Safety, Tolerability and Pharmacodynamic Activity of Sotagliflozin in Hemodynamically Stable Participants With Worsening Heart Failure

Phase 2

Terminated

• Conditions: Cardiac Failure Aggravated
• Interventions: Drug: Placebo; Drug: Sotagliflozin

• Registration Number: NCT03292653
• Lead Sponsor: Lexicon Pharmaceuticals

Brief Summary

Primary Objectives:

* Assess the safety and tolerability of sotagliflozin in hemodynamically stable participants with worsening of heart failure, compared to placebo.

* Estimate the effects of sotagliflozin on plasma volume changes in hemodynamically stable participants with worsening of heart failure, compared to placebo.

Secondary Objectives:

* Explore the effect of sotagliflozin on erythropoiesis, as assessed by changes in plasma erythropoietin levels, in hemodynamically stable participants with worsening of heart failure, compared to placebo.

* Explore the effect of sotagliflozin on changes in plasma N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels, in hemodynamically stable participants with worsening of heart failure, compared to placebo.

Detailed Description

The total study duration will be approximately 27-40 days, including a screening period of 1-10 days, a treatment period of 14 days, and a follow-up period of 14±2 days.

Study Timeline

• Study First Submitted: 2017-09-20
• Study First Submitted QC: 2017-09-20
• Study First Posted: 2017-09-25
• Study Start: 2017-12-04
• Primary Completion: 2019-08-17
• Study Completion: 2019-08-17
• Disposition First Submitted: 2020-08-14
• Disposition First Submitted QC: 2020-08-14
• Disposition First Posted: 2020-08-20
• Status Verified: 2021-04
• Results First Submitted: 2021-04-16
• Results First Submitted QC: 2021-04-16
• Last Update Submitted: 2021-04-16
• Results First Posted: 2021-05-11
• Last Update Posted: 2021-05-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants were randomized to matching placebo to sotagliflozin administered as two tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 14 days.
Sotagliflozin 200 mg	Sotagliflozin	Participants were randomized to Sotagliflozin 200 mg administered as 1 sotagliflozin tablet and 1 matching placebo tablet, once daily, before the first meal of the day in the double-blind treatment period for up to 14 days.
Sotagliflozin 200 mg	Placebo	Participants were randomized to Sotagliflozin 200 mg administered as 1 sotagliflozin tablet and 1 matching placebo tablet, once daily, before the first meal of the day in the double-blind treatment period for up to 14 days.
Sotagliflozin 400 mg	Sotagliflozin	Participants were randomized to Sotagliflozin 400 mg administered as two 200 mg sotagliflozin tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 14 days.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs of Special Interest (AESIs), AEs Leading to Discontinuation From the Investigational Medicinal Product (IMP) and Deaths	Baseline up to Day 14	AE: is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. SAEs: an event that results in death; an event that, in the view of the investigator, places the participants at immediate risk of death (a life-threatening event); an outcome that results in a congenital anomaly/birth defect diagnosed in a child of a participant; an event that requires or prolongs inpatient hospitalization; an event that results in persistent or significant disability/incapacity. AESI: is an adverse event (serious or nonserious) of scientific and medical concern, specific to the IMP or program, for which ongoing monitoring and rapid communication by the Investigator to the Sponsor may be appropriate.
Change From Baseline in Hemoconcentration as Assessed by Changes in Albumin to Day 14	Baseline to Day 14
Change From Baseline in Hemoconcentration as Assessed by Changes in Hematocrit to Day 14	Baseline to Day 14
Change From Baseline in Hemoconcentration as Assessed by Changes in Hemoglobin to Day 14	Baseline to Day 14
Change From Baseline in Hemoconcentration as Assessed by Changes in Total Protein to Day 14	Baseline to Day 14
Changes From Baseline in Plasma Volume to Day 14	Baseline to 14 Days	Change in plasma volume in milliliters (mL) was assessed by the indicator dilution method using 131I-labelled human albumin.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Erythropoietin to Day 14	Baseline to Day 14	Change in erythropoietin international units per liter (IU/L) was measured by chemiluminescent enzyme-labelled immunometric assay.
Change From Baseline in N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) to Day 14	Baseline to Day 14	Change in NT-proBNP picomoles per liter (pmol/L) was measured by standard electrochemiluminescence immunoassay.

Trial Locations

Locations (6)

Investigational Site Number 8400005; 🇺🇸 La Jolla, California, United States

Investigational Site Number 1240001; 🇨🇦 Toronto, Canada

Investigational Site Number 5280001; 🇳🇱 Groningen, Netherlands

Investigational Site Number 8400001; 🇺🇸 New Haven, Connecticut, United States

Investigational Site Number 8400002; 🇺🇸 Cleveland, Ohio, United States

Investigational Site Number 8400007; 🇺🇸 Rochester, Minnesota, United States