Error 1.18 |
| Placebo | Changes in Apolipoprotein B (apoB) | 0.9 mg/dL | Standard Error 1.19 |
Secondary
Changes in High Density Lipoprotein Cholesterol [HDL-C]
To assess the effects of Welchol on changes in high density lipoprotein cholesterol \[HDL-C\]
Time frame: from baseline to 24 weeks
Population: Some participants may not have had lab results for this specific analysis and therefore excluded.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Welchol | Changes in High Density Lipoprotein Cholesterol [HDL-C] | 1.7 md/dL | Standard Error 1.19 |
| Placebo | Changes in High Density Lipoprotein Cholesterol [HDL-C] | -0.1 md/dL | Standard Error 1.21 |
Secondary
Changes in Low Density Lipoprotein Cholesterol [LDL-C]
To assess the effects of Welchol on changes in low density lipoprotein cholesterol \[LDL-C\]
Time frame: from baseline to 24 weeks
Population: Some participants may not have had lab results for this specific analysis and therefore excluded.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Welchol | Changes in Low Density Lipoprotein Cholesterol [LDL-C] | -10.0 mg/dL | Standard Error 1.62 |
| Placebo | Changes in Low Density Lipoprotein Cholesterol [LDL-C] | 1.2 mg/dL | Standard Error 1.63 |
p-value: <0.00001ANCOVA
Secondary
Changes in Non-HDL-C
To assess the effects of Welchol on changes in non-HDL-C
Time frame: from baseline to 24 weeks
Population: Some participants may not have had lab results for this specific analysis and therefore excluded.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Welchol | Changes in Non-HDL-C | -4.4 mg/dL | Standard Error 1.34 |
| Placebo | Changes in Non-HDL-C | 3.0 mg/dL | Standard Error 1.36 |
Secondary
Changes in Total Cholesterol [TC]
To assess the effects of Welchol on changes in total cholesterol \[TC\]
Time frame: from baseline to 24 weeks
Population: Some participants may not have had lab results for this specific analysis and therefore excluded.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Welchol | Changes in Total Cholesterol [TC] | -3.3 mg/dL | Standard Error 1.02 |
| Placebo | Changes in Total Cholesterol [TC] | 1.8 mg/dL | Standard Error 1.03 |
Secondary
Changes in Triglycerides [TG]
To assess the effects of Welchol on changes in triglycerides \[TG\]
Time frame: from baseline to 24 weeks
Population: Some participants may not have had lab results for this specific analysis and therefore excluded.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Welchol | Changes in Triglycerides [TG] | 15.5 mg/dL | Standard Error 39.82 |
| Placebo | Changes in Triglycerides [TG] | 5.8 mg/dL | Standard Error 38.39 |
Secondary
% Subjects Achieving an HbA1C Goal of <7.0
% Subjects achieving an HbA1C goal of \<7.0 at 24 weeks
Time frame: 24 weeks
Population: Some participants may not have had lab results for this specific analysis and therefore excluded.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Welchol | % Subjects Achieving an HbA1C Goal of <7.0 | 20.0 percentage of participants |
| Placebo | % Subjects Achieving an HbA1C Goal of <7.0 | 13.6 percentage of participants |
Secondary
% Subjects With a Decrease in FPG >=30 mg/dL
% Subjects with a decrease in Fasting Plasma Glucose \>=30 mg/dL from baseline to 24 weeks
Time frame: from baseline to 24 weeks
Population: Some participants may not have had lab results for this specific analysis and therefore excluded.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Welchol | % Subjects With a Decrease in FPG >=30 mg/dL | 26.9 percentage of participants |
| Placebo | % Subjects With a Decrease in FPG >=30 mg/dL | 17.8 percentage of participants |
Secondary
% Subjects With a Decrease in HbA1c of >= 0.7 Percentage Units
to determine the percentage of participants who experience a reduction in HbA1c of at least 0.7 percentage units at 24 weeks from baseline.
Time frame: 24 weeks
Population: Some participants may not have had lab results for this specific analysis and therefore excluded.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Welchol | % Subjects With a Decrease in HbA1c of >= 0.7 Percentage Units | 33.1 percentage of participants |
| Placebo | % Subjects With a Decrease in HbA1c of >= 0.7 Percentage Units | 19.5 percentage of participants |