Type 1 Diabetes Mellitus MedDRA version: 17.1 Level: PT Classification code 10067584 Term: Type 1 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Product Name: LX4211
Product Code: LX4211
Pharmaceutical Form: Coated tablet
INN or Proposed INN: LX4211
CAS Number: 1018899-04-1
Current Sponsor code: LX4211
Concentration unit: mg milligram(s)
Conc
Sponsors
Lexicon Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Patient has given written informed consent to participate in the study in accordance with local regulations 2) Adult patients 18 years and older with a diagnosis of T1D made at least 1 year prior to informed consent 3) Patients are being treated with insulin or insulin analog delivered via CSII or MDI where the method of insulin delivery has not changed from CSII to MDI or vice-versa in the 3 months prior to the Screening Visit 4) At the Screening Visit, A1C must be 7.0% to 11.0%, inclusive 5) Must be willing and able to perform SMBG and complete the study diary as required per protocol 6) Females of childbearing potential must use an adequate method of contraception to avoid pregnancy throughout the duration of the study and for 30 days after the last dose of study drug. Females of childbearing potential include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal. Postmenopause is defined as no menses for =12 months without another cause. For females with questionable menopausal history (eg, irregular menstrual periods and age >40 years) a documented serum follicle-stimulating hormone (FSH) level must be =30 mIU/mL. 7) Females of childbearing potential must have a negative serum or urine pregnancy test prior to the start of study drug. In the case of positive urine pregnancy testing, a negative serum sample for pregnancy testing, to confirm that the patient is not pregnant, must be obtained prior to start of study. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 375 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 375
Exclusion criteria
Exclusion criteria: 1) Therapies and/or medications a) Use of antidiabetic agent other than insulin or insulin analog at the time of screening b) Any prior exposure to LX4211 c) Use of SGLT inhibitors within 8 weeks prior to randomization. d) Chronic systemic corticosteroid use, defined as any dose of systemic corticosteroid taken for more than 4 consecutive weeks within the 6 months prior to the Screening Visit. 2) Diabetes-related conditions: a) Type 2 diabetes mellitus, or severely uncontrolled diabetes mellitus as determined by the Investigator b) History of severe hypoglycemic event within 1 month prior to the Screening Visit. c) History of DKA within 1 month prior to Screening visit, or more than 2 episodes within 6 months prior to the Screening visit d) History of nonketotic hyperosmolar state within 6 months prior to the Screening Visit 3) Laboratory Results a) Estimated glomerular filtration rate 600 mg/dL. c) Abnormal liver function at Screening defined as any of the following: aspartate aminotransferase (AST) >2X upper limit of the normal reference range (ULN), alanine aminotransferase (ALT) >2X ULN, serum total bilirubin (TB) >1.5X ULN. d) Screening ß hydroxyl butyrate >0.6 mmol/L. 4) Reproductive status: a) Females who are pregnant or breastfeeding or intend to be during the course of the study 5) Gastrointestinal/hepatic: a) By known history, serologic evidence of current infectious liver disease (hepatitis A, B, or C), including antihepatitis A virus (immunoglobulin M), hepatitis B surface antigen, or antihepatitis C virus. b) Difficulty swallowing such that the patient cannot take the study drug c) History of pancreatitis within 12 months of screening 6) Renal: a) Initiation of chronic dialysis within 30 days prior to the Screening Visit or expected to occur within 180 days after the Screening Visit b) Renal disease that required treatment with immunosuppressive therapy, or a history of dialysis or renal transplant c) History of hereditary glucose-galactose malabsorption or primary renal glucosuria 7) Cardiovascular: a) New York Heart Association Class III or IV heart failure within 3 months prior to Screening Visit b) Hypertensive urgency or emergency within 30 days prior to randomization. c) Patients with unstable/symptomatic or life-threatening arrhythmia or heart block. d) Patient has had any of the following within 3 months prior to the Screening Visit: i. Hospitalization due to unstable angina ii. MI iii. Coronary artery bypass graft or percutaneous transluminal coronary angioplasty iv. Transient ischemic attack or significant cerebrovascular disease 8) Hematologic: a) History of hemoglobinopathies (sickle cell anemia, thalassemia major, sideroblastic anemia) or other disorder that may interfere with A1C determination b) Donation or loss of >400 mL of blood or blood product(s) within 8 weeks prior to Screening 9) Immune system: Known severe immunocompromised status, including, but not limited to, patients who have undergone organ transplantation. 10) Malignancy or active treatment for malignancy within 5 years prior to the Screening Visit. 11) Current eating disorder or increase or decrease of weight within the 12 weeks prior to Screening by more than 10% 12) Known allergies, hypersensitivity, or intolerance to LX4211 or any inactive comp
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Week 24;Secondary Objective: Secondary objectives of this study are to evaluate the change from Baseline of LX4211 versus placebo in hierarchical order on the following: -Proportion of patients with A1C <7.0% and no episode of severe hypoglycemia and no episode of diabetic ketoacidosis (DKA) -Body weight -Bolus insulin dose -Fasting plasma glucose (FPG) -Diabetes Treatment Satisfaction Questionnaire status (DTSQs) score, and 2-item Diabetes Distress Screening Scale (DDS2) questionnaire score;Main Objective: The primary objective of this study is to demonstrate superiority of either LX4211 400 mg or 200 mg versus placebo on glycosylated hemoglobin A1C (A1C) reduction at Week 24 when used as an adjunct in adult patients with type 1 diabetes mellitus (T1D) who have inadequate glycemic control with insulin therapy.;Primary end point(s): The primary endpoint is the change from Baseline to Week 24 in A1C of either dose of LX4211 (400 mg or 200 mg) treatment group compared to placebo. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy endpoints are to be measured as change from Baseline in either LX4211 dose compared to placebo for each of the following listed below. -Proportion of patients with A1C <7.0% (at Week 24) and no episode of severe hypoglycemia, and no episode of DKA (severe hypoglycemia and DKA occurrence over the cumulative randomized double-blind 24-week Core Treatment Period) -Body weight at Week 24 (absolute and percent change) -Mean change from Baseline in mean daily bolus insulin dose at Week 24 -FPG at Week 24 -Diabetes Treatment Satisfaction as measured by DTSQs scores at Week 24 -Diabetes Distress as measured by 2-item DDS2 scores at Week 24;Timepoint(s) of evaluation of this end point: Week 24 | — |
Countries
Austria, Belgium, Bulgaria, France, Germany, Hungary, Israel, Italy, Lithuania, Netherlands, Poland, Romania, Slovakia, Spain, Sweden, Switzerland, United Kingdom
Contacts
Public ContactSenior Medical Director
Lexicon Pharmaceuticals, Inc.
Outcome results
None listed