Dose-ranging Study in Patients With Type 1 Diabetes Mellitus - Clinical Trial for Type 1 Diabetes Mellitus | NCT02459899

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Placebo

Sotagliflozin

About this trial

This is an interventional treatment trial for Type 1 Diabetes Mellitus

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Participant had given written informed consent to participate in the study in accordance with local regulations.
Adult participants 18 years and older with a diagnosis of type 1 diabetes mellitus (T1D) made at least 1 year prior to informed consent.
Participants were being treated with insulin or insulin analog delivered via continuous subcutaneous insulin infusion (CSII) or multiple daily injection (MDI).
At the Screening Visit, A1C had to be between 7.0% and 10.0%.
Females of childbearing potential had to use an adequate method of contraception and have a negative pregnancy test.

Exclusion Criteria:

Use of antidiabetic agent other than insulin or insulin analog at the time of screening.
Use of sodium-glucose cotransporter (SGLT) inhibitors within 8 weeks prior to screening.
Chronic systemic corticosteroid use.
Type 2 diabetes mellitus (T2DM), or severely uncontrolled T1D as determined by the Investigator.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Sotagliflozin 75 mg

Sotagliflozin 200 mg

Sotagliflozin 400 mg

Arm Description

Two placebo-matching sotagliflozin tablets, once daily, orally for 12 weeks.

Sotagliflozin 75 mg (one 75 mg tablet and one placebo tablet), once daily, orally for 12 weeks.

Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally for 12 weeks.

Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally for 12 weeks.

Outcomes

Primary Outcome Measures

Change From Baseline in Hemoglobin A1C (A1C) at Week 12

Baseline was defined as the last value collected prior to the first dose of double-blind study medication. Post-baseline Least Square (LS) mean values were obtained from mixed-effects model repeated measures (MMRM) model with treatment, randomization strata of insulin delivery method (continuous subcutaneous insulin infusion [CSII] or multiple daily injection [MDI]), time (study week), and a treatment-by-time interaction as fixed categorical effects, and baseline A1C-by-time interaction as a covariate.

Secondary Outcome Measures

Change From Baseline to Week 12 in 2-Hour Postprandial Glucose (PPG) Following the Standardized Mixed Meal

A 2-hour PPG sample (plasma) was obtained 2-hours after a standardized Mixed Meal at Baseline (Day 1) and at the visit at Week 12. Post-Baseline LS mean was obtained from analysis of covariance (ANCOVA) model with treatment, randomization strata of insulin delivery method (CSII, MDI) as fixed categorical effects, and baseline postprandial glucose as a covariate.

Absolute Change From Baseline in Body Weight to Week 12

Baseline was defined as the last value collected prior to the first dose of double-blind study medication. Post-Baseline LS mean was obtained from MMRM model with treatment, randomization strata of insulin delivery method (CSII, MDI), time (study week), and a treatment-by-time interaction as fixed categorical effects, and baseline weight-by-time interaction as a covariate.

Percent Change From Baseline in Body Weight to Week 12

Baseline was defined as the last value collected prior to the first dose of double-blind study medication. Post-Baseline LS mean was obtained from MMRM model with treatment, randomization strata of insulin delivery method (CSII, MDI), time (study week), and a treatment-by-time interaction as fixed categorical effects, and baseline weight-by-time interaction as a covariate.

Change From Baseline to Week 12 in 24-Hour Urinary Glucose Excretion

Urine was collected over 24 hours to measure Urinary Glucose Excretion at baseline, and at the end of the 12-week treatment. Post-Baseline LS mean was obtained from ANCOVA model with treatment, randomization strata of insulin delivery method (CSII, MDI) as fixed categorical effects, and Baseline urinary glucose excretion as a covariate.

Change From Baseline to Week 12 in Fasting Plasma Glucose

Baseline was defined as the last value collected prior to the first dose of double-blind study medication. Post-Baseline LS mean was obtained from MMRM model with treatment, randomization strata of insulin delivery method (CSII, MDI), time (study week), and a treatment-by-time interaction as fixed categorical effects, and baseline fasting plasma glucose-by-time interaction as a covariate.

Full Information

NCT ID

NCT02459899

First Posted

May 29, 2015

Last Updated

February 10, 2020

Sponsor

Lexicon Pharmaceuticals

Collaborators

Sanofi

1. Study Identification

Unique Protocol Identification Number

NCT02459899

Brief Title

Dose-ranging Study in Patients With Type 1 Diabetes Mellitus

Acronym

inTandem4

Official Title

A Phase 2b, Dose-ranging, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study in Patients With Type 1 Diabetes Mellitus Who Have Inadequate Glycemic Control With Insulin Therapy

Study Type

Interventional

2. Study Status

Record Verification Date

February 2020

Overall Recruitment Status

Completed

Study Start Date

July 2015 (Actual)

Primary Completion Date

August 2016 (Actual)

Study Completion Date

August 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Lexicon Pharmaceuticals

Collaborators

Sanofi

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The primary objective of this study was to define the dose leading to desirable efficacy, as measured by the change in hemoglobin A1C (A1C) between Baseline and Week 12.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 1 Diabetes Mellitus

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

141 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Two placebo-matching sotagliflozin tablets, once daily, orally for 12 weeks.

Arm Title

Sotagliflozin 75 mg

Arm Type

Experimental

Arm Description

Sotagliflozin 75 mg (one 75 mg tablet and one placebo tablet), once daily, orally for 12 weeks.

Arm Title

Sotagliflozin 200 mg

Arm Type

Experimental

Arm Description

Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally for 12 weeks.

Arm Title

Sotagliflozin 400 mg

Arm Type

Experimental

Arm Description

Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally for 12 weeks.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo, once daily, before the first meal of the day

Intervention Type

Drug

Intervention Name(s)

Sotagliflozin

Intervention Description

Sotagliflozin,once daily, before the first meal of the day

Primary Outcome Measure Information:

Title

Change From Baseline in Hemoglobin A1C (A1C) at Week 12

Description

Baseline was defined as the last value collected prior to the first dose of double-blind study medication. Post-baseline Least Square (LS) mean values were obtained from mixed-effects model repeated measures (MMRM) model with treatment, randomization strata of insulin delivery method (continuous subcutaneous insulin infusion [CSII] or multiple daily injection [MDI]), time (study week), and a treatment-by-time interaction as fixed categorical effects, and baseline A1C-by-time interaction as a covariate.

Time Frame

Baseline to Week 12

Secondary Outcome Measure Information:

Title

Change From Baseline to Week 12 in 2-Hour Postprandial Glucose (PPG) Following the Standardized Mixed Meal

Description

A 2-hour PPG sample (plasma) was obtained 2-hours after a standardized Mixed Meal at Baseline (Day 1) and at the visit at Week 12. Post-Baseline LS mean was obtained from analysis of covariance (ANCOVA) model with treatment, randomization strata of insulin delivery method (CSII, MDI) as fixed categorical effects, and baseline postprandial glucose as a covariate.

Time Frame

Baseline, Week 12

Title

Absolute Change From Baseline in Body Weight to Week 12

Description

Baseline was defined as the last value collected prior to the first dose of double-blind study medication. Post-Baseline LS mean was obtained from MMRM model with treatment, randomization strata of insulin delivery method (CSII, MDI), time (study week), and a treatment-by-time interaction as fixed categorical effects, and baseline weight-by-time interaction as a covariate.

Time Frame

Baseline to Week 12

Title

Percent Change From Baseline in Body Weight to Week 12

Description

Baseline was defined as the last value collected prior to the first dose of double-blind study medication. Post-Baseline LS mean was obtained from MMRM model with treatment, randomization strata of insulin delivery method (CSII, MDI), time (study week), and a treatment-by-time interaction as fixed categorical effects, and baseline weight-by-time interaction as a covariate.

Time Frame

Baseline to Week 12

Title

Change From Baseline to Week 12 in 24-Hour Urinary Glucose Excretion

Description

Urine was collected over 24 hours to measure Urinary Glucose Excretion at baseline, and at the end of the 12-week treatment. Post-Baseline LS mean was obtained from ANCOVA model with treatment, randomization strata of insulin delivery method (CSII, MDI) as fixed categorical effects, and Baseline urinary glucose excretion as a covariate.

Time Frame

Baseline, Week 12

Title

Change From Baseline to Week 12 in Fasting Plasma Glucose

Description

Baseline was defined as the last value collected prior to the first dose of double-blind study medication. Post-Baseline LS mean was obtained from MMRM model with treatment, randomization strata of insulin delivery method (CSII, MDI), time (study week), and a treatment-by-time interaction as fixed categorical effects, and baseline fasting plasma glucose-by-time interaction as a covariate.

Time Frame

Baseline to Week 12

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: Participant had given written informed consent to participate in the study in accordance with local regulations. Adult participants 18 years and older with a diagnosis of type 1 diabetes mellitus (T1D) made at least 1 year prior to informed consent. Participants were being treated with insulin or insulin analog delivered via continuous subcutaneous insulin infusion (CSII) or multiple daily injection (MDI). At the Screening Visit, A1C had to be between 7.0% and 10.0%. Females of childbearing potential had to use an adequate method of contraception and have a negative pregnancy test. Exclusion Criteria: Use of antidiabetic agent other than insulin or insulin analog at the time of screening. Use of sodium-glucose cotransporter (SGLT) inhibitors within 8 weeks prior to screening. Chronic systemic corticosteroid use. Type 2 diabetes mellitus (T2DM), or severely uncontrolled T1D as determined by the Investigator.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Suman Wason, MD

Organizational Affiliation

Lexicon Pharmaceuticals, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

Lexicon Investigational Site

City

Concord

State/Province

California

ZIP/Postal Code

94520

Country

United States

Facility Name

Lexicon Investigational Site

City

Ventura

State/Province

California

ZIP/Postal Code

93003

Country

United States

Facility Name

Lexicon Investigational Site

City

Denver

State/Province

Colorado

ZIP/Postal Code

80209

Country

United States

Facility Name

Lexicon Investigational Site

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32225

Country

United States

Facility Name

Lexicon Investigational Site

City

Miami

State/Province

Florida

ZIP/Postal Code

33175

Country

United States

Facility Name

Lexicon Investigational Site

City

Springfield

State/Province

Illinois

ZIP/Postal Code

62711

Country

United States

Facility Name

Lexicon Investigational Site

City

Metairie

State/Province

Louisiana

ZIP/Postal Code

70006

Country

United States

Facility Name

Lexicon Investigational Site

City

Auburn

State/Province

Maine

ZIP/Postal Code

04210

Country

United States

Facility Name

Lexicon Investigational Site

City

Rockville

State/Province

Maryland

ZIP/Postal Code

20852

Country

United States

Facility Name

Lexicon Investigational Site

City

Great Falls

State/Province

Montana

ZIP/Postal Code

59405

Country

United States

Facility Name

Lexicon Investigational Site

City

Omaha

State/Province

Nebraska

ZIP/Postal Code

68114

Country

United States

Facility Name

Lexicon Investigational Site

City

High Point

State/Province

North Carolina

ZIP/Postal Code

27265

Country

United States

Facility Name

Lexicon Investigational Site

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43213

Country

United States

Facility Name

Lexicon Investigational Site

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

Facility Name

Lexicon Investigational Site

City

Salt Lake City

State/Province

Utah

ZIP/Postal Code

84107

Country

United States

Facility Name

Lexicon Investigational Site

City

Chesapeake

State/Province

Virginia

ZIP/Postal Code

23321

Country

United States

Facility Name

Lexicon Investigational Site

City

Manassas

State/Province

Virginia

ZIP/Postal Code

20110

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

31264767

Citation

Baker C, Wason S, Banks P, Sawhney S, Chang A, Danne T, Gesty-Palmer D, Kushner JA, McGuire DK, Mikell F, O'Neill M, Peters AL, Strumph P. Dose-dependent glycometabolic effects of sotagliflozin on type 1 diabetes over 12 weeks: The inTandem4 trial. Diabetes Obes Metab. 2019 Nov;21(11):2440-2449. doi: 10.1111/dom.13825. Epub 2019 Aug 1.

Results Reference

derived

Dose-ranging Study in Patients With Type 1 Diabetes Mellitus (inTandem4)

Type 1 Diabetes Mellitus

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial