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This study will assess the effects of colesevelam, alone or in combination with sitagliptin, on glucose metabolism in subjects with T2DM inadequately controlled by diet and exercise
The hypothesis is that co-administrationof colesevelam plus sitagliptin results in a greater reduction in HbA1c compared to colesevelam HCl treatment by
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Colesevelam HCl: 3 tablets, 2x/day | Active Comparator | Subjects will be given 3.75 g/day. Subjects will be given 3 tablets (625mg each) with breakfast and 3 tablets (625mg) with dinner for 12 weeks. |
|
| Colesevelam plus Sitagliptin | Active Comparator | Colesevelam: Subjects will be given 3.75 g/day. Subjects will be given 3 tablets (625mg each) with breakfast and 3 tablets (625mg) with dinner for 12 weeks. Sitagliptin: Subjects will be given 100mg/day. Subjects will be given 1 tablet (100mg) with breakfast for 12 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Colesevelam HCl | Drug | Subjects will be given 3.75 g/day. Subjects will be given 3 tablets (625mg each) with breakfast and 3 tablets (625mg) with dinner for 12 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Hemoglobin A1C | Change from baseline in hemoglobin A1C after 12 weeks of colesevelam or colesevelam plus sitagliptin treatments | Baseline and 12 weeks |
| Fasting Plasma Glucose | Change from baseline in fasting plasma glucose concentrations after 12 weeks of colesevelam or colesevelam plus sitagliptin treatments. | Baseline and 12 weeks |
| Fasting Endogenous Glucose Production | Change from baseline in fasting endogenous glucose production after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatment | baseline and 12 weeks |
| Fasting Gluconeogenesis | Change from baseline in fasting gluconeogenesis after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatment | baseline and 12 weeks |
| Fasting Glycogenolysis | Change from baseline in fasting glycogenolysis after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatment | baseline and 12 weeks |
| Fasting Plasma Glucose Clearance | Change from baseline in fasting plasma glucose clearance after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatments. | baseline and 12 weeks |
| Appearance Rate of Oral Glucose | Change from baseline in appearance rate of oral glucose after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatments |
| Measure | Description | Time Frame |
|---|---|---|
| Fasting Plasma C-peptide | To evaluate the effect of treatments on plamsa C-peptide concentrations. | Baseline and 12 weeks |
| Fasting Plamsa Glucagon | To evaluate the effect of treatments on plasma glucagon concentrations. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Carine Beysen, DPhil | KineMed, Inc. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, San Francisco | San Francisco | California | 94110 | United States | ||
| Clinical Pharmacology of Miami |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17379048 | Background | Zieve FJ, Kalin MF, Schwartz SL, Jones MR, Bailey WL. Results of the glucose-lowering effect of WelChol study (GLOWS): a randomized, double-blind, placebo-controlled pilot study evaluating the effect of colesevelam hydrochloride on glycemic control in subjects with type 2 diabetes. Clin Ther. 2007 Jan;29(1):74-83. doi: 10.1016/j.clinthera.2007.01.003. | |
| 18852398 |
| Label | URL |
|---|---|
| Ethics and Compliance | View source |
Not provided
Subjects treated with acarbose, sulfonylurea or metformin and an A1C ≥6.5% and ≤9% were eligible to enter the study after a 4 (acarbose and sulfonylurea) or 8 (metformin) week wash-out period when meeting all other criteria.
Study period from February 2010 to December 2010. This was a multi-center, randomized, open-label, prospective, parallel-group study consisting of 12 weeks of active treatment.
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| ID | Title | Description |
|---|---|---|
| FG000 | Colesevelam | Subjects were given 3.75 g colesevelem per day: 3 tablets (625mg each) with breakfast and 3 tablets with dinner for 12 weeks. |
| FG001 | Colesevelam Plus Sitagliptin | Colesevelam: Subjects were given 3.75 g colesevelem per day: 3 tablets (625mg each) with breakfast and 3 tablets with dinner for 12 weeks. Sitagliptin: In addition subjects were given 100mg sitagliptin/day. Subjects were given 1 tablet (100mg) with breakfast for 12 weeks. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Colesevelam | Subjects were given 3.75 g colesevelam per day: 3 tablets (625mg each) with breakfast and 3 tablets (625mg each) with dinner for 12 weeks. |
| BG001 | Colesevelam Plus Sitagliptin |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Hemoglobin A1C | Change from baseline in hemoglobin A1C after 12 weeks of colesevelam or colesevelam plus sitagliptin treatments | Posted | Mean | Standard Deviation | percentage | Baseline and 12 weeks |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Colesevelam | Subjects were given 3.75 g colesevelam per day: 3 tablets (625mg each) with breakfast and 3 tablets (625mg each) with dinner for 12 weeks. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tingling sensation in lower extremities | Nervous system disorders | Non-systematic Assessment | Subject complained of tingling sensation in lower extremities accompanied by headache and dry mouth. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Carine Beysen, PhD | KineMed, Inc. | 510-655-6525 | 123 | cbeysen@kinemed.com |
Not provided
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D000069472 | Colesevelam Hydrochloride |
| D000068900 | Sitagliptin Phosphate |
| ID | Term |
|---|---|
| D000499 | Allylamine |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D000498 | Allyl Compounds |
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|
| Sitagliptin | Drug | Subjects will be given 100mg/day. Subjects will be given 1 tablet (100mg) with breakfast for 12 weeks. |
|
|
| baseline and 12 weeks |
| Postprandial Endogenous Glucose Production | Change from baseline in postprandial endogenous glucose production after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatments Mean value was calculated using all results measured between 10 and 300 min post meal. | baseline and 12 weeks |
| Postprandial Rate of Total Glucose Disposal Area Under the Curve (AUC) | Change from baseline in postprandial rate of total glucose disposal (AUC) after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatments AUC was calculated by the trapezoid method using all results measured between 0 and 300 min during the meal tolerance test. | baseline and 12 weeks |
| Whole-body Glycolytic Disposal of Oral Glucose | Change in baseline in whole-body glycolytic disposal of oral glucose after 12 weeks of colesevelam alone or colesevelam plus glucose treatments | baseline and 12 weeks |
| Postprandial Glucose (AUC) | Comparison between baseline and 12 weeks values of postrandial glucose (AUC). | Baseline and 12 weeks |
| Baseline and 12 weeks |
| Fasting Active Plasma Glucagon Like-Peptide 1 (GLP-1) | To evaluate the effect of treatments on plasma GLP-1 concentrations. | Baseline and 12 weeks |
| Fasting Plasma Total Glucose-dependent Insulinotropic Peptide (GIP) | To evaluate the effect of treatments on plasma Glucose-dependent Insulinotropic Peptide (GIP) concentrations. | Baseline and 12 weeks |
| Fasting Insulin | To evaluate the effect of treatments on fasting insulin concentrations | Baseline and 12 weeks |
| Postprandial Insulin (AUC) | To evaluate the effect of treatments on postprandial insulin (AUC) | Baseline and 12 weeks |
| Postprandial C-peptide (AUC) | To evaluate the effect of treatments on postprandial C-peptide (AUC) | Baseline and 12 weeks |
| Postprandial Active GLP-1 (AUC) | To evaluate the effects of treatments on postprandial active GLP-1 (AUC) | Baseline and 12 weeks |
| Postprandial Total GIP (AUC) | To evaluate the effects of treatment on postprandial total GIP (AUC) | Baseline and 12 weeks |
| Postprandial Glucagon (AUC) | To evaluate the effects of treatment on postprandial glucagon (AUC) | Baseline and 12 weeks |
| Miami |
| Florida |
| 33014 |
| United States |
| Healthcare Discoveries, LLC d/b/a ICON Development Solutions | San Antonio | Texas | 78209 | United States |
| Bays HE, Goldberg RB, Truitt KE, Jones MR. Colesevelam hydrochloride therapy in patients with type 2 diabetes mellitus treated with metformin: glucose and lipid effects. Arch Intern Med. 2008 Oct 13;168(18):1975-83. doi: 10.1001/archinte.168.18.1975. |
| 18458145 | Background | Fonseca VA, Rosenstock J, Wang AC, Truitt KE, Jones MR. Colesevelam HCl improves glycemic control and reduces LDL cholesterol in patients with inadequately controlled type 2 diabetes on sulfonylurea-based therapy. Diabetes Care. 2008 Aug;31(8):1479-84. doi: 10.2337/dc08-0283. Epub 2008 May 5. |
| 18663165 | Background | Goldberg RB, Fonseca VA, Truitt KE, Jones MR. Efficacy and safety of colesevelam in patients with type 2 diabetes mellitus and inadequate glycemic control receiving insulin-based therapy. Arch Intern Med. 2008 Jul 28;168(14):1531-40. doi: 10.1001/archinte.168.14.1531. |
| 17130196 | Background | Aschner P, Kipnes MS, Lunceford JK, Sanchez M, Mickel C, Williams-Herman DE; Sitagliptin Study 021 Group. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care. 2006 Dec;29(12):2632-7. doi: 10.2337/dc06-0703. |
| 17300595 | Background | Nauck MA, Meininger G, Sheng D, Terranella L, Stein PP; Sitagliptin Study 024 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: a randomized, double-blind, non-inferiority trial. Diabetes Obes Metab. 2007 Mar;9(2):194-205. doi: 10.1111/j.1463-1326.2006.00704.x. |
| 17485570 | Background | Goldstein BJ, Feinglos MN, Lunceford JK, Johnson J, Williams-Herman DE; Sitagliptin 036 Study Group. Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin on glycemic control in patients with type 2 diabetes. Diabetes Care. 2007 Aug;30(8):1979-87. doi: 10.2337/dc07-0627. Epub 2007 May 7. |
| High fasting triglyceride |
|
| Adverse Event |
|
| Protocol Violation |
|
Colesevelam: Subjects will be given 3.75 g/day. Subjects will be given 3 tablets (625mg each) with breakfast and 3 tablets (625mg) with dinner for 12 weeks.
Sitagliptin: Subjects will be given 100mg/day. Subjects will be given 1 tablet (100mg) with breakfast for 12 weeks.
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Weight | Mean | Standard Deviation | kilograms |
|
| BMI | Mean | Standard Deviation | kilograms/square meter (kg/m2) |
|
| Fat Free Mass | Mean | Standard Deviation | kilograms |
|
| Hemoglobin A1c | Mean | Standard Deviation | percentage |
|
| Fasting Glucose | glucose measured in the plasma | Mean | Standard Deviation | millimole/liter (mmol/L) |
|
| HOMA-IR | There is no unit of measurement for HOMA-IR (Homeostatic model assessment - insulin resistance) | Mean | Standard Deviation | HOMA score |
|
| HOMA-beta cell | Mean | Standard Deviation | percentage |
|
| Fasting Insulin | Mean | Standard Deviation | microunits/milliters (uU/ml) |
|
| Fasting total-cholesterol | Mean | Standard Deviation | micrograms/deciliter (mg/dL) |
|
| Fasting LDL-cholesterol | Mean | Standard Deviation | micrograms/deciliter (mg/dL) |
|
| Fasting HDL-cholesterol | Mean | Standard Deviation | micrograms/deciliter (mg/dL) |
|
| fasting triglycerides | Mean | Standard Deviation | micrograms/deciliter (mg/dL) |
|
|
|
|
| Secondary | Fasting Plasma C-peptide | To evaluate the effect of treatments on plamsa C-peptide concentrations. | Posted | Mean | Standard Deviation | picomoles (pmol)/Liter (L) | Baseline and 12 weeks |
|
|
|
|
| Primary | Fasting Plasma Glucose | Change from baseline in fasting plasma glucose concentrations after 12 weeks of colesevelam or colesevelam plus sitagliptin treatments. | Posted | Mean | Standard Deviation | millimoles (mmol)/Liter (L) | Baseline and 12 weeks |
|
|
|
|
| Secondary | Fasting Plamsa Glucagon | To evaluate the effect of treatments on plasma glucagon concentrations. | Posted | Mean | Standard Deviation | picograms (pg)/milliliter (ml) | Baseline and 12 weeks |
|
|
|
|
| Secondary | Fasting Active Plasma Glucagon Like-Peptide 1 (GLP-1) | To evaluate the effect of treatments on plasma GLP-1 concentrations. | Posted | Mean | Standard Deviation | pmol/L | Baseline and 12 weeks |
|
|
|
|
| Secondary | Fasting Plasma Total Glucose-dependent Insulinotropic Peptide (GIP) | To evaluate the effect of treatments on plasma Glucose-dependent Insulinotropic Peptide (GIP) concentrations. | Posted | Mean | Standard Deviation | pmol/L | Baseline and 12 weeks |
|
|
|
|
| Primary | Fasting Endogenous Glucose Production | Change from baseline in fasting endogenous glucose production after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatment | Posted | Mean | Standard Deviation | micromoles (umol) per kg FFM per min | baseline and 12 weeks |
|
|
|
|
| Primary | Fasting Gluconeogenesis | Change from baseline in fasting gluconeogenesis after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatment | Posted | Mean | Standard Deviation | umol per kilogram (kg) FFM per min | baseline and 12 weeks |
|
|
|
|
| Primary | Fasting Glycogenolysis | Change from baseline in fasting glycogenolysis after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatment | Posted | Mean | Standard Deviation | umol per kg Fat-Free Mass (FFM) per min | baseline and 12 weeks |
|
|
|
|
| Primary | Fasting Plasma Glucose Clearance | Change from baseline in fasting plasma glucose clearance after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatments. | Posted | Mean | Standard Deviation | ml per kg FFM per minute (min) | baseline and 12 weeks |
|
|
|
|
| Primary | Appearance Rate of Oral Glucose | Change from baseline in appearance rate of oral glucose after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatments | Posted | Mean | Standard Deviation | umol per kg per min | baseline and 12 weeks |
|
|
|
|
| Primary | Postprandial Endogenous Glucose Production | Change from baseline in postprandial endogenous glucose production after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatments Mean value was calculated using all results measured between 10 and 300 min post meal. | Posted | Mean | Standard Deviation | umol per kg per min | baseline and 12 weeks |
|
|
|
|
| Primary | Postprandial Rate of Total Glucose Disposal Area Under the Curve (AUC) | Change from baseline in postprandial rate of total glucose disposal (AUC) after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatments AUC was calculated by the trapezoid method using all results measured between 0 and 300 min during the meal tolerance test. | Posted | Mean | Standard Deviation | umol per kg per min | baseline and 12 weeks |
|
|
|
|
| Primary | Whole-body Glycolytic Disposal of Oral Glucose | Change in baseline in whole-body glycolytic disposal of oral glucose after 12 weeks of colesevelam alone or colesevelam plus glucose treatments | Posted | Mean | Standard Deviation | Percent of Load | baseline and 12 weeks |
|
|
|
|
| Primary | Postprandial Glucose (AUC) | Comparison between baseline and 12 weeks values of postrandial glucose (AUC). | Posted | Mean | Standard Deviation | millimoles (mmol)/l x min | Baseline and 12 weeks |
|
|
|
|
| Secondary | Fasting Insulin | To evaluate the effect of treatments on fasting insulin concentrations | Posted | Mean | Standard Deviation | pmol/L | Baseline and 12 weeks |
|
|
|
|
| Secondary | Postprandial Insulin (AUC) | To evaluate the effect of treatments on postprandial insulin (AUC) | Posted | Mean | Standard Deviation | pmol/l x min | Baseline and 12 weeks |
|
|
|
|
| Secondary | Postprandial C-peptide (AUC) | To evaluate the effect of treatments on postprandial C-peptide (AUC) | Posted | Mean | Standard Deviation | pmol/l x min | Baseline and 12 weeks |
|
|
|
|
| Secondary | Postprandial Active GLP-1 (AUC) | To evaluate the effects of treatments on postprandial active GLP-1 (AUC) | Posted | Mean | Standard Deviation | pmol/l x min | Baseline and 12 weeks |
|
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|
|
| Secondary | Postprandial Total GIP (AUC) | To evaluate the effects of treatment on postprandial total GIP (AUC) | Posted | Mean | Standard Deviation | pmol/l x min | Baseline and 12 weeks |
|
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|
|
| Secondary | Postprandial Glucagon (AUC) | To evaluate the effects of treatment on postprandial glucagon (AUC) | Posted | Mean | Standard Deviation | picograms (pg)/milliter (ml) x min | Baseline and 12 weeks |
|
|
|
|
| 0 |
| 31 |
| 1 |
| 31 |
| EG001 | Colesevelam Plus Sitagliptin | Colesevelam: Subjects will be given 3.75 g/day. Subjects will be given 3 tablets (625mg each) with breakfast and 3 tablets (625mg) with dinner for 12 weeks. Sitagliptin: Subjects will be given 100mg/day. Subjects will be given 1 tablet (100mg) with breakfast for 12 weeks. | 0 | 30 | 1 | 30 |
|
| Non-related Adverse Event | General disorders | Non-systematic Assessment | Subject withdrawn due to a non-related adverse event |
|
Not provided
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| D004700 | Endocrine System Diseases |
| D000475 |
| Alkenes |
| D006839 | Hydrocarbons, Acyclic |
| D006838 | Hydrocarbons |
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011719 | Pyrazines |