A Study to Assess 11 Beta-hydroxysteroid Dehydrogenase Type 1 Inhibition in Adipose Tissue by SPI-62

Study Overview
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Brief Summary
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This will be an exploratory, open-label study of 11β-hydroxysteroid dehydrogenase type 1 (HSD-1) inhibition by SPI-62 in obese subjects with type 2 diabetes mellitus (T2DM)

Detailed Description
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The main objective of the study is to characterize the relationship between SPI-62 plasma concentration and adipose tissue inhibition of HSD-1 in obese subjects with T2DM.Additional objectives of the study are to characterize the relationship between adipose SPI-62 concentration and HSD-1 inhibition, to characterize the relationship between SPI-62 plasma concentration and liver inhibition of HSD-1, and to monitor the safety and tolerability of SPI-62, in obese subjects with T2DM. This will be a Phase I, open-label study in male and non-menstruating female subjects. Potential subjects will be screened to assess their eligibility to enter the study within 28 days prior to the first dose administration. Subjects will receive SPI-62 daily for up to 14 days. Subjects will also receive cortisone-d8, a mass-labeled HSD-1 substrate, by infusion during one or two confined study visits during the period of SPI-62 administration. Subjects may also receive cortisone-d8 during one to four additional confined study visits after cessation of SPI-62. Subjects will receive a follow-up call approximately 30 days after the last dose of study drug (SPI-62 or cortisone-d8). Results of population pharmacokinetic-pharmacodynamic modeling of data from this trial combined with those of prior trials will be reported separately from the Clinical Study Report.

Official Title
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A Study to Assess 11 Beta-hydroxysteroid Dehydrogenase Type 1 Inhibition in Adipose Tissue by SPI-62

Conditions
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Obesity, Type 2 Diabetes Mellitus in Obese, Type2Diabetes

Intervention / Treatment
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* Drug: SPI-62
* Drug: Cortisone-d8


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or non-menstruating female 18 to 65 years of age BMI 30.0 to 45.0 kg/m2 Diagnosis of T2DM for at least 3 months prior to the first dose of study drug. Exclusion Criteria: Uncontrolled T2DM with glycated hemoglobin ≥9.5%. Any other current or prior medical condition expected to interfere with the conduct of the trial or the evaluation of its results. Any clinically significant abnormal laboratory value which cannot be explained by a known and permitted clinical condition. Positive urine drug screen (except tetrahydrocannabinol) or positive alcohol breath test result. Participation in a clinical trial involving administration of an investigational drug (new chemical entity) in the past 30 days or 5 half-lives, whichever is longer, or 90 days for a biological, prior to the first dose of study drug. Use of, or intent to use, any medications/products (prescription or over-the-counter) or herbal supplements within 4 weeks prior to the first dose of study drug, except those specifically allowed in the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm<br>Each subject will receive between 1 to 15 mg SPI-62 QD PO for up to 14 days. Each subject will receive up to 12 mcg cortisone-d8 SC during each of one or more study visits. | Drug: SPI-62<br>* SPI-62 is supplied as 1 mg tablets for oral dosing.<br>* Other names: HSD-1 inhibitor;Drug: Cortisone-d8<br>* Cortisone-d8 is supplied as a 1 mcg/mL solution for infusion<br>* Other names: Glucocorticoid and anti-inflammatory agent;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (Cmax) | Pharmacokinetics of SPI-62 and its major metabolite AS2570469 by assessment of Observed Maximum Plasma Concentration (Cmax) | Days 1 through 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (tmax) | Pharmacokinetics of SPI-62 and its major metabolite AS2570469 by assessment of Time to Cmax (tmax) | Days 1 through 14 | 
| Pharmacokinetics (AUC0-t) | Pharmacokinetics of SPI-62 and its major metabolite AS2570469 by assessment of Area Under the Curve over the dosing interval | Days 1 through 14 | 
| Cortisone-d8 concentrations | individual values | Days 1 through 14 | 
| Urinary HSD-1 Ratio | Individual values of the urinary HSD-1 ratio defined as (tetrahydrocortisol + allotetrahydrocortisol) / tetrahydrocortisone | Days -1 to 15 |