Type 1 Diabetes MellitusPhase 2inTandem4NCT02459899

Dose-ranging Study in Patients With Type 1 Diabetes Mellitus

A Phase 2 study testing Sotagliflozin in people with Type 1 Diabetes Mellitus, run by Lexicon Pharmaceuticals at 17 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Type 1 Diabetes Mellitus
What is being tested?: Sotagliflozin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 141 participants
Where: 17 sitesUnited States
Study dates: Jul 2015to Aug 2016
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

17 sites in 1 country.

City, postcode or hospital

17 sites in 1 country

United States17 sites

Lexicon Investigational Site
Auburn, Maine, 04210
Lexicon Investigational Site
Chesapeake, Virginia, 23321
Lexicon Investigational Site
Columbus, Ohio, 43213
Lexicon Investigational Site
Concord, California, 94520
Lexicon Investigational Site
Denver, Colorado, 80209
Lexicon Investigational Site
Great Falls, Montana, 59405
Lexicon Investigational Site
High Point, North Carolina, 27265
Lexicon Investigational Site
Jacksonville, Florida, 32225
Lexicon Investigational Site
Manassas, Virginia, 20110
Lexicon Investigational Site
Metairie, Louisiana, 70006
Lexicon Investigational Site
Miami, Florida, 33175
Lexicon Investigational Site
Omaha, Nebraska, 68114
Lexicon Investigational Site
Rockville, Maryland, 20852
Lexicon Investigational Site
Salt Lake City, Utah, 84107
Lexicon Investigational Site
San Antonio, Texas, 78229
Lexicon Investigational Site
Springfield, Illinois, 62711
Lexicon Investigational Site
Ventura, California, 93003

Other trials in United States

About this study

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

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.

Conditions: Type 1 Diabetes Mellitus
Being tested: Placebo, Sotagliflozin
Medical subject headings: Diabetes Mellitus, Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PlaceboDrug
Placebo, once daily, before the first meal of the day
SotagliflozinDrug
Sotagliflozin,once daily, before the first meal of the day

Study groups in NCT02459899
Study group	Role	What they receive
Placebo	Placebo comparator	Two placebo-matching sotagliflozin tablets, once daily, orally for 12 weeks. Receives: Drug: Placebo
Sotagliflozin 75 mg	Experimental	Sotagliflozin 75 mg (one 75 mg tablet and one placebo tablet), once daily, orally for 12 weeks. Receives: Drug: Placebo; Drug: Sotagliflozin
Sotagliflozin 200 mg	Experimental	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally for 12 weeks. Receives: Drug: Placebo; Drug: Sotagliflozin
Sotagliflozin 400 mg	Experimental	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally for 12 weeks. Receives: Drug: Sotagliflozin

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline to Week 12

Secondary outcomes (5)

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.
Measured: Baseline, Week 12
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.
Measured: Baseline to Week 12
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.
Measured: Baseline to Week 12
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.
Measured: Baseline, Week 12
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.
Measured: Baseline to Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2015Aug 2016

First posted2 Jun 2015 (estimated)
Study startJul 2015
Primary completionAug 2016
Study completionAug 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Type 1 Diabetes MellitusStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 141 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02459899
Sponsor's protocol ID: LX4211.1-206-T1DM
Other IDs: LX4211.206
Acronym: inTandem4
Status last verified: Feb 2020
First submitted: 29 May 2015
Last updated: 12 Feb 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 31264767

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 12 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02459899
Acronym / sponsor ID: inTandem4 / LX4211.1-206-T1DM
Conditions: Type 1 Diabetes Mellitus
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 141 participants (actual)
Lead sponsor: Lexicon PharmaceuticalsIndustry (pharma, biotech, devices)
Collaborators: Sanofi
Study start: Jul 2015 (actual)
Primary completion: Aug 2016 (actual)
Study completion: Aug 2016 (actual)
First posted: 2 Jun 2015 (estimated)
Results: Posted 30 Oct 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
Placebo	Placebo comparator	Drug: PlaceboTwo placebo-matching sotagliflozin tablets, once daily, orally for 12 weeks.
Sotagliflozin 75 mg	Experimental	Drug: Placebo, Drug: SotagliflozinSotagliflozin 75 mg (one 75 mg tablet and one placebo tablet), once daily, orally for 12 weeks.
Sotagliflozin 200 mg	Experimental	Drug: Placebo, Drug: SotagliflozinSotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally for 12 weeks.
Sotagliflozin 400 mg	Experimental	Drug: SotagliflozinSotagliflozin 400 mg (two 200 mg tablets), once daily, orally for 12 weeks.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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.

Key exclusion criteria (4 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PlaceboPlacebo, once daily, before the first meal of the day	Drug	Placebo, Sotagliflozin 200 mg, Sotagliflozin 75 mg
SotagliflozinSotagliflozin,once daily, before the first meal of the day	Drug	Sotagliflozin 200 mg, Sotagliflozin 400 mg, Sotagliflozin 75 mg

Primary outcome

Change From Baseline in Hemoglobin A1C (A1C) at Week 12
Time frame: Baseline to 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.

5 secondary outcomes

Change From Baseline to Week 12 in 2-Hour Postprandial Glucose (PPG) Following the Standardized Mixed Meal
Time frame: Baseline, Week 12
Absolute Change From Baseline in Body Weight to Week 12
Time frame: Baseline to Week 12
Percent Change From Baseline in Body Weight to Week 12
Time frame: Baseline to Week 12
Change From Baseline to Week 12 in 24-Hour Urinary Glucose Excretion
Time frame: Baseline, Week 12
Change From Baseline to Week 12 in Fasting Plasma Glucose
Time frame: Baseline to Week 12

Results and safety

Results posted to the registry on 30 Oct 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	36	33
Sotagliflozin 75 mg	35	29
Sotagliflozin 200 mg	35	35
Sotagliflozin 400 mg	35	33

Primary outcome: Change From Baseline in Hemoglobin A1C (A1C) at Week 12

Time frame: Baseline to Week 12. Least squares mean (Standard Error). Unit: percentage of A1C

Measure	Placebo n = 33	Sotagliflozin 75 mg n = 29	Sotagliflozin 200 mg n = 35	Sotagliflozin 400 mg n = 33
Value	-0.35 (0.096)	-0.60 (0.100)	-0.84 (0.095)	-0.73 (0.096)

Placebo vs Sotagliflozin 75 mg: Least squares mean difference: -0.25 (95% CI -0.53 to 0.02), p = 0.07, MMRM
Placebo vs Sotagliflozin 200 mg: Least squares mean difference: -0.48 (95% CI -0.75 to -0.22), p <0.001, MMRM
Placebo vs Sotagliflozin 400 mg: Least squares mean difference: -0.38 (95% CI -0.65 to -0.11), p = 0.006, MMRM

Population analysed: Analysis included participants from the mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse event (AE) data were collected from first dose up to 30 days after date of last dose of double-blind study treatment (up to 114 days). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	1 of 36 (2.8%)	10 of 36 (27.8%)	0 of 36
Sotagliflozin 75 mg	1 of 35 (2.9%)	5 of 35 (14.3%)	0 of 35
Sotagliflozin 200 mg	1 of 35 (2.9%)	6 of 35 (17.1%)	0 of 35
Sotagliflozin 400 mg	1 of 35 (2.9%)	4 of 35 (11.4%)	0 of 35

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 31264767Baker 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Suman Wason, MD study director

Lexicon Pharmaceuticals, Inc.

17 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Sotagliflozin in people with Type 1 Diabetes Mellitus, run by Lexicon Pharmaceuticals at 17 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Hemoglobin A1C (A1C) at Week 12 (time frame: Baseline to Week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02459899, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2020.