Safety, Tolerability, PK, and PD of LIM-0705 in Subjects With Impaired Glucose Tolerance or Abnormal HOMA-IR

A Randomized, Single-Blind, Placebo-Controlled Phase 2 Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LIM-0705 in Subjects With Impaired Glucose Tolerance or Abnormal HOMA-IR

Preliminary research suggests that LIM-0705 improves insulin sensitivity with neutral effects on weight in obese and diabetic rodent models. Results from a Phase 1b clinical study, conducted in healthy volunteers, indicate that LIM-0705 and a major metabolite may be potential insulin sensitizers by OGTT.

Study Overview

• Status: Unknown
• Conditions: Insulin Resistance; Impaired Glucose Tolerance
• Intervention / Treatment: Drug: Placebo capsules; Drug: LIM-0705

Detailed Description

The primary objective of the study is to evaluate the safety and tolerability of LIM-0705 administered for 28 days in adult males and females with impaired glucose tolerance or abnormal HOMA-IR.

Secondary Objectives include:

• examine the pharmacokinetics (PK) of LIM-0705
• explore the pharmacodynamics (PD) of LIM-0705 in obese adult males and females with impaired glucose tolerance (defined as two-hour plasma glucose levels of ≥140 to ≤199 mg per dL [7.8 to 11.06 mmol/L] on the 75-g oral glucose tolerance test [OGTT]) or abnormal HOMA-IR (HOMA-IR value ≥ 2.5) as measured by change in response to hyperinsulinemic clamp, mixed-meal tolerance test (MMTT) between Days -2 and 27
• explore the effect of LIM-0705 on fasting lipid, insulin and glucose profiles compared to baseline levels

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Chula Vista, California, United States, 91911
      • Recruiting
      • Profil Institute of Clinical Research, Inc.
      • Contact: Linda Morrow, MD; Phone Number: 619-409-1268

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• males and females, age 18-75 years old, able and willing to provide written informed consent to participate in the study
• obesity-induced impaired glucose tolerance or abnormal HOMA-IR
• waist circumference of 40 inches or greater (men) or 35 inches or greater (women)
• good physical health based on EKG, electrolytes, LDH, creatinine, urea, AST, ALT, alkaline phosphatase, and renal function
• male subjects who are sexually active with a female partner of childbearing age must agree to use of 2 effective methods of contraception, including the use of a condom, throughout the course of the study or provide proof of surgical sterility. The second method of contraception must be the use by their female partners of any of the following: a diaphragm with spermicide, a cervical cap with spermicide, an IUD, a female condom, or an approved hormonally based contraceptive (e.g., an oral, transdermal, or implanted estrogen or progestin). Female subjects must be post menopausal or surgically sterile.

Exclusion Criteria:

• BMI equal to or greater than 40 kg/m2
• allergy to onions or red wine
• strict vegetarians
• use of any non-study medications other than thyroid replacement hormone or anti-hypertensives. Use of cardesarten cilexetil is not permitted. Note: acetaminophen should not be administered.
• use of chemotherapy agents or history of cancer, other than non-metastatic non-melanoma skin cancer that has been completely excised, within 5 years prior to the screening visit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 600 mg LIM-0705 BID for 28 days	Drug: LIM-0705
Placebo Comparator: Placebo LIM-0705 for 28 days	Drug: Placebo capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Evaluate the safety (number of subjects with adverse events) of LIM-0705 administered to adult males and females with impaired glucose tolerance or abnormal HOMA-IR	28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Examine the pharmacokinetics (PK) of LIM-0705 as measured by area under the curve (AUC).	28 days
Explore the pharmacodynamics (PD) of LIM-0705 in obese adult males and females with impaired glucose tolerance or abnormal HOMA-IR as measured by change in response to hyperinsulinemic clamp, mixed-meal tolerance test (MMTT) between Days -2 and 27	28 days
Explore the effect of LIM-0705 on fasting lipid, insulin and glucose profiles compared to baseline levels	28 days
Evaluate the tolerability (BID) of LIM-0705 administered to adult males and females with impaired glucose tolerance or abnormal HOMA-IR	28 days

Collaborators and Investigators

• Sponsor: Limerick BioPharma
• Investigators: Principal Investigator: Linda Morrow, MD, Profil Institute of Clinical Research, Inc.

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Anticipated): August 1, 2011
• Study Completion (Anticipated): August 1, 2011

Study Registration Dates

• First Submitted: May 25, 2011
• First Submitted That Met QC Criteria: May 31, 2011
• First Posted (Estimate): June 2, 2011

Study Record Updates

• Last Update Posted (Estimate): June 2, 2011
• Last Update Submitted That Met QC Criteria: May 31, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Hyperglycemia; Glucose Intolerance; Insulin Resistance
• Other Study ID Numbers: LIM-0705-CL-2001