Cardiac Failure AggravatedPhase 2NCT03292653
Safety, Tolerability and Pharmacodynamic Activity of Sotagliflozin in Hemodynamically Stable Participants With Worsening Heart Failure
A Phase 2 study testing Sotagliflozin in people with Cardiac Failure Aggravated, run by Lexicon Pharmaceuticals at 6 sites in 3 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiac Failure Aggravated
- What is being tested?
- Sotagliflozin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 6 sitesin 3 countries
- Study dates
- 4 Dec 2017to 17 Aug 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent.
- 18 years of age or older.
- Participants admitted to the hospital or had urgent visit to emergency department or heart failure unit/clinic or infusion center for Congestive Heart Failure (CHF), defined by:
- Presence of ≥2 of the following clinical signs and symptoms of congestion: jugular venous distension, pitting edema in lower extremities greater than trace, dyspnea, rales heard on auscultation, radiographic pulmonary congestion, weight gain above historical dry weight of at least 5 pounds (lbs) (2.27 Kilograms (kg)).
- Requiring treatment with intravenous (IV) diuretics.
- Estimated glomerular filtration rate (eGFR) ≥30 milliliter per minute (mL/min)/1.73 square meter (m^2) at the screening or randomization visit by the 4 variable Modification of Diet in Renal Disease (MDRD) equation.
Show all 10Show fewer
- Female participants must use a double contraception method during the study including a highly effective method of birth control, except if she has undergone sterilization at least 3 months earlier or is postmenopausal.
- Male participants, unless vasectomized and confirmed sterile by sperm analysis, must use condoms during the study and refrain from donating sperm up to 90 days after the day of last dose. If the participant has a female partner of childbearing potential, the participant must wear a condom and female partner must use at least 1 highly effective method of birth control during the study treatment period and the Follow-up period.
- Transitioning from IV to oral diuretics, and oral diuretic treatment has been prescribed or administered.
- Hemodynamically stable, defined as systolic blood pressure (SBP) >100 millimeters of mercury (mmHg) with no requirement for IV inotropes or IV vasodilators.
Who cannot join
- History of Type 1 diabetes mellitus.
- Appears unlikely or unable to participate in the required study procedures, as assessed by the study Investigator, study coordinator, or designee (ex: clinically-significant psychiatric, addictive, or neurological disease), or sectioned due to an official or court order.
- Current admission or visit for Worsening Heart Failure (HF) that is clearly and primarily triggered by causes such as tachyarrhythmia (example: sustained ventricular tachycardia, or atrial fibrillation/flutter with sustained ventricular response > 130 beats per minute), acute coronary syndrome, pulmonary embolism, cerebrovascular accident, heart valve disorders (such as severe aortic stenosis), as determined by the Investigator.
- Clinically significant myocardial infarction (MI) within past 1 month as determined by Investigator and with objective evidence from ECG, and/or cardiac imaging and/or coronary angiography. Small isolated elevations in troponin that often accompany HF hospitalization are not an exclusion, nor are clinically significant MIs that have been revascularized without complications.
- Participants who recently had or scheduled to have cardiac interventions may be eligible if:
- Stable 48 hours post procedure.
Show all 24Show fewer
- Have diuretic treatment planned for the duration of treatment in this study.
- Current use of or recent suspension of digoxin therapy with high levels of digoxin (level should be obtained and must be <1.2 nanograms per milliliter (ng/mL) at screening.
- History of heart or kidney transplant.
- Diagnosis of hypertrophic obstructive cardiomyopathy.
- End-stage HF defined as requiring left ventricular assist device insertion, intra-aortic balloon placement (IABP), or any type of mechanical support during the study period.
- Pregnancy (demonstrated by serum pregnancy test at screening), breast-feeding, or inability or refusal to undergo pregnancy testing.
- Use of any investigational drug(s) or prohibited therapy or sodium-glucose co-transporter 2 (SGLT2) 5 half-lives prior to screening.
- Participants with moderate or severe respiratory, hepatic, neurological, psychiatric, active malignant tumor or other major systemic disease (including any diseases with evidence of malabsorption), making implementation of the protocol and/or the interpretation of the study results difficult.
- Known allergies, hypersensitivity, or intolerance to sotagliflozin or any inactive component of sotagliflozin or placebo (ie, microcrystalline cellulose, croscarmellose sodium [disintegrant], talc, silicon dioxide, and magnesium stearate [non-bovine]), unless the reaction is deemed irrelevant to the study by the PI.
- Laboratory findings at the Screening Visit:
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 times the upper limit of the normal laboratory range (ULN) (1 repeat lab allowed).
- Total bilirubin >1.7 times the ULN (except in case of Gilbert's syndrome) (1 repeat lab allowed).
- Amylase and/or lipase >3 times the ULN (1 repeat lab allowed).
- Participants with a severe or persistent in spite of optimal treatment genitourinary tract infection at time of randomization.
- Participant is the Investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol.
- History of diabetic ketoacidosis or non-ketotic hyperosmolar coma within 3 months prior to the screening visit.
- Lower extremity diabetic complications (such as skin ulcers, infection, osteomyelitis and gangrene) identified during the Screening period, and still requiring treatment at randomization.
- The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Trial locations and contacts
6 sites in 3 countries.
6 sites in 3 countries
United States4 sites
Investigational Site Number 8400002
Cleveland, Ohio, 44195
Investigational Site Number 8400005
La Jolla, California, 92037
Investigational Site Number 8400001
New Haven, Connecticut, 06510
Investigational Site Number 8400007
Rochester, Minnesota, 55905
About this study
Official title: An Exploratory, Randomized, Double-blind, Placebo-controlled, Parallel Arm Trial of the Safety and Pharmacodynamic Activity of Sotagliflozin in Hemodynamically Stable Patients Hospitalized With Worsening Heart Failure
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.
Read more
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.
Read the 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.
- Conditions
- Cardiac Failure Aggravated
- Being tested
- Sotagliflozin, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SotagliflozinDrug
Also called SAR439954
Pharmaceutical form: Tablet; Route of administration: Oral
PlaceboDrug
Pharmaceutical form: Tablet; Route of administration: Oral
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
| Sotagliflozin 200 mg | Experimental | 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. Receives: Drug: Sotagliflozin; Drug: Placebo |
| Sotagliflozin 400 mg | Experimental | 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. Receives: Drug: Sotagliflozin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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.
Measured: Baseline up to Day 14
Change From Baseline in Hemoconcentration as Assessed by Changes in Albumin to Day 14
Measured: Baseline to Day 14
Change From Baseline in Hemoconcentration as Assessed by Changes in Hematocrit to Day 14
Measured: Baseline to Day 14
Change From Baseline in Hemoconcentration as Assessed by Changes in Hemoglobin to Day 14
Measured: Baseline to Day 14
Change From Baseline in Hemoconcentration as Assessed by Changes in Total Protein to Day 14
Measured: Baseline to Day 14
Changes From Baseline in Plasma Volume to Day 14
Change in plasma volume in milliliters (mL) was assessed by the indicator dilution method using 131I-labelled human albumin.
Measured: Baseline to 14 Days
Secondary outcomes (2)
Change From Baseline in Erythropoietin to Day 14
Change in erythropoietin international units per liter (IU/L) was measured by chemiluminescent enzyme-labelled immunometric assay.
Measured: Baseline to Day 14
Change From Baseline in N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) to Day 14
Change in NT-proBNP picomoles per liter (pmol/L) was measured by standard electrochemiluminescence immunoassay.
Measured: Baseline to Day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2017
- Study start4 Dec 2017
- Primary completion17 Aug 2019
- Study completion17 Aug 2019
Why it stopped: 1st two cohorts provided the required data, therefore 3rd cohort was not deemed necessary
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cardiac Failure AggravatedStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lexicon Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Sanofi
- Responsible party
- Sponsor
- Investigators
- Suman Wason, MD, Study director, Lexicon Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03292653
- Sponsor's protocol ID
- PDY15079
- Other IDs
- 2017-002774-39, U1111-1190-7962, 2017
- Status last verified
- Apr 2021
- First submitted
- 20 Sep 2017
- Last updated
- 11 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory, Randomized, Double-blind, Placebo-controlled, Parallel Arm Trial of the Safety and Pharmacodynamic Activity of Sotagliflozin in Hemodynamically Stable Patients Hospitalized With Worsening Heart Failure
- ClinicalTrials.gov ID
- NCT03292653
- Acronym / sponsor ID
- PDY15079
- Conditions
- Cardiac Failure Aggravated
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: 1st two cohorts provided the required data, therefore 3rd cohort was not deemed necessary
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Lexicon PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- Sanofi
- Study start
- 4 Dec 2017 (actual)
- Primary completion
- 17 Aug 2019 (actual)
- Study completion
- 17 Aug 2019 (actual)
- First posted
- 25 Sep 2017 (actual)
- Results
- Posted 11 May 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboParticipants 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 | Experimental | Drug: Sotagliflozin, Drug: PlaceboParticipants 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 | Experimental | Drug: SotagliflozinParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Written informed consent.
- 18 years of age or older.
- Participants admitted to the hospital or had urgent visit to emergency department or heart failure unit/clinic or infusion center for Congestive Heart Failure (CHF), defined by:
- Presence of ≥2 of the following clinical signs and symptoms of congestion: jugular venous distension, pitting edema in lower extremities greater than trace, dyspnea, rales heard on auscultation, radiographic pulmonary congestion, weight gain above historical dry weight of at least 5 pounds (lbs) (2.27 Kilograms (kg)).
- Requiring treatment with intravenous (IV) diuretics.
Key exclusion criteria (24 listed)
- History of Type 1 diabetes mellitus.
- Appears unlikely or unable to participate in the required study procedures, as assessed by the study Investigator, study coordinator, or designee (ex: clinically-significant psychiatric, addictive, or neurological disease), or sectioned due to an official or court order.
- Current admission or visit for Worsening Heart Failure (HF) that is clearly and primarily triggered by causes such as tachyarrhythmia (example: sustained ventricular tachycardia, or atrial fibrillation/flutter with sustained ventricular response > 130 beats per minute), acute coronary syndrome, pulmonary embolism, cerebrovascular accident, heart valve disorders (such as severe aortic stenosis), as determined by the Investigator.
- Clinically significant myocardial infarction (MI) within past 1 month as determined by Investigator and with objective evidence from ECG, and/or cardiac imaging and/or coronary angiography. Small isolated elevations in troponin that often accompany HF hospitalization are not an exclusion, nor are clinically significant MIs that have been revascularized without complications.
- Participants who recently had or scheduled to have cardiac interventions may be eligible if:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SotagliflozinAlso: SAR439954Pharmaceutical form: Tablet; Route of administration: Oral | Drug | Sotagliflozin 200 mg, Sotagliflozin 400 mg |
| PlaceboPharmaceutical form: Tablet; Route of administration: Oral | Drug | Placebo, Sotagliflozin 200 mg |
Primary outcome
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
Time frame: 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
Time frame: Baseline to Day 14
Change From Baseline in Hemoconcentration as Assessed by Changes in Hematocrit to Day 14
Time frame: Baseline to Day 14
Change From Baseline in Hemoconcentration as Assessed by Changes in Hemoglobin to Day 14
Time frame: Baseline to Day 14
Change From Baseline in Hemoconcentration as Assessed by Changes in Total Protein to Day 14
Time frame: Baseline to Day 14
Changes From Baseline in Plasma Volume to Day 14
Time frame: Baseline to 14 Days
Change in plasma volume in milliliters (mL) was assessed by the indicator dilution method using 131I-labelled human albumin.
2 secondary outcomes
Change From Baseline in Erythropoietin to Day 14
Time frame: Baseline to Day 14
Change From Baseline in N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) to Day 14
Time frame: Baseline to Day 14
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Suman Wason, MD study director
Lexicon Pharmaceuticals, Inc.
6 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sotagliflozin in people with Cardiac Failure Aggravated, run by Lexicon Pharmaceuticals at 6 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Canada, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: Baseline up to Day 14). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2021.