Clinical trial NCT01364155: Safety, Tolerability, PK, and PD of LIM-0705 in Subjects With Impaired Glucose Tolerance or Abnormal HOMA-IR
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Impaired Glucose Tolerance
Insulin Resistance
Lead sponsor: Limerick BioPharma
Sponsor class: INDUSTRY
First posted: 2011-06-02
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 28 days
Secondary outcomes:
measure: Examine the pharmacokinetics (PK) of LIM-0705 as measured by area under the curve (AUC).
timeFrame: 28 days
measure: 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
timeFrame: 28 days
measure: Explore the effect of LIM-0705 on fasting lipid, insulin and glucose profiles compared to baseline levels
timeFrame: 28 days
measure: Evaluate the tolerability (BID) of LIM-0705 administered to adult males and females with impaired glucose tolerance or abnormal HOMA-IR
timeFrame: 28 days
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: Profil Institute of Clinical Research, Inc.
state: California
Study officials:
affiliation: Profil Institute of Clinical Research, Inc.
name: Linda Morrow, MD
role: PRINCIPAL_INVESTIGATOR
References: