Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LGD-6972 in Healthy Subjects and Subjects With Type 2 Diabetes Mellitus

NCT01919684 | Completed Phase 1

• 1 other identifier: L6972-01
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to evaluate the safety and tolerability of a range of single oral doses of LGD-6972 in healthy subjects. Additionally, the study will characterize the Pharmacokinetic profile in healthy subjects under fed and fasted conditions and in subjects with Type 2 Diabetes Mellitus under fasted conditions.

Conditions

Type 2 Diabetes Mellitus

Keywords

Glucagon receptor antagonist

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of single oral doses of LGD-6972 in healthy subjects and in subjects with T2DM.

  Subjects in Groups A,B,C,D,E and F will be admitted to the study site on Day -1, and Group G will be admitted to the study site on Day -2. Each subject will be administered a specified dose of LGD-6972 or placebo under fasting conditions (and fed conditions for Group D to evaluate the effects of food on the LGD-6972 PK profile)and will be observed through the morning of Day 3 (48 hour post dose assessment). Safety assessments, LGD-6972 PK sample collection, and PD assessments will occur during this time. Subjects will be discharged from the study site after the 48 hour assessments and return to the study site on Day 7 for a follow up evaluation.

  Subjects observed through the morning of Day 3 (48 hour post dose assessment). Subjects will be discharged from the study site after the 48 hour assessments and return to the study site on Day 7 for a follow up evaluation..

Secondary Outcomes (3)

• Pharmacokinetic (PK) profile of LGD-6972 and its potential metabolites after a single oral dose in healthy subjects and in subjects with T2DM.

  Subjects observed through the morning of Day 3 (48 hour post dose assessment). Subjects will be discharged from the study site after the 48 hour assessments and return to the study site on Day 7 for a follow up evaluation..

• Pharmacodynamic (PD) profile of LGD-6972 after a single oral dose in healthy subjects and in subjects with T2DM.

  Subjects observed through the morning of Day 3 (48 hour post dose assessment). Subjects will be discharged from the study site after the 48 hour assessments and return to the study site on Day 7 for a follow up evaluation..

• The effect of food on the bioavailability and PK profile of LGD-6972 and its potential metabolites after a single oral 40 mg dose in healthy subjects.

  Subjects observed through the morning of Day 3 (48 hour post dose assessment). Subjects will be discharged from the study site after the 48 hour assessments and return to the study site on Day 7 for a follow up evaluation..

Study Arms (2)

Active

ACTIVE COMPARATOR

LGD-6972

Drug: LGD-6972

Placebo (Captisol®)

PLACEBO COMPARATOR

Vehicle Control (Captisol®)

Drug: Placebo (Captisol®)

Interventions

LGD-6972 DRUG

Active

Placebo (Captisol®) DRUG

Placebo (Captisol®)

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy, normoglycemic, adults (Groups A to D) or adults with uncomplicated T2DM (Group E), 21 to 65 years of age inclusive.
• Women must be of non-child-bearing potential and may not be pregnant, lactating, or breast-feeding.
• Non-childbearing potential is defined by at least one of the following criteria: a.\>2 years spontaneous amenorrhea (not attributable to environmental or pathological causes, eg, anorexia or excessive exercise) with follicle-stimulating hormone (FSH) in post-menopausal range at the Screening Visit (A naturally menopausal woman on a stable dose of hormone replacement medication does not require an FSH at the Screening Visit.), or b.at least 3 months post-surgical bilateral oophorectomy or tubal ligation, or c.hysterectomy (must be greater than 5 years post-hysterectomy, if due to cancer).
• Body weight ≥45 kg at the Screening Visit.
• No clinically significant abnormalities on the basis of medical history, physical examination, electrocardiogram (ECG), and vital signs, other than T2DM (Part 2 subjects, Group E) at the Screening Visit or at Day -1.
• All laboratory values for hematology, clinical chemistry, lipid profile, and urinalysis must be within the normal range ± 10% at the Screening Visit or at Day -1. If the values are not within the normal range, they must be deemed not clinically significant by the Investigator with documented agreement from the medical monitor. Liver transaminase levels (aspartate transaminase \[AST\] and alanine transaminase \[ALT\]) and creatine phosphokinase (CPK) levels must be below the upper limit of normal (ULN) + 10%.
• No history of liver function abnormality or liver disease (with the exception of asymptomatic non-alcoholic fatty liver disease \[NAFLD\] in T2DM subjects) at the Screening Visit or at Day -1.
• Male subjects must agree that they and any female partners will use 2 acceptable forms of contraception (eg, condoms, hormonal contraceptives) until 30 days after the last dose of study drug.
• Patient is willing to provide written informed consent prior to any study-specific evaluation and agrees to comply with visit schedule including willingness to remain at the study site.
• For healthy subjects:
• Screening body mass index (BMI) of 18.5 to 30 kg/m2 inclusive at the Screening Visit or at Day -1.
• Fasting blood glucose between 60-100 mg/dL inclusive at the Screening Visit or at Day -1 (1 retest allowed after 24 hours).
• For subjects with T2DM:
• Screening BMI of 18.5 to 35 kg/m2 inclusive at the Screening Visit or at Day -1.
• Fasting blood glucose \<200 mg/dL for treatment naïve T2DM subjects and \<180 mg/dL for T2DM subjects on antidiabetic therapy at the Screening Visit (1 retest allowed after 24 hours; \<220 mg/dL on all T2DM subjects on admission to the investigational site on Day -2).

You may not qualify if:

• Presence or history of cancer within 5 years prior to the Screening Visit (other than basal cell skin cancer without active lesions and adequately treated carcinoma in situ of cervix);
• Presence or history of gastrointestinal (GI), hepatic, or renal disease or any other condition (including surgery) known to interfere with the absorption, distribution, metabolism or excretion of medicines. History of appendectomy and cholecystectomy is permitted;
• Presence or history of significant cardiovascular, pulmonary (including asthma), hepatic, renal, gastrointestinal (including GI bleeding), hematologic (including coagulation disorders), immunologic, endocrine, psychiatric, or neurologic disease that, in the opinion of the Investigator, may cause an increase risk during the study or compromise interpretation of study data.
• History of uncontrolled high blood pressure, or systolic blood pressure outside the range of 90 mmHg to 140 mmHg, inclusive, and diastolic blood pressure outside the range of 60 mmHg to 90 mmHg, inclusive, at the Screening Visit or at Day -1, confirmed by at least 2 repeat measurements. Repeat blood pressure measurements are permitted within 24 hours at the discretion of the Investigator;
• History of Gilbert's disease or bilirubin \>1.5 X ULN at the Screening Visit or at Day -1;
• History of clinically significant drug allergies (including LGD 6972, PEG 400, or Captisol®) and/or clinically significant food allergies as determined by the Principal Investigator;
• Use of any alcohol or methylxanthine-containing beverages or food (eg, coffee, tea, cola, chocolate, and "power drinks") from 72 h prior to the first dose of study drug until after the last protocol specified blood sample;
• Use of any tobacco products, nicotine-containing products, or pharmacologic smoking cessation therapy during the 3 months immediately prior to the first dose of study drug, and/or not willing or able to refrain from use of any of these products for the duration of the study until after the last protocol specified blood sample;
• History of alcohol abuse within 2 years of the Screening Visit, in the judgment of the Investigator, or average weekly alcohol consumption of \>14 alcoholic drinks. One drink is defined as 1 glass of beer (approximately 10 oz to 12 oz) or 1 can (12 oz) of beer, 1 glass of wine (approximately 4 oz to 5 oz), or 1 glass of distilled spirits (hard liquor) containing 1 oz of the liquor (1 oz of liquid is approximately 30 mL);
• Plasma triglycerides \>400 mg/dL at the Screening Visit or at Day -1;
• History of drug abuse within 2 years of the Screening Visit, in the judgment of the Investigator;
• Positive urine test for drugs of abuse (opiates, methadone, cocaine, amphetamines, cannabinoids, barbiturates, benzodiazepines) or cotinine at the Screening Visit or at Day -1;
• Positive breath test for alcohol at the Screening Visit or at Day -1;
• Not willing to abstain from strenuous exercise (eg, heavy lifting, weight training, calisthenics, aerobics) for at least 48 hours prior to admission to the investigational site until after the last protocol specified blood sample;
• Use of substances known to be strong inhibitors or inducers of cytochrome P450 enzymes (eg, ritonavir, ketoconazole, nefazodone, grapefruit juice) within 14 days prior to the first dose of study drug through the last study visit. Chronic exposure to enzyme inducers such as paint solvents or pesticides, other investigational drug use, or illicit drug use within 30 days prior to study drug administration;

Sponsors & Collaborators

• Ligand Pharmaceuticals: lead
• Beckloff Associates, Inc.: collaborator
• Medpace, Inc.: collaborator

Study Sites (1)

Medpace Clinical Pharmacology

Cincinnati, Ohio, 45227, United States

Location

Related Links

• LGD-6972

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

RVT-1502; SBE4-beta-cyclodextrin

Condition Hierarchy (Ancestors)

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

Study Officials

• Douglas K Logan, M.D.

  Medpace Clinical Pharmacology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2013
• First Posted: August 9, 2013
• Study Start: November 1, 2013
• Primary Completion: February 1, 2014
• Study Completion: March 1, 2014
• Last Updated: September 25, 2014

Record last verified: 2014-03

Locations

US (1)