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

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)

Study Overview

• Status: Completed
• Conditions: Obesity; Type 2 Diabetes Mellitus in Obese; Type2Diabetes
• Intervention / Treatment: Drug: SPI-62; Drug: Cortisone-d8

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 Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Chula Vista, California, United States, 91911
      • ProSciento

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Arm; 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; SPI-62 is supplied as 1 mg tablets for oral dosing.; Other Names: HSD-1 inhibitor; Drug: Cortisone-d8; Cortisone-d8 is supplied as a 1 mcg/mL solution for infusion; Other Names: Glucocorticoid and anti-inflammatory agent

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sparrow Pharmaceuticals
• Investigators: Study Director: David Katz, PhD, Sparrow Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2021
• Primary Completion (Actual): March 10, 2022
• Study Completion (Actual): February 7, 2024

Study Registration Dates

• First Submitted: March 23, 2022
• First Submitted That Met QC Criteria: June 6, 2022
• First Posted (Actual): June 7, 2022

Study Record Updates

• Last Update Posted (Actual): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Inflammatory Agents; Cortisone; Glucocorticoids
• Other Study ID Numbers: SPI-62-CL-1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No