Trial Outcomes & Findings for Drug-drug Interaction (DDI) Study of Spironolactone (Perpetrator) and Digoxin (Substrate Drug) (NCT NCT03909529)
NCT ID: NCT03909529
Last Updated: 2023-05-01
Results Overview
Primary Pharmacokinetic parameter The following pharmacokinetic parameters for Digoxin were obtained using non-compartmental method Cmax, AUC0-96, and tmax using plasma data, Renal clearance (CLR) /Percent Recovered, Unchanged drug excreted in urine (fe)/Amount Recovered using urine data.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
28 participants
Primary outcome timeframe
4 days
Results posted on
2023-05-01
Participant Flow
Participant milestones
| Measure |
LANOXIN First, Then Carospir
14 Subjects first administered with LANOXIN® (digoxin) USP 250 mcg (Substrate drug) on Day 6 of in house, after overnight fasting of at least 10.00 hours.
After washout period of 28 days, these 14 subjects were administered with Spironolactone Oral Suspension 100 mg (perpetrator, Carospir® Oral Suspension 20 mL of 25 mg / 5 mL) from day 1 to day 5 and on day 6 the after overnight fasting of at least 10.00 hours, subject was administered with LANOXIN® (digoxin) USP 250 mcg (substrate drug) + Spironolactone Oral Suspension 100 mg (perpetrator; Carospir® Oral Suspension 20 mL of 25 mg / 5 mL). From day 7 to day 9 the subjects were administered with Spironolactone Oral Suspension 100 mg (perpetrator; Carospir® Oral Suspension 20 mL of 25 mg / 5 mL)
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First Carospir, Then LANOXIN
14 Subjects first administered with Spironolactone Oral Suspension 100 mg (perpetrator, Carospir® Oral Suspension 20 mL of 25 mg / 5 mL) from day 1 to day 5 and on day 6 the after overnight fasting of at least 10.00 hours, subject was administered with LANOXIN® (digoxin) USP 250 mcg (substrate drug) + Spironolactone Oral Suspension 100 mg (perpetrator; Carospir® Oral Suspension 20 mL of 25 mg / 5 mL). From day 7 to day 9 the subjects were administered with Spironolactone Oral Suspension 100 mg (perpetrator; Carospir® Oral Suspension 20 mL of 25 mg / 5 mL).
After washout period of 28 days these 14 Subjects administered with LANOXIN® (digoxin) USP 250 mcg (Substrate drug) on Day 6 of in house, after overnight fasting of at least 10.00 hours
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Open Label, Balanced, Randomized DDI
STARTED
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14
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14
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Open Label, Balanced, Randomized DDI
COMPLETED
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14
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14
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Open Label, Balanced, Randomized DDI
NOT COMPLETED
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0
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Drug-Drug Interaction Study
n=28 Participants
In both periods (Period-I and II), from Day 1 to Day 5 and Day 7 to Day 9, the subjects who were randomized to treatment B, were administered Spironolactone Oral Suspension 100 mg (Perpetrator; Carospir® Oral Suspension 20 mL of 25 mg / 5 mL), and the subject who were randomized to treatment A were not dosed.
On all these days the standard breakfast was served 0.50 hr (30 min) post dose.
On Day 6, after overnight fasting for at least 10.00 hours the subjects were dosed either with the Treatment (A) \[LANOXIN® (digoxin) USP 250 mcg (substrate drug)\] or Treatment (B) \[LANOXIN® (digoxin) USP 250 mcg (substrate drug) + Spironolactone Oral Suspension 100 mg (Perpetrator; Carospir® Oral Suspension 20 mL of 25 mg / 5 mL)\] as per the randomization scheme.
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Age, Categorical
<=18 years
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0 Participants
n=28 Participants
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Age, Categorical
Between 18 and 65 years
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28 Participants
n=28 Participants
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Age, Categorical
>=65 years
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0 Participants
n=28 Participants
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Age, Continuous
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29 Years
n=28 Participants
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Sex: Female, Male
Female
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0 Participants
n=28 Participants
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Sex: Female, Male
Male
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28 Participants
n=28 Participants
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Region of Enrollment
India
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28 participants
n=28 Participants
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PRIMARY outcome
Timeframe: 4 daysPopulation: The following pharmacokinetic parameters for Digoxin were obtained using non-compartmental method (WinNonlin, version 8.1, Pharsight Corporation, USA): Cmax, AUC0-96, and tmax using plasma data, Renal clearance (CLR) /Percent Recovered, Unchanged drug excreted in urine (fe)/Amount Recovered using urine data.
Primary Pharmacokinetic parameter The following pharmacokinetic parameters for Digoxin were obtained using non-compartmental method Cmax, AUC0-96, and tmax using plasma data, Renal clearance (CLR) /Percent Recovered, Unchanged drug excreted in urine (fe)/Amount Recovered using urine data.
Outcome measures
| Measure |
Drug-Drug Interaction Study
n=28 Participants
This was an open label, balanced, randomized, single-dose, two-treatment, two-sequence, two-period, crossover, drug drug interaction study in healthy adult human subjects with at least 28 days washout period between each treatment period under fasting condition
In both periods (Period-I and II), from Day 1 to Day 5 and Day 7 to Day 9, the subjects who were randomized to treatment B, were administered Spironolactone Oral Suspension 100 mg (Perpetrator; Carospir® Oral Suspension 20 mL of 25 mg / 5 mL), and the subject who were randomized to treatment A were not dosed.
On Day 6, after overnight fasting for at least 10.00 hours the subjects were dosed either with the Treatment (A) \[LANOXIN® (digoxin) USP 250 mcg (substrate drug)\] or Treatment (B) \[LANOXIN® (digoxin) USP 250 mcg (substrate drug) + Spironolactone Oral Suspension 100 mg (Perpetrator; Carospir® Oral Suspension 20 mL of 25 mg / 5 mL)\] as per the randomization scheme.
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Dogoxin Plasma Data for Cmax
Treatment A
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1530.188 pg/mL
Standard Deviation 502.810
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Dogoxin Plasma Data for Cmax
Treatment B
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2432.908 pg/mL
Standard Deviation 870.562
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PRIMARY outcome
Timeframe: 4 daysArea under the plasma concentration versus time curve from time 0 to the 96 hour time point concentration.
Outcome measures
| Measure |
Drug-Drug Interaction Study
n=28 Participants
This was an open label, balanced, randomized, single-dose, two-treatment, two-sequence, two-period, crossover, drug drug interaction study in healthy adult human subjects with at least 28 days washout period between each treatment period under fasting condition
In both periods (Period-I and II), from Day 1 to Day 5 and Day 7 to Day 9, the subjects who were randomized to treatment B, were administered Spironolactone Oral Suspension 100 mg (Perpetrator; Carospir® Oral Suspension 20 mL of 25 mg / 5 mL), and the subject who were randomized to treatment A were not dosed.
On Day 6, after overnight fasting for at least 10.00 hours the subjects were dosed either with the Treatment (A) \[LANOXIN® (digoxin) USP 250 mcg (substrate drug)\] or Treatment (B) \[LANOXIN® (digoxin) USP 250 mcg (substrate drug) + Spironolactone Oral Suspension 100 mg (Perpetrator; Carospir® Oral Suspension 20 mL of 25 mg / 5 mL)\] as per the randomization scheme.
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Digoxin Plasma Data for AUC0-96
Treatment A
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13715.974 pg.hr/mL
Standard Deviation 2669.003
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Digoxin Plasma Data for AUC0-96
Treatment B
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16551.500 pg.hr/mL
Standard Deviation 4108.500
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SECONDARY outcome
Timeframe: 4 daysIf the maximum value occurs at more than one time point, Tmax is defined as the first time point with this value.
Outcome measures
| Measure |
Drug-Drug Interaction Study
n=28 Participants
This was an open label, balanced, randomized, single-dose, two-treatment, two-sequence, two-period, crossover, drug drug interaction study in healthy adult human subjects with at least 28 days washout period between each treatment period under fasting condition
In both periods (Period-I and II), from Day 1 to Day 5 and Day 7 to Day 9, the subjects who were randomized to treatment B, were administered Spironolactone Oral Suspension 100 mg (Perpetrator; Carospir® Oral Suspension 20 mL of 25 mg / 5 mL), and the subject who were randomized to treatment A were not dosed.
On Day 6, after overnight fasting for at least 10.00 hours the subjects were dosed either with the Treatment (A) \[LANOXIN® (digoxin) USP 250 mcg (substrate drug)\] or Treatment (B) \[LANOXIN® (digoxin) USP 250 mcg (substrate drug) + Spironolactone Oral Suspension 100 mg (Perpetrator; Carospir® Oral Suspension 20 mL of 25 mg / 5 mL)\] as per the randomization scheme.
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Digoxin Plasma Data for Tmax
Treatment A
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0.744 hr
Standard Deviation 0.195
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Digoxin Plasma Data for Tmax
Treatment B
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0.901 hr
Standard Deviation 0.569
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SECONDARY outcome
Timeframe: 4 daysECG will be performed at 1.00 and 3.00 hours post dose in each period on Day 6 and at check-out of each period of the study
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 04 DaysSummary Statistics for Untransformed Urine PK Parameters of digoxin Per Treatment-Renal clearance (CLR)/Percent Recovered
Outcome measures
| Measure |
Drug-Drug Interaction Study
n=28 Participants
This was an open label, balanced, randomized, single-dose, two-treatment, two-sequence, two-period, crossover, drug drug interaction study in healthy adult human subjects with at least 28 days washout period between each treatment period under fasting condition
In both periods (Period-I and II), from Day 1 to Day 5 and Day 7 to Day 9, the subjects who were randomized to treatment B, were administered Spironolactone Oral Suspension 100 mg (Perpetrator; Carospir® Oral Suspension 20 mL of 25 mg / 5 mL), and the subject who were randomized to treatment A were not dosed.
On Day 6, after overnight fasting for at least 10.00 hours the subjects were dosed either with the Treatment (A) \[LANOXIN® (digoxin) USP 250 mcg (substrate drug)\] or Treatment (B) \[LANOXIN® (digoxin) USP 250 mcg (substrate drug) + Spironolactone Oral Suspension 100 mg (Perpetrator; Carospir® Oral Suspension 20 mL of 25 mg / 5 mL)\] as per the randomization scheme.
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Renal Clearance (CLR)/Percent Recovered
Treatment A
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54.687 % recovered
Standard Deviation 29.158
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Renal Clearance (CLR)/Percent Recovered
Treatment B
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53.378 % recovered
Standard Deviation 21.256
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OTHER_PRE_SPECIFIED outcome
Timeframe: 04 DaysSummary of Urine Pharmacokinetic parameters for digoxin -unchanged drug excreted in urine (fe)/ Amount Recovered
Outcome measures
| Measure |
Drug-Drug Interaction Study
n=28 Participants
This was an open label, balanced, randomized, single-dose, two-treatment, two-sequence, two-period, crossover, drug drug interaction study in healthy adult human subjects with at least 28 days washout period between each treatment period under fasting condition
In both periods (Period-I and II), from Day 1 to Day 5 and Day 7 to Day 9, the subjects who were randomized to treatment B, were administered Spironolactone Oral Suspension 100 mg (Perpetrator; Carospir® Oral Suspension 20 mL of 25 mg / 5 mL), and the subject who were randomized to treatment A were not dosed.
On Day 6, after overnight fasting for at least 10.00 hours the subjects were dosed either with the Treatment (A) \[LANOXIN® (digoxin) USP 250 mcg (substrate drug)\] or Treatment (B) \[LANOXIN® (digoxin) USP 250 mcg (substrate drug) + Spironolactone Oral Suspension 100 mg (Perpetrator; Carospir® Oral Suspension 20 mL of 25 mg / 5 mL)\] as per the randomization scheme.
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Unchanged Drug Excreted in Urine (fe)/ Amount Recovered
Treatment A
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136717.72 nanograms
Standard Deviation 72895.492
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Unchanged Drug Excreted in Urine (fe)/ Amount Recovered
Treatment B
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133446.07 nanograms
Standard Deviation 53141.044
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Adverse Events
Treatment-A- Single Dose of Digoxin (LANOXIN)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Treatment-B-Digoxin (LANOXIN) + Spiranolactone (Carospir)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place