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CompletedNCT03197324Updated Jul 23, 2021Results posted

Bexagliflozin Drug/Drug Interaction Study With Digoxin

A Phase 1 interventional study of Bexagliflozin and Digoxin in Type2 Diabetes Mellitus, sponsored by Theracos. Completed at 1 site in United States. Open to participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-07-23.

Sponsored by Theracos · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
20
Allocation
Randomized
Ages
18 Years to 55 Years
Sex
All
01

Study summary

The purpose of this study is to examine the drug-drug interaction in your body when given the study drug, bexagliflozin, with the heart failure medication digoxin. The study will evaluate whether bexagliflozin effects the amount of digoxin in your blood and how safe the study drug is and how well the study drug is tolerated when taken with digoxin.

Read the detailed description

This was a phase 1, single center, open-label, two-period, two-treatment, crossover study to evaluate the effect of bexagliflozin tablets, 20 mg, on the pharmacokinetics (PK) of digoxin, 0.5 mg after co-administration in healthy subjects. Each subject was randomized into one of 2 treatment groups and participated in 2 treatment periods as outlined below. During the duration of the study, each subject received 8 single doses of bexagliflozin and 2 single doses of digoxin. Clinical laboratory tests and safety monitoring were conducted during Periods 1 and 2.

Group 1 - Period 1, Treatment A Subjects were admitted to the clinic on Day 0. Subjects received daily oral doses of a bexagliflozin tablet, 20 mg, starting on Day 1 for 8 days, and a single oral dose of 0.5 mg digoxin (two 0.25 mg tablets) was co-administered with bexagliflozin on Day 3. Blood samples for PK were drawn at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (h) on Day 3, 24 h (Day 4), 48 h (Day 5), 72 h (Day 6), 96 h (Day 7), and 120 h (Day 8) after administration of digoxin. Subjects were discharged on Day 8.

Group 1 - Period 2, Treatment B Subjects were admitted to the clinic on Day 18. On Day 19, subjects received a single oral dose of 0.5 mg digoxin. Blood samples for PK were drawn at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 h on Day 19, 24 h (Day 20), 48 h (Day 21), 72 h (Day 22), 96 h (Day 23), and 120 h (Day 24) after administration of digoxin. Subjects were discharged on Day 24.

Group 2 - Period 1, Treatment B Subjects were admitted to the clinic on Day 0. On Day 1, subjects received a single oral dose of 0.5 mg digoxin. Blood samples for PK were drawn at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 h on Day 1, 24 h (Day 2), 48 h (Day 3), 72 h (Day 4), 96 h (Day 5), and 120 h (Day 6) after administration of digoxin. Subjects were discharged on Day 6.

Group 2 - Period 2, Treatment A Subjects were admitted to the clinic on Day 14. Subjects received daily oral doses of a bexagliflozin tablet, 20 mg, for 8 days starting on Day 15, and a single oral dose of 0.5 mg digoxin (two 0.25 mg tablets) was co-administered with bexagliflozin on Day 17. Blood samples for PK were drawn at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 h on Day 17, 24 h (Day 18), 48 h (Day 19), 72 h (Day 20), 96 h (Day 21), and 120 h (Day 22) after administration of digoxin. Subjects were discharged on Day 22.

02

Conditions studied

  • Type2 Diabetes Mellitus
03

Who can participate

Ages eligible
18 Years to 55 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  1. Subjects with body-mass index (BMI) between 18.0 kg/m2 and 32.0 kg/m2
  2. Subjects who are non-smokers for at least 6 months prior to first dose
  3. Subjects who are willing to use an adequate form of birth control during the study and for 30 days after discharge from clinic

Exclusion criteria

Exclusion Criteria:

  1. Subjects with a clinically significant history of allergy to drugs or latex
  2. Subjects with a history of alcohol or drug dependence in the past 12 months
  3. Subjects who have donated a significant amount of blood in the past 2 months
  4. Subjects who have taken an investigational drug in the past 30 days or 7 half-lives of the investigational drug, whichever is longer
  5. Subjects who had previously received digoxin or drugs of the same class, or SGLT2 inhibitors, in the past 3 months
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
20 participants (actual)

Study arms

  • Active comparator
    Digoxin Alone first, then Digoxin With Bexagliflozin

    Drug: Digoxin

  • Active comparator
    Digoxin with Bexagliflozin, then Digoxin alone

    Drug: Bexagliflozin · Drug: Digoxin

Interventions

  • DrugBexagliflozin

    Bexagliflozin tablets, 20 mg

    Also known as: EGT0001442, EGT0001474

  • DrugDigoxin

    2 0.25 mg Digoxin tablets (total dose 0.5 mg digoxin)

05

What researchers measure

Primary outcomes

  1. Digoxin Cmax (Maximum Observed Plasma Concentration)

    Blood samples for pharmacokinetic parameters were drawn at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 h after administration of digoxin

    Time frame: Up to 120 hours

  2. Digoxin Tmax (Time of Maximum Observed Plasma Concentration)

    Blood samples for pharmacokinetic parameters were drawn at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 h after administration of digoxin

    Time frame: Up to 120 hours

  3. Digoxin T1/2 (Apparent Terminal Elimination Half-life)

    Blood samples for pharmacokinetic parameters were drawn at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 h after administration of digoxin

    Time frame: Up to 120 hours

  4. AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity)

    Blood samples for pharmacokinetic parameters were drawn at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 h after administration of digoxin

    Time frame: Up to 120 hours

06

Results

Posted Jul 16, 2021

Participant flow

Participant flow — Overall Study
MilestoneDigoxin and Bexagliflozin Tablet, Then Digoxin AloneDigoxin, Then Digoxin and Bexagliflozin
Started1010
Completed109
Not completed01
Withdrew: Adverse event01

Outcome measures

PrimaryDigoxin Cmax (Maximum Observed Plasma Concentration)

Blood samples for pharmacokinetic parameters were drawn at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 h after administration of digoxin

Time frame:
Up to 120 hours
Reported as:
Geometric mean · ng/mL
Digoxin Cmax (Maximum Observed Plasma Concentration)
ng/mLDigoxin AloneDigoxin With Bexagliflozin
Digoxin Cmax (Maximum Observed Plasma Concentration)2.315 ± 28.82.301 ± 40.9
Statistical analysis
  • Digoxin Alone vs Digoxin With Bexagliflozin · Ratio of geometric lsm: 100.40 · 90% CI 86.49 to 116.56Digoxin group is the denominator and Digoxin with Bexagliflozin is the numerator. Confidence interval from ANOVA with treatment, period, and sequence as fixed effects, and subjects as a random effect.
PrimaryDigoxin Tmax (Time of Maximum Observed Plasma Concentration)

Blood samples for pharmacokinetic parameters were drawn at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 h after administration of digoxin

Time frame:
Up to 120 hours
Reported as:
Median · hours
Digoxin Tmax (Time of Maximum Observed Plasma Concentration)
hoursDigoxin AloneDigoxin With Bexagliflozin
Digoxin Tmax (Time of Maximum Observed Plasma Concentration)1.00 (1 to 2)1.00 (1 to 4)
PrimaryDigoxin T1/2 (Apparent Terminal Elimination Half-life)

Blood samples for pharmacokinetic parameters were drawn at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 h after administration of digoxin

Time frame:
Up to 120 hours
Reported as:
Geometric mean · hours
Digoxin T1/2 (Apparent Terminal Elimination Half-life)
hoursDigoxin AloneDigoxin With Bexagliflozin
Digoxin T1/2 (Apparent Terminal Elimination Half-life)34.3 ± 15.538.2 ± 15.7
PrimaryAUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity)

Blood samples for pharmacokinetic parameters were drawn at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 h after administration of digoxin

Time frame:
Up to 120 hours
Reported as:
Geometric mean · h*ng/mL
AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity)
h*ng/mLDigoxin AloneDigoxin With Bexagliflozin
AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity)35.558 ± 16.637.805 ± 27.5
Statistical analysis
  • Digoxin Alone vs Digoxin With Bexagliflozin · Ratio of geometric lsm: 106.12 · 90% CI 95.82 to 117.53Digoxin group is the denominator and Digoxin with Bexagliflozin is the numerator. Confidence interval from ANOVA with treatment, period, and sequence as fixed effects, and subjects as a random effect.

Adverse events

Collected over Adverse event data were collected from Day 0 up to Day 24 of the study. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Digoxin Alone0/20 (0%)0/20 (0%)3/20 (15%)
Digoxin With Bexagliflozin0/19 (0%)0/19 (0%)5/19 (26.3%)
Most frequent other events
Most frequent other events
EventDigoxin AloneDigoxin With Bexagliflozin
Upper respiratory tract infectionInfections and infestations1/201/19
Urinary tract infectionInfections and infestations0/201/19
FatigueGeneral disorders0/201/19
PalpitationsCardiac disorders0/201/19
NauseaGastrointestinal disorders1/201/19
ExcoriationInjury, poisoning and procedural complications0/201/19
HypoglycemiaMetabolism and nutrition disorders0/201/19
DizzinessNervous system disorders0/201/19
Medical device site reactionGeneral disorders1/200/19
Vision blurredEye disorders1/200/19

Baseline characteristics

Safety population includes subjects dosed with any study drug.

Age, Continuous
Age, Continuous(years)Bexagliflozin and Digoxin, Then Digoxin AloneDigoxin Alone, Then Bexagliflozin and DigoxinTotal
Mean44.8 ± 8.8435.2 ± 6.3740.0 ± 8.97
Sex: Female, Male
Sex: Female, Male(Participants)Bexagliflozin and Digoxin, Then Digoxin AloneDigoxin Alone, Then Bexagliflozin and DigoxinTotal
Female5510
Male5510
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Bexagliflozin and Digoxin, Then Digoxin AloneDigoxin Alone, Then Bexagliflozin and DigoxinTotal
Hispanic or Latino5712
Not Hispanic or Latino538
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Bexagliflozin and Digoxin, Then Digoxin AloneDigoxin Alone, Then Bexagliflozin and DigoxinTotal
American Indian or Alaska Native000
Asian011
Native Hawaiian or Other Pacific Islander000
Black or African American426
White6713
More than one race000
Unknown or Not Reported000
Weight
Weight(kg)Bexagliflozin and Digoxin, Then Digoxin AloneDigoxin Alone, Then Bexagliflozin and DigoxinTotal
Mean73.6 ± 11.2874.2 ± 13.6773.9 ± 12.20
Height
Height(cm)Bexagliflozin and Digoxin, Then Digoxin AloneDigoxin Alone, Then Bexagliflozin and DigoxinTotal
Mean167.1 ± 8.44165.6 ± 9.35166.4 ± 8.71
07

Study locations

1 site
  • Covance CRU
    Daytona Beach, Florida 32117, United States
08

References and documents

Study documents

  • Study protocol · Jun 13, 2017
  • Statistical analysis plan · Oct 18, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03197324
Lead sponsor
Theracos
Responsible party
Sponsor
First posted
Jun 23, 2017
Start date
Jul 24, 2017
Primary completion
Sep 17, 2017
Completion
Sep 17, 2017
Results posted
Jul 16, 2021
Last update
Jul 23, 2021

Study contacts

Mason Freeman, M.D.
study director · Massachusetts General Hospital

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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