Colesevelam for Children With Type 2 Diabetes

Study Overview
=================
Brief Summary
-----------------
This study will evaluate the efficacy and safety of the study drug in treating type 2 diabetes in children 10 to 17 years old. The groups will be low-dose (0.625 g Welchol) and high-dose (3.75 g Welchol). The children will have a 2 in 5 chance of being assigned to the low-dose group. They will have a 3 in 5 chance of being assigned to the high-dose group. We believe the study drug will be safe, well tolerated, and improve blood sugar control in children 10 to 17 years old.

Detailed Description
-----------------
Colesevelam oral suspension will be studied as treatment of type 2 diabetes mellitus (T2DM) to evaluate clinical safety and efficacy in patients aged 10-17 years. The patients may have been treated with Metformin or have had no antidiabetic drug treatment in the previous three months. Study Hypothesis: Colesevelam oral suspension for pediatric subjects with T2DM is safe, well tolerated, and shows improved blood sugar control (as evidenced by a significant change from baseline in hemoglobin A1C [HbA1c]).

Official Title
-----------------
Colesevelam Oral Suspension as Monotherapy or Add-on to Metformin Therapy in Pediatric Subjects With Type 2 Diabetes Mellitus

Conditions
-----------------
Type 2 Diabetes Mellitus

Intervention / Treatment
-----------------
* Drug: High-dose colesevelam
* Drug: Low-dose colesevelam


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of type 2 diabetes mellitus, as defined by the American Diabetes Association; Written informed consent of study participation Males and females aged 10 to 17 years, inclusive, at randomization (randomization must occur before 18th birthday); HbA1c at screening between 7.0% and 10.0%, inclusive; Fasting C-peptide >0.6 ng/mL; and Anti-diabetic treatment at screening: Treatment-naïve or untreated; OR On metformin monotherapy: Metformin monotherapy has been initiated prior to screening. Exclusion Criteria: Fasting plasma glucose >270 mg/dL; Diagnosis of type 1 diabetes; History of more than one episode of ketoacidosis after the initial diagnosis of type 2 diabetes mellitus; Clinical laboratory assessments/evaluations, eg. autoimmune markers, aminotransferases, triglycerides, creatinine clearance, and Hb variants, that are not within the protocol-defined parameters Systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥95 mmHg Use of medications not allowed by protocol-defined parameters, eg. insulin or any medication that affects insulin sensitivity or secretion, growth hormones/somatotropin, or anabolic steroids Genetic syndrome or disorder known to affect glucose Participation in a weight loss program or another interventional research study within 60 days; Female participants who are lactating, pregnant, or plan to become pregnant within 1 year of screening; Female participants who are sexually active and unwilling to use appropriate contraception for the duration of the study; History of bowel obstruction; Other significant organ system illness or condition (including psychiatric or developmental disorder) that, in the opinion of the Investigator, would prevent full participation

Ages Eligible for Study
-----------------
Minimum Age: 10 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Colesevelam<br>High-dose colesevelam suspended in a drink for oral administration once daily with dinner | Drug: High-dose colesevelam<br>* 3.75 grams colesevelam hydrochloride in oral suspension<br>* Other names: Welchol oral suspension;|
| Experimental: Placebo proxy<br>Low-dose colesevelam suspended in a drink for oral administration once daily with dinner | Drug: Low-dose colesevelam<br>* 0.625 grams colesevelam hydrochloride in oral suspension<br>* Other names: Welchol oral suspension;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Hemoglobin A1c (HbA1c) From Baseline to Month 6 | The percent change in HbA1c from baseline to Month 6 was assessed with the last observation after 1 month before any rescue therapy carried forward. | Baseline to Month 6 post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Hemoglobin A1c (HbA1c) From Baseline to Month 12 | The percent change in HbA1c from baseline to Month 6 was assessed with the last observation after 1 month before any rescue therapy carried forward. | Baseline to Month 12 post-dose | 
| Change in Fasting Plasma Glucose (FPG) From Baseline to Month 12 | Change from baseline was assessed for FPG values at Month 6 and Month 12 categorical time points. | Baseline to Month 12 post-dose | 
| Number of Participants Achieving a Response to Therapy to Month 12 | Participants achieving a response to therapy, ie, glycemic control, were assessed with the last observation after 1 month before any rescue therapy carried forward at Month 6 and Month 12. Response to therapy was defined as HbA1c <7.0% or <6.5%, reduction in HbA1c ≥0.7% or ≥0.5% from baseline, and/or reduction in FPG ≥30 mg/dL from baseline. | Baseline to Month 12 post-dose | 
| Percent Change From Baseline to Month 6 in Plasma Lipids | The percent change in plasma lipids from baseline to Month 6 was assessed with the last observation after 1 month before any rescue therapy carried forward. | Baseline to Month 6 post-dose | 
| Percent Change From Baseline to Month 6 in Triglycerides | The percent change in triglycerides from baseline to Month 6 was assessed with the last observation after 1 month before any rescue therapy carried forward. | Baseline to Month 6 post-dose | 
| Number of Participants Requiring Rescue Medication Who Initially Met Rescue Criteria | Rescue criteria was defined as HbA1c levels ≥8.5% after 3 months or ≥7.5% after 6 months (≥173 days) (confirmed persistent hyperglycemia) of study medication treatment, as measured by the central laboratory. | Baseline to Month 12 post-dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Type 2 diabetes mellitus, Blood glucose, Anti-diabetic, Bile acid sequestrant, Colesevelam HCl, Oral suspension, Pediatric, Add-on therapy, Add-on to metformin, Metformin, Adolescent, Lipid