Trial Outcomes & Findings for Safety, Tolerability and Pharmacodynamic Activity of Sotagliflozin in Hemodynamically Stable Participants With Worsening Heart Failure (NCT NCT03292653)

Last Updated: 2021-05-11

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

32 participants

Primary outcome timeframe

Baseline up to Day 14

Results posted on

2021-05-11

Participant Flow

Participants took part in the study at 6 investigative sites in the United States, Canada, and the Netherlands from 04 December 2017 to 17 August 2019.

Participants with a diagnosis of Congestive Heart Failure (CHF), were enrolled in 1 of 3 treatment groups: Placebo, Sotagliflozin 200 milligrams (mg) or Sotagliflozin 400 mg.

Participant milestones

Participant milestones
Measure	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 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 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.
Overall Study STARTED	11	10	11
Overall Study COMPLETED	10	10	10
Overall Study NOT COMPLETED	1	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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 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 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.
Overall Study Adverse Event	0	0	1
Overall Study Did not Receive Treatment	1	0	0

Baseline Characteristics

Pharmacodynamic (PD) population included all randomized and treated participants who had valid values of the main PD parameters at baseline.

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Baseline up to Day 14

Population: Safety population included all randomized participants who had exposure to any amount of IMP.

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants 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 n=10 Participants 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 n=11 Participants 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.
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 AESIs	0 percentage of participants	0 percentage of participants	0 percentage of participants
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 AEs	40 percentage of participants	30 percentage of participants	45.5 percentage of participants
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 SAEs	10 percentage of participants	0 percentage of participants	0 percentage of participants
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 AEs Leading to Discontinuation From the IMP	0 percentage of participants	0 percentage of participants	9.1 percentage of participants
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 Deaths	0 percentage of participants	0 percentage of participants	0 percentage of participants

PRIMARY outcome

Timeframe: Baseline to Day 14

Population: Pharmacodynamic (PD) population included all randomized and treated participants who had valid values of the main PD parameters at baseline and Day 14 End of Treatment (EOT). The number of participants analyzed is the number of participants with available data.

Outcome measures

Outcome measures
Measure	Placebo n=7 Participants 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 n=6 Participants 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 n=9 Participants 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.
Change From Baseline in Hemoconcentration as Assessed by Changes in Albumin to Day 14	1.17 g/L Standard Error 2.71	2.44 g/L Standard Error 2.40	0.15 g/L Standard Error 2.14

PRIMARY outcome

Timeframe: Baseline to Day 14

Population: PD population included all randomized and treated participants who had valid values of the main PD parameters at baseline and Day 14 (EOT). The number of participants analyzed is the number of participants with available data.

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants 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 n=9 Participants 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 n=10 Participants 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.
Change From Baseline in Hemoconcentration as Assessed by Changes in Hematocrit to Day 14	0.02 percentage of red blood cells Standard Error 0.02	-0.02 percentage of red blood cells Standard Error 0.02	-0.01 percentage of red blood cells Standard Error 0.02

PRIMARY outcome

Timeframe: Baseline to Day 14

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants 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 n=9 Participants 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 n=10 Participants 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.
Change From Baseline in Hemoconcentration as Assessed by Changes in Hemoglobin to Day 14	8.16 g/L Standard Error 6.80	-8.91 g/L Standard Error 6.02	-3.94 g/L Standard Error 5.37

PRIMARY outcome

Timeframe: Baseline to Day 14

Outcome measures

Outcome measures
Measure	Placebo n=7 Participants 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 n=6 Participants 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 n=9 Participants 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.
Change From Baseline in Hemoconcentration as Assessed by Changes in Total Protein to Day 14	5.31 g/L Standard Error 4.32	0.49 g/L Standard Error 3.83	-1.05 g/L Standard Error 3.41

PRIMARY outcome

Timeframe: Baseline to 14 Days

Change in plasma volume in milliliters (mL) was assessed by the indicator dilution method using 131I-labelled human albumin.

Outcome measures

Outcome measures
Measure	Placebo n=4 Participants 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 n=6 Participants 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 n=5 Participants 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.
Changes From Baseline in Plasma Volume to Day 14	-525.00 mL Standard Error 433.19	322.20 mL Standard Error 359.23	-35.67 mL Standard Error 392.43

SECONDARY outcome

Timeframe: Baseline to Day 14

Change in erythropoietin international units per liter (IU/L) was measured by chemiluminescent enzyme-labelled immunometric assay.

Outcome measures

Outcome measures
Measure	Placebo n=7 Participants 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 n=7 Participants 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 n=10 Participants 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.
Change From Baseline in Erythropoietin to Day 14	0.03 IU/L Standard Error 5.92	13.78 IU/L Standard Error 6.26	-0.07 IU/L Standard Error 5.04

SECONDARY outcome

Timeframe: Baseline to Day 14

Change in NT-proBNP picomoles per liter (pmol/L) was measured by standard electrochemiluminescence immunoassay.

Outcome measures

Outcome measures
Measure	Placebo n=7 Participants 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 n=6 Participants 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 n=9 Participants 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.
Change From Baseline in N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) to Day 14	91.36 pmol/L Standard Error 78.04	-59.53 pmol/L Standard Error 81.28	86.10 pmol/L Standard Error 65.87

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Sotagliflozin 200 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Sotagliflozin 400 mg

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=10 participants at risk 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 n=10 participants at risk Participants were randomized to Sotagliflozin 200 mg tablet 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 n=11 participants at risk 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.
Infections and infestations Upper respiratory tract infection	10.0% 1/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	0.00% 0/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	0.00% 0/11 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.

Other adverse events

Additional Information

Medical Affairs

Lexicon Pharmaceuticals, Inc.

Phone: (510) 338-6064

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Institution must provide any proposed publication or presentation to Sponsor for Sponsor's review, comment and approval at least thirty (30) days prior to the proposed submission for publication date or the proposed presentation date. Sponsor shall have the right to have deleted from the final version of the publication any confidential information, proprietary information, or patentable subject matter.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=10 Participants 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 n=10 Participants 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 n=11 Participants 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.	Total n=31 Participants Total of all reporting groups
Age, Continuous	60.8 years STANDARD_DEVIATION 13.05 • n=10 Participants	55.1 years STANDARD_DEVIATION 12.84 • n=10 Participants	65.1 years STANDARD_DEVIATION 13.41 • n=11 Participants	60.5 years STANDARD_DEVIATION 13.34 • n=31 Participants
Sex: Female, Male Female	3 Participants n=10 Participants	0 Participants n=10 Participants	4 Participants n=11 Participants	7 Participants n=31 Participants
Sex: Female, Male Male	7 Participants n=10 Participants	10 Participants n=10 Participants	7 Participants n=11 Participants	24 Participants n=31 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=10 Participants	0 Participants n=10 Participants	1 Participants n=11 Participants	1 Participants n=31 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=10 Participants	10 Participants n=10 Participants	10 Participants n=11 Participants	30 Participants n=31 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=11 Participants	0 Participants n=31 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=11 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Asian	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=11 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=11 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Black or African American	6 Participants n=10 Participants	5 Participants n=10 Participants	4 Participants n=11 Participants	15 Participants n=31 Participants
Race (NIH/OMB) White	4 Participants n=10 Participants	5 Participants n=10 Participants	6 Participants n=11 Participants	15 Participants n=31 Participants
Race (NIH/OMB) More than one race	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=11 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=10 Participants	0 Participants n=10 Participants	1 Participants n=11 Participants	1 Participants n=31 Participants
Albumin	40.9 gram per liter (g/L) STANDARD_DEVIATION 3.48 • n=7 Participants • Pharmacodynamic (PD) population included all randomized and treated participants who had valid values of the main PD parameters at baseline.	38.0 gram per liter (g/L) STANDARD_DEVIATION 6.76 • n=7 Participants • Pharmacodynamic (PD) population included all randomized and treated participants who had valid values of the main PD parameters at baseline.	41.2 gram per liter (g/L) STANDARD_DEVIATION 2.59 • n=9 Participants • Pharmacodynamic (PD) population included all randomized and treated participants who had valid values of the main PD parameters at baseline.	40.1 gram per liter (g/L) STANDARD_DEVIATION 4.51 • n=23 Participants • Pharmacodynamic (PD) population included all randomized and treated participants who had valid values of the main PD parameters at baseline.
Hematocrit	0.38 percentage of red blood cells STANDARD_DEVIATION 0.060 • n=10 Participants • PD population included all randomized and treated participants who had valid values of the main PD parameters at baseline.	0.42 percentage of red blood cells STANDARD_DEVIATION 0.092 • n=10 Participants • PD population included all randomized and treated participants who had valid values of the main PD parameters at baseline.	0.39 percentage of red blood cells STANDARD_DEVIATION 0.052 • n=10 Participants • PD population included all randomized and treated participants who had valid values of the main PD parameters at baseline.	0.40 percentage of red blood cells STANDARD_DEVIATION 0.070 • n=30 Participants • PD population included all randomized and treated participants who had valid values of the main PD parameters at baseline.
Hemoglobin	119.6 g/L STANDARD_DEVIATION 22.86 • n=10 Participants • PD population included all randomized and treated participants who had valid values of the main PD parameters at baseline.	138.9 g/L STANDARD_DEVIATION 28.23 • n=10 Participants • PD population included all randomized and treated participants who had valid values of the main PD parameters at baseline.	124.4 g/L STANDARD_DEVIATION 22.05 • n=10 Participants • PD population included all randomized and treated participants who had valid values of the main PD parameters at baseline.	127.6 g/L STANDARD_DEVIATION 25.10 • n=30 Participants • PD population included all randomized and treated participants who had valid values of the main PD parameters at baseline.
Total Protein	69.0 g/L STANDARD_DEVIATION 6.14 • n=7 Participants • PD population included all randomized and treated participants who had valid values of the main PD parameters at baseline.	65.3 g/L STANDARD_DEVIATION 9.88 • n=7 Participants • PD population included all randomized and treated participants who had valid values of the main PD parameters at baseline.	69.6 g/L STANDARD_DEVIATION 6.23 • n=9 Participants • PD population included all randomized and treated participants who had valid values of the main PD parameters at baseline.	68.1 g/L STANDARD_DEVIATION 7.39 • n=23 Participants • PD population included all randomized and treated participants who had valid values of the main PD parameters at baseline.
Plasma Volume	3797.3 milliliter (mL) STANDARD_DEVIATION 1281.16 • n=4 Participants • PD population included all randomized and treated participants who had valid values of the main PD parameters at baseline.	4489.3 milliliter (mL) STANDARD_DEVIATION 1306.41 • n=6 Participants • PD population included all randomized and treated participants who had valid values of the main PD parameters at baseline.	3604.7 milliliter (mL) STANDARD_DEVIATION 1100.69 • n=6 Participants • PD population included all randomized and treated participants who had valid values of the main PD parameters at baseline.	3984.6 milliliter (mL) STANDARD_DEVIATION 1212.44 • n=16 Participants • PD population included all randomized and treated participants who had valid values of the main PD parameters at baseline.

Measure	Placebo n=10 participants at risk 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 n=10 participants at risk Participants were randomized to Sotagliflozin 200 mg tablet 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 n=11 participants at risk 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.
Vascular disorders Hypotension	10.0% 1/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	0.00% 0/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	0.00% 0/11 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.
Investigations Gamma-glutamyltransferase increased	0.00% 0/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	0.00% 0/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	9.1% 1/11 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.
Cardiac disorders Cardiac failure	0.00% 0/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	0.00% 0/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	9.1% 1/11 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.
Cardiac disorders Myocardial infarction	0.00% 0/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	0.00% 0/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	9.1% 1/11 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.0% 1/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	0.00% 0/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	0.00% 0/11 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.
Respiratory, thoracic and mediastinal disorders Hypoxia	10.0% 1/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	0.00% 0/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	0.00% 0/11 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	0.00% 0/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	9.1% 1/11 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.
Nervous system disorders Dizziness	0.00% 0/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	10.0% 1/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	0.00% 0/11 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.
Psychiatric disorders Insomnia	0.00% 0/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	0.00% 0/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	9.1% 1/11 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.
Psychiatric disorders Stress	0.00% 0/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	0.00% 0/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	9.1% 1/11 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.
Gastrointestinal disorders Diarrhoea	20.0% 2/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	10.0% 1/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	9.1% 1/11 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.
Gastrointestinal disorders Nausea	0.00% 0/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	10.0% 1/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	9.1% 1/11 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	10.0% 1/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	0.00% 0/11 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.
Gastrointestinal disorders Vomiting	10.0% 1/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	0.00% 0/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	9.1% 1/11 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.
Skin and subcutaneous tissue disorders Dermatitis allergic	0.00% 0/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	0.00% 0/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	9.1% 1/11 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.
Metabolism and nutrition disorders Fluid intake reduced	0.00% 0/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	10.0% 1/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	0.00% 0/11 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	0.00% 0/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	9.1% 1/11 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	0.00% 0/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	9.1% 1/11 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.00% 0/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	0.00% 0/10 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.	9.1% 1/11 • First dose of study drug to last dose of study drug (up to Day 14) + 2 weeks Safety population included all randomized participants who had exposure to any amount of IMP.