A Study of LGD-6972 in Patients With Type 2 Diabetes Mellitus

NCT02851849 | Completed Phase 2

• 1 other identifier: L6972-04
• Study Type: interventional
• Target: 148
• Locations: 1 country
• Sites: 29

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)

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Change from baseline in HbA1c

  12 Weeks

Secondary Outcomes (8)

• 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 glucagon

  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

Other Outcomes (1)

• Exploratory Objective - Change from baseline from an Oral Glucose Tolerance Test (area under the curve for glucose, glucagon, insulin, C-peptide, and total and active GLP-1)

  Baseline, 12 Weeks

Study Arms (4)

LGD-6972-5 mg

ACTIVE COMPARATOR

5 mg LGD-6972 QD

Drug: LGD-6972-5 mg

LGD-6972-10 mg

ACTIVE COMPARATOR

10 mg LGD-6972 QD

Drug: LGD-6972-10 mg

LGD-6972-15 mg

ACTIVE COMPARATOR

15 mg LGD-6972 QD

Drug: LGD-6972-15 mg

Placebo

PLACEBO COMPARATOR

Placebo QD

Other: Placebo

Interventions

LGD-6972-5 mg DRUG

5 mg LGD-6972 QD

Also known as: LGD-6972 sodium salt capsules

LGD-6972-5 mg

LGD-6972-10 mg DRUG

10 mg LGD-6972 QD

Also known as: LGD-6972 sodium salt capsules

LGD-6972-10 mg

LGD-6972-15 mg DRUG

15 mg LGD-6972 QD

Also known as: LGD-6972 sodium salt capsules

LGD-6972-15 mg

Placebo OTHER

Placebo QD

Placebo

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Arm size in excess of the maximum limit of the largest cuff provided with the study blood pressure monitor
• History of malignancy (except adequately treated basal or squamous cell skin cancer or cervical carcinoma in situ) within 5 years prior to screening
• History or evidence of QT prolongation or clinically significant QT prolongation (QTcF \>450 msec) at screening, or other significant ECG findings at screening that may place the subject at increased risk by participating in the study
• Treatment with any type of insulin (injected or inhaled) for \> 6 consecutive days within 6 months prior to screening or any insulin therapy within 12 weeks prior to screening
• Treated with peroxisome proliferator-activated receptor-gamma agonists (thiazolidinediones \[TZDs\]), incretin therapy (GLP-1 agonists). or amylin mimetics within 12 weeks prior to screening

Sponsors & Collaborators

• Ligand Pharmaceuticals: lead

Study Sites (29)

Unknown Facility

Tuscumbia, Alabama, 35674, United States

Location

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Chandler, Arizona, 85224, United States

Location

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Surprise, Arizona, 85374, United States

Location

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Huntington Park, California, 90255, United States

Location

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Los Angeles, California, 90057, United States

Location

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Montclair, California, 91763, United States

Location

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North Hollywood, California, 91606, United States

Location

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San Diego, California, 92161, United States

Location

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Denver, Colorado, 80209, United States

Location

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Brooksville, Florida, 34601, United States

Location

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Miami, Florida, 33014, United States

Location

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Orlando, Florida, 32804, United States

Location

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Tampa, Florida, 33607, United States

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Chicago, Illinois, 60607, United States

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Las Vegas, Nevada, 89119, United States

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Albuquerque, New Mexico, 87102, United States

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Hopewell Junction, New York, 12533, United States

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Durham, North Carolina, 27710, United States

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Greensboro, North Carolina, 27410, United States

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Franklin, Ohio, 45005, United States

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Munroe Falls, Ohio, 44262, United States

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Summerville, South Carolina, 29485, United States

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Carrollton, Texas, 75007, United States

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Dallas, Texas, 75230, United States

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Houston, Texas, 77036, United States

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Houston, Texas, 77074, United States

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Houston, Texas, 77099, United States

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Katy, Texas, 77450, United States

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Unknown Facility

Manassas, Virginia, 20110, United States

Location

Related Publications (1)

• Pettus JH, D'Alessio D, Frias JP, Vajda EG, Pipkin JD, Rosenstock J, Williamson G, Zangmeister MA, Zhi L, Marschke KB. Efficacy and Safety of the Glucagon Receptor Antagonist RVT-1502 in Type 2 Diabetes Uncontrolled on Metformin Monotherapy: A 12-Week Dose-Ranging Study. Diabetes Care. 2020 Jan;43(1):161-168. doi: 10.2337/dc19-1328. Epub 2019 Nov 6.

  PMID: 31694861 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Keith Marschke, Ph.D.

  Ligand Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2016
• First Posted: August 2, 2016
• Study Start: September 1, 2016
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2017
• Last Updated: January 12, 2018

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (29)