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

Phase 1

Completed

• Conditions: Type 2 Diabetes Mellitus in Obese; Obesity; Type2Diabetes
• Interventions: Drug: SPI-62; Drug: Cortisone-d8

• Registration Number: NCT05409027
• Lead Sponsor: Sparrow Pharmaceuticals

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.

Study Timeline

• Study Start: 2021-07-23
• Primary Completion: 2022-03-10
• Study First Submitted: 2022-03-23
• Study First Submitted QC: 2022-06-06
• Study First Posted: 2022-06-07
• Study Completion: 2024-02-07
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-18
• Last Update Posted: 2024-04-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single Arm	SPI-62	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.
Single Arm	Cortisone-d8	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.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics (Cmax)	Days 1 through 14	Pharmacokinetics of SPI-62 and its major metabolite AS2570469 by assessment of Observed Maximum Plasma Concentration (Cmax)

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics (tmax)	Days 1 through 14	Pharmacokinetics of SPI-62 and its major metabolite AS2570469 by assessment of Time to Cmax (tmax)
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
Urinary HSD-1 Ratio	Days -1 to 15	Individual values of the urinary HSD-1 ratio defined as (tetrahydrocortisol + allotetrahydrocortisol) / tetrahydrocortisone

Trial Locations

Locations (1)

ProSciento; 🇺🇸 Chula Vista, California, United States