Colesevelam for Children With Type 2 Diabetes (WELKid DM)

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: High-dose colesevelam; Drug: Low-dose colesevelam

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]).

• Study Type: Interventional
• Enrollment (Actual): 236
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
  • California
    • Los Angeles, California, United States, 90027
    • Oakland, California, United States, 94609
    • San Diego, California, United States, 92123
  • Colorado
    • Aurora, Colorado, United States, 80045
  • Connecticut
    • Hartford, Connecticut, United States, 06106
  • Florida
    • Tampa, Florida, United States, 33612
  • Georgia
    • Atlanta, Georgia, United States, 30322
  • Illinois
    • Chicago, Illinois, United States, 60637
  • Kansas
    • Kansas City, Kansas, United States, 66160
  • Maryland
    • Baltimore, Maryland, United States, 21229
  • Massachusetts
    • Springfield, Massachusetts, United States, 01199
  • New York
    • New York, New York, United States, 10032
  • North Carolina
    • Raleigh, North Carolina, United States, 27610
  • Ohio
    • Cincinnati, Ohio, United States, 45229
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
    • Oklahoma City, Oklahoma, United States, 73104
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
  • South Carolina
    • Greenville, South Carolina, United States, 29615
  • Tennessee
    • Nashville, Tennessee, United States, 37232
  • Texas
    • Dallas, Texas, United States, 75235
    • Houston, Texas, United States, 77030
    • San Antonio, Texas, United States, 78207

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Colesevelam; High-dose colesevelam suspended in a drink for oral administration once daily with dinner	Drug: High-dose colesevelam; 3.75 grams colesevelam hydrochloride in oral suspension; Other Names: Welchol oral suspension
EXPERIMENTAL: Placebo proxy; Low-dose colesevelam suspended in a drink for oral administration once daily with dinner	Drug: Low-dose colesevelam; 0.625 grams colesevelam hydrochloride in oral suspension; 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

Collaborators and Investigators

• Sponsor: Daiichi Sankyo, Inc.
• Investigators: Study Director: Global Clinical Leader/Medical Monitor, Daiichi Sankyo, Inc.

Publications and helpful links

Helpful Links

• product information, FDA-approved labeling, usage instructions, dosage forms available

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 24, 2011
• Primary Completion (ACTUAL): November 1, 2019
• Study Completion (ACTUAL): April 21, 2020

Study Registration Dates

• First Submitted: December 9, 2010
• First Submitted That Met QC Criteria: December 9, 2010
• First Posted (ESTIMATE): December 10, 2010

Study Record Updates

• Last Update Posted (ACTUAL): May 13, 2021
• Last Update Submitted That Met QC Criteria: April 16, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Adolescent; Pediatric; Metformin; Lipid; Type 2 diabetes mellitus; Blood glucose; Oral suspension; Add-on therapy; Bile acid sequestrant; Anti-diabetic; Colesevelam HCl; Add-on to metformin
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Colesevelam Hydrochloride
• Other Study ID Numbers: WEL-A-U307

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No