Type 2 Diabetes Mellitus
Conditions
Keywords
diabetes mellitus
Brief summary
This study is intended to assess the effect on HbA1c of different dose regimens of LX4211 in combination with metformin in subjects with Type 2 Diabetes Mellitus who have inadequate glycemic control on metformin monotherapy.
Interventions
DRUG75 mg LX4211
Subjects will receive 75 mg LX4211 once daily
DRUG200 mg LX4211
Subjects will receive 200 mg LX4211 once daily.
DRUG400 mg LX4211
Subjects will receive 400 mg LX4211 once daily.
DRUGPlacebo
Subjects will receive placebo once daily.
Sponsors
Lexicon Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Adult subjects between the ages of 18 to 75 years, inclusive * Confirmed diagnosis of Type 2 diabetes mellitus * Meet required laboratory values at screening, including fasting plasma glucose less than 270 mg/dL * Stable dose of metformin monotherapy greater than 1500 mg/day for at least 8 weeks * Willing and able to provide written informed consent * Willing and able to maintain consistent dietary, physical activity, and sleeping patterns throughout the study
Exclusion criteria
* History of Type 1 diabetes mellitus, diabetic ketoacidosis, hyperosmolar nonketotic syndrome, or diabetes resulting from pancreatic disorder or secondary diabetes * History of renal disease or clinically significant abnormal kidney function tests * Presence of active hepatic disease or clinically significant abnormal liver function tests * Subjects with a history of heart attack, severe/unstable angina, or coronary revascularization procedure within 6 months prior to study Day 1 * History of clinically significant cardiac arrhythmias within one year of study Day 1 * Subjects with congestive heart failure * Subjects with uncontrolled Stage III hypertension * Triglycerides \>1000 mg/dL at Screening * Known history of HIV or hepatitis C * History of illicit drug or alcohol abuse with one year of study Day 1 * Have had 2 or more emergency room visits, doctor visits, or hospitalizations due to hypoglycemia within 6 months of study Day 1 * Use of any other investigational drug within 30 days of study Day 1 * Prior exposure to LX4211 * Use of any medication or herbal supplement for the purpose of weight loss * Chronic use of any antidiabetic therapy other than metformin in the 3 months prior to study Day 1 * Use of corticosteroids within 2 weeks prior to study Day 1 * Major surgery within 6 months of study Day 1 * Subjects with any history of severe gastroparesis * Inability or difficulty swallowing whole capsules or tablets * Women who are pregnant or breast feeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in HbA1c to Week 12 | 12 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants Achieving a HbA1c Value of <7% at Week 12 | 12 weeks |
| Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 | 12 weeks |
| Change From Baseline in Body Weight at Week 12 | 12 weeks |
| Change From Baseline in Systolic Blood Pressure (SPB) at Week 12 | 12 weeks |
| Change From Baseline in Triglycerides at Week 12 | 12 weeks |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 75 mg LX4211 qd Subjects will receive 75 mg LX4211 once daily | 59 |
| 200 mg LX4211 qd Subjects will receive 200 mg LX4211 once daily. | 60 |
| 400 mg LX4211 qd Subjects will receive 400 mg LX4211 once daily. | 60 |
| 200 mg LX4211 Bid Subjects will receive 200 mg LX4211 twice daily. | 60 |
| Placebo qd Placebo: Subjects will receive placebo once daily. | 60 |
| Total | 299 |
Baseline characteristics
| Characteristic | 75 mg LX4211 qd | Total | Placebo qd | 200 mg LX4211 Bid | 400 mg LX4211 qd | 200 mg LX4211 qd |
|---|---|---|---|---|---|---|
| Age, Continuous | 56.1 years STANDARD_DEVIATION 9.61 | 55.9 years STANDARD_DEVIATION 9.34 | 55.1 years STANDARD_DEVIATION 9.79 | 56.4 years STANDARD_DEVIATION 8.76 | 56.1 years STANDARD_DEVIATION 9.51 | 55.6 years STANDARD_DEVIATION 9.25 |
| Body Mass index (BMI) | 33.44 kg/m^2 STANDARD_DEVIATION 5.237 | 33.08 kg/m^2 STANDARD_DEVIATION 5.658 | 32.17 kg/m^2 STANDARD_DEVIATION 5.796 | 32.85 kg/m^2 STANDARD_DEVIATION 5.626 | 32.69 kg/m^2 STANDARD_DEVIATION 5.757 | 34.23 kg/m^2 STANDARD_DEVIATION 5.816 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants | 82 Participants | 15 Participants | 12 Participants | 21 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants | 217 Participants | 45 Participants | 48 Participants | 39 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 169.25 cm STANDARD_DEVIATION 10.419 | 167.96 cm STANDARD_DEVIATION 10.486 | 167.18 cm STANDARD_DEVIATION 10.24 | 169.39 cm STANDARD_DEVIATION 11.171 | 167.04 cm STANDARD_DEVIATION 9.849 | 166.99 cm STANDARD_DEVIATION 10.764 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 8 Participants | 3 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 31 Participants | 6 Participants | 5 Participants | 6 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 48 Participants | 252 Participants | 49 Participants | 53 Participants | 51 Participants | 51 Participants |
| Region of Enrollment United States | 59 participants | 299 participants | 60 participants | 60 participants | 60 participants | 60 participants |
| Sex: Female, Male Female | 25 Participants | 164 Participants | 34 Participants | 31 Participants | 31 Participants | 43 Participants |
| Sex: Female, Male Male | 34 Participants | 135 Participants | 26 Participants | 29 Participants | 29 Participants | 17 Participants |
| Weight | 96.16 kg STANDARD_DEVIATION 19.328 | 93.73 kg STANDARD_DEVIATION 20.093 | 90.57 kg STANDARD_DEVIATION 20.726 | 95.01 kg STANDARD_DEVIATION 22.202 | 91.38 kg STANDARD_DEVIATION 18.643 | 95.59 kg STANDARD_DEVIATION 19.368 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 31 / 57 | 34 / 60 | 26 / 59 | 26 / 60 | 27 / 60 |
| serious Total, serious adverse events | 0 / 57 | 1 / 60 | 2 / 59 | 0 / 60 | 1 / 60 |
Outcome results
Primary
Change From Baseline in HbA1c to Week 12
Time frame: 12 weeks
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 75 mg LX4211 qd | Change From Baseline in HbA1c to Week 12 | -0.42 % change | Standard Deviation 0.637 |
| 200 mg LX4211 qd | Change From Baseline in HbA1c to Week 12 | -0.52 % change | Standard Deviation 0.78 |
| 400 mg LX4211 qd | Change From Baseline in HbA1c to Week 12 | -0.92 % change | Standard Deviation 0.873 |
| 200 mg LX4211 Bid | Change From Baseline in HbA1c to Week 12 | -0.80 % change | Standard Deviation 0.932 |
| Placebo qd | Change From Baseline in HbA1c to Week 12 | -0.09 % change | Standard Deviation 0.77 |
Secondary
Change From Baseline in Body Weight at Week 12
Time frame: 12 weeks
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 75 mg LX4211 qd | Change From Baseline in Body Weight at Week 12 | -0.995 kg | Standard Deviation 3.113 |
| 200 mg LX4211 qd | Change From Baseline in Body Weight at Week 12 | -1.956 kg | Standard Deviation 2.536 |
| 400 mg LX4211 qd | Change From Baseline in Body Weight at Week 12 | -1.848 kg | Standard Deviation 1.9641 |
| 200 mg LX4211 Bid | Change From Baseline in Body Weight at Week 12 | -2.477 kg | Standard Deviation 2.561 |
| Placebo qd | Change From Baseline in Body Weight at Week 12 | -0.395 kg | Standard Deviation 1.9813 |
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12
Time frame: 12 weeks
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 75 mg LX4211 qd | Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 | -9.5 mg/dL | Standard Deviation 27.35 |
| 200 mg LX4211 qd | Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 | -17.4 mg/dL | Standard Deviation 40.45 |
| 400 mg LX4211 qd | Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 | -27.1 mg/dL | Standard Deviation 38.48 |
| 200 mg LX4211 Bid | Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 | -26.9 mg/dL | Standard Deviation 35.07 |
| Placebo qd | Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 | 2.2 mg/dL | Standard Deviation 45.35 |
Secondary
Change From Baseline in Systolic Blood Pressure (SPB) at Week 12
Time frame: 12 weeks
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 75 mg LX4211 qd | Change From Baseline in Systolic Blood Pressure (SPB) at Week 12 | -0.123 mm Hg | Standard Deviation 12.6921 |
| 200 mg LX4211 qd | Change From Baseline in Systolic Blood Pressure (SPB) at Week 12 | -3.878 mm Hg | Standard Deviation 12.1935 |
| 400 mg LX4211 qd | Change From Baseline in Systolic Blood Pressure (SPB) at Week 12 | -5.746 mm Hg | Standard Deviation 12.3675 |
| 200 mg LX4211 Bid | Change From Baseline in Systolic Blood Pressure (SPB) at Week 12 | -4.452 mm Hg | Standard Deviation 12.1401 |
| Placebo qd | Change From Baseline in Systolic Blood Pressure (SPB) at Week 12 | -0.283 mm Hg | Standard Deviation 13.5945 |
Secondary
Change From Baseline in Triglycerides at Week 12
Time frame: 12 weeks
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 75 mg LX4211 qd | Change From Baseline in Triglycerides at Week 12 | -16.2 mg/dL | Standard Deviation 84.17 |
| 200 mg LX4211 qd | Change From Baseline in Triglycerides at Week 12 | 6.6 mg/dL | Standard Deviation 77.05 |
| 400 mg LX4211 qd | Change From Baseline in Triglycerides at Week 12 | -16.8 mg/dL | Standard Deviation 121.9 |
| 200 mg LX4211 Bid | Change From Baseline in Triglycerides at Week 12 | -16.9 mg/dL | Standard Deviation 73.13 |
| Placebo qd | Change From Baseline in Triglycerides at Week 12 | -30.5 mg/dL | Standard Deviation 201.92 |
Secondary
Number of Participants Achieving a HbA1c Value of <7% at Week 12
Time frame: 12 weeks
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 75 mg LX4211 qd | Number of Participants Achieving a HbA1c Value of <7% at Week 12 | 16 participants |
| 200 mg LX4211 qd | Number of Participants Achieving a HbA1c Value of <7% at Week 12 | 15 participants |
| 400 mg LX4211 qd | Number of Participants Achieving a HbA1c Value of <7% at Week 12 | 22 participants |
| 200 mg LX4211 Bid | Number of Participants Achieving a HbA1c Value of <7% at Week 12 | 17 participants |
| Placebo qd | Number of Participants Achieving a HbA1c Value of <7% at Week 12 | 14 participants |