Clinical Trials/NCT02851849

NCT02851849

Completed

Phase 2

A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of Safety and Efficacy of LGD-6972 in Patients With Type 2 Diabetes Mellitus

Ligand Pharmaceuticals0 sites148 target enrollmentSeptember 2016

ConditionsType 2 Diabetes Mellitus

InterventionsLGD-6972-5 mg LGD-6972-10 mg LGD-6972-15 mg Placebo

DrugsLGD-6972-5 mg LGD-6972-10 mg LGD-6972-15 mg

Overview

Phase: Phase 2
Intervention: LGD-6972-5 mg
Conditions: Type 2 Diabetes Mellitus
Sponsor: Ligand Pharmaceuticals
Enrollment: 148
Primary Endpoint: Change from baseline in HbA1c
Status: Completed
Last Updated: 8 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

The purpose of this study is to evaluate the change from baseline in hemoglobin A1c (HbA1c) during 12 weeks of treatment with 3 dose levels of LGD-6972 compared to placebo in subjects with Type 2 Diabetes Mellitus (T2DM)

Detailed Description

This will be a 12-week, randomized, double-blind, placebo-controlled, 4-arm, parallel group, multi-center study to evaluate the safety and efficacy of LGD-6972 in subjects with T2DM inadequately controlled on metformin monotherapy (a stable \[≥12 weeks\], daily dose of ≥1000mg at randomization). Subjects with T2DM will be treated with one of 3 dose levels of LGD-6972 (5 mg, 10 mg, or 15 mg) or placebo once daily (QD) for 12 weeks. Randomization will be stratified by HbAlc ≤8.5% or \>8.5% at the Placebo Lead-in Visit. Qualified subjects who require adjustment or stabilization of their metformin dose will participate in a run-in period of up to 12 additional weeks prior to randomization. Subjects will have the option to participate in an oral glucose tolerance test (OGTT) at baseline and end of treatment for assessment of exploratory endpoints.

Registry

clinicaltrials.gov

Start Date

September 2016

End Date

June 2017

Last Updated

8 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Ligand Pharmaceuticals

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Female subjects must be surgically sterile (hysterectomy or bilateral oophorectomy or bilateral tubal ligation), or naturally post-menopausal for at least 12 months and with a follicle stimulating hormone (FSH) level in the post-menopausal range (if not taking hormone replacement therapy)
•Male subjects must either have a vasectomy or agree that they and any female partners will use 2 acceptable forms of contraception, one of which must be a condom, until 30 days after the last dose of study drug. Other acceptable forms of contraception include hormonal contraceptives that have been at stable dose for 12 weeks prior to randomization, intrauterine device, Depo-Provera®, Norplant® System Implants, bilateral tubal ligation, bilateral oophorectomy, hysterectomy, and contraceptive sponge, foam, or jelly. Also, male subjects must not donate sperm during the study and for 30 days after the last dose of study drug
•Willing and able to provide written informed consent
•Diagnosis of T2DM according to American Diabetes Association criteria
•Currently on stable metformin or metformin extended-release therapy (unchanged dose \[minimum daily dose of 1000 mg\] for ≥12 weeks prior to screening)
•Subjects must have an HbA1c value of ≥7.0% to ≤10.5%
•Subjects must have a fasting plasma glucose of ≤260 mg/dL
•Subjects must have a body mass index (BMI) between 25 kg/m2 and 40 kg/m2, inclusive, and must weigh more than 45 kg

Exclusion Criteria

•History of type 1 diabetes mellitus or history of diabetic ketoacidosis or persistent hypoglycemia or hypoglycemia unawareness
•Women of childbearing potential, lactating, or has a positive pregnancy test
•History or presence of alcoholism or drug abuse within 2 years prior to screening
•Unwilling to comply with study restrictions, including restrictions on strenuous exercise
•Presence of any of the following conditions: renal impairment (defined as history or estimated glomerular filtration rate at screening of \<45 mL/min using the Modification of Diet in Renal Disease equation), diabetic proliferative retinopathy, severely symptomatic diabetic neuropathy requiring treatment, diabetic gastroparesis, active liver disease (other than asymptomatic nonalcoholic fatty liver disease), cirrhosis, symptomatic gall bladder disease, or pancreatitis
•Serum triglyceride level \> 400 mg/dL at screening
•Liver transaminase levels (AST or ALT) \>150% ULN, total bilirubin \>2 ULN, or creatine kinase (CK) levels \> 3 × ULN at screening
•History or evidence of clinically significant cardiovascular, pulmonary, renal, endocrine (other than T2DM), hepatic, neurologic, psychiatric, immunologic, hematologic, gastrointestinal, or metabolic disease or surgical intervention (eg, bariatric surgery) or allergic conditions (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing)
•Myocardial infarction, unstable angina, arterial revascularization, stroke, symptomatic peripheral artery disease, deep vein thrombosis, New York Heart Association Functional Class III or IV heart failure, or transient ischemic attack within 6 months prior to screening
•History of malignant hypertension or a recent history of uncontrolled high blood pressure or at screening has a seated systolic blood pressure \>160 mmHg and/or diastolic blood pressure \>100 mmHg after at least a 5 minute rest. Blood pressure is determined as the mean of triplicate measurements collected at 2- minute intervals after the subject has been sitting quietly for at least 5 minutes. Therapy for hypertension (beta blockers excluded) that has been stable for at least 8 weeks prior to screening is permitted

Arms & Interventions

LGD-6972-5 mg

5 mg LGD-6972 QD

Intervention: LGD-6972-5 mg

LGD-6972-10 mg

10 mg LGD-6972 QD

Intervention: LGD-6972-10 mg

LGD-6972-15 mg

15 mg LGD-6972 QD

Intervention: LGD-6972-15 mg

Placebo

Placebo QD

Intervention: Placebo

Outcomes

Primary Outcomes

Change from baseline in HbA1c

Time Frame: 12 Weeks

Secondary Outcomes

Change from baseline values for fasting glucagon(Baseline to Weeks 2,4,8 and 12)
Change from baseline in HbA1C(Baseline to Weeks 2,4,8)
Change from baseline in fasting glucose(Baseline to Weeks 2,4,8 and 12)
Change from baseline values for fasting GLP-1 (total and active)(Baseline to Weeks 2,4,8 and 12)
Change from baseline values for fasting insulin(Baseline to Weeks 2,4,8 and 12)
Change from baseline values for fasting lipids (total, LDL, and HDL cholesterol and triglycerides)(Baseline to Weeks 2,4,8, and 12)
Change from baseline in blood pressure (systolic and diastolic)(Baseline to Weeks 2,4,8, and 12)
Change from baseline in body weight(Baseline to Weeks 2,4,8 and 12)