Colesevelam Oral Suspension as Monotherapy or Add-on to Metformin Therapy in Pediatric Subjects with Type 2 Diabetes Mellitus
This is a multi-center, randomized, double-blind, 2-group study in pediatric subjects with type 2 diabetes mellitus with suboptimal glycemic control with or without metformin. The study will consist of:
* a screening visit,
* a 2-week single-blind lead-in/stabilization period,
* a 12-month double-blind treatment period, and
* a follow-up visit approximately 2 weeks after the end of treatment.
Subjects may either be on metformin monotherapy or be currently untreated with antidiabetic agents. [Quote]untreated[Quote] includes subjects who have either
* never received antidiabetic therapy (naive) or
* received antidiabetic medications for less than 14 days within 3 months prior to screening but no insulin therapy within 14 days of screening.
The prior type 2 diabetes mellitus treatment status will be used as a stratification factor at randomization.
all subjects will enter a 2-week, single-blind lead-in/stabilization period after being confirmed as eligible to participate in this study. Subjects on metformin monotherapy will remain on the same dose as at screening throughout the stabilization period. a blinded once-daily medication (low-dose colesevelam HCl) will be provided to all subjects.
approximately 220 subjects will be randomized in a 3:2 ratio of high-dose colesevelam HCl oral suspension (3.75 g) once daily to low-dose colesevelam HCl oral suspension (0.625 g) once daily for the treatment period.
after randomization, subjects must continue on the same dose of metformin as during lead-in/stabilization, unless and until the subject meets the criteria for glycemic rescue. in the event that the subject's Hba1c level cannot be controlled below 8.5% after 3 months or below 7.5% (confirmed persistent hyperglycemia) after 6 months of study medication, as measured by the central laboratory, glycemic rescue must be started with metformin (by initiating or optimizing doses to a maximally tolerated dose up to 2 g/d), and if this is not adequate, with once-daily insulin such as insulin glargine.
Those low-dose subjects who complete Month 6 and are switched to the high dose prior to the approval of protocol version 2.0 and its informed Consent will continue on the high-dose to the end of the study, according to the original protocol.
Glucometers will be provided for self-monitoring of blood glucose levels, which will be recorded during the lead-in period and throughout the two 6-month treatment periods.
Subjects must satisfy all of the following criteria at screening to be included in the study:
1. Diagnosis of type 2 diabetes mellitus, as defined by the American Diabetes
2. Understand study procedures and agree to participate by giving written assent and
obtaining written consent from a parent or legal guardian at screening (Week <= -4);
3. Males and females aged 10 to 17 years, inclusive, at randomization (randomization must occur before 18th birthday);
4. HbA1c at screening between 7.0% and 10.0%, inclusive;
5. Fasting C-peptide >0.6 ng/mL
6. Anti-diabetic treatment at screening:
* On metformin monotherapy: Metformin monotherapy has been initiated prior to screening; or
* On no antidiabetic treatment (currently untreated), defined as:
o Naive, never received antidiabetic therapy or
o Untreated, received anti-diabetic medications for less than 14 days within 3 months prior to
screening but no insulin therapy within 14 days of screening.