Type 2 Diabetes Mellitus in Obese, Obesity, Type2Diabetes
Conditions
Brief summary
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
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.
Interventions
DRUGSPI-62
SPI-62 is supplied as 1 mg tablets for oral dosing.
DRUGCortisone-d8
Cortisone-d8 is supplied as a 1 mcg/mL solution for infusion
Sponsors
Sparrow Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (Cmax) | Days 1 through 14 | Pharmacokinetics of SPI-62 and its major metabolite AS2570469 by assessment of Observed Maximum Plasma Concentration (Cmax) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (AUC0-t) | Days 1 through 14 | Pharmacokinetics of SPI-62 and its major metabolite AS2570469 by assessment of Area Under the Curve over the dosing interval |
| Cortisone-d8 concentrations | Days 1 through 14 | individual values |
| Pharmacokinetics (tmax) | Days 1 through 14 | Pharmacokinetics of SPI-62 and its major metabolite AS2570469 by assessment of Time to Cmax (tmax) |
| Urinary HSD-1 Ratio | Days -1 to 15 | Individual values of the urinary HSD-1 ratio defined as (tetrahydrocortisol + allotetrahydrocortisol) / tetrahydrocortisone |
Countries
United States
Outcome results
None listed