Effects of KDT501 on Metabolic Features in Insulin Resistant Subjects
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|ClinicalTrials.gov Identifier: NCT02444910|
Recruitment Status : Completed
First Posted : May 15, 2015
Last Update Posted : October 20, 2017
KDT501 is an orally administered product designed to help control impaired glucose and insulin regulation in patients with insulin resistance. Nonclinical studies demonstrate agonist activity of KDT501 at the G-protein coupled receptor 120 as well as other G-protein receptors. Nonclinical studies have also documented the ability of KDT501 to improve insulin sensitivity and glucose regulation as well as reduce proinflammatory signals. These properties combined with antihyperglycemic activity and modest, partial agonist effect of KDT501 at the peroxisome proliferator-activated receptor-gamma (PPARγ) receptor suggests an atypical and pleiotropic mechanism of action for KDT501.
Following providing informed consent, potential subjects will undergo screening procedures to ensure that they meet all inclusion and exclusion criteria. Following registration on study, subjects will undergo baseline pretreatment studies, including two abdominal fat biopsies, one taken after cold challenge, as well as determination of resting metabolic rate, a 4 hour lipid tolerance test, and a 2 hour euglycemic clamp study. All pretreatment studies in registered subjects will be performed within 7 days prior to initiating therapy. On the first day of treatment (Day 0), subjects will take the first 600 mg dose of KDT501 in the clinic, followed by serum pharmacokinetic (PK) samples being obtained every hour for 6 hours after dosing. Subjects will then continue dosing as an outpatient, 600 mg po twice daily. All doses will be taken with meals (breakfast and dinner). On Day 7, subjects will return to the clinic to undergo safety and laboratory assessments, including PK. On Days 14 and 21, subjects will again return to the clinic to undergo safety and laboratory assessments. On Day 17 subjects will return to the clinic for PK studies, as noted below. Treatment in all subjects will end on Day 28. Rapid PK assessment of drug exposure, defined as AUC0-12h, will be performed following PK samples drawn at Time 0, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, and 12h on both Days 7 and 17. On Days 11 and 21 (±1day), based on the KDT501 drug exposure level, the subject will be provided instructions on dose adjustments of KDT501. The maximum allowed KDT501 exposure ceiling for all subjects enrolled is AUC0-12h = 22,500ng-hr/mL.
|Condition or disease||Intervention/treatment||Phase|
|Diabetes Mellitus, Type 2||Drug: KDT501||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||9 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Effects of KDT501 on Metabolic Features in Insulin Resistant Subjects|
|Study Start Date :||April 2015|
|Actual Primary Completion Date :||November 2015|
|Actual Study Completion Date :||November 2015|
Experimental drug, KDT501, is administered at 600mg for 10 consecutive days. On days 11 and 21 (+/- 1 day), based on the KDT501 drug exposure level, the subject will be provided instructions on dose adjustment of KDT501. Dose adjustments will be administered at 800mg for 10 consecutive days, determined at day 11; followed by 1,000mg for 8 consecutive days if determined at day 21.
600mg twice daily, Oral, for 10days; then 800mg twice daily, Oral, for 10 days; then 1,000mg twice daily, Oral, for 8 days.
- Change from baseline of the 2 hour oral glucose tolerance test (OGTT) at day 28. [ Time Frame: 28 days (± 2 days) ]The change in serum glucose 2 hours following the administration of 75gm of oral glucose (2 hour oral glucose tolerance test (OGTT)) will be calculated as the difference in 2 hour OGTT at Day 28 (±2 days) vs. baseline.
- Change in Resting Metabolic Rate (RMR) [ Time Frame: 27 days (±4 days) ]The change in RMR will be calculated as the difference in RMR at Day 27 (±4 days) vs. baseline.
- Change in Lipid Tolerance Test [ Time Frame: 27 days (±4 days) ]The change in lipid tolerance test parameters will be calculated as the difference at Day 27 (±4 days) vs. baseline.
- Change in HbA1c, fructosamine, and glycated albumin [ Time Frame: 27 days (±4 days) ]The change in each of these assay results will be calculated as the difference at Day 27 (±4 days) vs. baseline.
- Change in Fasting Plasma Glucose [ Time Frame: 27 days (±4 days) ]The change in fasting plasma glucose will be calculated as the difference at Day 27 (±4 days) vs. baseline.
- Change in Insulin Sensitivity Based on Euglycemic Clamp Study [ Time Frame: 27 days (±4 days) ]The change in insulin sensitivity will be calculated as the difference at Day 27 (±4 days) vs. baseline.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02444910
|United States, Kentucky|
|University of Kentucky's Center for Clinical and Translational Science (CCTS)|
|Lexington, Kentucky, United States, 40536-0298|
|Principal Investigator:||Philip Kern, MD||University of Kentucky's Center for Clinical and Translational Science (CCTS)|